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1.
Elife ; 122024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38814697

RESUMO

Almost all herbivorous insects feed on plants and use sucrose as a feeding stimulant, but the molecular basis of their sucrose reception remains unclear. Helicoverpa armigera as a notorious crop pest worldwide mainly feeds on reproductive organs of many plant species in the larval stage, and its adult draws nectar. In this study, we determined that the sucrose sensory neurons located in the contact chemosensilla on larval maxillary galea were 100-1000 times more sensitive to sucrose than those on adult antennae, tarsi, and proboscis. Using the Xenopus expression system, we discovered that Gr10 highly expressed in the larval sensilla was specifically tuned to sucrose, while Gr6 highly expressed in the adult sensilla responded to fucose, sucrose and fructose. Moreover, using CRISPR/Cas9, we revealed that Gr10 was mainly used by larvae to detect lower sucrose, while Gr6 was primarily used by adults to detect higher sucrose and other saccharides, which results in differences in selectivity and sensitivity between larval and adult sugar sensory neurons. Our results demonstrate the sugar receptors in this moth are evolved to adapt toward the larval and adult foods with different types and amounts of sugar, and fill in a gap in sweet taste of animals.


Assuntos
Larva , Mariposas , Sensilas , Sacarose , Animais , Sacarose/metabolismo , Sacarose/farmacologia , Larva/fisiologia , Mariposas/fisiologia , Mariposas/efeitos dos fármacos , Sensilas/fisiologia , Sensilas/metabolismo , Paladar/fisiologia , Percepção Gustatória/fisiologia , Helicoverpa armigera
2.
Int J Biol Macromol ; 264(Pt 2): 130660, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38460634

RESUMO

The emergence of SARS-CoV-2 presents a significant global public health dilemma. Vaccination has long been recognized as the most effective means of preventing the spread of infectious diseases. DNA vaccines have attracted attention due to their safety profile, cost-effectiveness, and ease of production. This study aims to assess the efficacy of plasmid-encoding GM-CSF (pGM-CSF) as an adjuvant to augment the specific humoral and cellular immune response elicited by DNA vaccines based on the receptor-binding domain (RBD) antigen. Compared to the use of plasmid-encoded RBD (pRBD) alone, mice that were immunized with a combination of pRBD and pGM-CSF exhibited significantly elevated levels of RBD-specific antibody titers in serum, BALF, and nasal wash. Furthermore, these mice generated more potent neutralization antibodies against both the wild-type and Omicron pseudovirus, as well as the ancestral virus. In addition, pGM-CSF enhanced pRBD-induced CD4+ and CD8+ T cell responses and promoted central memory T cells storage in the spleen. At the same time, tissue-resident memory T (Trm) cells in the lung also increased significantly, and higher levels of specific responses were maintained 60 days post the final immunization. pGM-CSF may play an adjuvant role by promoting antigen expression, immune cells recruitment and GC B cell responses. In conclusion, pGM-CSF may be an effective adjuvant candidate for the DNA vaccines against SARS-CoV-2.


Assuntos
COVID-19 , Vacinas de DNA , Humanos , Animais , Camundongos , Fator Estimulador de Colônias de Granulócitos e Macrófagos , SARS-CoV-2 , Vacinas contra COVID-19 , COVID-19/prevenção & controle , Adjuvantes Imunológicos/farmacologia , Adjuvantes Farmacêuticos , Vacinação , DNA , Anticorpos Antivirais , Anticorpos Neutralizantes
3.
Insect Sci ; 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38485691

RESUMO

The tobacco cutworm Spodoptera litura is one of the most destructive polyphagous crop pests. Olfaction and taste play a crucial role in its host plant selection and sexual communication, but the expression profile of chemosensory genes remains unclear. In this study, we identified 185 chemosensory genes from 7 organs in S. litura by transcriptome sequencing, of which 72 genes were published for the first time, including 27 odorant receptors (ORs), 26 gustatory receptors (GRs), 1 ionotropic receptor (IR), 16 odorant-binding proteins (OBPs), and 2 chemosensory proteins (CSPs). Phylogenetic analyses revealed that ORs, IRs, OBPs, and sensory neuron membrane proteins (SNMPs) were mainly expressed in antennae and sequence-conserved among Noctuidae species. The most differentially expressed genes (DEGs) between sexes were ORs and OBPs, and no DEGs were found in GRs. GR transcripts were enriched in proboscis, and the expression of sugar receptors was the highest. Carbon dioxide receptors, sugar receptor-SliuGR6, and bitter GRs-SlituGR43 and SlituGR66 had higher sequence identities between Noctuidae species. CSPs were broadly expressed in various organs, and SlituCSP13 was a DEG in adult antennae. The functional analysis in the Drosophila OR67d expression system found that SlituOR50, a receptor highly expressed in female antennae, is selectively tuned to farnesyl acetate. The results provide a solid foundation for understanding the molecular mechanisms by which chemosensory genes operate to elicit behavioral responses in polyphagous insects.

4.
J Vis Exp ; (204)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38465928

RESUMO

Cationic nanostructures have emerged as an adjuvant and antigen delivery system that enhances dendritic cell maturation, ROS generation, and antigen uptake and then promotes antigen-specific immune responses. In recent years, retinoic acid (RA) has received increasing attention due to its effect in activating the mucosal immune response; however, in order to use RA as a mucosal adjuvant, it is necessary to solve the problem of its dissolution, loading, and delivery. Here, we describe a cationic nanoemulsion-encapsulated retinoic acid (CNE-RA) delivery system composed of the cationic lipid 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOTAP), retinoic acid, squalene as the oil phase, polysorbate 80 as surfactant, and sorbitan trioleate 85 as co-surfactant. Its physical and chemical properties were characterized using dynamic light scattering and a spectrophotometer. Immunization of mice with the mixture of antigen (ovalbumin, OVA) and CNE-RA significantly elevated the levels of anti-OVA secretory immunoglobulin A (sIgA) in vaginal lavage fluid and the small intestinal lavage fluid of mice compared with OVA alone. This protocol describes a detailed method for the preparation, characterization, and evaluation of the adjuvant effect of CNE-RA.


Assuntos
Adjuvantes Imunológicos , Imunização , Feminino , Animais , Camundongos , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/química , Mucosa , Vacinação , Antígenos , Imunidade nas Mucosas , Tensoativos/farmacologia , Ovalbumina , Camundongos Endogâmicos BALB C
5.
Front Neurosci ; 18: 1362495, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38440394

RESUMO

The clinical rehabilitation assessment methods for hemiplegic upper limb motor function are often subjective, time-consuming, and non-uniform. This study proposes an automatic rehabilitation assessment method for upper limb motor function based on posture and distributed force measurements. Azure Kinect combined with MediaPipe was used to detect upper limb and hand movements, and the array distributed flexible thin film pressure sensor was employed to measure the distributed force of hand. This allowed for the automated measurement of 30 items within the Fugl-Meyer scale. Feature information was extracted separately from the affected and healthy sides, the feature ratios or deviation were then fed into a single/multiple fuzzy logic assessment model to determine the assessment score of each item. Finally, the total score of the hemiplegic upper limb motor function assessment was derived. Experiments were performed to evaluate the motor function of the subjects' upper extremities. Bland-Altman plots of physician and system scores showed good agreement. The results of the automated assessment system were highly correlated with the clinical Fugl-Meyer total score (r = 0.99, p < 0.001). The experimental results state that this system can automatically assess the motor function of the affected upper limb by measuring the posture and force distribution.

6.
J Agric Food Chem ; 71(49): 19408-19421, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38039319

RESUMO

Olfaction plays an instrumental role in host plant selection by phytophagous insects. Helicoverpa assulta and Helicoverpa armigera are two closely related moth species with different host plant ranges. In this study, we first comparatively analyzed the function of 11 female-biased odorant receptors (ORs) and their orthologs in the two species by the Drosophila T1 neuron expression system and then examined the electroantennography responses of the two species to the most effective OR ligands. Behavioral assays using a Y-tube olfactometer indicate that guaiene, the primary ligand of HassOR21-2 and HarmOR21-2, only attracts the females, while benzyl acetone, the main ligand of HassOR35 and HarmOR35, attracts both sexes of the two species. Oviposition preference experiments further confirm that guaiene and benzyl acetone are potent oviposition attractants for the mated females of both species. These findings deepen our understanding of the olfactory coding mechanisms of host plant selection in herbivorous insects and provide valuable attractants for managing pest populations.


Assuntos
Mariposas , Receptores Odorantes , Atrativos Sexuais , Feminino , Animais , Masculino , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Ligantes , Mariposas/metabolismo , Atrativos Sexuais/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo
7.
Biomater Res ; 27(1): 133, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102651

RESUMO

BACKGROUND: Drug nanocarriers can markedly reduce the toxicities and side effects of encapsulated chemotherapeutic drugs in the clinic. However, these drug nanocarriers have little effect on eradicating breast cancer stem cells (BCSCs). Although compounds that can inhibit BCSCs have been reported, these compounds are difficult to use as carriers for the widespread delivery of conventional chemotherapeutic drugs. METHODS: Herein, we synthesize a polymeric nanocarrier, hyaluronic acid-block-poly (curcumin-dithiodipropionic acid) (HA-b-PCDA), and explore the use of HA-b-PCDA to simultaneously deliver chemotherapeutic drugs and eradicate BCSCs. RESULTS: Based on molecular docking and molecular dynamics studies, HA-b-PCDA delivers 35 clinical chemotherapeutic drugs. To further verify the drug deliver ability of HA-b-PCDA, doxorubicin, paclitaxel, docetaxel, gemcitabine and camptothecin are employed as model drugs to prepare nanoparticles. These drug-loaded HA-b-PCDA nanoparticles significantly inhibit the proliferation and stemness of BCSC-enriched 4T1 mammospheres. Moreover, doxorubicin-loaded HA-b-PCDA nanoparticles efficiently inhibit tumor growth and eradicate approximately 95% of BCSCs fraction in vivo. Finally, HA-b-PCDA eradicates BCSCs by activating Hippo and inhibiting the JAK2/STAT3 pathway. CONCLUSION: HA-b-PCDA is a polymeric nanocarrier that eradicates BCSCs and potentially delivers numerous clinical chemotherapeutic drugs.

8.
Heliyon ; 9(11): e21531, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38027717

RESUMO

Background: Developing effective therapeutic strategies to delay the progression of chronic kidney disease (CKD) remains a significant challenge. Low-intensity pulsed ultrasound (LIPUS) has demonstrated potential for treating CKD, but the underlying molecular mechanisms are still elusive. This study aimed to evaluate the therapeutic efficacy of LIPUS and to elucidate the involved genes and signaling pathways. Methods: The CKD model was established in rats using Adriamycin (ADR). The bilateral kidneys of CKD rats were continuously stimulated with LIPUS for a period of four weeks. The therapeutic efficacy was defined by renal function and histopathological evaluation. RNA sequencing was employed to profile the transcriptome of rat kidneys in each group. Cluster analysis was utilized to identify differentially expressed genes (DEGs), followed by enrichment analysis of their associated pathways using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Results: LIPUS treatment improved ADR-induced renal dysfunction in the CKD group. Renal fibrosis and pathological damages were also alleviated in the ADR + LIPUS group compared to the ADR group. Cluster analysis identified 844 DEGs. GO enrichment analysis revealed enrichment in inflammatory response terms, while KEGG enrichment analysis highlighted the nuclear factor kappa B (NF-κB) signaling and ferroptosis-related pathways. Conclusion: Continuous LIPUS treatment improved ADR-induced renal fibrosis and dysfunction. The therapeutic effect of LIPUS was primarily due to its ability to suppress the CKD-related inflammation, which was associated with the modulation of the NF-κB and ferroptosis signaling pathways. These findings provide a new insight into the potential molecular mechanisms of LIPUS in treating CKD. Further research is necessary to confirm these findings and to identify potential therapeutic targets within these pathways.

9.
Trials ; 24(1): 637, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37794507

RESUMO

BACKGROUND: Antibiotics are over-used for patients with respiratory tract infections (RTIs) in primary care, especially in the rural areas of China. METHODS: A cluster randomized controlled trial (RCT) will be carried out to estimate the effectiveness of a tailored message package for educating patients to reduce antibiotic use for symptomatic respiratory tract infections (RTIs). In the intervention group, patients will receive 12 short messages in 12 consecutive days. The whole process of the message design, modification, translation (of substitution variables), and sending will be facilitated by a user-friendly mini-computer program. The primary measure for assessment is the reduction in number of days in which antibiotics are used by patients with symptomatic RTIs. The secondary measures include (1) patients' knowledge about and attitude toward antibiotics; (2) patients' quality of life (EQ-5D-5L) and symptom severity and duration; (3) times of re-visits to clinics and antibiotics re-prescription for the same RTI episode; and (4) times of re-occurrence of RTIs and related health service seeking and antibiotics consumption. DISCUSSION: This study will determine the efficacy of a 12-message intervention to educate patients to reduce excessive antibiotic use in rural China. TRIAL REGISTRATION: ISRCTN29801086 . Registered on 23 September 2022.


Assuntos
Antibacterianos , Infecções Respiratórias , Humanos , Antibacterianos/efeitos adversos , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/tratamento farmacológico , China , População Rural , Prescrições , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Int J Antimicrob Agents ; 62(5): 106972, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37741585

RESUMO

Eradication of methicillin-resistant Staphylococcus aureus (MRSA) is challenging due to multi-drug resistance of strains and biofilm formation, the latter of which is an important barrier to the penetration of antibiotics and host defences. As such, there is an urgent need to discover and develop novel agents to fight MRSA-associated infection. In this study, HL-J6, a novel indolylbenzoquinone compound, was shown to inhibit S. aureus strains, with a minimum inhibitory concentration against MRSA252 of 2 µg/mL. Moreover, HL-J6 exhibited potent antibiofilm activity in vitro and was able to kill bacteria in biofilm. In the mouse models of wound infection, HL-J6 treatment reduced the MRSA load significantly and inhibited biofilm formation on the wounds. The potent targets of its antibiofilm activity were explored by real-time reverse transcriptase polymerase chain rection, which indicated that HL-J6 downregulated the transcription levels of sarA, atlAE and icaADBC. Moreover, Western blot results showed that HL-J6 reduced the secretion level of α-toxin, a major virulence factor. These findings indicate that HL-J6 is a promising lead compound for the development of novel drugs against MRSA biofilm infections.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Animais , Camundongos , Staphylococcus aureus , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Biofilmes , Testes de Sensibilidade Microbiana
11.
JMIR Form Res ; 7: e42101, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37583117

RESUMO

BACKGROUND: Gastrointestinal symptoms (GISs) are caused by a combination of biopsychosocial factors and are highly prevalent worldwide. Given their complex nature, coupled with ineffective communication of diagnoses by physicians, patients with intimate GISs often feel stigmatized. This, in turn, can inhibit their ability to express their thoughts and feelings adequately, leading them to over- or underreport their symptoms. Moreover, selective service-seeking for and reporting of GISs have a direct bearing on the stage of disease at presentation and, consequently, on the overall prognosis. OBJECTIVE: This study aimed to investigate the usefulness of a web-based self-assessment of GISs as a supplementary means to cope with potential over- or underreporting during routine consultations. METHODS: GIS data were collected using a novel web-based self-assessment tool (n=475) and from nonparticipative observation of doctor-patient consultations (n=447) and household surveys (n=10,552) in Anhui, China. Data analysis focused primarily on the description of the composition of respondents and the occurrence rates of GISs by sociodemographics, and by symptom solicitation methods and settings. Chi-square power tests were used when necessary to compare differences in the occurrence rates between relevant groups. The level of significance for the 2-sided test was set at α<.05. RESULTS: The average occurrence rates of both upper and lower GISs derived from the web-based self-assessment were higher than those from the observation (upper GISs: n=661, 20.9% vs n=382, 14.2%; P<.001; lower GISs: n=342, 12.9% vs n=250, 10.8%; P=.02). The differences in 6 of the 9 upper GISs and 3 of the 11 lower GISs studied were tested with statistical significance (P<.05); moreover, a higher frequency rate was recorded for symptoms with statistical significance via self-assessment than via observation. For upper GISs, the self-assessed versus observed differences ranged from 17.1% for bloating to 100% for bad mood after a meal, while for lower GISs, the differences ranged from -50.5% for hematochezia or melena to 100% for uncontrollable stool. Stomachache, regurgitation, and dysphagia had higher occurrence rates among participants of the self-assessment group than those of the household survey group (20% vs 12.7%, 14% vs 11%, and 3% vs 2.3%, respectively), while the opposite was observed for constipation (5% vs 10.9%), hematochezia or melena (4% vs 5%), and anorexia (4% vs 5.2%). All differences noted in the self-assessed occurrence rates of specific, persistent GISs between sociodemographic groups were tested for nonsignificance (P>.05), while the occurrence rates of any of the 6 persistent GISs among respondents aged 51-60 years was statistically higher than that among other age groups (P=.03). CONCLUSIONS: The web-based self-assessment tool piloted in this study is useful and acceptable for soliciting more comprehensive GISs, especially symptoms with concerns about stigmatization, privacy, and shame. Further studies are needed to integrate the web-based self-assessment with routine consultations and to evaluate its efficacy.

12.
PLoS One ; 18(8): e0286619, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37611025

RESUMO

Prior studies revealed varying effects of resource scarcity on individuals' general categorization tendency. However, little is known about when and why such differences occur. Based on the self-regulatory model of resource scarcity, we examine whether resource scarcity generates higher or lower general categorization tendency depending on the perceived mutability of the resource discrepancy. We conducted two online experiments to test the hypotheses. The results affirmed that when individuals consider the resource discrepancy to be mutable, they are more likely to seek abundance to compensate for resource scarcity, thus reducing their general categorization tendency. In contrast, perceiving the scarcity as immutable triggers the intention to restore a sense of control undermined by the scarcity, increasing individuals' general categorization tendency. Our findings provide insights into the downstream consequences of resource scarcity and offer significant managerial implications for coping strategies.


Assuntos
Adaptação Psicológica , Intenção , Humanos
13.
Pest Manag Sci ; 79(12): 4828-4838, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37489868

RESUMO

BACKGROUND: The brown planthopper (Nilaparvata lugens, BPH) is the most destructive serious pest in rice production. Resistant varieties are effective means to defend against BPH, but the impact of the ingestion of resistant rice on BPH transcriptional regulation is still unclear. Here, we explore the molecular basis of the regulation by BPH feeding on resistant rice. RESULTS: BPH nymphs preferentially selected susceptible rice TN1 at 24 h after release in a choice test. Feeding on resistant rice IR56 under nonselective conditions increased mortality, decreased growth rate, and prolonged the molting time of BPH. Transcriptomic sequencing revealed 38 dysregulated genes, including 31 down-regulated and seven up-regulated genes in BPH feeding on resistant rice for 7 days compared with feeding on susceptible rice TN1. These genes were mainly involved in the pathways of growth and development, metabolism, energy synthesis, and transport. Finally, we showed that the toxicities of rice defensive compounds to BPH were dose-dependent, and silencing of the BPH gene dehydrogenase/reductase SDR family member 11 (NlDHRS11) increased sensibility to the rice secondary compounds ferulic acid and resorcinol. CONCLUSION: The adaption of BPH feeding on resistant rice is orchestrated by dynamically regulating gene expressions, and NlDHRS11 is a gene involved in the detoxification of plant defensive chemicals. The current work provides new insights into the interaction between insects and plants, and will help to develop novel BPH control strategies. © 2023 Society of Chemical Industry.


Assuntos
Hemípteros , Oryza , Animais , Oryza/química , Regulação da Expressão Gênica , Genes de Plantas , Hemípteros/fisiologia
14.
Adv Healthc Mater ; 12(23): e2300085, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37171889

RESUMO

Helicobacter pylori (H. pylori) colonizes the stomach epithelium of half the world's population and is responsible for various digestive diseases and even stomach cancer. Vaccine-mediated protection against H. pylori infection depends primarily on the specific mucosal and T-cell responses. In this study, the synthetic lipopeptide vaccines, Hp4 (Pam2 Cys modified UreB T-cell epitope) and Hp10 (Pam2 Cys modified CagA T/B cell combined epitope), not only induce the bone marrow derived dendritic cells (BMDCs) maturation by activating a variety of pattern-recognition receptors (PRRs) such as Toll-like receptor (TLR), Nod-like receptor (NLR), and retinoic acid-inducing gene (RIG) I-like receptor (RLR), and but also stimulate BMDCs to secret cytokines that have the potential to modulate T-cell activation and differentiation. Although intranasal immunization with Hp4 or Hp10 elicits robust epitope-specific T-cell responses in mice, only Hp10 confers protection against H. pylori infection, possibly due to the fact that Hp10 also induces substantial specific sIgA response at mucosal sites. Interestingly, Hp4 elevates the protective response against H. pylori infection of Hp10 when administrated in combination, characterized by better protective effect and enhanced specific T-cell and mucosal antibody responses. The results suggest that synthetic lipopeptide vaccines based on the epitopes derived from the protective antigens are promising candidates for protection against H. pylori infection.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Animais , Camundongos , Helicobacter pylori/genética , Infecções por Helicobacter/prevenção & controle , Lipopeptídeos/farmacologia , Vacinas Bacterianas , Adjuvantes Imunológicos , Epitopos de Linfócito T , Vacinas Sintéticas , Camundongos Endogâmicos BALB C
15.
Nano Lett ; 23(8): 3369-3376, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37052625

RESUMO

Lithium (Li) metal has attracted great attention as a promising high-capacity anode material for next-generation high-energy-density rechargeable batteries. Nonuniform Li+ transport and uneven Li plating/stripping behavior are two key factors that deteriorate the electrochemical performance. In this work, we propose an interphase acid-base interaction effect that could regulate Li plating/stripping behavior and stabilize the Li metal anode. ZSM-5, a class of zeolites with ordered nanochannels and abundant acid sites, was employed as a functional interface layer to facilitate Li+ transport and mitigate the cell concentration polarization. As a demonstration, a pouch cell with a high-areal-capacity LiNi0.95Co0.02Mn0.03O2 cathode (3.7 mAh cm-2) and a ZSM-5 modified thin lithium anode (50 µm) delivered impressive electrochemical performance, showing 92% capacity retention in 100 cycles (375.7 mAh). This work reveals the effect of acid-base interaction on regulating lithium plating/stripping behaviors, which could be extended to developing other high-performance alkali metal anodes.

16.
Gynecol Oncol ; 171: 39-48, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36804620

RESUMO

OBJECTIVE: Sirtuin-7 (SIRT7) is a class III histone deacetylase that plays an important role in cancer development and frequently overexpressed in carcinomas. In this study, the tumor-supporting role and underlying mechanisms of SIRT7 were characterized in ovarian cancer (OC) aggressiveness. METHODS: SIRT7 expression was examined in OC tissues and cells. Interactions among SIRT7, GATA4, Wnt signaling pathway were explored by bioinformatics tools and experimental validations. The effect of SIRT7 and GATA4 on malignant phenotypes of OC cells were examined with gain- and loss-of-function experiments. A nude mouse model of OC was developed to verify the in vitro findings. RESULTS: It was noted that SIRT7 was highly expressed in OC tissues and cells. Cell lines with higher SIRT7 expression (OVCAR-3 and OVCAR-8) were used for subsequent in vitro experiments. The experimental data indicated that silencing of SIRT7 suppressed the OC cell proliferation, colony formation, migration, and invasion, and promoted cell senescence, which could be abolished by GATA4 knockdown. Mechanistically, SIRT7 promoted deacetylation of GATA4 and consequently inhibited the transcriptional activity of GATA4. In addition, GATA4 induced OC cell senescence by inhibiting Wnt signaling pathway. Further in vivo experiments substantiated that SIRT7 knockdown or overexpressed GATA4 could effectively inhibit tumor growth of nude mice. CONCLUSION: Taken together, our findings indicated that SIRT7 enhanced development of OC by suppressing GATA4 and activating Wnt signaling pathway, suggesting the potential of SIRT7/GATA4/Wnt axis as a therapeutic target for OC.


Assuntos
Neoplasias Ovarianas , Sirtuínas , Animais , Camundongos , Humanos , Feminino , Via de Sinalização Wnt , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Linhagem Celular Tumoral , Apoptose/genética , Camundongos Nus , Sirtuínas/genética , Sirtuínas/metabolismo , Proliferação de Células/genética , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Fator de Transcrição GATA4/genética , Fator de Transcrição GATA4/metabolismo
17.
Adv Mater ; 35(2): e2207310, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36308044

RESUMO

The creation of fluorinated interphase has emerged as an effective strategy for improving Li-metal anodes for rechargeable high-energy batteries. In contrast to the introduction of fluorine-containing species through widely adopted electrolyte engineering, a Li-metal composite design is reported in which LiF can locally redistribute on the Li-metal surface in liquid electrolytes via a dissolution-reprecipitation mechanism, and enable the formation of a high-fluorine-content solid electrolyte interphase (SEI). For validation, a Li/Li22 Sn5 /LiF ternary composite is investigated, where the as-formed LiF-rich SEI locks the active Li metal from corrosive electrolyte. The Li/Li22 Sn5 /LiF anode displays an impressive average Coulombic efficiency (ACE, ≈99.2%) at 1 mA cm-2 and 1 mAh cm-2 in a carbonate electrolyte and a remarkable cycling life of over 1600 h at 1 mA cm-2 and 2 mAh cm-2 . Applied to a LiCoO2 full cell with a high cathode areal capacity of 4.0 mAh cm-2 , a high capacity retention of ≈91.1% is realized for 100 cycles at 0.5 C between 2.8 to 4.5 V with a low negative/positive (N/P) ratio of 2:1. This design is conceptually different from the design employing the widely used fluorine-containing electrolyte additive and provides an alternative approach to realize reliable Li-metal batteries.

18.
ACS Appl Mater Interfaces ; 14(46): 51954-51964, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36350880

RESUMO

Silicon (Si) is regarded as one of the most promising anode materials for high-energy-density lithium (Li)-ion batteries (LIBs). However, Li insertion/extraction induced large volume change, which can lead to the fracture of the Si material itself and the delamination/pulverization of electrodes, is the major challenge for the practical application of Si-based anodes. Herein, a facile and scalable multilayer coating approach was proposed for the large-scale fabrication of functionally gradient Si/graphite (Si/Gr) composite electrodes to simultaneously mitigate the volume change-caused structural degradation and realize high capacity by regulating the spatial distributions of Si and Gr particles in the electrodes. Both our experimental characterizations and chemomechanical simulations indicated that, with a parabolic gradient (PG) distribution of Si through the thickness direction that the two Si-poor surface layers guarantee the major mechanical support and the middle Si-rich layer ensures the high capacity, the as-prepared PG-Si/Gr electrode can not only effectively improve the stability of the electrode structure but also efficiently enable high capacity and stable electrochemical reactions. Consequently, the PG-Si/Gr electrode with a mass loading of 3.15 mg cm-2 exhibited a reversible capacity of 579.2 mAh g-1 (1.82 mAh cm-2) after 200 cycles at 0.2C. Even with a mass loading of 8.45 mg cm-2, the PG-Si/Gr anodes still delivered a high reversible capacity of 4.04 mAh cm-2 after 100 cycles and maintained excellent cycling stability. Moreover, when paired with a commercial LiNi0.5Mn0.3Co0.2O2 (NCM532) cathode (9.56 mg cm-2), the PG-Si/Gr||NCM532 full cell revealed an initial reversible areal capacity of 1.64 mAh cm-2 and sustained a stable areal capacity of 0.94 mAh cm-2 at 0.2C after 100 cycles.

19.
Proc Natl Acad Sci U S A ; 119(49): e2215442119, 2022 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-36442117

RESUMO

Sex pheromones are pivotal for insect reproduction. However, the mechanism of sex pheromone communication remains enigmatic in hymenopteran parasitoids. Here we have identified the sex pheromone and elucidated the olfactory basis of sex pheromone communication in Campoletis chlorideae (Ichneumonidae), a solitary larval endoparasitoid of over 30 lepidopteran pests. Using coupled gas chromatography-electroantennogram detection, we identified two female-derived pheromone components, tetradecanal (14:Ald) and 2-heptadecanone (2-Hep) (1:4.6), eliciting strong antennal responses from males but weak responses from females. We observed that males but not females were attracted to both single components and the blend. The hexane-washed female cadavers failed to arouse males, and replenishing 14:Ald and 2-Hep could partially restore the sexual attraction of males. We further expressed six C. chlorideae male-biased odorant receptors in Drosophila T1 neurons and found that CchlOR18 and CchlOR47 were selectively tuned to 14:Ald and 2-Hep, respectively. To verify the biological significance of this data, we knocked down CchlOR18 and CchlOR47 individually or together in vivo and show that the attraction of C. chlorideae to their respective ligands was abolished. Moreover, the parasitoids defective in either of the receptors were less likely to court and copulate. Finally, we show that the sex pheromone and (Z)-jasmone, a potent female attractant, can synergistically affect behaviors of virgin males and virgin females and ultimately increase the parasitic efficiency of C. chlorideae. Our study provides new insights into the molecular mechanism of sex pheromone communication in C. chlorideae that may permit manipulation of parasitoid behavior for pest control.


Assuntos
Receptores Odorantes , Atrativos Sexuais , Masculino , Animais , Insetos , Comunicação , Feromônios , Drosophila
20.
PLoS Genet ; 18(10): e1010455, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36206313

RESUMO

Many plant secondary substances are feeding deterrents for insects and play a key role in the selection of host plants. The taste sensilla of phytophagous insects contain gustatory sensory neurons sensitive to deterrents but the molecular basis of deterrent chemoreception remains unknown. We investigated the function of Gr180, the most highly expressed bitter gustatory receptor in the maxillary galea of Helicoverpa armigera larvae. Functional analyses using the Xenopus oocyte expression system and two-electrode voltage clamp revealed that the oocytes expressing Gr180 responded to coumarin. Tip recording results showed that the medial sensilla styloconica of the maxilla of fifth instar larvae exhibited electrophysiological responses to coumarin. Two-choice feeding bioassays confirmed that coumarin inhibited larval feeding. A homozygous mutant strain of H. armigera with truncated Gr180 proteins (Gr180-/-) was established using the CRISPR-Cas9 system. The responses of the medial sensilla styloconica in Gr180-/- to coumarin were almost abolished, and the responses to sinigrin and strychnine were also significantly decreased. Knockout of Gr180 alleviated the feeding deterrent effects of coumarin, sinigrin, and strychnine. Thus, we conclude that Gr180 is a receptor responding to coumarin,and also participates in sensing sinigrin and strychnine. These results enhance our understanding of the gustatory sensing mechanisms of phytophagous insects to deterrents.


Assuntos
Mariposas , Paladar , Animais , Larva/metabolismo , Paladar/genética , Estricnina/metabolismo , Estricnina/farmacologia , Maxila/metabolismo , Mariposas/genética , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Cumarínicos/metabolismo , Cumarínicos/farmacologia
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