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1.
Nat Mater ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38769206

ABSTRACT

Structurally ordered L10-PtM (M = Fe, Co, Ni and so on) intermetallic nanocrystals, benefiting from the chemically ordered structure and higher stability, are one of the best electrocatalysts used for fuel cells. However, their practical development is greatly plagued by the challenge that the high-temperature (>600 °C) annealing treatment necessary for realizing the ordered structure usually leads to severe particle sintering, morphology change and low ordering degree, which makes it very difficult for the gram-scale preparation of desirable PtM intermetallic nanocrystals with high Pt content for practical fuel cell applications. Here we report a new concept involving the low-melting-point-metal (M' = Sn, Ga, In)-induced bond strength weakening strategy to reduce Ea and promote the ordering process of PtM (M = Ni, Co, Fe, Cu and Zn) alloy catalysts for a higher ordering degree. We demonstrate that the introduction of M' can reduce the ordering temperature to extremely low temperatures (≤450 °C) and thus enable the preparation of high-Pt-content (≥40 wt%) L10-Pt-M-M' intermetallic nanocrystals as well as ten-gram-scale production. X-ray spectroscopy studies, in situ electron microscopy and theoretical calculations reveal the fundamental mechanism of the Sn-facilitated ordering process at low temperatures, which involves weakened bond strength and consequently reduced Ea via Sn doping, the formation and fast diffusion of low-coordinated surface free atoms, and subsequent L10 nucleation. The developed L10-Ga-PtNi/C catalysts display outstanding performance in H2-air fuel cells under both light- and heavy-duty vehicle conditions. Under the latter condition, the 40% L10-Pt50Ni35Ga15/C catalyst delivers a high current density of 1.67 A cm-2 at 0.7 V and retains 80% of the current density after extended 90,000 cycles, which exceeds the United States Department of Energy performance metrics and represents among the best cathodic electrocatalysts for practical proton-exchange membrane fuel cells.

2.
Hum Mol Genet ; 31(15): 2623-2638, 2022 08 17.
Article in English | MEDLINE | ID: mdl-35313349

ABSTRACT

The mitochondrial kinase PTEN-induced kinase 1 (PINK1) and cytosolic ubiquitin ligase (E3) Parkin/PRKN are involved in mitochondrial quality control responses. PINK1 phosphorylates ubiquitin and the Parkin ubiquitin-like (Ubl) domain at serine 65 and promotes Parkin activation and translocation to damaged mitochondria. Upon Parkin activation, the Ubl domain is ubiquitinated at lysine (K) 27 and K48 residues. However, the contribution of K27/K48 ubiquitination toward Parkin activity remains unclear. In this study, ubiquitination of K56 (corresponding to K27 in the human), K77 (K48 in the human) or both was blocked by generating Drosophila Parkin (dParkin) mutants to examine the effects of Parkin Ubl domain ubiquitination on Parkin activation in Drosophila. The dParkin, in which K56 was replaced with arginine (dParkin K56R), rescued pupal lethality in flies by co-expression with PINK1, whereas dParkin K77R could not. The dParkin K56R exhibited reduced abilities of mitochondrial fragmentation and motility arrest, which are mediated by degrading Parkin E3 substrates Mitofusin and Miro, respectively. Pathogenic dParkin K56N, unlike dParkin K56R, destabilized the protein, suggesting that not only was dParkin K56N non-ubiquitin-modified at K56, but also the structure of the Ubl domain for activation was largely affected. Ubiquitin attached to K27 of the Ubl domain during PINK1-mediated Parkin activation was likely to be phosphorylated because human Parkin K27R weakened Parkin self-binding and activation in trans. Therefore, our findings suggest a new mechanism of Parkin activation, where an activation complex is formed through phospho-ubiquitin attachment on the K27 residue of the Parkin Ubl domain.


Subject(s)
Drosophila Proteins , Ubiquitin , Animals , Drosophila/metabolism , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Humans , Lysine , Phosphorylation , Protein Kinases/genetics , Protein Serine-Threonine Kinases , Ubiquitin/genetics , Ubiquitin-Protein Ligases/metabolism , Ubiquitination
3.
Nucleic Acids Res ; 50(18): 10230-10248, 2022 10 14.
Article in English | MEDLINE | ID: mdl-36124682

ABSTRACT

Estrogen and estrogen receptor alpha (ERα)-induced gene transcription is tightly associated with ERα-positive breast carcinogenesis. ERα-occupied enhancers, particularly super-enhancers, have been suggested to play a vital role in regulating such transcriptional events. However, the landscape of ERα-occupied super-enhancers (ERSEs) as well as key ERα-induced target genes associated with ERSEs remain to be fully characterized. Here, we defined the landscape of ERSEs in ERα-positive breast cancer cell lines, and demonstrated that bromodomain protein BRD4 is a master regulator of the transcriptional activation of ERSEs and cognate ERα target genes. RET, a member of the tyrosine protein kinase family of proteins, was identified to be a key ERα target gene of BRD4-regulated ERSEs, which, in turn, is vital for ERα-induced gene transcriptional activation and malignant phenotypes through activating the RAS/RAF/MEK2/ERK/p90RSK/ERα phosphorylation cascade. Combination therapy with BRD4 and RET inhibitors exhibited additive effects on suppressing ERα-positive breast cancer both in vitro and in vivo, comparable with that of standard endocrine therapy tamoxifen. Furthermore, combination therapy re-sensitized a tamoxifen-resistant ERα-positive breast cancer cell line to tamoxifen treatment. Taken together, our data uncovered the critical role of a super-enhancer-associated positive feedback loop constituting BRD4/ERα-RET-ERα in ERα-positive breast cancer, and suggested that targeting components in this loop would provide a new therapeutic avenue for treating ERα-positive breast cancer in the clinic.


Subject(s)
Breast Neoplasms , Estrogen Receptor alpha , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Cycle Proteins , Cell Line, Tumor , Cell Proliferation , Drug Resistance, Neoplasm , Estrogen Receptor alpha/genetics , Estrogen Receptor alpha/metabolism , Estrogens , Feedback, Physiological , Female , Gene Expression Regulation, Neoplastic , Humans , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Protein-Tyrosine Kinases/metabolism , Proto-Oncogene Proteins c-ret/genetics , Proto-Oncogene Proteins c-ret/metabolism , Proto-Oncogene Proteins c-ret/therapeutic use , Tamoxifen/pharmacology , Transcription Factors/genetics , Transcription Factors/metabolism
4.
Opt Express ; 31(6): 10070-10081, 2023 Mar 13.
Article in English | MEDLINE | ID: mdl-37157564

ABSTRACT

Optical wireless communication is an attractive technique for data center interconnects due to its low latency line-of-sight connectivity. Multicast, on the other hand, is an important data center network function that can improve traffic throughput, reduce latency, and make efficient use of network resources. To enable reconfigurable multicast in data center optical wireless networks, we propose a novel 360° optical beamforming scheme based on the principle of superposition of orbital angular momentum modes, emitting beams from the source rack pointing towards any combination of other racks so that connections are established between the source and multiple destination racks. We experimentally demonstrate the scheme using solid state devices for a scenario where racks are arranged in a hexagonal formation in which a source rack can connect with any number of adjacent racks simultaneously, with each link transmitting 70 Gb/s on-off-keying modulations at bit error rates of <10-6 at 1.5-m and 2.0-m link distances.

5.
Opt Express ; 31(2): 2467-2479, 2023 Jan 16.
Article in English | MEDLINE | ID: mdl-36785260

ABSTRACT

A weakly-coupled few mode fiber (FMF) with a simple double-layer core is designed and fabricated that support five (seven) weakly coupled mode groups with average attenuation of 0.21 dB/km (0.39 dB/km) at the C + L (O) optical wavelength bands. Two data transmission experiments are demonstrated utilizing the fiber. A 2-km orbital angular momentum (OAM) mode-group multiplexing (MGM) experiment in the O band achieves error-free transmission for all five multiplexed mode groups without multiple multiple-input multiple-output (MIMO) processing. A 40-km OAM mode division multiplexing (MDM) experiment supporting 14 mode channels in the C + L bands achieves bit error rates (BER) of below 2.4 × 10-2 (20% soft-decision forward-error-correction threshold) for all channels, based on low-complexity 4 × 4 or 2 × 2 MIMO equalization. These demonstrations prove the capability of the fiber to support weakly coupled MDM/MGM transmission across O + C + L optical wavelength bands.

6.
Inflamm Res ; 72(3): 443-462, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36598534

ABSTRACT

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease, and is characterized by accumulation of α-synuclein (α-syn). Neuroinflammation driven by microglia is an important pathological manifestation of PD. α-Syn is a crucial marker of PD, and its accumulation leads to microglia M1-like phenotype polarization, activation of NLRP3 inflammasomes, and impaired autophagy and phagocytosis in microglia. Autophagy of microglia is related to degradation of α-syn and NLRP3 inflammasome blockage to relieve neuroinflammation. Microglial autophagy and phagocytosis of released α-syn or fragments from apoptotic neurons maintain homeostasis in the brain. A variety of PD-related genes such as LRRK2, GBA and DJ-1 also contribute to this stability process. OBJECTIVES: Further studies are needed to determine how α-syn works in microglia. METHODS: A keyword-based search was performed using the PubMed database for published articles. CONCLUSION: In this review, we discuss the interaction between microglia and α-syn in PD pathogenesis and the possible mechanism of microglial autophagy and phagocytosis in α-syn clearance and inhibition of neuroinflammation. This may provide a novel insight into treatment of PD.


Subject(s)
Neurodegenerative Diseases , Parkinson Disease , Humans , alpha-Synuclein/genetics , alpha-Synuclein/metabolism , Autophagy , Inflammasomes/metabolism , Microglia/metabolism , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/pathology , Neuroinflammatory Diseases , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Parkinson Disease/genetics , Parkinson Disease/metabolism , Parkinson Disease/pathology , Phagocytosis
7.
Environ Sci Technol ; 57(35): 13067-13078, 2023 09 05.
Article in English | MEDLINE | ID: mdl-37603309

ABSTRACT

Aerosol black carbon (BC) is a short-lived climate pollutant. The poorly constrained provenance of tropical marine aerosol BC hinders the mechanistic understanding of extreme climate events and oceanic carbon cycling. Here, we collected PM2.5 samples during research cruise NORC2016-10 through South China Sea (SCS) and Northeast Indian Ocean (NEIO) and measured the dual-carbon isotope compositions (δ13C-Δ14C) of BC using hydrogen pyrolysis technique. Aerosol BC exhibits six different δ13C-Δ14C isotopic spaces (i.e., isotope provinces). Liquid fossil fuel combustion, from shipping emissions and adjacent land, is the predominant source of BC over isotope provinces "SCS close to Chinese Mainland" (53.5%), "Malacca Strait" (53.4%), and "Open NEIO" (40.7%). C3 biomass burning is the major contributor to BC over isotope provinces "NEIO close to Southeast Asia" (55.8%), "Open NEIO" (41.3%), and "Open SCS" (40.0%). Coal combustion and C4 biomass burning show higher contributions to BC over "Sunda Strait" and "Open SCS" than the others. Overall, NEIO near the Bay of Bengal, Malacca Strait, and north SCS are three hot spots of fossil fuel-derived BC; the first two areas are also hot spots of biomass-derived BC. The comparable δ13C-Δ14C between BC in aerosol and dissolved BC in surface seawater may suggest atmospheric BC deposition as a potential source of oceanic dissolved BC.


Subject(s)
Fossil Fuels , Indian Ocean , Aerosols , Carbon Isotopes , China
8.
Environ Res ; 216(Pt 1): 114469, 2023 01 01.
Article in English | MEDLINE | ID: mdl-36195159

ABSTRACT

In order to investigate the impact of "Blue Sky War" implemented during 2018-2020 on carbonaceous aerosols in Beijing-Tianjin-Hebei (BTH) region, China, fine particulate matter (PM2.5) samples were collected simultaneously in Tianjin and Handan in three consecutive winters from 2018 to 2020. Organic carbon (OC) and elemental carbon (EC) in PM2.5 were measured with the same thermal-optical methods and analysis protocols. Significant reductions in primary organic carbon (POC) and EC concentrations were observed both in Tianjin and Handan, with decreasing rates of 0.65 and 2.95 µg m-3 yr-1 for POC and 0.13 and 0.64 µg m-3 yr-1 for EC, respectively. The measured absorption coefficients of EC (babs, EC) also decreased year by year, with a decreasing rate of 1.82 and 6.16 Mm-1 yr-1 in Tianjin and Handan, respectively. The estimated secondary organic carbon (SOC) concentrations decreased first and then increased in both Tianjin and Handan, accounting for more than half of the total OC in winter of 2020-2021 and with increasing contributions especially in highly polluted days. SOC was recognized as one of key factors influencing EC light absorption. EC in the two cities was relatively more related to coal combustion and industrial sources. The reductions of primary carbonaceous components may be attributed to the air quality regulations targeting coal combustion and industrial sources emissions in BTH area. Potential source contribution function (PSCF) analysis results indicated that the major source areas of OC and EC in Tianjin were the southwest region of the sampling site, while the southeast areas for Handan. These findings demonstrated the effectiveness of air quality regulation in primary emissions in typical polluted cities in BTH region and highlighted the needs for further control and in-depth investigation of SOC formation along with implementation of air pollution control act in the future.


Subject(s)
Air Pollutants , Cities , Air Pollutants/analysis , Beijing , Environmental Monitoring , Aerosols/analysis , Particulate Matter/analysis , Coal/analysis , Carbon/analysis , Seasons , China
9.
J Chem Phys ; 158(4): 044116, 2023 Jan 28.
Article in English | MEDLINE | ID: mdl-36725491

ABSTRACT

Understanding, predicting, and ultimately controlling exciton band structure and exciton dynamics are central to diverse chemical and materials problems. Here, we have developed a first-principles method to determine exciton dispersion and exciton-phonon interaction in semiconducting and insulating solids based on time-dependent density functional theory. The first-principles method is formulated in planewave bases and pseudopotentials and can be used to compute exciton band structures, exciton charge density, ionic forces, the non-adiabatic coupling matrix between excitonic states, and the exciton-phonon coupling matrix. Based on the spinor formulation, the method enables self-consistent noncollinear calculations to capture spin-orbital coupling. Hybrid exchange-correlation functionals are incorporated to deal with long-range electron-hole interactions in solids. A sub-Hilbert space approximation is introduced to reduce the computational cost without loss of accuracy. For validations, we have applied the method to compute the exciton band structure and exciton-phonon coupling strength in transition metal dichalcogenide monolayers; both agree very well with the previous GW-Bethe-Salpeter equation and experimental results. This development paves the way for accurate determinations of exciton dynamics in a wide range of solid-state materials.

10.
Ecotoxicol Environ Saf ; 263: 115277, 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37499390

ABSTRACT

Numerous antibiotic resistance genes (ARGs) and virulence factors (VFs) found in animal manure pose significant risks to human health. However, the effects of graphene sodium selenite (GSSe), a novel chemical nano-Selenium, and biological nano-Selenium (BNSSe), a new bioaugmentation nano-Se, on bacterial Se metabolism, chemotaxis, ARGs, and VFs in animal manure remain unknown. In this study, we investigated the effects of GSSe and BNSSe on ARGs and VFs expression in broiler manure using high-throughput sequencing. Results showed that BNSSe reduced Se pressure during anaerobic fermentation by inhibiting bacterial selenocompound metabolism pathways, thereby lowering manure Selenium pollution. Additionally, the expression levels of ARGs and VFs were lower in the BNSSe group compared to the Sodium Selenite and GSSe groups, as BNSSe inhibited bacterial chemotaxis pathways. Co-occurrence network analysis identified ARGs and VFs within the following phyla Bacteroidetes (genera Butyricimonas, Odoribacter, Paraprevotella, and Rikenella), Firmicutes (genera Lactobacillus, Candidatus_Borkfalkia, Merdimonas, Oscillibacter, Intestinimonas, and Megamonas), and Proteobacteria (genera Desulfovibrio). The expression and abundance of ARGs and VFs genes were found to be associated with ARGs-VFs coexistence. Moreover, BNSSe disruption of bacterial selenocompound metabolism and chemotaxis pathways resulted in less frequent transfer of ARGs and VFs. These findings indicate that BNSSe can reduce ARGs and VFs expression in animal manure by suppressing bacterial selenocompound metabolism and chemotaxis pathways.


Subject(s)
Selenium , Humans , Animals , Selenium/pharmacology , Manure/analysis , Genes, Bacterial , Anti-Bacterial Agents/pharmacology , Chemotaxis/genetics , Sodium Selenite/pharmacology , Chickens/genetics , Bacteria , Drug Resistance, Microbial/genetics , Bacteroidetes , Firmicutes
11.
Int J Mol Sci ; 24(10)2023 May 19.
Article in English | MEDLINE | ID: mdl-37240367

ABSTRACT

To explore the mechanism of inconsistent relationships between plasma lipid profiles and post-traumatic stress disorder (PTSD) reported before, we hypothesized that interplays might exist between PTSD and a variation of rs5925 at low-density lipoprotein receptor (LDLR) gene on plasma lipid profiles. To test our hypothesis, we analyzed the plasma lipid profiles of 709 high school pupils with various genotypes of LDLR rs5925 and with or without PTSD. The results demonstrated that PTSD prevalence in the C allele carriers was higher than that in the TT homozygotes regardless of gender. The C allele carriers had higher levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), ratios of TC to high-density lipoprotein cholesterol (TC/HDL-C) and LDL-C/HDL-C than the TT homozygotes in the male controls, and only higher TC in the female controls, but no differences in the male or female PTSD subjects. PTSD increased TC in the female TT homozygotes but not in the female C allele carriers. PTSD increased TC/HDL-C in the male TT homozygotes but not in the C allele carriers. These results suggest interactions between PTSD and LDLR rs5925 on plasma lipid profiles, which may be among the explanations for previously reported inconsistent relationships between LDLR rs5925 or PTSD and plasma lipid profiles, and facilitate the development of precision medicine interferences in hypercholesterolemia in individuals with different genetic backgrounds and psychiatric status. Psychiatric care or drug supplement may particularly be needed by female hypercholesterolemic subjects with the TT genotype of LDLR rs5925 in Chinese adolescents.


Subject(s)
Hypercholesterolemia , Stress Disorders, Post-Traumatic , Adolescent , Humans , Male , Female , Homozygote , Stress Disorders, Post-Traumatic/genetics , Cholesterol, LDL , Lipids , Genotype , Cholesterol, HDL
12.
Pharm Biol ; 61(1): 1274-1285, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37599625

ABSTRACT

CONTEXT: Clerodendranthus spicatus Thunb. (Labiatae) (CS), a perennial traditional Chinese medicinal herb that can reduce serum uric acid (sUA) levels and ameliorate renal function is widely used to treat hyperuricaemic nephropathy (HN). OBJECTIVE: To investigate the molecular mechanism of action of CS in HN treatment using in vivo and in vitro experiments. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into control, HN, CS and positive control allopurinol groups. The HN group was intraperitoneally injected with 750 mg/kg oxonic acid potassium (OA), whereas the CS group was injected with OA along with a gavage of CS (low dose 3.125 g/kg, high dose 6.25 g/kg) for five weeks. For in vitro studies, uric acid-treated HK2 cells were used to verify the therapeutic mechanism of CS in HN. RESULTS: HN rats exhibit pathological phenotypes of elevated sUA levels and renal injury. CS significantly improved these symptoms and sUA (p < 0.05) and blood urea nitrogen (p < 0.01) levels, and dramatically improved renal tubular injury in HN rats. The IC50 value of UA (uric acid) in HK2 cells was 826.32 ± 3.55 µg/mL; however, 120 ng/mL CS had no significant cytotoxicity on HK2 cells. In vivo and in vitro studies showed that CS inhibited NF-κB phosphorylation and inhibited α-smooth muscle actin (α-SMA) and vimentin expression while increasing E-cadherin expression, suggesting that CS inhibited the fibrotic process in renal cells, thus protecting renal function. DISCUSSION AND CONCLUSIONS: These findings provide a fundamental understanding of the application of CS in HN treatment to better guide clinical interventions.


Subject(s)
Hyperuricemia , NF-kappa B , Animals , Rats , Rats, Sprague-Dawley , Hyperuricemia/drug therapy , Uric Acid , Epithelial-Mesenchymal Transition , Kidney/physiology
13.
BMC Bioinformatics ; 23(Suppl 3): 427, 2022 Oct 14.
Article in English | MEDLINE | ID: mdl-36241972

ABSTRACT

BACKGROUND: Increasing evidence shows that circRNA plays an essential regulatory role in diseases through interactions with disease-related miRNAs. Identifying circRNA-disease associations is of great significance to precise diagnosis and treatment of diseases. However, the traditional biological experiment is usually time-consuming and expensive. Hence, it is necessary to develop a computational framework to infer unknown associations between circRNA and disease. RESULTS: In this work, we propose an efficient framework called MSPCD to infer unknown circRNA-disease associations. To obtain circRNA similarity and disease similarity accurately, MSPCD first integrates more biological information such as circRNA-miRNA associations, circRNA-gene ontology associations, then extracts circRNA and disease high-order features by the neural network. Finally, MSPCD employs DNN to predict unknown circRNA-disease associations. CONCLUSIONS: Experiment results show that MSPCD achieves a significantly more accurate performance compared with previous state-of-the-art methods on the circFunBase dataset. The case study also demonstrates that MSPCD is a promising tool that can effectively infer unknown circRNA-disease associations.


Subject(s)
MicroRNAs , RNA, Circular , Computational Biology/methods , Gene Ontology , MicroRNAs/genetics , Neural Networks, Computer
14.
Opt Express ; 30(11): 18199-18207, 2022 May 23.
Article in English | MEDLINE | ID: mdl-36221626

ABSTRACT

A successful transmission of 14 multiplexed orbital angular momentum (OAM) channels each carrying 80 wavelengths over a 100-km single-span ring-core fiber (RCF) is experimentally demonstrated. Each transmission channel is modulated by a 20-GBaud quadrature phase-shift keying (QPSK) signal, achieving a record spectral-efficiency-distance product of 1870 (bit/s/Hz)·km for the single-core RCF based mode division multiplexing (MDM) transmissions. In addition, only low-complexity 2×2 or 4×4 multiple-input multiple-output (MIMO) equalization with time-domain equalization tap number no more than 25 is required to deal with the crosstalk among the highly degenerate intra-MG modes at the receiving end of the demonstrated OAM-MDM-WDM system, showing great potential in large-capacity and relatively long-distance MDM transmission with low digital signal processing (DSP) complexity.

15.
Environ Res ; 209: 112791, 2022 06.
Article in English | MEDLINE | ID: mdl-35101394

ABSTRACT

Due to the lack of black carbon (BC) measurement data in some cases, elemental carbon (EC) is often used as a surrogate of BC, with a simple assumption that they are interchangeable. Such assumption will inevitably lead to uncertainties in radiative forcing estimation and health impact assessment. In order to quantitatively and systematically evaluate the relationship between BC and EC as well as factors responsible for their difference, 3-year collocated equivalent BC (eBC) and EC measurements with 1-h resolution were performed in Beijing, China continuously from 2016 to 2019. EBC concentration was measured by the multi-wavelength aethalometer (AE-33) based on optical analysis, while EC concentration was determined by semi-continuous OC/EC analyzer with thermal-optical method. The results showed that around 90% of eBC concentration was higher than that of EC, with average difference between eBC and EC as 1.21 µg m-3 (accounting for 33% of average eBC in Beijing). EBC and EC concentrations exhibited strong correlation (r = 0.90) during the whole study period, but the slopes (or eBC/EC ratio) and correlation coefficients varied across seasons (spring: 1.67 and 0.94; summer: 0.91 and 0.65; fall: 1.15 and 0.88; winter: 1.09 and 0.91, respectively). Based on the information from shell/core ratios by Single Particle Soot Photometer (SP2), source apportionment results by positive matrix factorization model, and chemical composition of PM2.5, the differences between eBC and EC concentrations were found to be primarily related to BC aging process and secondary components as evidenced by strong positive correlation with secondary species (e.g., secondary organic carbon and nitrate). This study provided seasonal specific conversion factors of eBC and EC in Beijing and helpful reference for other areas, which will contribute new knowledge of carbonaceous aerosol and reduce uncertainty in assessing future climate change and health studies of BC.


Subject(s)
Air Pollutants , Soot , Aerosols/analysis , Air Pollutants/analysis , Beijing , Carbon/analysis , China , Environmental Monitoring/methods , Particulate Matter/analysis , Seasons , Soot/analysis
16.
Mol Ther ; 29(10): 3011-3026, 2021 10 06.
Article in English | MEDLINE | ID: mdl-34058385

ABSTRACT

Glioblastoma (GBM) is the deadliest brain malignancy without effective treatments. Here, we reported that epidermal growth factor receptor-targeted chimeric antigen receptor T cells (EGFR CAR-T) were effective in suppressing the growth of GBM cells in vitro and xenografts derived from GBM cell lines and patients in mice. However, mice soon acquired resistance to EGFR CAR-T cell treatment, limiting its potential use in the clinic. To find ways to improve the efficacy of EGFR CAR-T cells, we performed genomics and transcriptomics analysis for GBM cells incubated with EGFR CAR-T cells and found that a large cohort of genes, including immunosuppressive genes, as well as enhancers in vicinity are activated. BRD4, an epigenetic modulator functioning on both promoters and enhancers, was required for the activation of these immunosuppressive genes. Accordingly, inhibition of BRD4 by JQ1 blocked the activation of these immunosuppressive genes. Combination therapy with EGFR CAR-T cells and JQ1 suppressed the growth and metastasis of GBM cells and prolonged survival in mice. We demonstrated that transcriptional modulation by targeting epigenetic regulators could improve the efficacy of immunotherapy including CAR-T, providing a therapeutic avenue for treating GBM in the clinic.


Subject(s)
Azepines/administration & dosage , Brain Neoplasms/therapy , Cell Cycle Proteins/metabolism , ErbB Receptors/immunology , Glioblastoma/therapy , Immunotherapy, Adoptive/methods , Receptors, Chimeric Antigen/metabolism , Transcription Factors/metabolism , Triazoles/administration & dosage , Animals , Azepines/pharmacology , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Cell Cycle Proteins/antagonists & inhibitors , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Combined Modality Therapy , Epigenesis, Genetic/drug effects , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic/drug effects , Glioblastoma/genetics , Glioblastoma/metabolism , Humans , Mice , Neoplasm Metastasis , Transcription Factors/antagonists & inhibitors , Triazoles/pharmacology , Xenograft Model Antitumor Assays
17.
Mediators Inflamm ; 2022: 5400592, 2022.
Article in English | MEDLINE | ID: mdl-36254157

ABSTRACT

Background: Traumatic optic neuropathy (TON) refers to damage to the optic nerve resulting from direct and indirect trauma to the head and face. One of the important pathological processes in TON is the death of retinal ganglion cells (RGCs), but the cause of RGCs death remains unclear. We aimed to explore the mechanisms of RGCs death in an experimental TON model. Methods: Optic nerve crush injury was induced in ten New Zealand white rabbits. On the 1st, 3rd, 7th, 14th, and 28th days after the operation, the retinal tissues of the rabbits were observed pathologically by hematoxylin-eosin staining. The expression of POU-homeodomain transcription factor Brn3a and glial fibrillary acidic protein (GFAP) was measured by immunofluorescence to evaluate the number of RGCs and astrocytes, respectively. miRNA expression and protein levels were assessed by RT-qPCR and western blot methods, respectively. Finally, the malondialdehyde content, superoxide dismutase activity, and proinflammatory factor levels were measured by ELISA. Western blot and dual-luciferase reporter assays were used to elucidate the relationship between miR-181d-5p and nuclear factor I-A (NFIA). Results: Blunt ocular trauma increased oxidative stress and apoptosis and reduced ganglion cell layer (GCL) density. The expression of miR-181d-5p was decreased in retinal tissues, and its overexpression relieved RGCs death, astrocyte development, oxidative stress, and inflammation of the retina, which were reversed by NFIA overexpression. Conclusion: miR-181d-5p can protect against the deterioration of TON by inhibiting RGCs death, astrocyte development, oxidative stress, and inflammation by targeting NFIA. This study provides new insight into early medical intervention in patients with TON.


Subject(s)
MicroRNAs , Optic Nerve Injuries , Animals , Rabbits , Astrocytes/metabolism , Eosine Yellowish-(YS)/metabolism , Eosine Yellowish-(YS)/therapeutic use , Glial Fibrillary Acidic Protein/metabolism , Hematoxylin/metabolism , Hematoxylin/therapeutic use , Inflammation/metabolism , Malondialdehyde/metabolism , MicroRNAs/metabolism , NFI Transcription Factors/metabolism , Retinal Ganglion Cells/metabolism , Retinal Ganglion Cells/pathology , Superoxide Dismutase/metabolism
18.
Sensors (Basel) ; 22(17)2022 Aug 28.
Article in English | MEDLINE | ID: mdl-36080931

ABSTRACT

With the wide application of Internet of things (IoT) devices in enterprises, the traditional boundary defense mechanisms are difficult to satisfy the demands of the insider threats detection. IoT insider threat detection can be more challenging, since internal employees are born with the ability to escape the deployed information security mechanism, such as firewalls and endpoint protection. In order to detect internal attacks more accurately, we can analyze users' web browsing behaviors to identify abnormal users. The existing web browsing behavior anomaly detection methods ignore the dynamic change of the web browsing behavior of the target user and the behavior consistency of the target user in its peer group, which results in a complex modeling process, low system efficiency and low detection accuracy. Therefore, the paper respectively proposes the individual user behavior model and the peer-group behavior model to characterize the abnormal dynamic change of user browsing behavior and compare the mutual behavioral inconsistency among one peer-group. Furthermore, the fusion model is presented for insider threat detection which simultaneously considers individual behavioral abnormal dynamic changes and mutual behavioral dynamic inconsistency from peers. The experimental results show that the proposed fusion model can accurately detect insider threat based on the abnormal user web browsing behaviors in the enterprise networks.


Subject(s)
Internet , Humans
19.
Br J Nutr ; 126(6): 892-902, 2021 09 28.
Article in English | MEDLINE | ID: mdl-33256855

ABSTRACT

The aim was to systematically analyse the association of the specific flavonoids, Mg and their interactions from different food sources with the metabolic syndrome (MetS) and its components in a cohort study. A total of 6417 participants aged 20 to 74 years from the Harbin Cohort Study on Diet, Nutrition and Chronic Non-communicable Diseases were included. Multivariate logistic regression analyses, forest plot and restricted cubic spline were performed in the study. After a 5·3-year follow-up, 1283 incident cases of the MetS were reported. Those with a higher total flavonoid intake had a lower risk of the MetS (fourth v. first quartile, relative risk (RR) 0·58; 95 % CI 0·37, 0·93; P = 0·024) and central obesity (RR 0·56; 95 % CI 0·33, 0·95; P = 0·032). Further analysis showed that the specific flavonoids quercetin, kaempferol, isorhamnetin, luteolin, and flavonoids from fruits, potatoes and legumes had the similar associations with risk of the MetS and central obesity (P < 0·05 for all). A higher intake of total flavonoids, quercetin and luteolin combined with a high level of Mg was more strongly associated with a lower risk of the MetS (RR 0·60; 95 % CI 0·45, 0·81 for total; RR 0·61; 95 % CI 0·45, 0·82 for quercetin; RR 0·52; 95 % CI 0·38, 0·71 for luteolin; all Pfor interaction < 0·01). Dose-response effects showed an L-shaped curve between the total intake of five flavonoids and the risk of the MetS. A higher flavonoid intake is associated with a lower risk of the MetS and central obesity; their combination with Mg helps to strengthen their negative association with the MetS.


Subject(s)
Diet , Flavonoids/administration & dosage , Magnesium , Metabolic Syndrome , Adult , Aged , China/epidemiology , Humans , Kaempferols , Luteolin , Magnesium/administration & dosage , Metabolic Syndrome/epidemiology , Middle Aged , Obesity , Obesity, Abdominal/epidemiology , Polyphenols , Prospective Studies , Quercetin , Risk Factors , Young Adult
20.
Inorg Chem ; 60(4): 2117-2121, 2021 Feb 15.
Article in English | MEDLINE | ID: mdl-33400525

ABSTRACT

Flexible olefinic trans-1,2-bis(4-pyridyl)ethene linkers were postsynthetically introduced into the metal-organic frameworks (MOFs) containing parallel rigid 4,4'-bipyridine linkers with a spacing of less than 4.2 Å by the linker exchange strategy, and then, the MOF satisfied Schmidt criteria could be obtained. Eventually, MOF products connected by cyclobutane derivatives were formed by the photochemical [2 + 2] cycloaddition reaction under UV irradiation.

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