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1.
Cell ; 183(4): 1013-1023.e13, 2020 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-32970990

RESUMO

Understanding how potent neutralizing antibodies (NAbs) inhibit SARS-CoV-2 is critical for effective therapeutic development. We previously described BD-368-2, a SARS-CoV-2 NAb with high potency; however, its neutralization mechanism is largely unknown. Here, we report the 3.5-Å cryo-EM structure of BD-368-2/trimeric-spike complex, revealing that BD-368-2 fully blocks ACE2 recognition by occupying all three receptor-binding domains (RBDs) simultaneously, regardless of their "up" or "down" conformations. Also, BD-368-2 treats infected adult hamsters at low dosages and at various administering windows, in contrast to placebo hamsters that manifested severe interstitial pneumonia. Moreover, BD-368-2's epitope completely avoids the common binding site of VH3-53/VH3-66 recurrent NAbs, evidenced by tripartite co-crystal structures with RBDs. Pairing BD-368-2 with a potent recurrent NAb neutralizes SARS-CoV-2 pseudovirus at pM level and rescues mutation-induced neutralization escapes. Together, our results rationalized a new RBD epitope that leads to high neutralization potency and demonstrated BD-368-2's therapeutic potential in treating COVID-19.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Animais , Anticorpos Neutralizantes/química , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/química , Anticorpos Antivirais/uso terapêutico , Reações Antígeno-Anticorpo , Sítios de Ligação , COVID-19 , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Cricetinae , Microscopia Crioeletrônica , Modelos Animais de Doenças , Epitopos/química , Epitopos/imunologia , Feminino , Pulmão/patologia , Masculino , Simulação de Dinâmica Molecular , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Estrutura Quaternária de Proteína , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia
2.
Nature ; 633(8031): 952-959, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39169187

RESUMO

Immunoglobulin E (IgE) plays a pivotal role in allergic responses1,2. The high-affinity IgE receptor, FcεRI, found on mast cells and basophils, is central to the effector functions of IgE. FcεRI is a tetrameric complex, comprising FcεRIα, FcεRIß and a homodimer of FcRγ (originally known as FcεRIγ), with FcεRIα recognizing the Fc region of IgE (Fcε) and FcεRIß-FcRγ facilitating signal transduction3. Additionally, FcRγ is a crucial component of other immunoglobulin receptors, including those for IgG (FcγRI and FcγRIIIA) and IgA (FcαRI)4-8. However, the molecular basis of FcεRI assembly and the structure of FcRγ have remained elusive. Here we elucidate the cryogenic electron microscopy structure of the Fcε-FcεRI complex. FcεRIα has an essential role in the receptor's assembly, interacting with FcεRIß and both FcRγ subunits. FcεRIß is structured as a compact four-helix bundle, similar to the B cell antigen CD20. The FcRγ dimer exhibits an asymmetric architecture, and coils with the transmembrane region of FcεRIα to form a three-helix bundle. A cholesterol-like molecule enhances the interaction between FcεRIß and the FcεRIα-FcRγ complex. Our mutagenesis analyses further indicate similarities between the interaction of FcRγ with FcεRIα and FcγRIIIA, but differences in that with FcαRI. These findings deepen our understanding of the signalling mechanisms of FcεRI and offer insights into the functionality of other immune receptors dependent on FcRγ.


Assuntos
Multimerização Proteica , Receptores de IgE , Animais , Humanos , Ratos , Colesterol/química , Microscopia Crioeletrônica , Imunoglobulina E/química , Imunoglobulina E/imunologia , Imunoglobulina E/metabolismo , Imunoglobulina E/ultraestrutura , Modelos Moleculares , Mutação , Ligação Proteica , Subunidades Proteicas/química , Subunidades Proteicas/metabolismo , Receptores de IgE/química , Receptores de IgE/genética , Receptores de IgE/imunologia , Receptores de IgE/metabolismo , Receptores de IgE/ultraestrutura
3.
Nature ; 602(7898): 657-663, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35016194

RESUMO

The SARS-CoV-2 B.1.1.529 (Omicron) variant contains 15 mutations of the receptor-binding domain (RBD). How Omicron evades RBD-targeted neutralizing antibodies requires immediate investigation. Here we use high-throughput yeast display screening1,2 to determine the profiles of RBD escaping mutations for 247 human anti-RBD neutralizing antibodies and show that the neutralizing antibodies can be classified by unsupervised clustering into six epitope groups (A-F)-a grouping that is highly concordant with knowledge-based structural classifications3-5. Various single mutations of Omicron can impair neutralizing antibodies of different epitope groups. Specifically, neutralizing antibodies in groups A-D, the epitopes of which overlap with the ACE2-binding motif, are largely escaped by K417N, G446S, E484A and Q493R. Antibodies in group E (for example, S309)6 and group F (for example, CR3022)7, which often exhibit broad sarbecovirus neutralizing activity, are less affected by Omicron, but a subset of neutralizing antibodies are still escaped by G339D, N440K and S371L. Furthermore, Omicron pseudovirus neutralization showed that neutralizing antibodies that sustained single mutations could also be escaped, owing to multiple synergetic mutations on their epitopes. In total, over 85% of the tested neutralizing antibodies were escaped by Omicron. With regard to neutralizing-antibody-based drugs, the neutralization potency of LY-CoV016, LY-CoV555, REGN10933, REGN10987, AZD1061, AZD8895 and BRII-196 was greatly undermined by Omicron, whereas VIR-7831 and DXP-604 still functioned at a reduced efficacy. Together, our data suggest that infection with Omicron would result in considerable humoral immune evasion, and that neutralizing antibodies targeting the sarbecovirus conserved region will remain most effective. Our results inform the development of antibody-based drugs and vaccines against Omicron and future variants.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Evasão da Resposta Imune/imunologia , Testes de Neutralização , SARS-CoV-2/imunologia , Enzima de Conversão de Angiotensina 2/metabolismo , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/classificação , Anticorpos Antivirais/classificação , COVID-19/imunologia , COVID-19/virologia , Vacinas contra COVID-19/imunologia , Células Cultivadas , Convalescença , Epitopos de Linfócito B/química , Epitopos de Linfócito B/imunologia , Humanos , Soros Imunes/imunologia , Modelos Moleculares , Mutação , SARS-CoV-2/química , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo
4.
Nature ; 608(7923): 593-602, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35714668

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility than the BA.2 lineage1. The receptor binding and immune-evasion capability of these recently emerged variants require immediate investigation. Here, coupled with structural comparisons of the spike proteins, we show that BA.2.12.1, BA.4 and BA.5 (BA.4 and BA.5 are hereafter referred collectively to as BA.4/BA.5) exhibit similar binding affinities to BA.2 for the angiotensin-converting enzyme 2 (ACE2) receptor. Of note, BA.2.12.1 and BA.4/BA.5 display increased evasion of neutralizing antibodies compared with BA.2 against plasma from triple-vaccinated individuals or from individuals who developed a BA.1 infection after vaccination. To delineate the underlying antibody-evasion mechanism, we determined the escape mutation profiles2, epitope distribution3 and Omicron-neutralization efficiency of 1,640 neutralizing antibodies directed against the receptor-binding domain of the viral spike protein, including 614 antibodies isolated from people who had recovered from BA.1 infection. BA.1 infection after vaccination predominantly recalls humoral immune memory directed against ancestral (hereafter referred to as wild-type (WT)) SARS-CoV-2 spike protein. The resulting elicited antibodies could neutralize both WT SARS-CoV-2 and BA.1 and are enriched on epitopes on spike that do not bind ACE2. However, most of these cross-reactive neutralizing antibodies are evaded by spike mutants L452Q, L452R and F486V. BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1. Nevertheless, these neutralizing antibodies are largely evaded by BA.2 and BA.4/BA.5 owing to D405N and F486V mutations, and react weakly to pre-Omicron variants, exhibiting narrow neutralization breadths. The therapeutic neutralizing antibodies bebtelovimab4 and cilgavimab5 can effectively neutralize BA.2.12.1 and BA.4/BA.5, whereas the S371F, D405N and R408S mutations undermine most broadly sarbecovirus-neutralizing antibodies. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants.


Assuntos
Anticorpos Antivirais , Deriva e Deslocamento Antigênicos , COVID-19 , Epitopos de Linfócito B , Tolerância Imunológica , Mutação , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2/metabolismo , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Deriva e Deslocamento Antigênicos/genética , Deriva e Deslocamento Antigênicos/imunologia , COVID-19/imunologia , COVID-19/transmissão , COVID-19/virologia , Vacinas contra COVID-19/imunologia , Epitopos de Linfócito B/química , Epitopos de Linfócito B/genética , Epitopos de Linfócito B/imunologia , Humanos , Imunidade Humoral , Imunização Secundária , Testes de Neutralização , SARS-CoV-2/classificação , SARS-CoV-2/genética , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo
5.
Nano Lett ; 24(6): 2041-2047, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38300839

RESUMO

Exceptional points (EPs), known as non-Hermitian singularities, have been observed and investigated in parity-time symmetric metasurfaces. However, the chirality and tunability in non-Hermitian metasurfaces still need to be explored. Here, we propose a dynamic topological metasurface with the meta-atom consisting of two orthogonally oriented nanorods, which are placed on the phase change material Ge2Sb2Te5 (GST) and SiO2 dielectric layer, respectively. When GST is converted from the amorphous state (a-GST) to the crystalline state (c-GST), an EP can be dynamically switched from the "ON" state to the "OFF" state in a parameter space. Moreover, based on the topologically protected phase and amplitude modulations of the cross-polarization component, the phase-only hologram and amplitude-only hologram are engineered in the a-GST case and concealed in the c-GST case. Finally, we explore the 2D-chiral symmetry of meta-atoms and further propose two spin-selective meta-deflectors and a hybrid meta-deflector operating with arbitrary polarizations. The GST-based hybrid metasurface offers richer possibilities to realize various wavefront controls.

6.
J Biol Chem ; 298(3): 101702, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35148990

RESUMO

GlcNAc-1-phosphotransferase catalyzes the initial step in the formation of the mannose-6-phosphate tag that labels ∼60 lysosomal proteins for transport. Mutations in GlcNAc-1-phosphotransferase are known to cause lysosomal storage disorders such as mucolipidoses. However, the molecular mechanism of GlcNAc-1-phosphotransferase activity remains unclear. Mammalian GlcNAc-1-phosphotransferases are α2ß2γ2 hexamers in which the core catalytic α- and ß-subunits are derived from the GNPTAB (N-acetylglucosamine-1-phosphate transferase subunits alpha and beta) gene. Here, we present the cryo-electron microscopy structure of the Drosophila melanogaster GNPTAB homolog, DmGNPTAB. We identified four conserved regions located far apart in the sequence that fold into the catalytic domain, which exhibits structural similarity to that of the UDP-glucose glycoprotein glucosyltransferase. Comparison with UDP-glucose glycoprotein glucosyltransferase also revealed a putative donor substrate-binding site, and the functional requirements of critical residues in human GNPTAB were validated using GNPTAB-knockout cells. Finally, we show that DmGNPTAB forms a homodimer that is evolutionarily conserved and that perturbing the dimer interface undermines the maturation and activity of human GNPTAB. These results provide important insights into GlcNAc-1-phosphotransferase function and related diseases.


Assuntos
Lisossomos , Mucolipidoses , Transferases (Outros Grupos de Fosfato Substituídos) , Animais , Microscopia Crioeletrônica , Drosophila melanogaster , Lisossomos/química , Lisossomos/genética , Lisossomos/metabolismo , Mamíferos/metabolismo , Mucolipidoses/genética , Proteínas , Relação Estrutura-Atividade , Transferases (Outros Grupos de Fosfato Substituídos)/química , Transferases (Outros Grupos de Fosfato Substituídos)/metabolismo
7.
BMC Oral Health ; 23(1): 372, 2023 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-37291567

RESUMO

OBJECTIVE: This cross-sectional study aimed to investigate socioeconomic inequalities in dental caries among adults (35 years and older) in China and explore the contributions of various factors to these inequalities. METHODS: This study included 10,983 adults (3,674 aged 35-44 years, 3,769 aged 55-64 years and 3,540 aged 65-74 years) who participated in the 4th National Oral Health Survey (2015-2016) in China. Dental caries status was evaluated by the decayed, missing and filled teeth (DMFT) index. Concentration indices (CIs) were applied to quantify the different degrees of socioeconomic-related inequality in DMFT, decayed teeth with crown or root caries (DT), missing teeth due to caries or other reasons (MT), and filled teeth without any primary or secondary caries (FT) among adults of different age groups. Decomposition analyses were conducted to identify the determinants and their associations with inequalities in DMFT. RESULTS: The significant negative CI indicated that DMFT for the total sample were concentrated among socioeconomically disadvantaged adults (CI = - 0.06; 95% confidence interval [CI], - 0.073 to - 0.047). The CIs for DMFT for adults aged 55-64 and 65-74 years were - 0.038 (95% CI, - 0.057 to - 0.018) and - 0.039 (95% CI, - 0.056 to - 0.023), respectively, while the CI for DMFT for adults aged 35-44 years was not statistically significant (CI = - 0.002; 95% CI, - 0.022 to 0.018). The concentration indices of DT were negative and concentrated in disadvantaged populations, while FT showed pro-rich inequalities in all age groups. Decomposition analyses showed that age, education level, toothbrushing frequency, income and type of insurance contributed substantially to socioeconomic inequalities, accounting for 47.9%, 29.9%, 24.5%,19.1%, and 15.3%, respectively. CONCLUSION: Dental caries was disproportionately concentrated among socioeconomically disadvantaged adults in China. The results of these decomposition analyses are informative for policy-makers attempting to develop targeted health policy recommendations to reduce dental caries inequalities in China.


Assuntos
Cárie Dentária , Adulto , Humanos , Estudos Transversais , Cárie Dentária/epidemiologia , Inquéritos de Saúde Bucal , Índice CPO , População do Leste Asiático , Renda , Saúde Bucal , Fatores Socioeconômicos , Pessoa de Meia-Idade , Idoso
8.
Macromol Rapid Commun ; 43(18): e2200176, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35451187

RESUMO

Bacterial infection can delay wound healing, causing wounds to deteriorate and even threaten the patient's life. Recently, although many composite hydrogels as wound dressing have been developed, it is still highly desired to construct photothermal hydrogels with antimicrobial and antioxidant properties to accelerate the infected wound healing. In this work, a hyaluronic acid (HA)-based composite hydrogel consisting of a dopamine-substituted antimicrobial peptide (DAP) and Iron (III) ions is developed, which exhibits photothermal-assisted promotion and acceleration of healing process of bacteria-infected wounds. DAP, serving as both antimicrobial agent and ROS-scavenger, forms Schiff's base bonds with aldehyde hyaluronic acid (AHA) and iron-catechol coordination bonds to reinforce the composite hydrogel. The presence of Fe3+ can also promote covalent polymerization of dopamine, which endows the hydrogel with photothermal capacity. The in vitro and in vivo experiments prove that the composite hydrogel can effectively accelerate the infected wound healing process, including antibacterial, accelerated collagen deposition, and re-epithelization. This study suggests that the multifunctional composite hydrogel possesses remarkable potential for bacteria-infected wound healing by combining inherent antimicrobial activity, antioxidant capability, and photothermal effect.


Assuntos
Anti-Infecciosos , Hidrogéis , Adesivos/química , Aldeídos , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Peptídeos Antimicrobianos , Antioxidantes/química , Antioxidantes/farmacologia , Catecóis , Colágeno , Dopamina , Humanos , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Íons , Ferro , Espécies Reativas de Oxigênio , Cimentos de Resina , Cicatrização
9.
Nano Lett ; 21(4): 1792-1799, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33570422

RESUMO

Recently, multidimensional metasurfaces, which can modulate multiple optical parameters of input and output lights simultaneously, have aroused intensive interest. Here, we demonstrate multidimensional switchable images and 3D integrated beam splitters based on hyperbolic metamaterials (HMMs). On one hand, a switchable image controlled by output helicity and input wavelengths is achieved by arranging HMMs with different polarization conversion performance. On the other hand, polarization-multiplexed broadband beam splitter is generated by spatially engineering the subunit with broadband half-plate performance. By integrating the multiplexed beam splitter with a filter metamaterial, this multidimensional beam splitter can further realize the separation of output light by space and wavelength. This cascaded multilayer metamaterial achieves a brand new optical functionality and offers more inspiring possibilities for the design of multifunctional optical devices in the future.

10.
BMC Oral Health ; 22(1): 215, 2022 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-35641983

RESUMO

BACKGROUND: The aim of this study was to assess the income-related inequality of edentulism among the aged in China and identify the contributing factors. METHODS: A secondary analysis of data from the 4th National Oral Health Epidemiology Survey in China was conducted, and 65-74 years old were selected for the analysis of income-related inequality of edentulism. The concentration curve, Concentration index (CI) and Erreygers-corrected concentration index (EI) were used to represent inequality and its degree qualitatively and quantitatively, respectively. A decomposition method based on probit model was employed to determine the contributors of inequality, including demographic factors, income status, oral health-related knowledge, attitude and practices and self-perceived general health status. RESULTS: In China, aged people with edentulism were concentrated in the poor. The CI was - 0.2337 (95% CIs: - 0.3503, - 0.1170). The EI was - 0.0413 (95% CIs: - 0.0619, - 0.0207). The decomposition results showed that income (75.02%) and oral health-related knowledge, attitude and practices (15.52%) were the main contributors to the inequality. CONCLUSION: This study showed that pro-poor inequality among the elderly with edentulism existed in China. Corresponding policies against the contributors could be considered to promote the health equality of the elders.


Assuntos
Nível de Saúde , Renda , Idoso , China/epidemiologia , Serviços de Saúde , Humanos , Fatores Socioeconômicos
11.
Small ; 17(41): e2103271, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34510737

RESUMO

With the ever-growing demands for flexible smart interactive electronics, it remains highly desirable yet challenging to design and fabricate interactive ionic skin with multiple signal synergistic outputs. Herein, high-performance photonic ionogels (PIGs) with excellent stability and synergy sensitivity are designed by locking a non-volatile and non-hygroscopic ionic liquid (IL), that is, 1-ethyl-3-methylimidazolium bis-(trifluoromethylsulfonyl)imide ([EMIm][TFSI]), into photonic elastomers based on polymer networks of poly(ethylene glycol) phenyl ether acrylate (PEGPEA). Through manipulating the degree of crosslinking, PIGs exhibit high sensitivity that can output distinct and intuitive color change in visual with the mechanochromic sensitivity of ≈1.76 nm per percent strain and clear electrical signal with the gauge factor of 1, in response to a tiny stretch of millimeter scale. Thanks to the stable photonic elastomers and IL employed, the PIGs developed in this study exhibit good performance under harsh and complex environmental conditions, including high/low temperature (from -35 °C to 100 °C), dry/wet air, and high vacuum. This study provides a novel strategy for developing integrated, stable, and multifunctional photonic ionogels for ionic skin sensors and flexible interactive devices with synergistically optical and electrical output.


Assuntos
Líquidos Iônicos , Eletricidade , Géis , Íons , Polímeros
12.
PLoS Pathog ; 15(6): e1007876, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31216343

RESUMO

The guanylate-binding proteins (GBPs) belong to the dynamin superfamily of GTPases and function in cell-autonomous defense against intracellular pathogens. IpaH9.8, an E3 ligase from the pathogenic bacterium Shigella flexneri, ubiquitinates a subset of GBPs and leads to their proteasomal degradation. Here we report the structure of a C-terminally truncated GBP1 in complex with the IpaH9.8 Leucine-rich repeat (LRR) domain. IpaH9.8LRR engages the GTPase domain of GBP1, and differences in the Switch II and α3 helix regions render some GBPs such as GBP3 and GBP7 resistant to IpaH9.8. Comparisons with other IpaH structures uncover interaction hot spots in their LRR domains. The C-terminal region of GBP1 undergoes a large rotation compared to previously determined structures. We further show that the C-terminal farnesylation modification also plays a role in regulating GBP1 conformation. Our results suggest a general mechanism by which the IpaH proteins target their cellular substrates and shed light on the structural dynamics of the GBPs.


Assuntos
Proteínas de Bactérias/química , Simulação de Dinâmica Molecular , Shigella flexneri/enzimologia , Ubiquitina-Proteína Ligases/química , Proteínas de Bactérias/genética , Domínios Proteicos , Shigella flexneri/genética , Ubiquitina-Proteína Ligases/genética
13.
BMC Oral Health ; 21(1): 436, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493249

RESUMO

BACKGROUND: To analyze the potential cost savings in dental care associated with increased sugar-free gum (SFG) use among Chinese teenagers and adults. METHODS: The amount of SFG chewed per year and decayed, missing and filled teeth (DMFT) was collected from a cross-sectional survey to create a dose-response curve assumption. A cost analysis of dental restoration costs was carried out. A budget impact analysis was performed to model the decrease in DMFT and the subsequent cost savings for dental care. Three different scenarios for the increase in the number of SFG were calculated. RESULTS: The average cost savings per person in the Chinese population due to increasing SFG use ranged from 45.95 RMB (6.94 USD) per year to 67.41 RMB (10.19 USD) per year. It was estimated that 21.51-31.55 billion RMB (3.25-4.77 billion USD) could be saved annually if all SFG chewers among Chinese teenagers and adults chewed SFG regularly. CONCLUSION: This study suggests that dental care costs could be significantly reduced if SFG use increased in the Chinese population.


Assuntos
Goma de Mascar , Cárie Dentária , Adolescente , Adulto , Orçamentos , China/epidemiologia , Estudos Transversais , Cárie Dentária/epidemiologia , Cárie Dentária/prevenção & controle , Humanos
14.
Sensors (Basel) ; 20(7)2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32230961

RESUMO

Construction sites are dangerous due to the complex interaction of workers with equipment, building materials, vehicles, etc. As a kind of protective gear, hardhats are crucial for the safety of people on construction sites. Therefore, it is necessary for administrators to identify the people that do not wear hardhats and send out alarms to them. As manual inspection is labor-intensive and expensive, it is ideal to handle this issue by a real-time automatic detector. As such, in this paper, we present an end-to-end convolutional neural network to solve the problem of detecting if workers are wearing hardhats. The proposed method focuses on localizing a person's head and deciding whether they are wearing a hardhat. The MobileNet model is employed as the backbone network, which allows the detector to run in real time. A top-down module is leveraged to enhance the feature-extraction process. Finally, heads with and without hardhats are detected on multi-scale features using a residual-block-based prediction module. Experimental results on a dataset that we have established show that the proposed method could produce an average precision of 87.4%/89.4% at 62 frames per second for detecting people without/with a hardhat worn on the head.


Assuntos
Indústria da Construção/tendências , Redes Neurais de Computação , Exposição Ocupacional/prevenção & controle , Segurança , Humanos , Processamento de Imagem Assistida por Computador
15.
Org Lett ; 26(15): 2945-2948, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38567811

RESUMO

Cranomycin and jogyamycin, two aminocyclopentitol natural products, possess complex structures and potential medicinal properties. This review describes synthetic studies about the process of making an advanced intermediate of cranomycin and jogyamycin. This highly functionalized intermediate, featuring three contiguous amine-substituted stereocenters, was constructed from cyclopentadiene through a series of reactions including the nitroso Diels-Alder reaction, nitrogen radical cyclization reaction, 1,2-nitrogen migration, and stereoselective nitrogen addition.

16.
Int J Biol Macromol ; 257(Pt 1): 128636, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38065459

RESUMO

Injectable hydrogel has attracted appealing attention for skin wound treatment. Although multifunctional injectable hydrogels can be prepared by introducing bioactive ingredients with antibacterial and anti-inflammatory capabilities, their preparation remains complicated. Herein, a polyphenol-based supramolecular injectable hydrogel (PBSIH) based on polyphenol gallic acid and biological macromolecule sodium alginate is developed as a wound dressing to accelerate wound healing. We show that such PBSIH can be rapidly formed within 15 s by mixing the sodium alginate and gallic acid solutions based on the hydrogen bonding and hydrophobic interactions. The PBSIH shows excellent cytocompatibility, antibacterial, and antioxidant properties, which enhance infected wound healing by inhibiting bacterial infection and alleviating inflammation after treatment of 11 days. Moreover, we show that the preparative strategies of injectable supramolecular hydrogels can be extended to other polyphenols, including protocatechuic and tannic acids. This study provides a facile yet highly effective method to design injectable polyphenol- sodium alginate hydrogel for wound dressing based on naturally bioactive ingredients.


Assuntos
Hidrogéis , Cicatrização , Anti-Inflamatórios/farmacologia , Antibacterianos/farmacologia , Alginatos , Ácido Gálico/farmacologia , Veículos Farmacêuticos , Polifenóis/farmacologia
17.
Nanoscale ; 16(18): 8907-8914, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38625084

RESUMO

On-chip polarization-sensitive photodetectors are highly desired for ultra-compact optoelectronic systems. It has been demonstrated that polarization-sensitive photodetection can be realized using intrinsic chiral and anisotropy materials. However, these photodetectors can only realize the detection of either circularly polarized light (CPL) or linear polarized light (LPL) and are not applicable to multiple-polarization-sensitive photodetection. Herein, we experimentally demonstrate a metasurface-integrated semiconductor to realize multiple-polarization-sensitive photodetection at visible wavelengths. This device is composed of a MoSe2 monolayer on an H-shaped plasmonic nanostructure. The geometric chirality and anisotropy of the H-shaped nanostructure result in CPL and LPL resolved optical responses. By integrating a plasmonic metasurface with monolayer MoSe2, we converted polarization-sensitive optical absorption to the polarization-sensitive photocurrent of the device through the photoconductive effect. Polarization-sensitive photocurrent responses to both CPL and LPL are systematically investigated, which demonstrate a high photocurrent circular dichroism (CD) of 0.35 at a wavelength of 810 nm and photocurrent linear polarization (LP) of 0.4 at a wavelength of 633 nm. Our results provide a potential pathway to realize multiple-polarization-sensitive applications in medicine analysis, biology, and remote sensing.

18.
Int Dent J ; 74(5): 968-977, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38821780

RESUMO

INTRODUCTION AND AIMS: Early childhood caries (ECC) is a widespread oral disease that harms children's health in China. Although previous studies have linked ECC prevalence to socioeconomic status, few have measured the degree of socioeconomic inequality. This study aimed to evaluate the socioeconomic inequality of ECC in children aged 3 to 5 years in China and identify the contributor to the inequality. METHODS: We extracted data on 3 to 5-year-old children from the fourth National Oral Health Survey. We measured the inequality of ECC by the average household income per capita. We used the average household income per capita to measure the inequality of ECC. To describe inequality both qualitatively and quantitatively, we used the following methods: concentration curve, Erreygers-corrected concentration index, relative index of inequality and slope index of inequality. We also applied a decomposition based on the probit model to identify the factors that contributed to inequality. RESULTS: The prevalence of ECC in Chinese preschool children was 63.11% (95% CIs: 60.54%, 65.61%). The negative value of the Erreygers-corrected concentration index (-0.0459; 95% CIs: -0.0594, -0.0324), slope index of inequality (-0.0674; 95% CIs: -0.0876, -0.0471) and the positive value of relative index of inequality (0.7484; 95% CIs: 0.6856, 0.8169) all indicated that ECC prevalence was higher among children from low-income families. The main factors contributing to inequality were average household income, parents' educational level and living areas. CONCLUSION: There is a pro-poor inequality in ECC among 3 to 5-year-old children in China. CLINICAL RELEVANCE: To improve oral health equality, policymakers should focus more on children from low-income families, with less educated parents and living in rural areas.


Assuntos
Cárie Dentária , Fatores Socioeconômicos , Humanos , China/epidemiologia , Cárie Dentária/epidemiologia , Pré-Escolar , Masculino , Feminino , Prevalência , Renda/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Classe Social , Inquéritos de Saúde Bucal
19.
J Integr Med ; 22(3): 245-257, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38616445

RESUMO

Acupuncture is one of the most effective complementary therapies for allergic rhinitis (AR) and has been recommended by several clinical practice guidelines (CPGs) for AR. However, these CPGs mentioned acupuncture without making recommendations for clinical implementation and therapeutic protocols, therefore limiting the applicability of acupuncture therapies for AR. Hence, for the benefit of acupuncture practitioners around the world, the World Federation of Acupuncture-moxibustion Societies have initiated a project to develop the CPG for the use of acupuncture and moxibustion to treat AR. This CPG was developed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, referring to the principles of the World Health Organization Handbook for Guideline Development. During the development of the CPG, the guideline development group (GDG) played an important role. The clinical questions, recommendations and therapeutic protocols were all formulated by the GDG using the modified Delphi method. The CPG contains recommendations for 15 clinical questions about the use of acupuncture and moxibustion interventions. These include one strong recommendation for the intervention based on high-quality evidence, three conditional recommendations for either the intervention or standard care, and 11 conditional recommendations for the intervention based on very low quality of evidence. The CPG also provides one filiform needle acupuncture protocol and five moxibustion protocols extracted based on the protocols presented in randomized controlled trials reviewed by the GDG. Please cite this article as: Du SH, Chen S, Wang SZ, Wang GQ, Du S, Guo W, Xie XL, Peng BH, Yang C, Zhao JP. Clinical practice guideline for acupuncture and moxibustion: Allergic rhinitis. J Integr Med. 2024; 22(3): 245-257.


Assuntos
Terapia por Acupuntura , Moxibustão , Rinite Alérgica , Humanos , Rinite Alérgica/terapia , Guias de Prática Clínica como Assunto
20.
J Integr Med ; 22(3): 258-269, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38677968

RESUMO

Urinary incontinence (UI) is a common problem worldwide. It has a major impact on physical and social activities and interpersonal relationships. UI is common in women, but is under-reported and under-treated. It affects the quality of life of female patients severely. Acupuncture and moxibustion have been proposed as potentially effective interventions for female UI. Hence, for the benefit of acupuncture practitioners around the world, the World Federation of Acupuncture-moxibustion Societies initiated a project to develop a clinical practice guideline (CPG) for the use of acupuncture and moxibustion to treat female UI. This CPG was developed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, referring to the principles of the World Health Organization Handbook for Guideline Development. During the development of the CPG, the guideline development group (GDG) played an important role. The clinical questions, recommendations and therapeutic protocols were all formulated by GDG using the modified Delphi method. This CPG contains ten recommendations about the use of acupuncture and moxibustion interventions for ten clinical questions, which include nine conditional recommendations for the intervention and one conditional recommendation for either the intervention or the comparison. This CPG also provides one protocol for conventional filiform needle therapy, two therapy protocols for deep needling stimulation on lumbosacral acupoints, and four moxibustion therapy protocols, based on the protocols presented in randomized controlled trials reviewed by the GDG. Please cite this article as: Yang C, Wang SZ, Chen S, Du S, Wang GQ, Guo W, Xie XL, Peng BH, Du SH, Zhao JP. Clinical practice guideline for acupuncture and moxibustion: Female urinary incontinence. J Integr Med. 2024; 22(3): 258-269.


Assuntos
Terapia por Acupuntura , Moxibustão , Incontinência Urinária , Humanos , Feminino , Incontinência Urinária/terapia , Guias de Prática Clínica como Assunto
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