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Cisplatin-induced hearing loss is a common side effect of cancer chemotherapy in clinics; however, the mechanism of cisplatin-induced ototoxicity is still not completely clarified. Cisplatin-induced ototoxicity is mainly associated with the production of reactive oxygen species, activation of apoptosis, and accumulation of intracellular lipid peroxidation, which also is involved in ferroptosis induction. In this study, the expression of TfR1, a ferroptosis biomarker, was upregulated in the outer hair cells of cisplatin-treated mice. Moreover, several key ferroptosis regulator genes were altered in cisplatin-damaged cochlear explants based on RNA sequencing, implying the induction of ferroptosis. Ferroptosis-related Gpx4 and Fsp1 knockout mice were established to investigate the specific mechanisms associated with ferroptosis in cochleae. Severe outer hair cell loss and progressive damage of synapses in inner hair cells were observed in Atoh1-Gpx4-/- mice. However, Fsp1-/- mice showed no significant hearing phenotype, demonstrating that Gpx4, but not Fsp1, may play an important role in the functional maintenance of HCs. Moreover, findings showed that FDA-approved luteolin could specifically inhibit ferroptosis and alleviate cisplatin-induced ototoxicity through decreased expression of transferrin and intracellular concentration of ferrous ions. This study indicated that ferroptosis inhibition through the reduction of intracellular ferrous ions might be a potential strategy to prevent cisplatin-induced hearing loss.
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Cisplatino , Ferroptose , Perda Auditiva , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Animais , Cisplatino/efeitos adversos , Ferroptose/efeitos dos fármacos , Ferroptose/genética , Camundongos , Perda Auditiva/induzido quimicamente , Perda Auditiva/genética , Perda Auditiva/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Modelos Animais de Doenças , Receptores da Transferrina/metabolismo , Receptores da Transferrina/genética , Espécies Reativas de Oxigênio/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Células Ciliadas Auditivas Externas/metabolismo , Células Ciliadas Auditivas Externas/efeitos dos fármacos , Células Ciliadas Auditivas Externas/patologia , Ototoxicidade/etiologia , Ototoxicidade/metabolismo , Antineoplásicos/efeitos adversos , Apoptose/efeitos dos fármacosRESUMO
The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the emergence of different variants of concerns with immune evasion that have been prevalent over the past three years. Nanobodies, the functional variable regions of camelid heavy-chain-only antibodies, have garnered interest in developing neutralizing antibodies due to their smaller size, structural stability, ease of production, high affinity, and low immunogenicity, among other characteristics. In this work, we describe an integrated proteomics platform for the high-throughput screening of nanobodies against different SARS-CoV-2 spike variants. To demonstrate this platform, we immunized a camel with subunit 1 (S1) of the wild-type spike protein and constructed a nanobody phage library. The binding and neutralizing activities of the nanobodies against 72 spike variants were then measured, resulting in the identification of two nanobodies (C-282 and C-39) with broad neutralizing activity against six non-Omicron variants (D614G, Alpha, Beta, Gamma, Delta, Kappa) and five Omicron variants (BA.1-5). Their neutralizing capability was validated using in vitro pseudovirus-based neutralization assays. All these results demonstrate the utility of our proteomics platform to identify new nanobodies with broad neutralizing capability and to develop a treatment for patients with SARS-CoV-2 variant infection in the future.
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Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19 , Camelus , Proteômica , SARS-CoV-2 , Anticorpos de Domínio Único , Glicoproteína da Espícula de Coronavírus , SARS-CoV-2/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos de Domínio Único/imunologia , Anticorpos de Domínio Único/química , Proteômica/métodos , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Animais , Humanos , COVID-19/imunologia , COVID-19/virologia , Anticorpos Antivirais/imunologia , Testes de NeutralizaçãoRESUMO
A growing number of clinical and animal studies suggest that the nucleus accumbens (NAc), especially the shell, is involved in the pathogenesis of temporal lobe epilepsy (TLE). However, the role of parvalbumin (PV) GABAergic neurons in the NAc shell involved in TLE is still unclear. In this study, we induced a spontaneous TLE model by intrahippocampal administration of kainic acid (KA), which generally induce acute seizures in first 2 h (acute phase) and then lead to spontaneous recurrent seizures after two months (chronic phase). We found that chemogenetic activation of NAc shell PV neurons could alleviate TLE seizures by reducing the number and period of focal seizures (FSs) and secondary generalized seizures (sGSs), while selective inhibition of PV exacerbated seizure activity. Ruby-virus mapping results identified that the hippocampus (ventral and dorsal) is one of the projection targets of NAc shell PV neurons. Chemogenetic activation of the NAc-Hip PV projection fibers can mitigate seizures while inhibition has no effect on seizure ictogenesis. In summary, our findings reveal that PV neurons in the NAc shell could modulate the seizures in TLE via a long-range NAc-Hip circuit. All of these results enriched the investigation between NAc and epilepsy, offering new targets for future epileptogenesis research and precision therapy.
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Epilepsia do Lobo Temporal , Animais , Epilepsia do Lobo Temporal/patologia , Núcleo Accumbens/metabolismo , Parvalbuminas/metabolismo , Convulsões/patologia , Hipocampo/patologia , Neurônios GABAérgicos/metabolismo , Ácido Caínico/toxicidade , Modelos Animais de DoençasRESUMO
MAIN CONCLUSION: The expression peak of VcAP1.4, VcAP1.6, VcAP3.1, VcAP3.2, VcAG3, VcFLC2, and VcSVP9 coincided with the endo-dormancy release of flower buds. Additionally, GA4+7 not only increased the expression of these genes but also promoted flower bud endo-dormancy release. The MIKCC-type MADS-box gene family is involved in the regulation of flower development. A total of 109 members of the MIKCC-type MADS-box gene family were identified in blueberry. According to the phylogenetic tree, these 109 MIKCC-type MADS-box proteins were divided into 13 subfamilies, which were distributed across 40 Scaffolds. The results of the conserved motif analysis showed that among 20 motifs, motifs 1, 3, and 9 formed the MADS-box structural domain, while motifs 2, 4, and 6 formed the K-box structural domain. The presence of 66 pairs of fragment duplication events in blueberry suggested that gene duplication events contributed to gene expansion and functional differentiation. Additionally, the presence of cis-acting elements revealed that VcFLC2, VcAG3, and VcSVP9 might have significant roles in the endo-dormancy release of flower buds. Meanwhile, under chilling conditions, VcAP3.1 and VcAG7 might facilitate flower bud dormancy release. VcSEP11 might promote flowering following the release of endo-dormancy, while the elevated expression of VcAP1.7 (DAM) could impede the endo-dormancy release of flower buds. The effect of gibberellin (GA4+7) treatment on the expression pattern of MIKCC-type MADS-box genes revealed that VcAP1.4, VcAP1.6, VcAP3.1, VcAG3, and VcFLC2 might promote flower bud endo-dormancy release, while VcAP3.2, VcSEP11, and VcSVP9 might inhibit its endo-dormancy release. These results indicated that VcAP1.4, VcAP1.6, VcAP1.7 (DAM), VcAP3.1, VcAG3, VcAG7, VcFLC2, and VcSVP9 could be selected as key regulatory promoting genes for controlling the endo-dormancy of blueberry flower buds.
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Mirtilos Azuis (Planta) , Mirtilos Azuis (Planta)/genética , Filogenia , Reprodução , Flores/genética , Duplicação GênicaRESUMO
BACKGROUND: Predictive markers for fecal microbiota transplantation (FMT) outcomes in patients with active ulcerative colitis (UC) are poorly defined. We aimed to investigate changes in gut microbiota pre- and post-FMT and to assess the potential value in determining the total copy number of fecal bacterial siderophore genes in predicting FMT responsiveness. METHODS: Patients with active UC (Mayo score ≥ 3) who had undergone two FMT procedures were enrolled. Fecal samples were collected before and 8 weeks after each FMT session. Patients were classified into clinical response and non-response groups, based on their Mayo scores. The fecal microbiota profile was accessed using metagenomic sequencing, and the total siderophore genes copy number via quantitative real-time polymerase chain reaction. Additionally, we examined the association between the total siderophore genes copy number and FMT efficacy. RESULTS: Seventy patients with UC had undergone FMT. The clinical response and remission rates were 50% and 10% after the first FMT procedure, increasing to 72.41% and 27.59% after the second FMT. The cumulative clinical response and clinical remission rates were 72.86% and 25.71%. Compared with baseline, the response group showed a significant increase in Faecalibacterium, and decrease in Enterobacteriaceae, consisted with the changes of the total bacterial siderophore genes copy number after the second FMT (1889.14 vs. 98.73 copies/ng, P < 0.01). Virulence factor analysis showed an enriched iron uptake system, especially bacterial siderophores, in the pre-FMT response group, with a greater contribution from Escherichia coli. The total baseline copy number was significantly higher in the response group than non-response group (1889.14 vs. 94.86 copies/ng, P < 0.01). A total baseline copy number cutoff value of 755.88 copies/ng showed 94.7% specificity and 72.5% sensitivity in predicting FMT responsiveness. CONCLUSIONS: A significant increase in Faecalibacterium, and decrease in Enterobacteriaceae and the total fecal siderophore genes copy number were observed in responders after FMT. The siderophore genes and its encoding bacteria may be of predictive value for the clinical responsiveness of FMT to active ulcerative colitis.
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Colite Ulcerativa , Transplante de Microbiota Fecal , Fezes , Microbioma Gastrointestinal , Sideróforos , Humanos , Colite Ulcerativa/terapia , Colite Ulcerativa/microbiologia , Colite Ulcerativa/genética , Masculino , Feminino , Fezes/microbiologia , Adulto , Pessoa de Meia-Idade , Microbioma Gastrointestinal/genética , Sideróforos/metabolismo , Resultado do Tratamento , Bactérias/genética , Genes Bacterianos , Dosagem de Genes , Curva ROCRESUMO
Plant-mediated interactions between herbivores play an important role in regulating the composition of herbivore community. The fall armyworm (FAW), Spodoptera frugiperda, which has become one of the most serious pests on corn in China since it invaded in 2018, has been found feeding rice in the field. However, how FAW interacts with native rice insect pests remains largely unknown. Here, we investigated the interaction between FAW and a resident herbivore, striped stem borer (SSB, Chilo suppressalis) on rice. The infestation of rice leaf sheaths (LSs) by SSB larvae systemically enhanced the level of jasmonic acid (JA), abscisic acid (ABA), and trypsin proteinase inhibitors (TPIs), reduced relative water content (RWC) in leaf blades (LBs), and suppressed the growth of FAW larvae. In contrast, because FAW larvae infested LBs and did not affect defence responses in LSs, they did not influence the performance of SSB larvae. Using different mutants, together with bioassays and chemical analysis, we revealed that SSB-induced suppression of FAW larvae growth depended on both the SSB-activated JA pathway and RWC in LBs, whereas the ABA pathway activated by SSB larvae promoted the growth of FAW larvae by impeding water loss. These results provide new insights into mechanisms underlying plant-mediated interactions between herbivores.
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BACKGROUND: Desensitization of G protein-coupled receptors (GPCRs) refers to the attenuation of receptor responsiveness by prolonged or intermittent exposure to agonists. The binding of ß-arrestin to the cytoplasmic cavity of the phosphorylated receptor, which competes with the G protein, has been widely accepted as an extensive model for explaining GPCRs desensitization. However, studies on various GPCRs, including dopamine D2-like receptors (D2R, D3R, D4R), have suggested the existence of other desensitization mechanisms. The present study employed D2R/D3R variants with different desensitization properties and utilized loss-of-function approaches to uncover the mechanisms underlying GPCRs homologous desensitization, focusing on the signaling cascade that regulates the ubiquitination of AKT. RESULTS: AKT undergoes K8/14 ubiquitination by TRAF6, which occurs in the nucleus and promotes its membrane recruitment, phosphorylation and activation under receptor desensitization conditions. The nuclear entry of TRAF6 relies on the presence of the importin complex. Src regulates the nuclear entry of TRAF6 by mediating the interaction between TRAF6 and importin ß1. Ubiquitinated AKT translocates to the plasma membrane where it associates with Mdm2 to phosphorylate it at the S166 and S186 residues. Thereafter, phosphorylated Mdm2 is recruited to the nucleus, resulting in the deubiquitination of ß-Arr2. The deubiquitinated ß-Arr2 then forms a complex with Gßγ, which serves as a biomarker for GPCRs desensitization. Like in D3R, ubiquitination of AKT is also involved in the desensitization of ß2 adrenoceptors. CONCLUSION: Our study proposed that the property of a receptor that causes a change in the subcellular localization of TRAF6 from the cytoplasm to the nucleus to mediate AKT ubiquitination could initiate the desensitization of GPCRs.
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Proteínas Proto-Oncogênicas c-akt , Fator 6 Associado a Receptor de TNF , Fator 6 Associado a Receptor de TNF/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Ubiquitinação , Fosforilação , CarioferinasRESUMO
High-resolution transmission electron microscopy (HRTEM) images can capture the atomic-resolution details of the dynamically changing structure of nanomaterials. Here, we propose a new scheme and an improved reconstruction algorithm to reconstruct the exit wave function for each image in a focal series of HRTEM images to reveal structural changes. In this scheme, the wave reconstructed from the focal series of images is treated as the initial wave in the reconstruction process for each HRTEM image. Additionally, to suppress noise at the frequencies where the signal is weak due to the modulation of the lens transfer function, a weight factor is introduced in the improved reconstruction algorithm. The advantages of the new scheme and algorithms are validated by using the HRTEM images of a natural specimen and a single-layer molybdenum disulphide. This algorithm enables image resolution enhancement and lens aberration removal, while potentially allowing the visualisation of the structural evolution of nanostructures.
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The coexistence of amyloid-ß (Aß) and human islet amyloid polypeptide (hIAPP) in the brain and pancreas is associated with an increased risk of Alzheimer's disease (AD) and type 2 diabetes (T2D) due to their coaggregation and cross-seeding. Despite this, the molecular mechanisms underlying their interaction remain elusive. Here, we systematically investigated the cross-talk between Aß and hIAPP using atomistic discrete molecular dynamics (DMD) simulations. Our results revealed that the amyloidogenic core regions of both Aß (Aß10-21 and Aß30-41) and hIAPP (hIAPP8-20 and hIAPP22-29), driving their self-aggregation, also exhibited a strong tendency for cross-interaction. This propensity led to the formation of ß-sheet-rich heterocomplexes, including potentially toxic ß-barrel oligomers. The formation of Aß and hIAPP heteroaggregates did not impede the recruitment of additional peptides to grow into larger aggregates. Our cross-seeding simulations demonstrated that both Aß and hIAPP fibrils could mutually act as seeds, assisting each other's monomers in converting into ß-sheets at the exposed fibril elongation ends. The amyloidogenic core regions of Aß and hIAPP, in both oligomeric and fibrillar states, exhibited the ability to recruit isolated peptides, thereby extending the ß-sheet edges, with limited sensitivity to the amino acid sequence. These findings suggest that targeting these regions by capping them with amyloid-resistant peptide drugs may hold potential as a therapeutic approach for addressing AD, T2D, and their copathologies.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Diabetes Mellitus Tipo 2 , Polipeptídeo Amiloide das Ilhotas Pancreáticas , Simulação de Dinâmica Molecular , Doença de Alzheimer/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Polipeptídeo Amiloide das Ilhotas Pancreáticas/química , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Humanos , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/química , Agregados ProteicosRESUMO
Antibiotic resistance genes (ARGs) are a kind of emerging environmental contamination, and are commonly found in antibiotic application situations, attracting wide attention. Fish skin mucosal surface (SMS), as the contact interface between fish and water, is the first line of defense against external pollutant invasion. Antibiotics are widely used in aquaculture, and SMS may be exposed to antibiotics. However, what happens to SMS when antibiotics are applied, and whether ARGs are enriched in SMS are not clear. In this study, Zebrafish (Danio rerio) were exposed to antibiotic and antibiotic resistant bacteria in the laboratory to simulate the aquaculture situation, and the effects of SMS on the spread of ARGs were explored. The results showed that SMS maintained the stability of the bacterial abundance and diversity under apramycin (APR) and bacterial exposure effectively. Until 11 days after stopping APR exposure, the abundance of ARGs in SMS (mean value was 3.32 × 10-3 copies/16S rRNA copies) still did not recover to the initial stage before exposure, which means that enriched ARGs in SMS were persistently remained. Moreover, non-specific immunity played an important role in resisting infection of external contamination. Besides, among antioxidant proteins, superoxide dismutase showed the highest activity. Consequently, it showed that SMS became a barrier of antibiotic resistance genes under APR exposure, and ARGs in SMS were difficult to remove once colonized. This study provided a reference for understanding the transmission, enrichment process, and ecological impact of antibiotics and ARGs in aquatic environments.
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Antibacterianos , Nebramicina , Pele , Peixe-Zebra , Animais , Peixe-Zebra/genética , Nebramicina/análogos & derivados , Nebramicina/farmacologia , Antibacterianos/farmacologia , Antibacterianos/toxicidade , Pele/efeitos dos fármacos , Pele/microbiologia , Resistência Microbiana a Medicamentos/genética , Mucosa/efeitos dos fármacos , Mucosa/microbiologia , Poluentes Químicos da Água/toxicidadeRESUMO
To achieve the AUC-guided dosing, we proposed three methods to estimate polymyxin B AUC across 24 h at steady state (AUCSS,24h) using limited concentrations after its first dose.Monte Carlo simulation based on a well-established population PK model was performed to generate the PK profiles of 1000 patients with normal or abnormal renal function. Polymyxin B AUCSS,24h was estimated for each subject using three methods (two-point PK approach, three-point PK approach, and four-point PK approach) based on limited concentration data in its first dose and compared with the actual AUC at steady state calculated using the linear-trapezoidal formula.In patients with normal renal function, the mean bias of two-point PK approach, three-point PK approach, and four-point PK approach was -8.73%, 1.37%, and -0.48%, respectively. The corresponding value was -11.15%, 1.99%, and -0.28% in patients with renal impairment, respectively. The largest mean bias of two-point PK approach, three-point PK approach, and four-point PK approach was -12.63%, -6.47%, and -0.54% when the sampling time shifted.The Excel calculators designed based on the three methods can be potentially used to optimise the dosing regimen of polymyxin B in the clinic.
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Intravenous immunoglobulin (IVIg) is a first-line treatment for children with newly diagnosed immune thrombocytopenia (ITP). Higher doses of IVIg are associated with a more insupportable financial burden to pediatric patients' families and may produce more adverse reactions. Whether low-dose IVIg (LD-IVIg) can replace high-dose IVIg (HD-IVIg) has yet to be established. We conducted a comprehensive literature search from the establishment of the database to May 1, 2023, and eventually included 22 RCTs and 3 cohort studies compared different dosages of IVIg. A total of 1989 patients were included, with 991 patients in the LD-IVIg group and 998 patients in the HD-IVIg group. Our results showed no significant differences between the two groups in the effective rate (LD-IVIg: 91% vs. HD-IVIg: 93%; RR: 0.99; 95%CI: 0.96-1.02) and the durable remission rate (LD-IVIg: 65% vs. HD-IVIg: 67%; RR: 0.97; 95%CI: 0.89-1.07). Similar results were also found in the time of platelet counts (PC) starting to rise (MD: 0.01, 95%CI: -0.06-0.09), rising to normal (MD: 0.16, 95%CI: -0.03-0.35), and achieving hemostasis (MD: 0.11, 95%CI: -0.02-0.23) between the two groups. Subgroup analysis showed the effective rate of 0.6 g/kg was equal to 1 g/kg subgroup (91%) but higher than 0.8 g/kg subgroup (82%), and a combination with glucocorticoid may contribute to effect enhancement (combined with glucocorticoid: 91% vs. IVIg alone: 86%) whether combined with dexamethasone (92%) or methylprednisolone (91%). Besides, the incidence rate of adverse reactions in the LD-IVIg group (3%) was significantly lower than the HD-IVIg group (6%) (RR: 0.61; 95%CI: 0.38-0.98). So low-dose IVIg (≤ 1 g/kg) is effective, safe, and economical, which can replace high-dose IVIg (2 g/kg) as an initial treatment. This systematic review was registered in PROSPERO (CRD42022384604).
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Imunoglobulinas Intravenosas , Púrpura Trombocitopênica Idiopática , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/uso terapêutico , Imunoglobulinas Intravenosas/efeitos adversos , Criança , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Relação Dose-Resposta a Droga , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/uso terapêuticoRESUMO
The toxicity of nanoparticles to freshwater microalgae is of significant importance in maintaining the overall stability of aquatic ecosystems. However, the transport mechanism and toxicity response of microalgae towards nanoplastics (NPs) remain to be further investigated. In this study, we examined the toxicity and internalization mechanisms of polystyrene nanoplastics (PS-NPs) in the microalga Chlorella sorokiniana. The results revealed that the PS-NPs inhibited algal cells' growth and disrupted cell integrity upon contact, leading to cell shrinkage or rupture. Moreover, amino-modified PS-NPs (Nano-PS-NH2) exhibited greater toxicity to C. sorokiniana than carboxyl-modified PS-NPs (Nano-PS-COOH). Furthermore, significant inhibition of PS-NPs internalization was observed when four different endocytosis-related inhibitors were used, indicating that internalized PS-NPs can enter algal cells through endocytic pathways. More importantly, C. sorokiniana exposed to Nano-PS-NH2 responded to the reduction in carbon sources and energy resulting from the suppression of photosynthesis by regulating the metabolism of carbohydrates. These findings elucidate the effects of PS-NPs on C. sorokiniana, including their impact on cell morphology and metabolism, while shedding light on the internalization mechanisms of NPs by C. sorokiniana which deepen our understanding of the toxicity of nanoplastics on algae and provide important theoretical support for solving such aquatic ecological environment problems.
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Chlorella , Microalgas , Nanopartículas , Poluentes Químicos da Água , Microplásticos/toxicidade , Poliestirenos/toxicidade , Ecossistema , Poluentes Químicos da Água/toxicidade , Nanopartículas/toxicidadeRESUMO
This study aimed to develop a relatively natural and safe botanical insecticide for controlling the storage pest Tribolium castaneum in the egg and pupal stages. It examined how Elsholtzia densa Benth. essential oil (EO) and its primary components, ß-caryophyllene and limonene, affected T. castaneum eggs and pupae through contact and fumigation. Among th, the contact activities of ß-caryophyllene against T. castaneum eggs and pupae are LD50 (median lethal dose, 50%) = 0.156 mg/cm2 and ED50 (median effective dose, 50%) = 16.35 mg/pupa respectively. The study also investigated the effect of ß-caryophyllene and limonene on T. castaneum eggs and pupae through synergistic contact and fumigation. When the mixing ratio of ß-caryophyllene and limonene was 7:1, the LD50 value of contact activity against T. castaneum eggs was reduced to 0.100 mg/cm2, displaying an obvious synergistic effect. Experiments were conducted to investigate the antitoxic effect of ß-caryophyllene on T. castaneum eggs and pupae, as well as its effects on the enzymatic activity of acetylcholinesterase, succinate dehydrogenase, glutathione S-transferase and carboxylesterase in T. castaneum pupae. Finally, the molecular docking techniques were employed to confirm the aforementioned effects on enzyme function. The findings of this study might help improve storage pest control with T. castaneum and create eco-friendly insecticides using E. densa EO, ß-caryophyllene, and limonene.
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Inseticidas , Lamiaceae , Óleos Voláteis , Pupa , Tribolium , Animais , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Tribolium/efeitos dos fármacos , Lamiaceae/química , Inseticidas/farmacologia , Inseticidas/química , Pupa/efeitos dos fármacos , Óvulo/efeitos dos fármacos , Limoneno/farmacologia , Sesquiterpenos Policíclicos/farmacologia , Sesquiterpenos Policíclicos/químicaRESUMO
BACKGROUND: Atopic dermatitis (AD) has various detrimental effects on individuals with limited drug cure rates which necessitate the development of new treatment methods. PL-ReliefTMplus (PLR) is composed of SupraOlive, Crocus Sativus extracts and Citrus reticulata extracts. The effect of PLR on AD remains to be explored. METHODS: 2,4-dinitrofluorobenzene-induced AD model mice were involved and the histopathology of the skin lesions was observed along with the levels of inflammatory chemokines levels were measured. To further validate the molecular mechanism of PLR, RNA-seq was performed in HaCaT cells. Western blotting and immunofluorescence were performed to investigate NF-κB signaling pathways response in AD. RESULTS: Due to PLR treatment, the thickening of the epidermis and dermis was inhibited and the number of eosinophils, mast cells, and CD4+ T cells in the skin lesion was decreased. In addition, the levels of inflammatory cytokines were decreased in dorsal skin tissues and LPS-stimulated HaCat cells. Furthermore, KEGG pathway analysis suggested that most identified downstream biological functions were associated with inflammatory response. PLR inhibited NF-κB signaling in AD mice and HaCaT cells. CONCLUSIONS: These results indicate that PLR is a potent therapeutic agent for attenuating symptoms of AD.
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Dermatite Atópica , NF-kappa B , Transdução de Sinais , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/patologia , Dermatite Atópica/metabolismo , NF-kappa B/metabolismo , NF-kappa B/antagonistas & inibidores , Animais , Transdução de Sinais/efeitos dos fármacos , Camundongos , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Dinitrofluorbenzeno , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Inflamação/induzido quimicamente , Modelos Animais de Doenças , Citrus/química , Células HaCaT , Camundongos Endogâmicos BALB C , Citocinas/metabolismoRESUMO
Permeable surface mapping, which mainly is the identification of surface materials that will percolate, is essential for various environmental and civil engineering applications, such as urban planning, stormwater management, and groundwater modeling. Traditionally, this task involves labor-intensive manual classification, but deep learning offers an efficient alternative. Although several studies have tackled aerial image segmentation, the challenges in permeable surface mapping arid environments remain largely unexplored because of the difficulties in distinguishing pixel values of the input data and due to the unbalanced distribution of its classes. To address these issues, this research introduces a novel approach using a parallel U-Net model for the fine-grained semantic segmentation of permeable surfaces. The process involves binary classification to distinguish between entirely and partially permeable surfaces, followed by fine-grained classification into four distinct permeability levels. Results show that this novel method enhances accuracy, particularly when working with small, unbalanced datasets dominated by a single category. Furthermore, the proposed model is capable of generalizing across different geographical domains. Domain adaptation is explored to transfer knowledge from one location to another, addressing the challenges posed by varying environmental characteristics. Experiments demonstrate that the parallel U-Net model outperforms the baseline methods when applied across domains. To support this research and inspire future research, a novel permeable surface dataset is introduced, with pixel-wise fine-grained labeling for five distinct permeable surface classes. In summary, in this work, we offer a novel solution to permeable surface mapping, extend the boundaries of arid environment mapping, introduce a large-scale permeable surface dataset, and explore cross-area applications of the proposed model. The three contributions are enhancing the efficiency and accuracy of permeable surface mapping while progressing in this field.
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OBJECTIVE: The free gingival graft (FGG) has been identified as the most effective method for increasing keratinized mucosa width (KMW). However, the challenge emerges in cases of extensive keratinized mucosa deficiency, where efficient utilization of the patient's limited keratinized tissue to achieve optimal results is crucial. This article introduces a modified geometric technique to address this clinical issue. CLINICAL CONSIDERATIONS: Utilizing geometric principles, the modified technique involves dividing the rectangular graft into two triangular or trapezoidal sections, which are then reassembled to form an approximate diamond shape. Through strategic cut and splice, the graft is reshaped to suit the recipient site. CONCLUSION: Preliminary observations in cases employing the modified geometric technique have increased the KMW around implants. This method enhances graft utilization and offers a viable clinical option for surgical plans aimed at widening keratinized mucosa in instances of large-area KMW deficiency. CLINICAL SIGNIFICANCE: This article proposed a modified method to increase KMW, which may be an optimal choice for patients with insufficient KMW in large area, avoiding the waste of limited graft, decreasing patient morbidity, and effectively widening keratinized mucosa.
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Gengiva , Queratinas , Humanos , Gengiva/transplante , Feminino , Implantes Dentários , Masculino , Pessoa de Meia-Idade , Adulto , Gengivoplastia/métodos , Mucosa Bucal/transplanteRESUMO
OBJECTIVE: The principal aim of this report is to address the challenge of integrating prosthetic crowns with natural dentition in the esthetic zone. It highlights the utilization of a prosthetically driven treatment plan, designed to ensure predictable esthetic outcomes. CLINICAL CONSIDERATIONS: This report details a technique that utilizes three digital guides, all derived from a 3-dimensional digital smile design. The integration of a restoration guide, an implant drilling guide, and an alveoloplasty guide is described. These tools collectively facilitate the precise execution of both surgical and prosthetic procedures, enhancing treatment accuracy and esthetic integration. CONCLUSIONS: This technique considers the esthetic prosthetic crowns, implant positions, and alveoloplasty collectively. It enhances the predictability of esthetic outcomes in oral implantology and potentially provides an integrated prosthetically driven workflow in cosmetic dental treatments. CLINICAL SIGNIFICANCE: The application of multiple digital guides derived from the same prosthetically driven treatment significantly enhances the predictability of esthetic outcomes in oral implantology.
RESUMO
Microplastics (MPs) have been found in remote high-altitude areas, but the main source and migration process remained unclear. This work explored the characteristics and potential sources of MPs in the Yarlung Tsangpo River Basin. The average abundances of MPs in water, sediment, and soil samples were 728.26 ± 100.53 items/m3, 43.16 ± 5.82 items/kg, and 61.92 ± 4.29 items/kg, respectively, with polypropylene and polyethylene as the main polymers. The conditional fragmentation model revealed that the major source of MPs lower than 4000 m was human activities, while that of higher than 4500 m was atmospheric deposition. Community analysis was further conducted to explore the migration process and key points of MPs among different compartments in the basin. It was found that Lhasa (3600 m) and Shigatse (4100 m) were vital sources of MPs inputs in the midstream and downstream, respectively. This work would provide new insights into the fate of MPs in high-altitude areas.
Assuntos
Altitude , Monitoramento Ambiental , Microplásticos , Rios , Rios/química , Microplásticos/análise , Poluentes Químicos da Água/análise , Sedimentos Geológicos/química , Sedimentos Geológicos/análiseRESUMO
Investigations have shown that storage bugs seriously harm grains during storage. In the interim, essential oils (EOs) have been proven to be a good botanical pesticide. The anti-Lasioderma serricorne properties of Elsholtzia ciliata essential oil, which was obtained by steam distillation, were evaluated using DL-limonene, carvone, and their two optical isomer components using contact, repelling, and fumigation techniques. Simultaneously, the fumigation, contact, and repellent activities of carvone and its two optical isomers mixed with DL-limonene against L. serruricorne were evaluated. The results showed that E. ciliata, its main components (R-carvone, DL-limonene), and S-carvone exhibited both fumigations (LC50 = 14.47, 4.42, 20.9 and 3.78 mg/L) and contact (LD50 = 7.31, 4.03, 28.62 and 5.63 µg/adult) activity against L.serricorne. A binary mixture (1:1) of R-carvone and DL-limonene displayed an obvious synergistic effect. A binary mixture (1:1) of carvone and its two optical isomers exhibited an obvious synergistic effect, too. Furthermore, the repellent activity of the EO, carvone, and its two optical isomers, DL-limonene, and a combination of them varied. To stop insect damage during storage, E. ciliata and its components can be utilized as bio-insecticides.