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1.
Environ Sci Technol ; 58(1): 760-770, 2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38149879

RESUMEN

The photochemically generated oxidative organic radicals (POORs) in dissolved black carbon (DBC) was investigated and compared with that in dissolved organic matter (DOM). POORs generated in DBC solutions exhibited higher one-electron reduction potential values (1.38-1.56 V) than those in DOM solutions (1.22-1.38 V). We found that the photogeneration of POORs from DBC is enhanced with dissolved oxygen (DO) increasing, while the inhibition of POORs is observed in reference to DOM solution. The behavior of the one-electron reducing species (DBC•-/DOM•-) was employed to explain this phenomenon. The experimental results revealed that the DO concentration had a greater effect on DBC•- than on DOM•-. Low DO levels led to a substantial increase in the steady-state concentration of DBC•-, which quenched the POORs via back-electron reactions. Moreover, the contribution of POORs to the degradation of 19 emerging organic contaminants (EOCs) in sunlight-exposed DBC and DOM solutions was estimated. The findings indicate that POORs play an important role in the photodegradation of EOCs previously known to react with triplets, especially in DBC solutions. Compared to DOM solutions, POOR exhibits a lower but considerable contribution to EOC attenuation. This study enhances the understanding of pollutant fate in aquatic environments by highlighting the role of DBC in photochemical pollutant degradation and providing insights into pollutant transformation mechanisms involving POORs.


Asunto(s)
Contaminantes Ambientales , Energía Solar , Fotólisis , Oxígeno , Hollín , Materia Orgánica Disuelta , Carbono , Estrés Oxidativo
2.
Bioorg Chem ; 147: 107371, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38643564

RESUMEN

Due to the strong selectivity and permeability of tumor tissue, anti-cancer peptide-drug conjugates (PDCs) can accumulate high concentration of toxic payloads at the target, effectively killing tumor cells. This approach holds great promise for tumor-targeted treatment. In our previous study, we identified the optimal peptide P1 (NPNWGRSWYNQRFK) targeting HER2 from pertuzumab, a monoclonal antibody that blocks the HER2 signaling pathway. Here, a series of PDCs were constructed through connecting P1 and CPT with different linkers. Among these, Z8 emerged as the optimal compound, demonstrating good antitumor activity and targeting ability in biological activity tests. Z8 exhibited IC50 values of 1.04 ± 0.24 µM and 1.91 ± 0.71 µM against HER2-positive SK-BR-3 and NCI-N87 cells, respectively. Moreover, superior antitumor activity and higher biosafety of Z8 were observed compared to the positive control CPT in vivo, suggesting a novel idea for the construction of PDCs.


Asunto(s)
Antineoplásicos , Camptotecina , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Péptidos , Receptor ErbB-2 , Humanos , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inhibidores , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Camptotecina/farmacología , Camptotecina/química , Relación Estructura-Actividad , Animales , Proliferación Celular/efectos de los fármacos , Péptidos/química , Péptidos/farmacología , Péptidos/síntesis química , Estructura Molecular , Relación Dosis-Respuesta a Droga , Ratones , Descubrimiento de Drogas , Línea Celular Tumoral , Femenino , Ratones Endogámicos BALB C , Ratones Desnudos
3.
Bioorg Chem ; 147: 107405, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38696843

RESUMEN

The prolonged intravitreal administration of anti-vascular endothelial growth factor (VEGF) drugs is prone to inducing aberrant retinal vascular development and causing damage to retinal neurons. Hence, we have taken an alternative approach by designing and synthesizing a series of cyclic peptides targeting CC motif chemokine receptor 3 (CCR3). Based on the binding mode of the N-terminal region in CCR3 protein to CCL11, we used computer-aided identification of key amino acid sequence, conformational restriction through different cyclization methods, designed and synthesized a series of target cyclic peptides, and screened the preferred compound IB-2 through affinity. IB-2 exhibits excellent anti-angiogenic activity in HRECs. The apoptosis level of 661W cells demonstrated a significant decrease with the escalating concentration of IB-2. This suggests that IB-2 may have a protective effect on photoreceptor cells. In vivo experiments have shown that IB-2 significantly reduces retinal vascular leakage and choroidal neovascularization (CNV) area in a laser-induced mouse model of CNV. These findings indicate the potential of IB-2 as a safe and effective therapeutic agent for AMD, warranting further development.


Asunto(s)
Degeneración Macular , Péptidos Cíclicos , Receptores CCR3 , Animales , Péptidos Cíclicos/química , Péptidos Cíclicos/farmacología , Péptidos Cíclicos/síntesis química , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/patología , Ratones , Receptores CCR3/antagonistas & inhibidores , Receptores CCR3/metabolismo , Humanos , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/síntesis química , Inhibidores de la Angiogénesis/química , Estructura Molecular , Relación Estructura-Actividad , Ratones Endogámicos C57BL , Relación Dosis-Respuesta a Droga , Apoptosis/efectos de los fármacos , Neovascularización Coroidal/tratamiento farmacológico , Neovascularización Coroidal/patología , Neovascularización Coroidal/metabolismo , Células Fotorreceptoras de Vertebrados/efectos de los fármacos , Células Fotorreceptoras de Vertebrados/patología , Angiogénesis
4.
Angew Chem Int Ed Engl ; 63(23): e202403415, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38573437

RESUMEN

Metal-backboned polymers (MBPs), with a unique backbone consisting of bonded metal atoms, are promising for optic, electric, magnetic, and thermoelectric fields. However, the application of MBP remains relatively understudied. Here, we develop a shear-induced orientation method to construct a flexible nickel-backboned polymer/carbon nanotube (NBP/CNT) thermoelectric composite fiber. It demonstrated a power factor of 719.48 µW ⋅m-1 K-2, which is ca. 3.5 times as high as the bare CNT fiber. Remarkably, with the regulation of carrier mobility and carrier concentration of NBP, the composite fiber further showed simultaneous increases in electrical conductivity and Seebeck coefficient in comparison to the bare CNT fiber. The NBP/CNT fiber can be integrated into fabrics to harvest thermal energy of human body to generate an output voltage of 3.09 mV at a temperature difference of 8 K. This research opens a new avenue for the development of MBPs in power supply.

5.
Virol J ; 20(1): 193, 2023 08 28.
Artículo en Inglés | MEDLINE | ID: mdl-37641134

RESUMEN

Influenza A viruses cause severe respiratory illnesses in humans and animals. Overreaction of the innate immune response to influenza virus infection results in hypercytokinemia, which is responsible for mortality and morbidity. The influenza A virus surface glycoprotein neuraminidase (NA) plays a vital role in viral attachment, entry, and virion release from infected cells. NA acts as a sialidase, which cleaves sialic acids from cell surface proteins and carbohydrate side chains on nascent virions. Here, we review progress in understanding the role of NA in modulating host immune response to influenza virus infection. We also discuss recent exciting findings targeting NA protein to interrupt influenza-induced immune injury.


Asunto(s)
Virus de la Influenza A , Gripe Humana , Infecciones por Orthomyxoviridae , Animales , Humanos , Neuraminidasa , Inmunidad Innata
6.
Bioorg Med Chem Lett ; 88: 129284, 2023 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-37060933

RESUMEN

Cyclin-dependent kinase 2 (CDK2) is considered as an important target in the research of antitumor drugs. Taking the CDK2/4/6 inhibitor Ebvaciclib as the positive control and an in-house library compound (23) as the lead compound, three classes of 30 target compounds with pteridin-7(8H)-one as the core structure were designed to establish structure-activity relationships (SAR). In general, SAR of pteridin-7(8H)-one CDK2 inhibitors is systematically described in this paper, resulting in the discovery of two compounds (KII-17 and KII-21) with further research value. After the above compounds were tested for CDK2/4/6 kinase selectivity, we found that compound KII-21 was about 3 and 4 times more selective to CDK2-cyclinE2 than CDK4-cyclinD1 and CDK6-cyclinD3, respectively. This work also provides a reference basis for the subsequent research on CDK2 inhibitors.


Asunto(s)
Antineoplásicos , Inhibidores de Proteínas Quinasas , Antineoplásicos/química , Quinasa 2 Dependiente de la Ciclina , Quinasa 4 Dependiente de la Ciclina , Inhibidores de Proteínas Quinasas/química , Relación Estructura-Actividad
7.
Bioorg Med Chem Lett ; 88: 129265, 2023 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-37011767

RESUMEN

Son of sevenless 1 (SOS1) is a vital guanine nucleotide exchange factor (GEFs) that activates rat sarcoma (Ras) protein in cells. SOS1 inhibitors can effectively inhibit the expression of downstream signaling pathways by blocking the interaction between SOS1 and Ras protein. Here, we designed and synthesized a series of quinazoline-based compounds, and conducted subsequent evaluations of their biological activities. Among them, the comparable compounds I-2 (IC50 = 20 nM, against SOS1) I-5 (IC50 = 18 nM, against SOS1) and I-10 (IC50 = 8.5 nM, against SOS1) have kinase activity equivalent to BAY-293 (IC50 = 6.6 nM, against SOS1), and I-10 also has cell activity equivalent to BAY-293, providing a theoretical reference for subsequent related researches on SOS1 inhibitors.


Asunto(s)
Núcleo Familiar , Transducción de Señal , Proteínas Son Of Sevenless , Factores de Intercambio de Guanina Nucleótido/metabolismo , Fosforilación , Proteínas Son Of Sevenless/antagonistas & inhibidores , Quinazolinas/química , Quinazolinas/farmacología
8.
Environ Sci Technol ; 57(30): 11144-11151, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37462617

RESUMEN

Photosensitized renoxification of HNO3 is found to produce HONO in an unexpectedly high yield, which has been considered an important source for atmospheric HONO. Conventionally, the production of HONO is ascribed to the secondary photolysis of the primarily formed NO2. In this study, by using humic acid (HA) as a model environmental photosensitizer, we provide evidence of the direct formation of NO2 in its electronic excited state (NO2*) as a key intermediate during the photosensitizing renoxification of HNO3. Moreover, the high HONO yield originates from the heterogeneous reaction of the primarily formed NO2* with the co-adsorbed water molecules on HA. Such a mechanism is supported by the increase of the product selectivity of HONO with relative humidity. Further luminescence measurements demonstrate clearly the occurrence of an electronic excited state (NO2*) from photolysis of adsorbed HNO3 on HA. This work deepens our understanding of the formation of atmospheric HONO and gives insight into the transformation of RNS.


Asunto(s)
Dióxido de Nitrógeno , Ácido Nitroso , Sustancias Húmicas , Fotólisis , Agua
9.
Environ Sci Technol ; 57(11): 4434-4442, 2023 03 21.
Artículo en Inglés | MEDLINE | ID: mdl-36883325

RESUMEN

Fe(III) and carboxylic acids are common compositions in atmospheric microdroplet systems like clouds, fogs, and aerosols. Although photochemical processes of Fe(III)-carboxylate complexes have been extensively studied in bulk aqueous solution, relevant information on the dynamic microdroplet system, which may be largely different from the bulk phase, is rare. With the help of the custom-made ultrasonic-based dynamic microdroplet photochemical system, this study examines the photochemical process of Fe(III)-citric acid complexes in microdroplets for the first time. We find that when the degradation extent of citric acid is similar between the microdroplet system and the bulk solution, the significantly lower Fe(II) ratio is present in microdroplet samples due to the rapider reoxidation of photogenerated Fe(II). However, by replacing citric acid with benzoic acid, no much difference in the Fe(II) ratio between microdroplets and bulk solution is observed, which indicates distinct reoxidation pathways of Fe(II). Moreover, the presence of •OH scavenger, namely, methanol, greatly accelerates the reoxidation of photogenerated Fe(II) in both citric acid and benzoic acid situations. Further experiments reveal that the high availability of O2 and the citric acid- or methanol-derived carbon-centered radicals are responsible for the rapider reoxidation of Fe(II) in iron-citric acid microdroplets by prolonging the length of HO2•- and H2O2-involved radical reaction chains. The results in this study may provide a new understanding about iron-citric acid photochemistry in atmospheric liquid particles, which can further influence the photoactivity of particles and the formation of secondary organic aerosols.


Asunto(s)
Ácido Cítrico , Hierro , Hierro/química , Ácido Cítrico/química , Peróxido de Hidrógeno/química , Fotoquímica , Metanol , Oxidación-Reducción , Ácidos Carboxílicos/química , Compuestos Ferrosos , Aerosoles , Benzoatos , Compuestos Férricos/química
10.
J Virol ; 95(3)2021 01 13.
Artículo en Inglés | MEDLINE | ID: mdl-33177200

RESUMEN

Influenza A viruses cause severe respiratory illnesses in humans and animals. Overreaction of the innate immune response to influenza virus infection results in hypercytokinemia, which is responsible for mortality and morbidity. However, the mechanism by which influenza induces hypercytokinemia is not fully understood. In this study, we established a mouse-adapted H9N2 virus, MA01, to evaluate the innate immune response to influenza in the lung. MA01 infection caused high levels of cytokine release, enhanced pulmonary injury in mice, and upregulated CD83 protein in dendritic cells and macrophages in the lung. Influenza virus neuraminidase (NA) unmasked CD83 protein and contributed to high cytokine levels. Furthermore, we provide evidence that CD83 is a sialylated glycoprotein. Neuraminidase treatment enhanced lipopolysaccharide (LPS)-stimulated NF-κB activation in RAW264.7 cells. Anti-CD83 treatment alleviated influenza virus-induced lung injury in mice. Our study indicates that influenza virus neuraminidase modulates CD83 status and contributes to the "cytokine storm," which may suggest a new approach to curb this immune injury.IMPORTANCE The massive release of circulating mediators of inflammation is responsible for lung injury during influenza A virus infection. This phenomenon is referred to as the "cytokine storm." However, the mechanism by which influenza induces the cytokine storm is not fully understood. In this study, we have shown that neuraminidase unmasked CD83 protein in the lung and contributed to high cytokine levels. Anti-CD83 treatment could diminish immune damage to lung tissue. The NA-CD83 axis may represent a target for an interruption of influenza-induced lung damage.


Asunto(s)
Antígenos CD/metabolismo , Interacciones Huésped-Patógeno/inmunología , Inmunidad Innata/inmunología , Inmunoglobulinas/metabolismo , Subtipo H9N2 del Virus de la Influenza A/patogenicidad , Lesión Pulmonar/etiología , Glicoproteínas de Membrana/metabolismo , Neuraminidasa/metabolismo , Infecciones por Orthomyxoviridae/complicaciones , Proteínas Virales/metabolismo , Animales , Antígenos CD/genética , Células Dendríticas/inmunología , Células Dendríticas/virología , Femenino , Inmunoglobulinas/genética , Subtipo H9N2 del Virus de la Influenza A/enzimología , Lesión Pulmonar/patología , Macrófagos/inmunología , Macrófagos/virología , Glicoproteínas de Membrana/genética , Ratones , Ratones Endogámicos C57BL , Neuraminidasa/genética , Infecciones por Orthomyxoviridae/virología , Transducción de Señal , Proteínas Virales/genética , Virulencia , Antígeno CD83
11.
Allergy ; 77(2): 483-498, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34365653

RESUMEN

BACKGROUND: Alteration of commensal microbiota is highly correlated with the prevalence of allergic reactions to food in the gastrointestinal tract. The mechanisms by which microbiota modulate food allergen sensitization in the mucosal site are not fully understood. METHODS: We generate DCs specific knockout of retinoic acid receptor α (Rara) gene mice (DC KO Rara) to evaluate food sensitization. The bile acid-activated retinoic acid response was evaluated by flow cytometry, real-time RT-PCR and Illumina transcriptome sequencing. The global effect of Abx treatment on BA profiles in the mucosal lymph tissue mLN in mice was examined by UPLC-MS analysis. RESULTS: In this study, we demonstrate that depletion of commensal gut bacteria leads to enhanced retinoic acid (RA) signaling in mucosal dendritic cells (DCs). RA signaling in DCs is required for the production of food allergen-specific IgE and IgG1. Antibiotics induced an enlarged bile acid (BA) pool, and dysregulated BA profiles contributed to enhanced RA signaling in mucosal DCs. BA-activated RA signaling promoted DC upregulation of interferon I signature, RA signature, OX40L, and PDL2, which may lead to T helper 2 differentiation of CD4+ T cells. BA-activated RA signaling involved the farnesoid X receptor and RA receptor α (RARa) interaction. Depletion of bile acid reduces food allergen specific IgE and IgG1 levels in mice. CONCLUSION: Our research unveils a mechanism of food sensitization modulated by BA-RA signaling in DCs, which suggests a potential new approach for the intervention of food allergic reactions.


Asunto(s)
Hipersensibilidad a los Alimentos , Tretinoina , Alérgenos/farmacología , Animales , Ácidos y Sales Biliares/farmacología , Cromatografía Liquida , Células Dendríticas , Humanos , Inmunoglobulina E , Inmunoglobulina G , Ratones , Espectrometría de Masas en Tándem , Tretinoina/farmacología
12.
Reprod Biomed Online ; 45(3): 608-614, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35680518

RESUMEN

RESEARCH QUESTION: Is there an association between fructose and dislipidaemia in polycystic ovary syndrome (PCOS)? DESIGN: Serum fructose levels were measured in 250 women with PCOS (113 with dislipidaemia, 137 with normolipidaemia) and 460 controls (70 with dislipidaemia, 390 with normolipidaemia). Logistic regression was used to model the relationship between serum fructose levels and dyslipidaemia. Receiver operating characteristic curve analysis was used to assess the ability of serum fructose levels to predict dislipidaemia in women with PCOS, and PCOS in women with dislipidaemia. RESULTS: Patients with PCOS and dislipidaemia had higher serum fructose levels. Triglycerides, total cholesterol and low-density lipoprotein cholesterol increased with increasing serum fructose quartiles in patients with PCOS, whereas high-density lipoprotein cholesterol decreased (all P < 0.001). Among the lipid metabolism-related indicators, triglycerides were most associated with fructose (R = 0.626, P < 0.001). Serum fructose at a cut-off value of 9.79 pmol/µl had a sensitivity of 83.2% and specificity of 66.4% for predicting dislipidaemia in women with PCOS. Lower serum fructose levels were strongly associated with a decreased risk of dislipidaemia in women with PCOS (P < 0.001; OR 0.067; 95% CI 0.027 to 0.170). Moreover, high fructose levels are predictive of PCOS in women with dislipidaemia, with a better diagnostic performance than the androgens typically used as markers. CONCLUSION: Serum fructose levels are significantly correlated with dislipidaemia in women with PCOS, highlighting the importance of investigating the role of fructose in lipid metabolism of PCOS.


Asunto(s)
Dislipidemias , Fructosa , Síndrome del Ovario Poliquístico , Estudios de Casos y Controles , LDL-Colesterol/sangre , Dislipidemias/diagnóstico , Dislipidemias/etiología , Femenino , Fructosa/sangre , Humanos , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/complicaciones , Triglicéridos/sangre
13.
Bioorg Med Chem Lett ; 63: 128646, 2022 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-35231576

RESUMEN

As a receptor tyrosine kinase (RTK), tropomyosin receptor kinase (Trk) is a key drug target in solid tumors. However, the use of the First-generation Trk inhibitors was greatly restricted due to mutant drug resistance. Fortunately, the emergence of the Second-generation of Trk inhibitors has brought an effective solution to this mutant resistance, such as TPX-0005 (Repotrectinib). Here, we reported a series of pyrizolo[1,5-a]pyrimidine derivatives as the second-generation Trk inhibitors, and carried out the subsequent biological activity evaluation. Among them, the best compound 14h (IC50 = 1.40, 1.80 nM, against TrkA, TrkAG595R, respectively) and 14j (IC50 = 0.86, 6.92 nM, against TrkA, TrkAG595R, respectively) has a kinase activity comparable to TPX-0005, and 14j (IC50 = 350 nM against ALK) has a higher selectivity of Trk inhibition than TPX-0005, which may be of great significance for reducing toxicity.


Asunto(s)
Neoplasias , Receptor trkA , Humanos , Neoplasias/patología , Inhibidores de Proteínas Quinasas/farmacología , Pirimidinas/farmacología
14.
BMC Urol ; 22(1): 79, 2022 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-35610639

RESUMEN

BACKGROUND: To observe and explore the effect of metformin on the migration and proliferation of bladder cancer T24 and 5637 cells in vitro. METHODS: Bladder cancer T24 and 5637 cell lines were cultured in vitro, and were divided into group A (blank control group) and group B (metformin group: 5, 10, 15, and 20 mmol/L); both groups were plated on 6-well plates at the same time. Culture in 24-well plates was used for wound healing assays and in 96-well plates for Transwell migration and invasion, and Cell Counting Kit-8 proliferation experiments. We observed and detected the cell migration and proliferation ability of each group at 48 h, and calculated the cell migration area and survival rate. Flow cytometry was used to detect cell apoptosis in the groups. The apoptosis-related proteins, cleaved-caspase 3, cleaved-PARP, and the PI3K/AKT/mTOR signaling pathway member proteins PI3K, phosphorylated (p)-PI3K, AKT, p-AKT, mTOR, and p-mTOR were detected using western blotting. RESULTS: After 48 h of treatment with different concentrations of metformin, the cell migration and proliferation capabilities were significantly lower than those in the blank control group. The proliferation and migration abilities of T24 and 5637 cells decreased in a metformin concentration-dependent manner (P < 0.05). The apoptosis rate under different concentrations of metformin, as detected by flow cytometry, showed a significantly higher rate in the metformin group than in the control group (P < 0.05). Compared with that in the control group, the level of cleaved-caspase 3 and cleaved-PARP protein in the metformin group was increased in each treatment group, and the levels of p-mTOR, p-AKT, and p-PI3K decreased significantly compared with those in the control group (P < 0.05). CONCLUSION: Metformin inhibited bladder cancer T24 and 5637 cell migration and proliferation, and induced their apoptosis. The mechanism might involve inhibition of the activation of the PI3K/AKT/mTOR signaling pathway.


Asunto(s)
Metformina , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Neoplasias de la Vejiga Urinaria , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Humanos , Metformina/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/metabolismo
15.
Sensors (Basel) ; 21(24)2021 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-34960346

RESUMEN

A feature-based automatic modulation classification (FB-AMC) algorithm has been widely investigated because of its better performance and lower complexity. In this study, a deep learning model was designed to analyze the classification performance of FB-AMC among the most commonly used features, including higher-order cumulants (HOC), features-based fuzzy c-means clustering (FCM), grid-like constellation diagram (GCD), cumulative distribution function (CDF), and raw IQ data. A novel end-to-end modulation classifier based on deep learning, named CCT classifier, which can automatically identify unknown modulation schemes from extracted features using a general architecture, was proposed. Features except GCD are first converted into two-dimensional representations. Then, each feature is fed into the CCT classifier for modulation classification. In addition, Gaussian channel, phase offset, frequency offset, non-Gaussian channel, and flat-fading channel are also introduced to compare the performance of different features. Additionally, transfer learning is introduced to reduce training time. Experimental results showed that the features HOC, raw IQ data, and GCD obtained better classification performance than CDF and FCM under Gaussian channel, while CDF and FCM were less sensitive to the given phase offset and frequency offset. Moreover, CDF was an effective feature for AMC under non-Gaussian and flat-fading channels, and the raw IQ data can be applied to different channels' conditions. Finally, it showed that compared with the existing CNN and K-S classifiers, the proposed CCT classifier significantly improved the classification performance for MQAM at N = 512, reaching about 3.2% and 2.1% under Gaussian channel, respectively.


Asunto(s)
Algoritmos , Redes Neurales de la Computación
16.
Angew Chem Int Ed Engl ; 60(49): 25719-25722, 2021 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-34761498

RESUMEN

Rational nanostructure design has proved fruitful in addressing the bottlenecks of diverse fields. Especially hollow multi-shelled structures (HoMS) have stood out due to their temporal-spatial ordering mass transfer and buffering effect. Localizing multiple cores in a HoMS is highly desired, which could endow it with more fascinating properties. However, such a structure has been barely reported due to the highly challenging fabrication. Here, we develop a controllable synthesis strategy to realize such a structure, which is applicable for diverse cores and shells. Additionally, cores and shells could be tuned to be homogeneous or heterogeneous, with the core and shell number well controlled. In situ TEM analysis verifies that the inner shell confines the expansion orientation of cores, while the outer shell maintains a stable interface. In addition to energy storage, such structure is also promising for multi-drug co-delivery and sequential responsive release as well as tandem catalysis applications.

17.
Angew Chem Int Ed Engl ; 60(13): 6926-6931, 2021 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-33496361

RESUMEN

In the study of structure-property relationships for rational materials design, hollow multishell structures (HoMSs) have attracted tremendous attention owing to the optimal balance between mass transfer and surface exposure. Considering the shell structure can significantly affect the properties of HoMSs, in this paper, we provide a novel one-step strategy to continually regulate the shell structures of HoMSs. Through a simple phosphorization process, we can effectively modify the shell from solid to bubble-like and even duplicate the shells with a narrow spacing. Benefitting from the structure merits, the fabricated CoP HoMSs with close duplicated shells can promote gas release owing to the unbalanced Laplace pressure, while accelerating liquid transfer for enhanced capillary force. It can provide effective channels for water and gas and thus exhibits a superior electrocatalytic performance in the hydrogen and oxygen evolution reaction.

18.
Clin Infect Dis ; 71(1): 158-165, 2020 06 24.
Artículo en Inglés | MEDLINE | ID: mdl-31630166

RESUMEN

BACKGROUND: Distal sensory peripheral neuropathy (DSPN) is a complication of human immunodeficiency virus (HIV). We estimate DSPN prevalence in 7 resource-limited settings (RLSs) for combination antiretroviral therapy (cART)-naive people living with HIV (PLWH) compared with matched participants not living with HIV and in PLWH virally suppressed on 1 of 3 cART regimens. METHODS: PLWH with a CD4+ count <300 cells/mm3 underwent standardized neurological examination and functional status assessments before and every 24 weeks after starting cART. Matched individuals not living with HIV underwent the same examinations once.Associations between covariates with DSPN at entry were assessed using the χ2 test, and virally suppressed PLWH were assessed using generalized estimating equations. RESULTS: Before initiating cART, 21.3% of PLWH had DSPN compared with 8.5% of people not living with HIV (n = 2400; χ2(df = 1) = 96.5; P < .00001). PLWH with DSPN were more likely to report inability to work [χ2(df = 1) = 10.6; P = .001] and depression [χ2(df = 1) = 8.9; P = .003] than PLWH without DSPN. Overall prevalence of DSPN among those virally suppressed on cART decreased: 20.3%, week 48; 15.3%, week 144; and 10.3%, week 192. Incident DSPN was seen in 127 PLWH. Longitudinally, DSPN was more likely in older individuals (P < .001) and PLWH with less education (P = .03). There was no significant association between cART regimen and DSPN. CONCLUSIONS: Although the prevalence of DSPN decreased following cART initiation in PLWH, further research could identify strategies to prevent or ameliorate residual DSPN after initiating cART in RLSs.


Asunto(s)
Infecciones por VIH , Seropositividad para VIH , VIH-1 , Enfermedades del Sistema Nervioso Periférico , Anciano , Recuento de Linfocito CD4 , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Enfermedades del Sistema Nervioso Periférico/epidemiología
19.
Haemophilia ; 26(1): 47-55, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31778283

RESUMEN

INTRODUCTION: SHP656 is the first factor VIII (FVIII) product developed using polysialylation (PSA) technology, in which full-length recombinant (r) FVIII (anti-haemophilic factor [recombinant]) is conjugated with a 20 kDa PSA polymer. AIM: To compare the safety, immunogenicity and pharmacokinetics of SHP656 vs the parent rFVIII (octocog alfa) after single infusions of 25-75 IU/kg in patients with severe haemophilia A (FVIII activity <1%). METHODS: Multinational, phase 1, prospective, open-label, two-period, fixed-sequence, dose-escalation trial (clinicaltrials.gov NCT02716194). Patients received single doses of rFVIII and then SHP656 sequentially at the same dose: 25 ± 3 IU/kg (Cohort 1), 50 ± 5 IU/kg (Cohort 2) and 75 ± 5 IU/kg (Cohort 3). RESULTS: Forty patients received rFVIII: 11 in Cohort 1, 16 in Cohort 2 and 13 in Cohort 3. Two patients withdrew before receiving SHP656, leaving 38 patients who completed the study and received both treatments. No treatment-related adverse events (AEs), serious AEs, deaths, study withdrawals, thrombotic events or allergic reactions were reported; and no significant treatment-related changes in laboratory parameters or vital signs. No patients developed FVIII inhibitors or antibodies to PSA. FVIII activity was significantly prolonged following SHP656 administration vs rFVIII with an approximately 1.5-fold extension in mean residence time (P < .05). Exposure increased proportional to the SHP656 dose over the 25-75 IU/kg dose range. CONCLUSION: Polysialylation of rFVIII confers a half-life extension similar to that of approved extended half-life products that use either PEGylation or Fc fusion technology and was not associated with any treatment-related adverse events.


Asunto(s)
Factor VIII/farmacocinética , Factor VIII/uso terapéutico , Hemofilia A/tratamiento farmacológico , Proteínas Recombinantes/uso terapéutico , Ácidos Siálicos/química , Adulto , Factor VIII/efectos adversos , Factor VIII/inmunología , Humanos
20.
Environ Sci Technol ; 54(6): 3121-3128, 2020 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-32084312

RESUMEN

The active nitrogen species (HONO, NO, and NO2) have important impacts on the atmospheric oxidative capacity and the transformation of many atmospheric species. In this study, a fast photochemical renoxification rate of adsorbed HNO3/NO3- to active nitrogen species (HONO, NO, and NO2) was detected on real urban PM2.5, and sulfate was found to play a key role in this process. Different from the reported direct photolysis pathway, the photochemical reaction of HNO3/NO3- on PM2.5 is dominated by a photosensitizing mechanism. Acidic protons are proved to be essential for this pathway. The role of sulfate, because of the nonvolatility of its conjugated acid, is to conserve the necessary acidic protons when interacting with HNO3 and thus maintain its photoreactivity. This work implies that sulfate will have important implications in atmospheric nitrogen cycling by accelerating the release of nitrogen oxides from photochemical renoxification of HNO3/NO3- adsorbed on ambient particulates and thus can cause major environmental problems.


Asunto(s)
Óxidos de Nitrógeno , Sulfatos , Nitrógeno , Material Particulado , Óxidos de Azufre
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