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1.
Nature ; 601(7893): 366-373, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35046606

RESUMO

Chirality is a unifying structural metric of biological and abiological forms of matter. Over the past decade, considerable clarity has been achieved in understanding the chemistry and physics of chiral inorganic nanoparticles1-4; however, little is known about their effects on complex biochemical networks5,6. Intermolecular interactions of biological molecules and inorganic nanoparticles show some commonalities7-9, but these structures differ in scale, in geometry and in the dynamics of chiral shapes, which can both impede and strengthen their mirror-asymmetric complexes. Here we show that achiral and left- and right-handed gold biomimetic nanoparticles show different in vitro and in vivo immune responses. We use irradiation with circularly polarized light (CPL) to synthesize nanoparticles with controllable nanometre-scale chirality and optical anisotropy factors (g-factors) of up to 0.4. We find that binding of nanoparticles to two proteins from the family of adhesion G-protein-coupled receptors (AGPCRs)-namely cluster-of-differentiation 97 (CD97) and epidermal-growth-factor-like-module receptor 1 (EMR1)-results in the opening of mechanosensitive potassium-efflux channels, the production of immune signalling complexes known as inflammasomes, and the maturation of mouse bone-marrow-derived dendritic cells. Both in vivo and in vitro immune responses depend monotonically on the g-factors of the nanoparticles, indicating that nanoscale chirality can be used to regulate the maturation of immune cells. Finally, left-handed nanoparticles show substantially higher (1,258-fold) efficiency compared with their right-handed counterparts as adjuvants for vaccination against the H9N2 influenza virus, opening a path to the use of nanoscale chirality in immunology.


Assuntos
Proteínas de Ligação ao Cálcio , Células Dendríticas , Inflamassomos , Nanopartículas Metálicas , Receptores Acoplados a Proteínas G , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Células Dendríticas/imunologia , Ouro , Vírus da Influenza A Subtipo H9N2 , Mecanotransdução Celular , Nanopartículas Metálicas/química , Camundongos , Canais de Potássio/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Estereoisomerismo
2.
Proc Natl Acad Sci U S A ; 121(13): e2310469121, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38502692

RESUMO

The incessant mutations of viruses, variable immune responses, and likely emergence of new viral threats necessitate multiple approaches to novel antiviral therapeutics. Furthermore, the new antiviral agents should have broad-spectrum activity and be environmentally stable. Here, we show that biocompatible tapered CuS nanoparticles (NPs) efficiently agglutinate coronaviruses with binding affinity dependent on the chirality of surface ligands and particle shape. L-penicillamine-stabilized NPs with left-handed curved apexes display half-maximal inhibitory concentrations (IC50) as low as 0.66 pM (1.4 ng/mL) and 0.57 pM (1.2 ng/mL) for pseudo-type SARS-CoV-2 viruses and wild-type Wuhan-1 SARS-CoV-2 viruses, respectively, which are about 1,100 times lower than those for antibodies (0.73 nM). Benefiting from strong NPs-protein interactions, the same particles are also effective against other strains of coronaviruses, such as HCoV-HKU1, HCoV-OC43, HCoV-NL63, and SARS-CoV-2 Omicron variants with IC50 values below 10 pM (21.8 ng/mL). Considering rapid response to outbreaks, exposure to elevated temperatures causes no change in the antiviral activity of NPs while antibodies are completely deactivated. Testing in mice indicates that the chirality-optimized NPs can serve as thermally stable analogs of antiviral biologics complementing the current spectrum of treatments.


Assuntos
COVID-19 , Coronavirus Humano OC43 , Humanos , Animais , Camundongos , SARS-CoV-2/genética , Anticorpos/farmacologia , Antivirais/farmacologia , Antivirais/uso terapêutico
3.
J Immunol ; 210(9): 1351-1362, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36961438

RESUMO

Studies have shown that elevated plasma levels of platelet-derived soluble TREM-like transcript-1 (sTLT-1) are associated with an unfavorable outcome in patients with septic shock. However, the underlying molecular mechanisms are not well defined. This research aimed to study the role of sTLT-1 in mediating immune dysfunction during the development of sepsis. Our study demonstrated that patients with septic shock have significantly higher plasma concentrations of sTLT-1, whereas sTLT-1 is not detectable in healthy subjects. Plasma concentrations of sTLT-1 were correlated with the degree of immunosuppressive parameters in monocytes from patients with septic shock. sTLT-1 can first activate monocytes by binding to the TLR4/MD2 complex but subsequently induce immunosuppressive phenotypes in monocytes. Blocking Abs against TLR4 and MD2 led to a significant decrease in sTLT-1-induced activation. Treatment with an anti-TLT-1 Ab also significantly reduces sTLT-1 binding to monocytes and proinflammatory cytokine secretion in a mouse model of endotoxemia. sTLT-1 acts as an endogenous damage-associated molecular pattern molecule, triggering the activation of monocytes through the TLR4/MD2 complex followed by sustained immune suppression. This process plays a crucial role in the development of sepsis-associated pathophysiology. Our findings outline, to our knowledge, a novel pathway whereby platelets counteract immune dynamics against infection through sTLT-1.


Assuntos
Sepse , Choque Séptico , Animais , Camundongos , Receptor 4 Toll-Like/metabolismo , Alarminas , Receptores Imunológicos/metabolismo
4.
Anal Chem ; 96(14): 5677-5685, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38533607

RESUMO

Reactive oxygen species (ROS) are closely associated with the redox balance of the physiological environment, and monitoring ROS can aid in the early diagnosis of many diseases, including cancer. In this study, chiral vanadium trioxide/vanadium nitride (V2O3/VN) nanoparticles (NPs) modified with an organic dye (cyanine 3 [Cy3]) were prepared for ROS sensing. Chiral V2O3/VN NPs were prepared with the "ligand-induced chirality" strategy and showed a g-factor of up to 0.12 at a wavelength of 512 nm. To the best of our knowledge, this g-factor is the highest value of all chiral ceramic nanomaterials. The very high g-factor of the nanoprobe confers very high sensitivity, because the higher g-factor, the higher sensitivity. In the presence of ROS, V3+ in the chiral V2O3/VN nanoprobe undergoes a redox reaction to form V2O5, reducing the circular dichroism and absorbance signals, whereas the fluorescence signal of Cy3 is restored. With this nanoprobe, the limits of detection for the circular dichroic and fluorescence signals in living cells are 0.0045 nmol/106 and 0.018 nmol/106 cells, respectively. This chiral nanoprobe can also monitor ROS levels in vivo by fluorescence. This strategy provides an innovative approach to the detection of ROS and is expected to promote the wider application of chiral nanomaterials for biosensing.


Assuntos
Nanopartículas , Neoplasias , Humanos , Espécies Reativas de Oxigênio , Vanádio
5.
Diabetes Metab Res Rev ; 40(3): e3784, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38402457

RESUMO

AIMS: Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) have been demonstrated to be associated with cancer cell mechanisms. However, whether they increase the risk of cancer remains unclear. Thus, this study aimed to determine the association between SGLT-2i use and the incidence of cancer in patients with diabetes mellitus (DM) in Taiwan. MATERIALS AND METHODS: This retrospective cohort study was based on the Taiwan National Health Insurance database. The study population comprised patients with DM, and those who first used SGLT-2is during 2016-2018 were assigned to the study group. Greedy propensity score matching was performed to select patients who first used dipeptidyl peptidase 4 inhibitors (DPP-4is), and these patients were assigned to the control group. A Cox proportional hazards model was used to estimate the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for cancer risk in the study and control groups; this model was adjusted for demographic characteristics, DM severity, comorbidities and concomitant medication use. RESULTS: After controlling for relevant variables, the SGLT-2i cohort (aHR = 0.90, 95% CI = 0.87-0.93) had a significantly lower risk of developing cancer than the DPP-4i cohort, particularly when the SGLT-2i was dapagliflozin (aHR = 0.91, 95% CI = 0.87-0.95) or empagliflozin (aHR = 0.90, 95% CI = 0.86-0.94). Regarding cancer type, the SGLT-2i cohort's risk of cancer was significantly lower than that of the DPP-4i cohort for leukaemia, oesophageal, colorectal, liver, pancreatic, lung, skin and bladder cancer. CONCLUSIONS: SGLT-2i use was associated with a significantly lower risk of cancer than DPP-4i use.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Neoplasias , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Glucose , Hipoglicemiantes/efeitos adversos , Neoplasias/epidemiologia , Neoplasias/etiologia , Estudos Retrospectivos , Sódio/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos
6.
Analyst ; 149(2): 467-474, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38044701

RESUMO

Chloridazon (CLZ) is a selective herbicide used in the control of annual broadleaf weeds. The misuse or abuse of CLZ may result in the accumulation of CLZ in crops and water, which can pose a risk to human health. In this study, a hapten of CLZ with three carbon spacer arms was designed and a highly sensitive and specific antibody against CLZ was prepared with a half-maximal inhibitory concentration of 0.630 ng mL-1 and a linear range of 0.181-2.195 ng mL-1.Based on this antibody, we developed an immunochromatographic assay (ICA) strip for the detection of CLZ in oranges and celery. Under optimized conditions, the visual limit of detection was 2 ng mL-1 and 10 ng mL-1 in oranges and celery, respectively, and the cut-off value was 50 ng mL-1. In CLZ-spiked samples and the recovery test, the results of the ICA strip were consistent with those of indirect competitive enzyme-linked immunosorbent assay (ic-ELISA). Therefore, the ICA strip developed in our study represents an efficient and reliable method for the rapid screening of CLZ in oranges and celery.


Assuntos
Apium , Citrus sinensis , Piridazinas , Humanos , Anticorpos Monoclonais/química , Ensaio de Imunoadsorção Enzimática/métodos , Limite de Detecção , Cromatografia de Afinidade/métodos
7.
Analyst ; 149(9): 2747-2755, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38563739

RESUMO

Avian leukemia is an infectious tumorous disease of chickens caused by subgroup A of the avian leukemia virus (ALV-A), which mainly causes long-term viremia, slow growth, immune suppression, decreased production performance, multi-tissue tumors, and even death. The infection rate of this disease is very high in chicken herds in China, causing huge economic losses to the poultry industry every year. We successfully expressed the specific antigen protein of ALV (P27) through recombinant protein technology and screened a pair of highly sensitive monoclonal antibodies (mAbs) through mouse immunity, cell fusion, and antibody pairing. Based on this pair of antibodies, we established a dual antibody sandwich ELISA and gold nanoparticle immunochromatographic strip (AuNP-ICS) detection method. In addition, the parameters of the dual antibody sandwich ELISA and AuNP-ICS were optimized under different reaction conditions, which resulted in the minimum detection limits of 0.2 ng mL-1 and 1.53 ng ml-1, respectively. Commonly available ELISA and AuNP-ICS products on the market were compared, and we found that our established immune rapid chromatography had higher sensitivity. This established AuNP-ICS had no cross-reactivity with Influenza A (H1N1), Influenza A (H9N2), respiratory syncytial virus (RSV), varicella-zoster virus (VZV), Listeria monocytogenes listeriolysin (LLO), and Staphylococcal enterotoxin SED or SEC. Finally, the established AuNP-ICS was used to analyze 35 egg samples, and the results showed 5 positive samples and 30 negative samples. The AuNP-ICS rapid detection method established by our group had good specificity, high sensitivity, and convenience, and could be applied to the clinical sample detection of ALV-A.


Assuntos
Vírus da Leucose Aviária , Cromatografia de Afinidade , Ensaio de Imunoadsorção Enzimática , Ouro , Nanopartículas Metálicas , Ouro/química , Nanopartículas Metálicas/química , Animais , Vírus da Leucose Aviária/isolamento & purificação , Vírus da Leucose Aviária/imunologia , Cromatografia de Afinidade/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Antígenos Virais/imunologia , Antígenos Virais/análise , Clara de Ovo/química , Fitas Reagentes , Galinhas , Limite de Detecção , Camundongos , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/química
8.
J Pathol ; 260(2): 165-176, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36815532

RESUMO

Hepatic angiosarcoma (HAS) is an aggressive mesenchymal malignancy that remains underexplored with respect to its etiology and mutational landscapes. To clarify the association between HAS and end-stage renal disease (ESRD), we used nationwide data of the National Health Insurance Research Database (NHIRD) in Taiwan, covering ~99% of the population, from 2001 to 2016. To investigate molecular signatures, we performed whole-exome sequencing (WES) in 27 surgical specimens, including nine ESRD-associated cases. The NHIRD analysis demonstrated that HAS ranked second among all angiosarcomas in Taiwan, with the incidence rates of HAS being 0.08, 2.49, and 5.71 per 100,000 person-years in the general population, chronic kidney disease (CKD), and ESRD patients, respectively. The standardized incidence ratios of HAS in CKD and ESRD patients were 29.99 and 68.77, respectively. In comparison with nonhepatic angiosarcoma, the multivariate regression analysis of our institutional cohort confirmed CKD/ESRD as an independent risk factor for HAS (odds ratio: 9.521, 95% confidence interval: 2.995-30.261, p < 0.001). WES identified a high tumor mutation burden (TMB; median: 8.66 variants per megabase) and dominant A:T-to-T:A transversion in HAS with frequent TP53 (81%) and ATRX (41%) mutations, KDR amplifications/gains (56%), and CDKN2A/B deletions (48%). Notably, ESRD-associated HAS had a significantly higher TMB (17.62 variants per megabase, p = 0.01) and enriched mutational signatures of aristolochic acid exposure (COSMIC SBS22, p < 0.001). In summary, a significant proportion of HAS in Taiwan is associated with ESRD and harbors a distinctive mutational signature, which concomitantly links nephrotoxicity and mutagenesis resulting from exposure to aristolochic acid or related compounds. A high TMB may support the eligibility for immunotherapy in treating ESRD-associated HAS. © 2023 The Pathological Society of Great Britain and Ireland.


Assuntos
Hemangiossarcoma , Falência Renal Crônica , Neoplasias Hepáticas , Insuficiência Renal Crônica , Humanos , Hemangiossarcoma/epidemiologia , Hemangiossarcoma/genética , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/genética , Insuficiência Renal Crônica/complicações , Fatores de Risco , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/genética , Incidência , Mutação
9.
Environ Sci Technol ; 58(6): 2672-2682, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38290497

RESUMO

Flubendiamide (FLU), a widely used diamide insecticide, has been observed to potentiate adipogenesis in 3T3-L1 preadipocytes in vitro. Whether exposure to FLU disrupts hepatic lipid homeostasis in mammals and induces visceral obesity, however, remains unclear. The aim of this study was to assess the effects of FLU when administered orally to male C57BL/6J mice under normal diet (ND) and high-fat diet (HFD) conditions. FLU accumulated at higher levels in the tissues of the HFD group than those of the ND group, indicating that an HFD contributed to the accumulation of lipophilic pesticides in vivo. Notably, FLU (logP = 4.14) is highly lipophilic and easily accumulates in fat. Exposure to FLU had opposing effects on the lipid metabolism of the liver in the ND and HFD groups. Liver triacylglycerol levels in the ND group were reduced, while those in the HFD group were increased, resulting in more severe hepatic steatosis. More lipid accumulation was also observed in HepG2 cells exposed to FLU. Changes in hepatic lipid deposition in vivo occurred as the enhanced transcriptional regulation of the genes involved in lipid uptake, de novo lipogenesis, and fatty acid ß-oxidation (FAO). Moreover, an excessive increase in FAO caused oxidative stress, which in turn exacerbated the inflammation of the liver. This study revealed the disruptive effect of FLU exposure on hepatic lipid homeostasis, which may facilitate the triggering of nonalcoholic fatty liver disease in HFD-fed mice.


Assuntos
Fluorocarbonos , Hepatopatia Gordurosa não Alcoólica , Ftalimidas , Sulfonas , Masculino , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Metabolismo dos Lipídeos , Lipídeos , Mamíferos
10.
Food Microbiol ; 121: 104510, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38637074

RESUMO

Mycotoxins, as secondary metabolites produced by fungi, have been the focus of researchers in various countries and are considered to be one of the major risk factors in agricultural products. There is an urgent need for a rapid, simple and high-performance method to detect residues of harmful mycotoxins in agricultural foods. We have developed a gold nanoparticle-based multiplexed immunochromatographic strip biosensor that can simultaneously detect fifteen mycotoxins in cereal samples. With this optimized procedure, five representative mycotoxins, deoxynivalenol (DON), zearalenone (ZEN), T-2 toxin (T-2), tenuazonic acid (TEA) and alternariol (AOH) were detected in the range of 0.91-4.77, 0.04-0.56, 0.11-0.68, 0.12-1.02 and 0.09-0.75 ng/mL, respectively. The accuracy and stability of these measurements were demonstrated by analysis of spiked samples with recoveries of 91.8%-115.3% and coefficients of variation <8.7%. In addition, commercially available samples of real cereals were tested using the strips and showed good agreement with the results verified by LC-MS/MS. Therefore, Our assembled ICA strips can be used for the simultaneous detection of 5 mycotoxins and their analogs (15 mycotoxins in total) in grain samples, and the results were consistent between different types of cereal foods, this multiplexed immunochromatographic strip biosensor can be used as an effective tool for the primary screening of mycotoxin residues in agricultural products.


Assuntos
Nanopartículas Metálicas , Micotoxinas , Micotoxinas/análise , Ouro/análise , Ouro/química , Cromatografia Líquida , Contaminação de Alimentos/análise , Nanopartículas Metálicas/análise , Nanopartículas Metálicas/química , Espectrometria de Massas em Tandem , Grão Comestível/microbiologia
11.
J Formos Med Assoc ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38729818

RESUMO

BACKGROUND: Vitamin D deficiency is associated with mortality and morbidity in critically ill patients. This study investigated the safety and effectiveness of enteral high-dose vitamin D supplementation in intensive care unit (ICU) patients in Asia. METHODS: This was a multicenter, prospective, randomized-controlled study. Eligible participants with vitamin D deficiency were randomly assigned to the control or vitamin D supplementation group. In the vitamin D supplementation group, the patients received 569,600 IU vitamin D. The primary outcome was the serum 25(OH)D level on day 7. RESULTS: 41 and 20 patients were included in the vitamin D supplementation and control groups, respectively. On day 7, the serum 25(OH)D level was significantly higher in the vitamin D supplementation group compared to the control group (28.5 [IQR: 20.2-52.6] ng/mL and 13.9 [IQR: 11.6-18.8] ng/mL, p < 0.001). Only 41.5% of the patients achieved serum 25(OH)D levels higher than 30 ng/mL in the supplementation group. This increased level was sustained in the supplementation group on both day 14 and day 28. There were no significant adverse effects noted in the supplementation group. Patients who reached a serum 25(OH)D level of >30 ng/mL on day 7 had a significantly lower 30-day mortality rate than did those who did not (5.9% vs 37.5%, p < 0.05). CONCLUSIONS: In our study, less than half of the patients reached adequate vitamin D levels after the enteral administration of high-dose vitamin D. A reduction in 30-day mortality was noted in the patients who achieved adequate vitamin D levels. TRIAL REGISTRATION CLINICALTRIALS. GOV ID: NCT04292873, Registered, March 1, 2020.

12.
J Formos Med Assoc ; 123(1): 7-15, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37690868

RESUMO

Melanoma is rare in Taiwan. Asian melanoma is distinct from Western melanoma because acral and mucosal melanoma accounts for the majority of melanoma cases, leading to distinct tumor behaviors and genetic profiling. With consideration of the clinical guidelines in Western countries, Taiwanese experts developed a local clinical practice consensus guideline. This consensus includes diagnosis, staging, and surgical and systemic treatment, based only on clinical evidence, local epidemiology, and available resources evaluated by experts in Taiwan. This consensus emphasizes the importance of surgical management, particularly for sentinel lymph node biopsies. In addition, molecular testing for BRAF is mandatory for patients before systemic treatment. Furthermore, immunotherapy and targeted therapy are prioritized for systemic treatment. This consensus aimed to assist clinicians in Taiwan in diagnosing and treating patients according to available evidence.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/diagnóstico , Melanoma/terapia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/genética , Taiwan , Imunoterapia , Consenso
13.
Int Nurs Rev ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38577808

RESUMO

AIM: This study investigated the levels of depression and anxiety in nurses and nursing assistants working in long-term care facilities during the COVID-19 pandemic. We also explored the potential causes of depression and anxiety in nurses and nursing assistants working in long-term care facilities during the pandemic. BACKGROUND: The COVID-19 pandemic has had a considerable impact on long-term care facilities. The high infection and mortality rates for COVID-19 have resulted in an increased workload for caregivers. INTRODUCTION: The COVID-19 pandemic exposed caregivers working in long-term care facilities to higher risks of anxiety and depression. Additionally, the high risk of infection in the work environment and concerns about spreading COVID-19 to family members and long-term care facility residents led to various forms of stress among caregivers. METHODS: The present study was a cross-sectional study. Questionnaires were used to investigate depression and anxiety among regarding nurses and nursing assistants working in long-term care facilities during the pandemic. RESULTS: The depression and anxiety levels of the nurses were higher than nursing assistants, but had no statistically significant difference (p = 0.551). The factors influencing levels of depression and anxiety in nurses contained facility affiliation and experience working. In terms of nursing assistants, age, marital status, and facility affiliation were correlated with the levels of depression and anxiety. DISCUSSION: The pandemic has severely impacted caregivers. In the process of implementing pandemic prevention measures and providing care for COVID-19 patients, safeguarding the psychological health of caregivers is also essential. CONCLUSION: The levels of depression and anxiety in nurses were higher than in nursing assistants working in long-term care facilities during the pandemic. IMPLICATION FOR NURSING AND HEALTH POLICY: Long-term care facilities managers are recommended to enhance the education and training process for caregivers. Managers are also recommended to ensure provision of sufficient amounts of pandemic prevention equipment and resources.

14.
J Am Chem Soc ; 145(44): 24375-24385, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37883809

RESUMO

Here, we develop a novel methodology for synthesizing chiral CdSe@ZnS quantum dots (QDs) with enhanced circularly polarized luminescence (CPL) by incorporating l-/d-histidine (l-/d-His) ligands during ZnS shell growth at the water/oil interface. The resulting chiral QDs exhibit exceptional absolute photoluminescence quantum yield of up to 67.2%, surpassing the reported limits of 40.0% for chiral inorganic QDs, along with absorption dissymmetry factor (|gabs|) and luminescence dissymmetry factor (|glum|) values of 10-2, exceeding the range of 10-5-10-3 and 10-4-10-2, respectively. Detailed investigations of the synthetic pathway reveal that the interface, as a binary synthetic environment, facilitates the coordinated ligand exchange and shell growth mediated by chiral His-Zn2+ coordination complexes, leading to a maximum fluorescent brightness and chiroptical activities. The growth process, regulated by the His-Zn2+ coordination complex, not only reduces trap states on the CdSe surface, thereby enhancing the fluorescence intensity, but also significantly promotes the orbital hybridization between QDs and chiral ligands, effectively overcoming the shielding effect of the wide bandgap shell and imparting pronounced chirality. The proposed growth pathway elucidates the origin of chirality and provides insights into the regulation of the CPL intensity in chiral QDs. Furthermore, the application of CPL QDs in multilevel anticounterfeiting systems overcomes the limitations of replication in achiral fluorescence materials and enhances the system's resistance to counterfeiting, thus opening new opportunities for chiral QDs in optical anticounterfeiting and intelligent information encryption.

15.
Anal Chem ; 95(5): 3108-3118, 2023 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-36693709

RESUMO

Here, the transcriptomics and metabolomics on a model of exposure to a cocktail of neonicotinoids (Neo) containing seven commercial compounds and a synergist piperonyl butoxide (PBO) were established. The results showed that Neo and PBO disrupted mRNA and metabolite levels in a dose-dependent manner. Neo caused tryptophan pathway-related neurotoxicity, reduced lipolysis, and promoted fat mass accumulation in the liver, while PBO induced an increase in inflammatory factors and damage to intercellular membranes. Co-exposure enhanced Neo-induced liver steatosis, focal necrosis, and oxidative stress by inhibiting oxidative phosphorylation (OXPHOS). Furthermore, diglycerides and metabolic biomarkers demonstrated that the activation of insulin signaling is associated with restricted OXPHOS, which commonly leads to a high risk of non-alcoholic fatty liver disease (NAFLD) and Alzheimer's disease (AD) as the result of over-synthesis of lipids, low energy supply, and high thermogenesis. The study demonstrates that chronic disease can be induced by Neo and the synergist PBO at the molecular level.


Assuntos
Sinergistas de Praguicidas , Butóxido de Piperonila , Butóxido de Piperonila/farmacologia , Sinergistas de Praguicidas/toxicidade , Neonicotinoides , Transcriptoma , Fígado
16.
Faraday Discuss ; 246(0): 356-369, 2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37462093

RESUMO

In this study, we present nanofluidic diodes fabricated from straight glass nanochannels and functionalized using bio-inspired polydopamine (PDA) and poly-L-lysine (PLL) coatings. The resulting PDA coatings are shown to be asymmetric due to a combination of transport considerations which can be leveraged to provide a measure of control over the effective channel geometry. By subsequently introducing a layer of amine-bearing PLL chains covalently bound to the PDA, we enhance heterogeneities in the charge and ion distributions within the channel and enable significant current rectification between forward-bias and reverse-bias modes; our PDA-PLL-coated channels yielded a rectification ratio greater than 1000 in a 100 nm channel filled with 0.01× phosphate-buffered saline solution (PBS). We further demonstrated that at higher ionic strength conditions, reducing the solution pH increased the number of protonated amines within the PLL layer, amplifying the charge disparities along the channel and leading to greater rectification. As nanofluidic diodes with bipolar surface charge distributions tend to provide superior performance compared to those with a single wall charge polarity, we imposed a more bipolar charge distribution in our devices by partially coating our PDA-PLL-coated channels with negatively charged polyacrylic acid (PAA). These enhanced bipolar channels exhibited greater current rectification than the PDA-PLL-coated channels, reaching rectification ratios in excess of 100 even in more physiologically-relevant 1× PBS solutions. Our fabrication approach and the results herein provide a promising platform from which the scientific community can build upon in the relentless endeavor for improved sensitivity in biosensors and other analytical devices.

17.
Analyst ; 148(2): 381-390, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36537261

RESUMO

The synthetic antibiotics fluoroquinolones are popular due to their good antibacterial performance and low price, but the risk to human health caused by their residues has attracted great attention. In this study, an ultra-sensitive mAb, 4D7, was prepared with an IC50 of 0.027 ng mL-1 to norfloxacin (NOR) and cross-reactivity of 19.7-47.7% to lomefloxacin (LOM), pefloxacin (PEF), ofloxacin (OFL), enrofloxacin (ENR), ciprofloxacin (CIP), and danofloxacin (DAN). Based on mAb 4D7 and Eu-fluorescent microspheres, a rapid and sensitive immunochromatographic strip was developed for the detection of fluoroquinolone residues in fish and milk. The detection ranges (IC20-IC80) of the strip for the detection of NOR, PEF, LOM, OFL, ENR, CIP and DAN were 0.19-1.1 µg kg-1, 0.39-2.1 µg kg-1, 0.5-2.6 µg kg-1, 0.43-3.3 µg kg-1, 0.61-3.5 µg kg-1, 0.69-5.5 µg kg-1, 0.52-3.4 µg kg-1 in fish, and 0.027-0.19 µg kg-1, 0.049-0.34 µg kg-1, 0.069-0.39 µg kg-1, 0.06-0.41 µg kg-1, 0.089-0.65 µg kg-1, 0.12-0.81 µg kg-1, 0.091-0.52 µg kg-1 in milk, respectively. The recovery rates in spiked sample tests were 88.6-113.6% with a coefficient of variation less than 8.4%. Thus the newly-developed strip was sensitive and reliable for rapid on-site detection of fluoroquinolone residues in fish and milk.


Assuntos
Fluoroquinolonas , Leite , Animais , Humanos , Leite/química , Fluoroquinolonas/análise , Antibacterianos/análise , Pefloxacina/análise , Ciprofloxacina/análise , Norfloxacino , Ofloxacino
18.
Analyst ; 148(5): 985-994, 2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36722989

RESUMO

In 2022, the outbreak of the monkeypox virus occurred in many non-endemic countries, and the World Health Organization (WHO) assessed that this outbreak was "atypical". The establishment of a rapid and effective assay that can be used for the early diagnosis of monkeypox virus infection is crucial for outbreak prevention and control. In this study, the monkeypox virus A29 protein and the homologous vaccinia virus A27 protein and cowpox virus 162 protein were expressed in Escherichia coli BL21 for screening. We synthesized the monkeypox virus A2917-49 peptide as the immunogen and obtained 25 monoclonal antibodies (mAbs) against the A29 protein using mouse hybridoma techniques. Then an immunochromatographic test strip method for detecting A29 was established. The strips utilizing mAb-7C5 and 5D8 showed the best sensitivity and lowest limit of detection: 50 pg mL-1 for purified A29 and specificity tests showed that the strips did not cross-react with other orthopox viruses (vaccinia virus or cowpox virus) as well as common respiratory pathogens (SARS-CoV-2, influenza A and influenza B). Therefore, this method can be used for early and rapid diagnosis of monkeypox virus infection by antigen detection.


Assuntos
Monkeypox virus , Mpox , Animais , Humanos , Camundongos , Ouro , Mpox/diagnóstico , Monkeypox virus/isolamento & purificação
19.
Analyst ; 148(8): 1703-1711, 2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-36916524

RESUMO

Cannabidiol (CBD), the most predominant cannabinoid, may cause addiction and liver damage. In this study, we synthesized a CBD hapten containing the carboxyl group of the spacer arm by derivatizing CBD. A highly specific and sensitive monoclonal antibody (mAb) was prepared with a half-maximal inhibitory concentration of 2.03 ng mL-1 and a limit of detection of 0.32 ng mL-1. MAb was highly specific for CBD. We developed an immunochromatographic assay (ICA) for the detection of CBD in functional beverages with a visible limit of detection of 100 ng mL-1 and a cut-off of 1000 ng mL-1. Compared with HPLC, ICA is more efficient and accurate and can be used for the rapid on-site detection of CBD in samples.


Assuntos
Canabidiol , Nanopartículas Metálicas , Ouro/química , Limite de Detecção , Nanopartículas Metálicas/química , Bebidas , Anticorpos Monoclonais
20.
Analyst ; 148(11): 2449-2458, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37144547

RESUMO

In this study, we synthesized two haptens similar in structure to nitrofen (NIT), and screened out five monoclonal antibodies with the ability to recognize NIT and bifenox (BIF) by competitive ELISA, with the lowest IC50 values of 0.87 ng mL-1 and 0.86 ng mL-1, respectively. The antibody 5G7 was selected to be combined with colloidal gold to establish a lateral flow immunochromatographic assay strip. This method was shown to qualitatively and quantitatively detect the residues of NIT and BIF in fruit samples. The visual limits of detection for qualitative detection were 5 µg kg-1 and 10 µg kg-1 for NIT and BIF, respectively. The calculated limits of detection for quantitative detection were 0.75 µg kg-1, 1.77 µg kg-1 and 2.55 µg kg-1 respectively, for nitrofen in orange, apple and grapes, and 3.54 µg kg-1, 4.96 µg kg-1 and 5.26 µg kg-1, respectively, for bifenox. Thus the strip assay could be used for rapid analysis of fruit samples.


Assuntos
Frutas , Coloide de Ouro , Coloide de Ouro/química , Haptenos , Anticorpos Monoclonais , Cromatografia de Afinidade/métodos
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