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The microscopic unfolding process of a cytosine-rich DNA forming i-motif by hemi-protonated base pairs is related to gene regulation. However, the detailed thermal unfolding mechanism and the protonation/deprotonation status of site-specific cytosine in DNA in a physiological environment are still obscure. To address this issue, a vibration-enhanced CîC probe tagged on 5'E terminal cytosine of human telomere i-motif DNA was examined using linear and nonlinear infrared (IR) spectroscopies and quantum-chemistry calculations. The CîC probe extended into the major groove of the i-motif was found using nonlinear IR results only to introduce a minor steric effect on both steady-state structure and local structure dynamics; however, its IR absorption profile effectively reports the cleavage of the hemi-protonated base pair of C1-C13 upon the unfolding with C1 remaining protonated. The temperature mid-point (Tm) of the local transition reported using the CîC tag was slightly lower than the Tm of global transition, and the enthalpy of the former exceeds 60% of the global transition. It is shown that the base-pair unraveling is noncooperative, with outer base pairs breaking first and being likely the rate limiting step. Our results offered an in-depth understanding of the macroscopic unfolding characteristics of the i-motif DNA and provided a nonlinear IR approach to monitoring the local structural transition and dynamics of DNA and its complexes.
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DNA , Telômero , Humanos , DNA/química , Pareamento de Bases , Temperatura , Citosina/química , Conformação de Ácido NucleicoRESUMO
Gastric cancer is one of the most common cancers worldwide, particularly in China, with over half a million new cases and over 400 thousand deaths in 2022. Zolbetuximab, a first-in-class investigational monoclonal antibody (mAb) targeting tumor-associated antigen CLDN18.2 which is highly expressed on gastric cancer cells, was recently reported to meet the primary endpoint in Phase III trial as first-line treatment in CLDN18.2 positive and HER2-negative gastric cancers. In the present study, we developed a humanized bispecific antibody (bsAb) CLDN18.2/4-1BB named PM1032. PM1032 activates immune cells via CLDN18.2 mediated crosslinking of 4-1BB, a potent stimulator of T/NK cells. It induced strong immunological memory in multiple tumor-bearing animal models, indicating significant potential as an effective treatment for CLDN18.2 positive cancers such as gastric cancer. Since liver and gastrointestinal (GI) related toxicities were reported in 4-1BB and CLDN18.2 targeting programs during the clinical development, respectively, extensive pharmacokinetics (PK) and safety profile characterization of PM1032 was performed in rhesus monkeys. PM1032 had a half-life comparable to a conventional IgG1 mAb, and serum drug concentration increased in a dose-dependent pattern. Furthermore, PM1032 was generally well tolerated, with no significant abnormalities observed in toxicity studies, including the liver and stomach. In summary, PM1032 demonstrated good PK and an exceptional safety profile in rhesus monkeys supporting further investigation in clinical studies.
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Anticorpos Biespecíficos , Macaca mulatta , Animais , Anticorpos Biespecíficos/farmacocinética , Anticorpos Biespecíficos/toxicidade , Feminino , Humanos , Claudinas/imunologia , Masculino , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/tratamento farmacológico , Linhagem Celular TumoralRESUMO
OBJECTIVES: To evaluate the clinical value of contrast-enhanced ultrasound (CEUS) with time-intensity curve (TIC) in distinguishing different types of hypovascular solid pancreatic lesions. METHODS: A total of 89 patients with 90 pancreatic lesions (all confirmed by surgery or biopsy pathology) that manifested hypoenhancement on contrast-enhanced ultrasound (CEUS) were included in this study. Six peak enhancement patterns were proposed for differentiating hypovascular pancreatic lesions. CEUS qualitative and TIC-based quantitative parameters were analyzed, and each lesion was scored based on the statistically significant qualitative parameters to evaluate the diagnostic ability of CEUS for hypovascular solid pancreatic lesions. RESULTS: Qualitative parameters such as peak enhancement pattern II/III/IV, penetrating vessels, centripetal enhancement, and early washout were reliable indicators of malignant lesions, and lesions scored based on these qualitative parameters, with a score ≥ 2, were highly suspected to be malignant lesions. Pattern I had an accuracy of 83.33% for predicting mass-forming pancreatitis (MFP), pattern V had an accuracy of 96.67% for predicting solid pseudopapillary tumors of the pancreas (SPTP), and pattern VI had an accuracy of 81.11% for predicting neuroendocrine tumors/carcinomas (NETs/NECs). For quantitative analysis, nodule/pancreatic parenchyma echo intensity reduction ratio was significantly greater in malignant lesions. CONCLUSIONS: CEUS qualitative and TIC-based quantitative parameters have clinical value in distinguishing malignant from benign hypovascular pancreatic lesions. KEY POINTS: ⢠Contrast-enhanced ultrasound helps clinicians assess patients with pancreatic lesions. ⢠Six peak enhancement patterns are proposed for differentiating pancreatic hypovascular lesions. ⢠Qualitative parameters such as peak enhancement pattern II/III/IV, penetrating vessels, centripetal enhancement, early washout, and quantitative parameter nodule/pancreatic parenchyma echo intensity reduction ratio were important characteristics to discriminate malignant from hypovascular benign lesions.
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Carcinoma Neuroendócrino , Neoplasias Pancreáticas , Humanos , Meios de Contraste , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Ultrassonografia , Neoplasias Pancreáticas/diagnóstico , Carcinoma Neuroendócrino/patologia , Diagnóstico DiferencialRESUMO
The rapid and efficient recognition of facial expressions is crucial for adaptive behaviors, and holistic processing is one of the critical processing methods to achieve this adaptation. Therefore, this study integrated the effects and attentional characteristics of the authenticity of facial expressions on holistic processing. The results show that both regulated and spontaneous expressions were processed holistically. However, the spontaneous expression details did not indicate typical holistic processing, with the congruency effect observed equally for aligned and misaligned conditions. No significant difference between the two expressions was observed in terms of reaction times and eye movement characteristics (i.e., total fixation duration, fixation counts, and first fixation duration). These findings suggest that holistic processing strategies differ between the two expressions. Nevertheless, the difference was not reflected in attentional engagement.
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Reconhecimento Facial , Reconhecimento Psicológico , Humanos , Atenção , Tempo de Reação , Expressão FacialRESUMO
This paper proposes an improved 3D-Vector Field Histogram (3D-VFH) algorithm for autonomous flight and local obstacle avoidance of multi-rotor unmanned aerial vehicles (UAVs) in a confined environment. Firstly, the method employs a target point coordinate system based on polar coordinates to convert the point cloud data, considering that long-range point cloud information has no effect on local obstacle avoidance by UAVs. This enables UAVs to effectively utilize obstacle information for obstacle avoidance and improves the real-time performance of the algorithm. Secondly, a sliding window algorithm is used to estimate the optimal flight path of the UAV and implement obstacle avoidance control, thereby maintaining the attitude stability of the UAV during obstacle avoidance flight. Finally, experimental analysis is conducted, and the results show that the UAV has good attitude stability during obstacle avoidance flight, can autonomously follow the expected trajectory, and can avoid dynamic obstacles, achieving precise obstacle avoidance.
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Algoritmos , Dispositivos Aéreos não TripuladosRESUMO
BACKGROUND: The occurrence and development of developmental dysplasia of the hip (DDH) are related to a variety of factors, which have been reported in the literature, but the literature does not mention factors related to the severity of DDH. The purpose of this study is to analyze the related factors of the occurrence and severity of DDH in combination with the Graf ultrasonic diagnostic classification. METHODS: This study was a monocentric retrospective study describing the factors associated with DDH in a large hospital of northwest China. A total of 3046 infants (6092 hips) within 6 months after birth using the Graf method were admitted to our department between 2014 and 2018. We analyzed data of DDH. After reviewing medical charts and diagnostic examination results, we assessed whether factors such as ethnicity, gender, gestational age, birth weight, diagnosis age, maternal age, mode of delivery, fetal presentation, amniotic fluid volume and birth order, had any effect on development of hip. RESULT: â Analysis showed that DDH mostly occurs in female and left hip joint, related to intrauterine fetal presentation, amniotic fluid volume, gestational age, mode of delivery, prenatal weight, and diagnosis age after birth, and the occurrence of DDH is also related to maternal age (All Pï¼0.05). Ethnicity and first born showed have no obvious correlation with DDH incidence (p = 0.718, 0.147, respectively). â¡ The strongest correlation was found with amniotic fluid, followed by birth weight. ⢠The severity of DDH was correlated with ethnicity, births, prenatal weight, gestational age, diagnosis age and maternal age (All Pï¼0.05, respectively). ⣠There were significant differences in treatment methods, duration and prognosis among different types of DDH. CONCLUSIONS: The occurrence and development of DDH are related to a variety of factors. Ultrasound examination can provide an early assessment of the hip development status of infants and may play an important role in establishing an early clinical diagnosis treatment and monitoring and prognosis.
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BACKGROUND: Accurate diagnosis of unexplained cervical lymphadenopathy (CLA) using medical images heavily relies on the experience of radiologists, which is even worse for CLA patients in underdeveloped countries and regions, because of lack of expertise and reliable medical history. This study aimed to develop a deep learning (DL) radiomics model based on B-mode and color Doppler ultrasound images for assisting radiologists to improve their diagnoses of the etiology of unexplained CLA. METHODS: Patients with unexplained CLA who received ultrasound examinations from three hospitals located in underdeveloped areas of China were retrospectively enrolled. They were all pathologically confirmed with reactive hyperplasia, tuberculous lymphadenitis, lymphoma, or metastatic carcinoma. By mimicking the diagnosis logic of radiologists, three DL sub-models were developed to achieve the primary diagnosis of benign and malignant, the secondary diagnosis of reactive hyperplasia and tuberculous lymphadenitis in benign candidates, and of lymphoma and metastatic carcinoma in malignant candidates, respectively. Then, a CLA hierarchical diagnostic model (CLA-HDM) integrating all sub-models was proposed to classify the specific etiology of each unexplained CLA. The assistant effectiveness of CLA-HDM was assessed by comparing six radiologists between without and with using the DL-based classification and heatmap guidance. RESULTS: A total of 763 patients with unexplained CLA were enrolled and were split into the training cohort (n=395), internal testing cohort (n=171), and external testing cohorts 1 (n=105) and 2 (n=92). The CLA-HDM for diagnosing four common etiologies of unexplained CLA achieved AUCs of 0.873 (95% CI: 0.838-0.908), 0.837 (95% CI: 0.789-0.889), and 0.840 (95% CI: 0.789-0.898) in the three testing cohorts, respectively, which was systematically more accurate than all the participating radiologists. With its assistance, the accuracy, sensitivity, and specificity of six radiologists with different levels of experience were generally improved, reducing the false-negative rate of 2.2-10% and the false-positive rate of 0.7-3.1%. CONCLUSIONS: Multi-cohort testing demonstrated our DL model integrating dual-modality ultrasound images achieved accurate diagnosis of unexplained CLA. With its assistance, the gap between radiologists with different levels of experience was narrowed, which is potentially of great significance for benefiting CLA patients in underdeveloped countries and regions worldwide.
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Carcinoma , Aprendizado Profundo , Linfadenopatia , Linfoma , Tuberculose dos Linfonodos , Humanos , Hiperplasia , Linfadenopatia/diagnóstico por imagem , Linfoma/diagnóstico por imagem , Linfoma/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: More and more new ultrasound techniques with their own characteristics are applied in the differential diagnosis of thyroid nodules. This study amied to assess and compare the diagnostic value of the Demetics ultrasound-assisted diagnosis system and contrast-enhanced ultrasound (CEUS) combined with the Thyroid Image Reporting and Data Systems (TI-RADS) for thyroid nodules. DESIGN AND PATIENTS: A total of 600 thyroid nodules with pathological findings were retrospectively analysed. Demetics and CEUS were performed for all nodules. The diagnostic efficacy of Demetics and CEUS for nodules of different sizes was evaluated and compared in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+) and negative likelihood ratio (LR-). The characteristics of nodules diagnosed and misdiagnosed by Demetics were compared to analyse the factors affecting the diagnostic accuracy of Demetics. The necessity of CEUS for nodules that are prone to misdiagnosis in Demetics was assessed. RESULTS: Both Demetics and CEUS can be used for the differential diagnosis of benign and malignant thyroid nodules of different sizes. The diagnostic agreement between Demetics and CEUS for thyroid nodules of different sizes was moderate, substantial and fair, respectively. The sensitivity and NPV of Demetics were higher than those of CEUS, and the specificity, PPV and LR+ of CEUS were higher than that of Demetics. The LR- of Demetics was lower than those of CEUS. There were significant differences in age, calcification and margin in analysing the factors affecting Demetics. CEUS correctly diagnosed 50 of the 101 nodules misdiagnosed by Demetics. CONCLUSIONS: Demetics showed high sensitivity in diagnosing thyroid nodules, while CEUS showed high specificity. In clinical practice, CEUS can further improve the diagnostic accuracy for nodules that are easily misdiagnosed by Demetics.
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Nódulo da Glândula Tireoide , Meios de Contraste , Sistemas de Dados , Diagnóstico Diferencial , Humanos , Estudos Retrospectivos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Ultrassonografia/métodosRESUMO
BACKGROUND: Ultrasound-targeted microbubble destruction (UTMD) technology is a new drug and gene delivery strategy. This study investigates novel ultrasound (US) sensitive siRNA-loaded nanobubbles (siRNA-NBs) to explore the relationship between PDLIM5 mediated autophagy and drug resistance development using epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of non-small cell lung cancer (NSCLC). METHODS: US sensitive siRNA-NBs were designed to inhibit the expression of PDLIM5 in gefitinib-resistant human NSCLC PC9GR cells in vitro. The expression of autophagy-related proteins (P62 and LC3-II/I) and autophagosomes in PC9GR cells after PDLIM5 gene silencing were explored. RESULTS: US-sensitive PDLIM5-targeted siRNA-NBs were effectively delivered into PC9GR cells, inhibiting PDLIM5 expression, increasing LC3-II/I and p62 expressions and increasing autophagosomes in PC9GR cells in vitro. CONCLUSIONS: Using UTMD, US-sensitive siRNA-NBs have the potential as an ideal delivery vector to mediate highly effective RNA interference for NSCLC cells. Furthermore, PDLIM5 plays a role in the autophagy-mediated resistance in gefitinib-resistant PC9GR cells.
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Monitoring the site-specific local structure and dynamics of polynucleotides and DNA is important for understanding their biological functions. However, structurally characterizing these biomolecules with high time resolution has been known to be experimentally challenging. In this work, several 5-silylethynyl-2'-deoxynucleosides and 5-substituted phenylethynyl-2'-deoxynucleosides on the basis of deoxycytidine (dC) and deoxythymidine (dT) were synthesized, in which the alkynyl group shows intensified CîC stretching vibration with infrared transition dipole moment magnitude close to that of typical CîO stretching, and exhibits structural sensitivities in both vibrational frequency and spectral width. In particular, 5-trimethylsilylethynyl-2'-dC (TMSEdC, molecule 1a) was examined in detail using femtosecond nonlinear IR spectroscopy. The solvent dependent CîC stretching frequency of 1a can be reasonably interpreted mainly as the hydrogen-bonding effect between the solvent and cytosine base ring structure. Transient 2D IR and pump-probe IR measurements of 1a carried out comparatively in two aprotic solvents (DMSO and THF) and one protic solvent (MeOH) further reveal solvent dependent ultrafast vibrational properties, including diagonal anharmonicity, spectral diffusion, vibrational relaxation and anisotropy dynamics. These observed sensitivities are rooted in an extended π-conjugation of the base ring structure in which the CîC group is actively involved. Our results show that the intensified CîC stretching vibration can potentially provide a site-specific IR probe for monitoring the equilibrium and ultrafast structural dynamics of polynucleotides.
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Nucleotídeos , Vibração , Espectrofotometria Infravermelho/métodos , Ligação de Hidrogênio , Solventes/química , PolinucleotídeosRESUMO
Steady-state and time-resolved infrared (IR) studies of cyclotetramethylene tetranitramine (HMX) were carried out, using the asymmetric nitro-stretch as probe, to investigate its solution structures and vibrational energy transfer processes in pure dimethyl sulfoxide (DMSO) and in a DMSO/water mixture. A linear IR spectrum in the nitro-stretching mode region shows two major bands and one minor band in DMSO but changes to the two major bands mainly picture when adding water as an antisolvent of HMX, suggesting a transition from well-solvated and less perfect ß-conformation to a less-solvated and close-to-perfect ß-conformation. The latter bears a similar asymmetric nitro-stretch vibration profile to the ß-polymorph in the crystal form. Density functional theory computations of the nitro-stretching vibrations suggest that HMX in DMSO may be in a NO2 group rotated ß-conformation. Two-dimensional IR cross-peak intensity reveals intramolecular energy transfer between the axial and equatorial nitro-groups in the ß-HMX on the ps time scale, which is slightly faster in the mixed solvent case. The importance of water as an antisolvent in influencing the equilibrium solvation structure, as well as the vibrational and orientational relaxation dynamics of HMX, is discussed.
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Dimetil Sulfóxido , Vibração , Azocinas , Dimetil Sulfóxido/química , Solventes/química , Água/químicaRESUMO
For layered transition metal oxides cathode-based lithium batteries, the chemical degradation of electrolytes leads to fast battery capacity decay, severely challenging their practical applications. This kind of chemical degradation of electrolytes is caused by the oxidation of reactive oxygen (e.g., singlet oxygen) and the attack of free radicals during cycling. To address this, we first report a biologically inspired antiaging strategy of developing the photostabilizer with singlet oxygen- and free radicals-scavenging abilities as a cathode binder additive. It is fully evidenced that this binder system consisting of the binder additive and a commercially available polyvinylidene difluoride can scavenge singlet oxygen and free radicals generated during high-voltage cycling, thus significantly restraining electrolyte decomposition. As a result, high-voltage layered transition metal oxides-based lithium batteries with reproducibly superior electrochemical performance, even under elevated temperatures, can be achieved. This bioinspired strategy to scavenge reactive oxygen and free radicals heralds a new paradigm for manipulating the cathode/electrolyte interphase chemistry of various rechargeable batteries involving layered transition metal oxides-based cathodes.
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Methyl jasmonate (MeJA) is an airborne signaling phytohormone that can induce changes in endogenous jasmonates (JAs) and cause photosynthetic responses. However, the response of these two aspects of citrus plants at different MeJA concentrations is still unclear. Four MeJA concentrations were used in two citrus varieties, Huangguogan (C. reticulata × C. sinensis) and Shiranuhi [C. reticulata × (C. reticulata × C. sinensis)], to investigate the effects of MeJA dose on the endogenous JAs pathway and photosynthetic capacity. We observed that MeJA acted in a dose-dependent manner, and its stimulation in citrus leaves showed a bidirectional character at different concentrations. This work demonstrates that MeJA at only a concentration of 2.2 mM or less contributed to the activation of magnesium protoporphyrin IX methyltransferase (ChlM, EC 2.1.1.11) and protochlorophyllide oxidoreductase (POR, EC 1.3.1.11) and the simultaneous accumulation of Chl a and Chl b, which in turn contributed to an improved photosynthetic capacity and PSII photochemistry efficiency of citrus. Meanwhile, the inhibition of endogenous JAs synthesis by exogenous MeJA was observed. This was achieved by reducing the ratio of monogalactosyl diacylglycerol (MGDG) to diagalactosyl diacylglycerol (DGDG) and inhibiting the activities of key enzymes in JAs synthesis, especially 12-oxo-phytodienoic acid reductase (OPR, EC 1.3.1.42). Another noteworthy finding is that there may exist a JA-independent pathway that could regulate 12-oxo-phytodienoic acid (OPDA) synthesis. This study jointly analyzed the internal hormone regulation mechanism and the external physiological response, as well as revealed the effects of exogenous MeJA on promoting the photosynthesis and inhibiting the endogenous JAs synthesis.
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Citrus , Acetatos/farmacologia , Ciclopentanos/farmacologia , Oxilipinas/farmacologia , FotossínteseRESUMO
This study examined the physiological effects of different amounts of nitrogen (N) supplementation (0 to 2.72 kg/year) on the citrus cultivar Huangguogan (Citrus reticulata × Citrus sinensis). Root activity, chlorophyll content, and fruit quality were measured, and the activities of the antioxidant enzymes superoxide dismutase (SOD), guaiacol peroxidase (POD), and catalase (CAT), and the contents of malondialdehyde (MDA) and soluble protein in root, leaf, and fruit tissues were examined at different developmental stages. Root activity, chlorophyll content, fruit quality, antioxidant enzyme activity, MDA content, and soluble protein content increased in plants treated with an appropriate amount of N. Both excessive N and N deficiency decreased the content of MDA and the activities of antioxidant enzymes. Application of 1.36-1.81 kg N/year is suggested for citrus fertilization and the lower end of this range is recommended for minimizing environmental impact and production cost.
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Antioxidantes/metabolismo , Catalase/metabolismo , Citrus/enzimologia , Citrus/crescimento & desenvolvimento , Nitrogênio/administração & dosagem , Peroxidase/metabolismo , Superóxido Dismutase/metabolismo , Clorofila/metabolismo , Citrus/metabolismo , Malondialdeído/metabolismo , Proteínas de Plantas/metabolismo , Estruturas Vegetais/enzimologia , Estruturas Vegetais/metabolismoRESUMO
Conventional liquid electrolytes based lithium-ion batteries (LIBs) might suffer from serious safety hazards. Solid-state polymer electrolytes (SPEs) are very promising candidate with high security for advanced LIBs. However, the quintessential frailties of pristine polyethylene oxide/lithium salts SPEs are poor ionic conductivity (≈10-8 S cm-1 ) at 25 °C and narrow electrochemical window (<4 V). Many innovative researches are carried out to enhance their lithium-ion conductivity (10-4 S cm-1 at 25 °C), which is still far from meeting the needs of high-performance power LIBs at ambient temperature. Therefore, it is a pressing urgency of exploring novel polymer host materials for advanced SPEs aimed to develop high-performance solid lithium batteries. Aliphatic polycarbonate, an emerging and promising solid polymer electrolyte, has attracted much attention of academia and industry. The amorphous structure, flexible chain segments, and high dielectric constant endow this class of polymer electrolyte excellent comprehensive performance especially in ionic conductivity, electrochemical stability, and thermally dimensional stability. To date, many types of aliphatic polycarbonate solid polymer electrolyte are discovered. Herein, the latest developments on aliphatic polycarbonate SPEs for solid-state lithium batteries are summarized. Finally, main challenges and perspective of aliphatic polycarbonate solid polymer electrolytes are illustrated at the end of this review.
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This study describes a novel electrochemical immunosensor to amplify the electrochemiluminescence (ECL) signal for the ultrasensitive detection of salbutamol (SAL) using quantum dots (QDs) and gold nanoparticle (AuNP) conjugated horseradish peroxidase (HRP). The electrochemical detection was based on the HRP catalyzed consumption of self-produced H2O2, which has been extensively used as a co-reactant of QDs, by o-phenylenediamine (OPD). The enzymatic reaction rate is proportional to the amount of HRP bound to the electrode. In the presence of a SAL standard solution, the immobilized SAL coating antigens competed with the SAL solution for the Ab-AuNPs-HRP complexes. With an increase in the SAL concentration, the amount of immobilized HRP decreases, which leads to an increase in the ECL intensity. Under optimized conditions, the ECL intensity changes linearly with the logarithm of the SAL concentration in the range of 0.05-500 ng mL(-1) with a detection limit of 0.017 ng mL(-1) (S/N = 3). The ECL immunosensor possesses high sensitivity, satisfactory reproducibility and selectivity, and may provide a feasible route for practical application.
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Albuterol/análise , Ouro/química , Peroxidase do Rábano Silvestre/metabolismo , Medições Luminescentes/métodos , Nanopartículas Metálicas/química , Pontos Quânticos/química , Albuterol/imunologia , Animais , Anticorpos Imobilizados/química , Anticorpos Imobilizados/imunologia , Eletrodos , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Peroxidase do Rábano Silvestre/química , Imunoensaio , Limite de Detecção , Fígado/metabolismo , Nanopartículas Metálicas/ultraestrutura , Pontos Quânticos/ultraestrutura , SuínosRESUMO
In the present work, a simple and sensitive flow injection chemiluminescent competitive immunoassay was developed for the determination of mercury(II) ion (Hg(2+)) based on carboxylic resin beads, a novel specific monoclonal antibody (McAb) and HRP enzyme-amplification. Resin beads with carboxyl groups were creatively employed as supports for immobilizing more coating antigen through acylamide bonds. With a competitive-type assay mode, the Hg(2+) in solution competed with the immobilized coating antigen for the limited McAb. Then, the second antibody labeled with HRP was introduced, and an effectively increased CL was obtained, which was ascribed to the catalytic activity of HRP for the luminol-PIP-H2O2 reaction. With increasing concentration of Hg(2+), the CL of this system decreases because less HRP is present in the CL reaction. At optimal conditions, the CL signal displayed a good linear relation toward Hg(2+) in the range of 0.05-200 ng mL(-1) with a detection limit (3σ) of 0.015 ng mL(-1). The immunosensor possessed high specificity, acceptable accuracy and reproducibility, and was examined in real samples with favorable results. This immunoassay will have intriguing application prospects for the determination of other heavy metal ions and environmental contaminants.
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Anticorpos Monoclonais/imunologia , Técnicas Biossensoriais/métodos , Análise de Injeção de Fluxo/métodos , Peroxidase do Rábano Silvestre/metabolismo , Imunoensaio/métodos , Medições Luminescentes/métodos , Mercúrio/análise , Animais , Resinas de Troca Iônica/química , Cinética , Limite de DetecçãoRESUMO
In the title compound, [Sn(CH3)2(C18H13N3O2)], the Sn(IV) ion is coordinated by one N and two O atoms from the tridentate 4-amino-N'-[(2-oxidonaphthalen-1-yl)methyl-idene]benzohydrazidate(2-) ligand and two C atoms from methyl ligands in a distorted trigonal-bipyramidal geometry. The dihedral angle between the naphthalene ring system and the benzene ring is 19.2â (2)°. In the crystal, weak N-Hâ¯O hydrogen bonds link the mol-ecules into zigzag chains along [010].
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There has been a long-standing debate as to how many hydrogen bonds a peptide backbone amide can form in aqueous solution. Hydrogen-bonding structural dynamics of N-ethylpropionamide (a ß-peptide model) in water was examined using infrared (IR) spectroscopy. Two amide-I sub bands arise mainly from amide C=O group that forms strong H-bonds with solvent water molecules (SHB state), and minorly from that involving one weak H-bond with water (WHB state). This picture is supported by molecular dynamics simulations and ab-initio calculations. Further, thermodynamics and kinetics of the SHB and WHB species were examined mainly by chemical-exchange two-dimensional IR spectroscopy, yielding an activation energy for the SHB-to-WHB exchange of 13.25 ± 0.52 kJ molâ1, which occurs in half picosecond at room temperature. Our results provided experimental evidence of an unstable water molecule near peptide backbone, allowing us to gain more insights into the dynamics of the protein backbone hydration.
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Ankylosing spondylitis (AS) stands as a persistent inflammatory ailment predominantly impacting the axial skeleton, with the immune system and inflammation intricately entwined in its pathogenesis. This study endeavors to elucidate gender-specific patterns in immune cell infiltration and diverse forms of cell demise within the AS milieu. The aim is to refine the diagnosis and treatment of gender-specific AS patients, thereby advancing patient outcomes. In the pursuit of our investigation, two datasets (GSE25101 and GSE73754) pertinent to ankylosing spondylitis (AS) were meticulously collected and normalized from the GEO database. Employing the CIBERSORT algorithm, we conducted a comprehensive analysis of immune cell infiltration across distinct demographic groups and genders. Subsequently, we discerned differentially expressed genes (DEGs) associated with various cell death modalities in AS patients and their healthy counterparts. Our focus extended specifically to ferroptosis-related DEGs (FRDEGs), cuproptosis-related DEGs (CRDEGs), anoikis-related DEGs (ARDEGs), autophagy-related DEGs (AURDEGs), and pyroptosis-related DEGs (PRDEGs). Further scrutiny involved discerning disparities in these DEGs between AS patients and healthy controls, as well as disparities between male and female patients. Leveraging machine learning (ML) methodologies, we formulated disease prediction models employing cell death-related DEGs (CDRDEGs) and identified biomarkers intertwined with cell death in AS. Relative to healthy controls, a myriad of differentially expressed genes (DEGs) linked to cell death surfaced in AS patients. Among AS patients, 82 FRDEGs, 29 CRDEGs, 54 AURDEGs, 21 ARDEGs, and 74 PRDEGs were identified. In male AS patients, these numbers were 78, 33, 55, 24, and 94, respectively. Female AS patients exhibited 66, 41, 40, 17, and 82 DEGs in the corresponding categories. Additionally, 36 FRDEGs, 14 CRDEGs, 19 AURDEGs, 10 ARDEGs, and 36 PRDEGs exhibited differential expression between male and female AS patients. Employing machine learning techniques, LASSO, RF, and SVM-RFE were employed to discern key DEGs related to cell death (CDRDDEGs). The six pivotal CDRDDEGs in AS patients, healthy controls, were identified as CLIC4, BIRC2, MATK, PKN2, SLC25A5, and EDEM1. For male AS patients, the three crucial CDRDDEGs were EDEM1, MAP3K11, and TRIM21, whereas for female AS patients, COX7B, PEX2, and RHEB took precedence. Furthermore, the trio of DDX3X, CAPNS1, and TMSB4Y emerged as the key CDRDDEGs distinguishing between male and female AS patients. In the realm of immune correlation, the immune infiltration abundance in female patients mirrored that of healthy controls. Notably, key genes exhibited a positive correlation with T-cell CD4 memory activation when comparing male and female patient samples. This study engenders a more profound comprehension of the molecular underpinnings governing immune cell infiltration and cell death in ankylosing spondylitis (AS). Furthermore, the discernment of gender-specific disparities among AS patients underscores the clinical significance of these findings. By identifying DEGs associated with diverse cell death modalities, this study proffers invaluable insights into potential clinical targets for AS patients, taking cognizance of gender-specific nuances. The identification of gender-specific biological targets lays the groundwork for the development of tailored diagnostic and therapeutic strategies, heralding a pivotal step toward personalized care for AS patients.