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Determination of protein-ligand interactions is crucial for structure-based drug design. But, accurate prediction of the binding structures of protein-ligand is still a major challenge for molecular docking methods. Herein, we developed molecular docking with conformer-dependent charges (MDCC), a docking method to combine conformational search with RESP charges. Compared to the conventional Glide SP method (51.9%) and Glide XP method (52.6%), the MDCC method (60%) exhibited a higher docking success rate based on 285 protein-small molecule ligand complexes from the PDBbind core set. And when the ligand met one of the conditions (the total hydrophobic surface area > 438, the number of hydrophobic atoms > 10, and molecular weight > 235), the docking success rate of the MDCC method (>90%) was higher than that of the Glide SP method (â¼72%). Furthermore, we also applied the MDCC method to predict the protein-ligand interactions in GPCR Dock 2021 competition, with our prediction models ranking 2nd out of all 202 participating models for APJ and 5th out of all 193 participating models for GPR139, demonstrating the relatively high docking accuracy of the MDCC method. In addition, we also found that the MDCC method combined with molecular dynamics simulations could facilitate the application of AlphaFold 2 in drug discovery. The above results all set the stage for the application of the MDCC method in future practical drug design.
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The study aimed to develop a rapid and sensitive colorimetric platform based on the Emerson reaction to visualize and determine total aflatoxins (AFs) in peanut oil. This method offers the advantage of fast screening for AFs (AFB1, AFB2, AFG1, and AFG2), eliminating the need for specific antibodies. The proposed approach combined colorimetric detection with magnetic dummy imprinted solid-phase extraction and purification, enhancing sensitivity and selectivity. The oxidizer aided the colorless AFs in reacting with 4-aminoantipyrine, producing green condensates. Thus, a dual-mode approach was developed for AFs detection, employing both UV-vis colorimetric and smartphone-based colorimetry. Both methods showed a good linear relationship with the concentration of AFs. Notably, the smartphone-based method demonstrated a detection range of 0.5-57 µg/kg, with a detection limit as low as 0.21 µg/kg. The suggested colorimetric methods present a promising potential for onsite detection and fast screening of AFs in actual samples.
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Aflatoxinas , Colorimetria , Contaminação de Alimentos , Óleo de Amendoim , Smartphone , Extração em Fase Sólida , Colorimetria/métodos , Extração em Fase Sólida/métodos , Extração em Fase Sólida/instrumentação , Aflatoxinas/análise , Aflatoxinas/isolamento & purificação , Óleo de Amendoim/química , Contaminação de Alimentos/análise , Limite de Detecção , Impressão MolecularRESUMO
Purpose: The purpose of this study is to examine whether phonetic information functions and how phonetic information affects voice identity processing in blind people. Method: To address the first inquiry, 25 normal sighted participants and 30 blind participants discriminated voice identity, when listening forward speech and backward speech from their own native language and another unfamiliar language. To address the second inquiry, combining articulatory suppression paradigm, 26 normal sighted participants and 26 blind participants discriminated voice identity, when listening forward speech from their own native language and another unfamiliar language. Results: In Experiment 1, not only in the voice identity discrimination task with forward speech, but also in the discrimination task with backward speech, both the sighted and blind groups showed the superiority of the native language. This finding supports the view that backward speech still retains some phonetic information, and indicates that phonetic information can affect voice identity processing in sighted and blind people. In addition, only the superiority of the native language of sighted people was regulated by the speech manner, which is related to articulatory rehearsal. In Experiment 2, only the superiority of the native language of sighted people was regulated by articulatory suppression. This indicates that phonetic information may act in different ways on voice identity processing in sighted and blind people. Conclusion: The heightened dependence on voice source information in blind people appears not to undermine the function of phonetic information, but it appears to change the functional mechanism of phonetic information. These findings suggest that the present phonetic familiarity model needs to be improved with respect to the mechanism of phonetic information.
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Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system and the unmet need for MS treatment demands new therapeutic development. Particularly, PI3Kδ is a high-value target for autoimmune disease, while the investigation of PI3Kδ inhibitors for MS therapy is relatively scarce. Herein, we report a novel class of azaindoles as PI3Kδ inhibitors for MS treatment. Compound 31, designed via nitrogen bioisosterism, displayed excellent PI3Kδ inhibitory activity and selectivity. In vitro assay showed that 31 exhibited superior activity on T lymphocytes to inhibit the proliferation of CD4+, CD8+, and CD3+ T cells. In the experimental autoimmune encephalomyelitis (EAE) model, 31 showed a comparable therapeutical efficacy with Dexamethasone to significantly ameliorate EAE symptoms. Mechanistic studies showed that compound 31 could significantly inhibit the PI3K/AKT/mTOR signaling pathway and inhibited T-cell proliferation and differentiation. Overall, this work provides a new structural PI3Kδ inhibitor and a new vision for MS therapy.
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Classe I de Fosfatidilinositol 3-Quinases , Encefalomielite Autoimune Experimental , Indóis , Esclerose Múltipla , Inibidores de Fosfoinositídeo-3 Quinase , Animais , Esclerose Múltipla/tratamento farmacológico , Humanos , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase/síntese química , Inibidores de Fosfoinositídeo-3 Quinase/química , Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico , Encefalomielite Autoimune Experimental/tratamento farmacológico , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Indóis/farmacologia , Indóis/química , Indóis/síntese química , Indóis/uso terapêutico , Camundongos , Proliferação de Células/efeitos dos fármacos , Compostos Aza/química , Compostos Aza/farmacologia , Compostos Aza/síntese química , Relação Estrutura-Atividade , Linfócitos T/efeitos dos fármacos , Descoberta de Drogas , Camundongos Endogâmicos C57BL , Feminino , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
PI3Kδ is an essential target correlated to the occurrence and development of acute myeloid leukemia (AML). Herein, we investigated the pyrazolo[3,4-d]pyrimidine derivatives as potent and selective PI3Kδ inhibitors with high therapeutic efficacy toward AML. There were 44 compounds designed and prepared in a four-round optimization, and the biological evaluation showed that (S)-36 exhibited potent PI3Kδ inhibitory activity, high selectivity, and high antiproliferative activities against MV-4-11 and MOLM-13 cells, coupled with high oral bioavailability (F = 59.6%). In the MOLM-13 subcutaneous xenograft model, (S)-36 could significantly suppress the tumor progression with a TGI of 67.81% at an oral administration dosage of 10 mg/kg without exhibiting obvious toxicity. Mechanistically, (S)-36 could robustly inhibit the PI3K/AKT pathway for significant suppression of cell proliferation and remarkable induction of apoptosis both in vitro and in vivo. Thus, compound (S)-36 represents a promising PI3Kδ inhibitor for the treatment of acute myeloid leukemia with high efficacy.
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Antineoplásicos , Proliferação de Células , Classe I de Fosfatidilinositol 3-Quinases , Leucemia Mieloide Aguda , Inibidores de Fosfoinositídeo-3 Quinase , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Animais , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase/síntese química , Inibidores de Fosfoinositídeo-3 Quinase/química , Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico , Inibidores de Fosfoinositídeo-3 Quinase/farmacocinética , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacocinética , Proliferação de Células/efeitos dos fármacos , Camundongos , Linhagem Celular Tumoral , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Relação Estrutura-Atividade , Apoptose/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/farmacocinética , Ensaios Antitumorais Modelo de Xenoenxerto , Descoberta de Drogas , Camundongos Nus , Simulação de Acoplamento Molecular , MasculinoRESUMO
Previous studies have shown that alertness is closely related to executive control function, but its impact on components of post-error adjustment is unknown. This study applied the Attentional Networks Test and the Four-choice Flanker task with three response stimulus intervals (RSIs) to explore the correlation between alertness and post-error adjustment. The linear mixed-effects model of alertness and RSI on the post-error processing indicators showed a significant negative correlation between the alertness and post-error slowing (PES) under 200â¯ms RSI , as well as between alertness and post-error improvement in accuracy (PIA) under both 700 ms RSI and 1200 ms RSI. Participants with lower alertness showed larger post-error slowing in the early stages, while those with higher alertness had smaller PIA in later stages. This study revealed the effects of alertness on different processing components of post-error adjustment. The control strategies utilized by individuals with high and low levels of alertness differed in preparation for performance monitoring. Alertness improved post-error response speed in a task-unspecific manner, but not post-error adaptation.
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Atenção , Função Executiva , Desempenho Psicomotor , Tempo de Reação , Humanos , Masculino , Feminino , Atenção/fisiologia , Adulto Jovem , Tempo de Reação/fisiologia , Função Executiva/fisiologia , Adulto , Desempenho Psicomotor/fisiologia , Adaptação Psicológica/fisiologiaRESUMO
Background: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are clinically severe respiratory disorders without available pharmacological therapies. Dynasore is a cell-permeable molecule that inhibits GTPase activity and exerts protective effects in several disease models. However, whether dynasore can alleviate lipopolysaccharide (LPS)-induced ALI is unknown. This study investigated the effect of dynasore on macrophage activation and explored its potential mechanisms in LPS-induced ALI in vitro and in vivo. Methods: Bone marrow-derived macrophages (BMDMs) were activated classically with LPS or subjected to NLRP3 inflammasome activation with LPS+ATP. A mouse ALI model was established by the intratracheal instillation (i.t.) of LPS. The expression of PYD domains-containing protein 3 (NLRP3), caspase-1, and gasdermin D (GSDMD) protein was detected by Western blots. Inflammatory mediators were analyzed in the cell supernatant, in serum and bronchoalveolar lavage fluid (BALF) by enzyme-linked immunosorbent assays. Morphological changes in lung tissues were evaluated by hematoxylin and eosin staining. F4/80, Caspase-1 and GSDMD distribution in lung tissue was detected by immunofluorescence. Results: Dynasore downregulated nuclear factor (NF)-κB signaling and reduced proinflammatory cytokine production in vitro and inhibited the production and release of interleukin (IL)-1ß, NLRP3 inflammasome activation, and macrophage pyroptosis through the Drp1/ROS/NLRP3 axis. Dynasore significantly reduced lung injury scores and proinflammatory cytokine levels in both BALF and serum in vivo, including IL-1ß and IL-6. Dynasore also downregulated the co-expression of F4/80, caspase-1 and GSDMD in lung tissue. Conclusion: Collectively, these findings demonstrated that dynasore could alleviate LPS-induced ALI by regulating macrophage pyroptosis, which might provide a new therapeutic strategy for ALI/ARDS.
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Lesão Pulmonar Aguda , Inflamassomos , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Animais , Masculino , Camundongos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/patologia , Células Cultivadas , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Inflamassomos/antagonistas & inibidores , Inflamassomos/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Piroptose/efeitos dos fármacosRESUMO
Tuberculosis (TB) is a global lethal disease caused by Mycobacterium tuberculosis (Mtb). The flavoenzyme decaprenylphosphoryl-ß-d-ribose 2'-oxidase (DprE1) plays a crucial part in the biosynthesis of lipoarabinomannan and arabinogalactan for the cell wall of Mtb and represents a promising target for anti-TB drug development. Therefore, there is an urgent need to discover DprE1 inhibitors with novel scaffolds, improved bioactivity and high drug-likeness. Recent studies have shown that artificial intelligence/computer-aided drug design (AI/CADD) techniques are powerful tools in the discovery of novel DprE1 inhibitors. This review provides an overview of the discovery of DprE1 inhibitors and their underlying mechanism of action and highlights recent advances in the discovery and optimization of DprE1 inhibitors using AI/CADD approaches.
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Antituberculosos , Inteligência Artificial , Humanos , Antituberculosos/farmacologia , Oxirredutases do Álcool/antagonistas & inibidores , Oxirredutases do Álcool/metabolismo , Mycobacterium tuberculosis/efeitos dos fármacos , Desenho de Fármacos , Desenho Assistido por Computador , Desenvolvimento de Medicamentos/métodos , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/metabolismo , Tuberculose/tratamento farmacológico , Animais , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Descoberta de Drogas/métodosRESUMO
The ecological validity of bilingual code-switching has garnered increasing attention in recent years. Contrary to traditional studies that have focused on forced language switching, emerging theories posit that voluntary switching may not incur such a cost. To test these claims and understand differences between forced and voluntary switching, the present study conducted a systematic comparison through both behavioral and neural perspectives. Utilizing fMRI alongside picture-naming tasks, our findings diverge from prior work. Voluntary language switching not only demonstrated switching costs at the behavioral level but also significantly activated brain regions associated with inhibitory control. Direct comparisons of voluntary and forced language switching revealed no significant behavioral differences in switching costs, and both shared several common brain regions that were activated. On the other hand, a nuanced difference between the two types of language switching was revealed by whole-brain analysis: voluntary switching engaged fewer language control regions than forced switching. These findings offer a comprehensive view of the neural and behavioral dynamics involved in bilingual language switching, challenging prior claims that voluntary switching imposes no behavioral or neural costs, and thus providing behavioral and neuroimaging evidence for the involvement of inhibitory control in voluntary language switching.
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Imageamento por Ressonância Magnética , Multilinguismo , Humanos , Idioma , Cognição , ChinaRESUMO
Viral infections have a major impact in human health. Ongoing viral transmission and escalating selective pressure have the potential to favor the emergence of vaccine- and antiviral drug-resistant viruses. Target-based approaches for the design of antiviral drugs can play a pivotal role in combating drug-resistant challenges. Drug design computational tools facilitate the discovery of novel drugs. This review provides a comprehensive overview of current drug design strategies employed in the field of antiviral drug resistance, illustrated through the description of a series of successful applications. These strategies include technologies that enhance compound-target affinity while minimizing interactions with mutated binding pockets. Furthermore, emerging approaches such as virtual screening, targeted protein/RNA degradation, and resistance analysis during drug design have been harnessed to curtail the emergence of drug resistance. Additionally, host targeting antiviral drugs offer a promising avenue for circumventing viral mutation. The widespread adoption of these refined drug design strategies will effectively address the prevailing challenge posed by antiviral drug resistance.
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Antivirais , Desenho de Fármacos , Humanos , Antivirais/farmacologia , Antivirais/uso terapêutico , Antivirais/metabolismo , Farmacorresistência Viral/genética , MutaçãoRESUMO
BACKGROUND: Due to spatial resolution limitations, conventional NaI-SPECT typically overestimates the left ventricular (LV) ejection fraction (EF) in patients with small LV volumes. The purpose of this study was to explore the clinical application value of the small heart (SH) reconstruction protocol embedded in the postprocessing procedure of D-SPECT. METHODS: We retrospectively analyzed patients who undergo both D-SPECT and echocardiography (Echo) within one week. Patients with small LV volume were defined as those with a rest end-systolic volume (rESV) ≤ 25 mL and underwent reconstruction using the standard (SD) reconstruction protocol. The SH protocol was deemed successful in correcting the LVEF value if it decreased by 5% or more compared to the SD protocol. The ROC curve was used to calculate the optimal cutoff value of the SH protocol. LVEF, ESV and EDV were computed with SD and SH, respectively. Echo was performed as a reference, and Echo-LVEF, ESV, and EDV were calculated using the Teichholz formula. One-way ANOVA was used to compare these parameters among the three groups. RESULTS: The final study included 209 patients (73.21% female, age 67.34 ± 7.85 years). Compared with the SD protocol, the SH protocol significantly decreased LVEF (67.43 ± 7.38% vs. 71.30 ± 7.61%, p < 0.001). The optimal cutoff value for using the SH protocol was rESV > 17 mL (AUC = 0.651, sensitivity = 78.43%, specificity = 45.57%, p = 0.001). In the subgroup of rESV > 17 mL, there was no significant difference in LVEF (61.84 ± 4.67% vs. 62.83 ± 2.85%, p = 0.481) between the SH protocol and Echo, and no significant difference was observed in rESV (26.92 ± 3.25 mL vs. 27.94 ± 7.96 mL, p = 0.60) between the SH protocol and Echo. CONCLUSION: This pilot study demonstrated that the SH reconstruction protocol was able to effectively correct the overestimation of LVEF in patients with small LV volumes. Particularly, in the rESV > 17 mL subgroup, the time and computing power waste could be reduced while still ensuring the accuracy of the LVEF value and image quality.
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With the advancement of globalization, our world is becoming increasingly interconnected. However, this interconnection means that once an infectious disease emerges, it can rapidly spread worldwide. Specifically, viral diseases pose a growing threat to human health. The COVID-19 pandemic has underscored the pressing need for expedited drug development to combat emerging viral diseases. Traditional drug discovery methods primarily rely on random screening and structure-based optimization, and new approaches are required to address more complex scenarios in drug discovery. Emerging antiviral strategies include phase separation and lysosome/exosome targeting. The widespread implementation of these innovative drug design strategies will contribute towards tackling existing viral infections and future outbreaks.
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Exossomos , Viroses , Humanos , Antivirais/farmacologia , Antivirais/uso terapêutico , Pandemias , Separação de Fases , Viroses/tratamento farmacológicoRESUMO
Decaprenylphosphoryl-ß-d-ribose oxidase (DprE1) is a promising target for treating tuberculosis (TB). Currently, most novel DprE1 inhibitors are discovered through high-throughput screening, while computer-aided drug design (CADD) strategies are expected to promote the discovery process. In this study, with the aid of structure-based virtual screening and computationally guided design, a series of novel scaffold N-(1-(6-oxo-1,6-dihydropyrimidine)-pyrazole) acetamide derivatives with significant antimycobacterial activities were identified. Among them, compounds LK-60 and LK-75 are capable of effectively suppressing the proliferation of Mtb with MICMtb values of 0.78-1.56 µM, comparable with isoniazid and much superior to the phase II candidate TBA-7371 (MICMtb = 12.5 µM). LK-60 is also the most active DprE1 inhibitor derived from CADD so far. Further studies confirmed their high affinity to DprE1, good safety profiles to gut microbiota and human cells, and synergy effects with either rifampicin or ethambutol, indicating their broad potential for clinical applications.
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Mycobacterium tuberculosis , Humanos , Antituberculosos/farmacologia , Oxirredutases do Álcool , Pirazóis/farmacologia , Acetamidas/farmacologia , Proteínas de BactériasRESUMO
Acute lung injury (ALI) is one of the most common complications in COVID-19 and also a syndrome of acute respiratory failure with high mortality rates, but lacks effective therapeutic drugs. Natural products provide inspiration and have proven to be the most valuable source for bioactive molecule discovery. In this study, the chemical evolution of the natural product Tanshinone IIA (Tan-IIA) to achieve a piperidine-fused scaffold through a synthetic route of pre-activation, multi-component reaction, and post-modification is presented. Through biological evaluation, it is pinpointed that compound 8b is a standout candidate with remarkable anti-inflammation and anti-oxidative stress properties, coupled with low toxicity. The mechanistic study unveils a multifaceted biological profile of 8b and shows that 8b is highly efficient in vivo for the treatment of ALI. Therefore, this work not only provides an effective strategy for the treatment of ALI, but also offers a distinctive natural product-inspired drug discovery.
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Lesão Pulmonar Aguda , Síndrome do Desconforto Respiratório , Humanos , Evolução Química , Lesão Pulmonar Aguda/tratamento farmacológico , Estresse OxidativoRESUMO
Morin suggested that one of the reasons for the difficulty in standardizing graphic codes is that the production of spoken language reduces the need for graphic codes. Here we try to extend their claims from a psychological perspective, which allows us to conclude that the puzzle of ideography is perhaps related to human psychological traits and psychological evolution.
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Idioma , HumanosRESUMO
PI3Kδ is a promising target for the treatment of inflammatory disease; however, the application of PI3Kδ inhibitors in acute respiratory inflammatory diseases is rarely investigated. In this study, through scaffold hopping design, we report a new series of 1H-pyrazolo[3,4-d]pyrimidin-4-amine-tethered 3-methyl-1-aryl-1H-indazoles as highly selective and potent PI3Kδ inhibitors with significant anti-inflammatory activities for treatment of acute lung injury (ALI). There were 29 compounds designed, prepared, and subjected to PI3Kδ inhibitory activity evaluation and anti-inflammatory activity evaluation in macrophages. (S)-29 was identified as a candidate with high PI3Kδ inhibitory activity, isoform selectivity, and high oral bioavailability. The in vivo administration of (S)-29 at 10 mg/kg dosage could significantly ameliorate histopathological changes and attenuate lung inflammation in lung tissues of LPS-challenged mice. Molecular docking demonstrated the success of scaffold hopping design. Overall, (S)-29 is a potent PI3Kδ inhibitor which might be a promising candidate for the treatment of ALI.
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Lesão Pulmonar Aguda , Animais , Camundongos , Simulação de Acoplamento Molecular , Lesão Pulmonar Aguda/tratamento farmacológico , Aminas , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Disponibilidade BiológicaRESUMO
The development of histone deacetylase (HDAC) inhibitors for treating hematologic malignancies has been widely investigated, while their role in hepatocellular carcinoma (HCC) remains unexplored. In this study, we employed a scaffold-hopping design and a multicomponent synthesis approach to develop a novel series of 1,2,3,4-tetrahydrobenzofuro[2,3-c]pyridines as HDAC inhibitors. There were a total of 29 compounds achieved with flexible linkers and zinc-binding groups, wherein compound 12k was identified as a promising candidate with good HDAC inhibitory activity, pharmacokinetic profiles, and potency. It exhibited significant therapeutic efficacy in HCC cell lines (IC50 = 30 nM for Bel-7402) and xenograft models (76% inhibition for Bel-7402 xenografts, P.O. at 20 mg/kg, QOD, for 14 days) and was found to upregulate the acetylation of histone H3 and α-tubulin, leading to apoptosis and autophagy in HCC models. Molecular docking studies indicated a unique T-shaped conformation of 12k with the catalytic domain of HDAC1. Therefore, this work provides a new structure design for HDAC inhibitors and also offers a promising treatment for HCC.
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Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Inibidores de Histona Desacetilases/química , Neoplasias Hepáticas/patologia , Simulação de Acoplamento Molecular , Apoptose , Piridinas/farmacologia , Piridinas/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células , Histona Desacetilase 1/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêuticoRESUMO
Interpersonal communication through vocal information is very important for human society. During verbal interactions, our vocal cord vibrations convey important information regarding voice identity, which allows us to decide how to respond to speakers (e.g., neither greeting a stranger too warmly or speaking too coldly to a friend). Numerous neural studies have shown that identifying familiar and unfamiliar voices may rely on different neural bases. However, the mechanism underlying voice identification of individuals of varying familiarity has not been determined due to vague definitions, confusion of terms, and differences in task design. To address this issue, the present study first categorized three kinds of voice identity processing (perception, recognition and identification) from speakers with different degrees of familiarity. We defined voice identity perception as passively listening to a voice or determining if the voice was human, voice identity recognition as determining if the sound heard was acoustically familiar, and voice identity identification as ascertaining whether a voice is associated with a name or face. Of these, voice identity perception involves processing unfamiliar voices, and voice identity recognition and identification involves processing familiar voices. According to these three definitions, we performed activation likelihood estimation (ALE) on 32 studies and revealed different brain mechanisms underlying processing of unfamiliar and familiar voice identities. The results were as follows: (1) familiar voice recognition/identification was supported by a network involving most regions in the temporal lobe, some regions in the frontal lobe, subcortical structures and regions around the marginal lobes; (2) the bilateral superior temporal gyrus was recruited for voice identity perception of an unfamiliar voice; (3) voice identity recognition/identification of familiar voices was more likely to activate the right frontal lobe than voice identity perception of unfamiliar voices, while voice identity perception of an unfamiliar voice was more likely to activate the bilateral temporal lobe and left frontal lobe; and (4) the bilateral superior temporal gyrus served as a shared neural basis of unfamiliar voice identity perception and familiar voice identity recognition/identification. In general, the results of the current study address gaps in the literature, provide clear definitions of concepts, and indicate brain mechanisms for subsequent investigations.
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Encéfalo , Voz , Humanos , Funções Verossimilhança , Encéfalo/fisiologia , Percepção Auditiva/fisiologia , Reconhecimento Psicológico/fisiologiaRESUMO
The world's hunger is continuously rising due to conflicts, climate change, pandemics (such as the recent COVID-19), and crop pests and diseases. It is widely accepted that zero hunger is impossible without using agrochemicals to control crop pests and diseases. Diamide insecticides are one of the widely used green insecticides developed in recent years and play important roles in controlling lepidopteran pests. Currently, eight diamine insecticides have been commercialized, which target the insect ryanodine receptors. This review summarizes the development and optimization processes of diamide derivatives acting as ryanodine receptor activators. The review also discusses pest resistance to diamide derivatives and possible solutions to overcome the limitations posed by the resistance. Thus, with reference to structural biology, this study provides an impetus for designing and developing diamide insecticides with improved insecticidal activities.