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1.
Environ Int ; 193: 109073, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39442321

RESUMO

Vanadium(V) contaminated soil is abundant in iron(Fe) oxides due to co-occurrence of V and Fe bearing minerals. However, biogeochemical transformation of redox-active V and Fe in soil, and the bacteria involved, has remained less investigated. This study explored the extent to which microbial mediated organic decomposition coupled to Fe(III) reduction contributed to V(V) release/reduction in V-contaminated paddy soil under different organic amendments. Soil flooding decreased toxic reducible V while increased less toxic oxidizable V. Glucose and straw promoted V(V) release with temporarily increasing V(V) concentration by 73.59-106.34 mg/kg compared to the control treatment and subsequently promoted V(V) reduction with decreasing V(V) to concentrations eventually similar to the control treatment. Biochar incorporation under glucose and straw amendments moderately alleviated V(V) release. The significantly positive correlation between Fe(II) and V(V) concentrations during the V solubilization process indicated a temporal coupling of Fe(III) reduction and V(V) release. Clostridium and Massilia mediated Fe(III) reductive dissolution and V(V) release, while Anaeromyxobacter, Sphingomonas, Bryobacter, Acidobacteriaceae and Anaerolineaceae contributed to V(V) reduction. This study provides a deeper understanding of V biotransformation coupled to Fe and C cycling and suggests a remediation strategy for V-contaminated soils via regulating Fe(III) reduction to weaken V(V) release or to promote V(V) reduction.

2.
Microorganisms ; 12(9)2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39338435

RESUMO

Chronic pancreatitis is a progressive fibroinflammatory disorder with no currently satisfactory treatment. Emerging evidence suggests an association between gut microbial dysbiosis and chronic pancreatitis. Although direct causative evidence is lacking, it is hypothesized that the gut microbiota may play a pivotal role in modulating pancreatic function via the gut-pancreas axis. Thus, modulating the gut microbiota through the administration of probiotics or prebiotics may alleviate pancreatic disorders. In this review, we first propose the potential mechanisms by which specific probiotics or prebiotics may ameliorate chronic pancreatitis, including the alleviation of small intestinal bacterial overgrowth (SIBO), the facilitation of short-chain fatty acids' (SCFAs) production, and the activation of glucagon-like peptide-1 receptors (GLP-1Rs) in the pancreas. Since there are currently no probiotics or prebiotics used for the treatment of chronic pancreatitis, we discuss research in other disease models that have used probiotics or prebiotics to modulate pancreatic endocrine and exocrine functions and prevent pancreatic fibrosis. This provides indirect evidence for their potential application in the treatment of chronic pancreatitis. We anticipate that this research will stimulate further investigation into the gut-pancreas axis and the potential therapeutic value of probiotics and prebiotics in chronic pancreatitis.

3.
BMC Public Health ; 24(1): 905, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38539126

RESUMO

BACKGROUND: Electronic health records (EHRs) are digital records of individual health information. However, their adoption and utilization remain low. This study explores the factors influencing the implementation of EHRs through a questionnaire survey to enhance individual awareness and adoption of EHRs. METHODS: A questionnaire and an expert rating scale were developed sequentially, and the consistency of the scores from five experts was calculated using Kendall's W to generate a final questionnaire. A non-parametric test was utilized to analyze differences in continuous data that did not follow a normal distribution. Categorical variables were expressed as percentages (%), the chi-square test was employed for group comparisons, and multiple logistic regression was implemented to assess individuals' awareness and adoption of EHRs. RESULTS: In total, 1,341 survey questionnaires were distributed between January and December 2022, with 1,337 valid responses (99.7%). The results indicated that the proportion of participants who were aware of EHRs and had a bachelor's degree or higher education, an income of ≥$700 per month, residence in urban areas, possessed self-care abilities, and underwent annual physical examinations was significantly higher than that without awareness of EHRs (P < 0.05), while in hearing problems and walking abilities was markedly lower than that of participants without awareness of EHRs (P < 0.05). Additionally, the proportion of individuals willing to self-manage EHRs was significantly higher than those reluctant to do so (P < 0.05) among participants with a bachelor's degree or higher education, an income of ≥$700 per month, residence in urban areas, possession of self-care abilities, annual physical examinations, hearing problems, and poor walking abilities. Age (Odds Ratio [OR] = 1.104, 95% Confidence Interval [CI] 1.001-1.028, P = 0.033), hearing problems (OR = 0.604, 95% CI 0.377-0.967, P = 0.036), self-care ability (OR = 5.881, 95% CI 1.867-18.529, P = 0.002), and annual physical examinations (OR = 3.167, 95% CI 2.31-4.34, P < 0.001) were independently associated with willingness to self-manage EHRs. Annual physical examination (OR = 2.507, 95%CI 1.585-2.669, P < 0.001) also independently made a difference to the awareness of EHRs. CONCLUSIONS: Our findings suggest that annual physical examinations, age, hearing problems, and self-care abilities are significant factors in assessing individuals' awareness and adoption of EHRs. Understanding the characteristics of individuals who are aware of or are willing to take advantage of EHRs plays a positive role in promoting their popularization and application.


Assuntos
Registros Eletrônicos de Saúde , Renda , Humanos , Inquéritos e Questionários , Modelos Logísticos , China
4.
Lupus ; 32(12): 1369-1380, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37769649

RESUMO

Immune dysregulation is not only a pathogenic mechanism in systemic lupus erythematosus (SLE) but also a potential cause of the link between SLE and cancer. The current understanding of SLE monocyte-associated biomarkers is limited, and the precise mechanism behind the link between SLE and cancer is uncertain. By using WGCNA and immune infiltration to analyze the GSE72326 dataset, we determined the most pertinent modules for monocytes and discovered eight candidate hub genes from them. The limma software was used to find genes that were differently expressed in SLE. The genes that overlapped between the two were chosen using a Venn diagram as the essential genes related to monocytes in SLE, and the essential genes were verified by several datasets. Correlation analysis and GSEA analysis were used to examine the probable immunological pathways connected to key genes. We examined the expression of hub genes in cancer and their interaction with monocytes using the GEPIA and TIMER databases to understand the significance of essential genes in tumorigenesis. In addition, we performed transcription factor identification. We discovered three biomarkers (IFI30, BLVRA, and RIN2) that are mostly involved in interferon-related signaling pathways and are associated with monocyte-mediated immune responses in SLE. The three important genes are also strongly expressed in a number of malignancies and have a relationship with monocytes. As a result, IFI30, BLVRA, and RIN2 may act as SLE-associated biomarkers of monocytes and as a bridge between SLE and tumors. We proposed that interferon-related signaling pathways might function as possible mediators of cancer risk in SLE.


Assuntos
Lúpus Eritematoso Sistêmico , Neoplasias , Humanos , Monócitos , Lúpus Eritematoso Sistêmico/complicações , Biomarcadores/metabolismo , Neoplasias/genética , Neoplasias/complicações , Interferons , Proteínas de Transporte/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo
5.
J Phys Chem Lett ; 14(17): 4026-4032, 2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-37093583

RESUMO

Photoelectrocatalytic water splitting using metal sulfides is a promising method for green hydrogen production. However, in situ probing of the hydrogen evolution reaction (HER) on sulfides with excellent performance remains a challenge. Here, we construct Au@CdS core-shell nanoparticles to study the HER on CdS, a typical HER catalyst, by surface-enhanced Raman spectroscopy (SERS) using a "borrowing" strategy. We directly capture the spectroscopic evidence of S-H intermediate under HER condition, further verified by isotopic experiments. Moreover, the population of S-H intermediates is improved by injecting charge carriers through light illumination and the S-H bond is weakened by introducing Pt to form a Au@Pt@CdS structure to change the interfacial electronic structure, both of them resulting in significant HER performance improvement. These findings can deepen the understanding of the HER mechanism and offer strategies for designing of cost-effective HER catalyst with high performance.

6.
Br J Psychol ; 114(4): 778-796, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37010697

RESUMO

Previous studies examining the relationship between ingroup bias and resource scarcity have produced heterogeneous findings, possibly due to their focus on the allocation of positive resources (e.g. money). This study aims to investigate whether ingroup bias would be amplified or eliminated when perceived survival resources for counteracting negative stimuli are scarce. For this purpose, we exposed the participants and another confederate of the experimenters (ingroup/outgroup member) to a potential threat of unpleasant noise. Participants received some 'relieving resources' to counteract noise administration, the amount of which may or may not be enough for them and the confederate in different conditions (i.e. abundance vs. scarcity). First, a behavioural experiment demonstrated that intergroup discrimination manifested only in the scarcity condition; in contrast, the participants allocated similar amounts of resource to ingroup and outgroup members in the abundance condition, indicating a context-dependent allocation strategy. This behavioural pattern was replicated in a follow-up neuroimaging experiment, which further revealed that when contrasting scarcity with abundance, there was higher activation in the anterior cingulate cortex (ACC) as well as stronger functional connectivity of the ACC with the empathy network (including the temporoparietal junction and medial prefrontal cortex) for ingroup compared to outgroup members. We suggest that ACC activation reflects the mentalizing process toward ingroup over outgroup members in the scarcity condition. Finally, the ACC activation level significantly predicted the influence of resource scarcity on ingroup bias in hypothetical real-life situations according to a follow-up examination.


Assuntos
Viés , Empatia , Humanos
7.
Hum Brain Mapp ; 44(9): 3859-3872, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37086449

RESUMO

In real life, it is not unusual that we face potential threats (i.e., physical stimuli and environments that may cause harm or danger) with other individuals together, yet it remains largely unknown how threat-induced anxious feelings influence prosocial behaviors such as resource sharing. In this study, we investigated this question by combining functional magnetic resonance imaging and a novel paradigm. Together with an anonymous partner, each participant faced the possibility of receiving a 10-s noise administration, which had a low or high probability to be a threat (i.e., the intensity of noise can induce a high level of unpleasantness). Each participant first reported her/his immediate feeling of anxiety about the current situation (being threatened by the unpleasant noise), then decided how to split a number of resources (which could relieve the noise) between her/him and the partner. Behavioral results revealed that the participants showed a selfish bias in the threat conditions than in the safe conditions, and that self-reported anxiety feeling significantly predicted this bias. Functional magnetic resonance imaging results revealed that: (1) the activation level of the anterior insula was correlated with self-reported anxiety and (2) the connectivity between the anterior insula and the temporoparietal junction was sensitive to the modulating effect of anxiety on the selfish bias. These findings indicate the neural correlates of the association between threat-induced anxiety and prosocial tendencies in social interactions.


Assuntos
Transtornos de Ansiedade , Ansiedade , Humanos , Masculino , Feminino , Ansiedade/diagnóstico por imagem , Emoções/fisiologia , Autorrelato , Imageamento por Ressonância Magnética/métodos
8.
Environ Int ; 168: 107486, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36030743

RESUMO

Microbial communities are responsible for biological treatment of many industrial wastewater, but our knowledge of their diversity, assembly patterns, and function is still poor. Here, we analyzed the bacterial communities of wastewater and activated sludge samples taken from 11 full-scale industrial wastewater treatment plants (IWWTPs) characterized by the same process design but different wastewater types and WWTP compartments. We found significantly different diversity and compositions of bacterial assemblages among distinct wastewater types and IWWTPs compartments. IWWTPs bacterial communities exhibited a clear species abundance distribution. The dispersal-driven process was weak in shaping IWWTP communities. Meanwhile, environmental and operating conditions were important factors in regulating the structure of the activated sludge community and pollutants removal, indicating that bacterial community was largely driven by deterministic mechanisms. The core microbial community in IWWTPs was different from that in municipal wastewater treatment plants (MWWTPs), and many taxa (e.g. the genus Citreitalea) rarely were detected before, indicating IWWTPs harbored unique core bacterial communities. Furthermore, we found that bacterial community compositions were strongly linked to activated sludge function. These findings are important to both microbial ecologists and environmental engineers, who may optimize the operation strategies jointly for maintaining biodiversity, which in turn may promote a more stable performance of the IWWTP. Overall, our study enhances the mechanistic understanding of the IWWTP microbial community diversity, assembly patterns, and function, and provides important implications for microbial ecology and wastewater treatment processes.


Assuntos
Microbiota , Purificação da Água , Águas Residuárias , Esgotos/química , Bactérias
9.
J Immunother Cancer ; 10(6)2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35688558

RESUMO

BACKGROUND: Oncolytic viruses (OVs) are capable to inflame the tumor microenvironment (TME) and elicit infiltrating tumor-specific T cell responses. However, OV treatment negatively alters the cancer-immune set point in tumors to attenuate the antitumor immune response, which suggests the necessity of dissecting the immune landscape of the virus-treated tumors and developing novel strategies to maximize the potential of OVs. The aim of this study is to investigate the effect of the single-chain variable fragment (scFv)-armed OVs targeting PD-1 on the TME, and ultimately overcome localized immunosuppression to sensitize tumors to immunotherapies. METHODS: A tumor-selective oncolytic herpes simplex virus vector was engineered to encode a humanized scFv against human PD-1 (hPD-1scFv) (YST-OVH). The antitumor efficacy of YST-OVH was explored in multiple therapeutic mouse models. The neurotoxicity and safety of YST-OVH were evaluated in nonhuman primates. The precise dynamics in the TME involved in YST-OVH treatment were dissected using cytometry by time-of-flight (CyTOF). RESULTS: The identified hPD-1scFv showed superior T-cell activating activity. Localized delivery of hPD-1scFv by YST-OVH promotes systemic antitumor immunity in humanized PD-1 mouse models of established cancer. Immune profiling of tumors using CyTOF revealed the enhanced antitumor effect of YST-OVH, which largely relied on CD8+ T cell activity by augmenting the tumor infiltration of effector CD8+ T cells and establishment of memory CD8+ T cells and reducing associated CD8+ T cell exhaustion. Furthermore, YST-OVH treatment modified the cancer-immune set point of tumors coupled to coexpression of CTLA-4 and TIM-3 on exhausted CD8+ T cells and high levels of CTLA-4+ Treg cells. A combination approach incorporating anti-CTLA-4 or anti-TIM-3 further improved efficacy by increasing tumor immunogenicity and activating antitumor adaptive immune responses. Moreover, this therapeutic strategy showed no neurotoxicity and was well tolerated in nonhuman primates. The benefit of intratumoral hPD-1scFv expression was also observed in humanized mice bearing human cancer cells. CONCLUSION: Localized delivery of PD-1 inhibitors by engineered YST-OVH was a highly effective and safe strategy for cancer immunotherapy. YST-OVH also synergized with CTLA-4 or TIM-3 blockade to enhance the immune response to cancer. These data provide a strong rationale for further clinical evaluation of this novel therapeutic approach.


Assuntos
Terapia Viral Oncolítica , Vírus Oncolíticos , Animais , Linfócitos T CD8-Positivos , Antígeno CTLA-4 , Linhagem Celular Tumoral , Modelos Animais de Doenças , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Humanos , Inibidores de Checkpoint Imunológico , Imunidade , Camundongos , Receptor de Morte Celular Programada 1
10.
Antiviral Res ; 201: 105298, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35341808

RESUMO

Infections caused by herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) remain a serious global health issue, and the medical countermeasures available thus far are limited. Virus-neutralizing monoclonal antibodies (NAbs) are crucial tools for studying host-virus interactions and designing effective vaccines, and the discovery and development of these NAbs could be one approach to treat or prevent HSV infection. Here, we report the isolation of five HSV NAbs from mice immunized with both HSV-1 and HSV-2. Among these were two antibodies that potently cross-neutralized both HSV-1 and HSV-2 with the 50% virus-inhibitory concentrations (IC50) below 200 ng/ml, one of which (4A3) exhibited high potency against HSV-2, with an IC50 of 59.88 ng/ml. 4A3 neutralized HSV at the prebinding stage and prevented HSV infection and cell-to-cell spread. Significantly, administration of 4A3 completely prevented weight loss and improved survival of mice challenged with a lethal dose of HSV-2. Using structure-guided molecular modeling combined with alanine-scanning mutagenesis, we observed that 4A3 bound to a highly conserved continuous epitope (residues 216 to 220) within the receptor-binding domain of glycoprotein D (gD) that is essential for viral infection and the triggering of membrane fusion. Our results provide guidance for developing NAb drugs and vaccines against HSV.


Assuntos
Herpes Simples , Herpesvirus Humano 1 , Animais , Anticorpos Antivirais , Epitopos , Herpes Simples/tratamento farmacológico , Herpes Simples/prevenção & controle , Herpesvirus Humano 2 , Camundongos , Camundongos Endogâmicos BALB C , Proteínas do Envelope Viral/metabolismo
11.
Cereb Cortex ; 32(23): 5330-5342, 2022 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-35134875

RESUMO

Resource scarcity challenges individuals' willingness to share limited resources with other people. Still, lots of field studies and laboratory experiments have shown that sharing behaviors do not disappear under scarcity. Rather, some individuals are willing to share their scarce resources with others in a similar way as when the resource is abundant, which is crucial for the maintenance and development of human society. Here, we designed a novel paradigm in which subjects decided whether (and how much) to share an amount of "relieving resources" for counteracting unpleasant noises, which mimics real-life situations that people cost their own resources to help others escape from adversity. Overall, the robustness of resource sharing under scarcity was positively correlated with individual level of the cognitive component of empathy across two independent experiments. Resource insufficiency modulated the activations of several brain regions (including the TPJ, mPFC, and PCC) as well as the functional connection (from the rTPJ to the mPFC) within the mentalizing brain network, but the modulatory effect decreased as a function of cognitive empathy. We also applied the administration of oxytocin and found significant effects on sharing behavior among individuals with a higher level of cognitive empathy, but not their low-level counterparts. These findings highlight the importance of empathy to resource sharing under scarcity and explain the underlying neurobiological mechanisms.


Assuntos
Empatia , Imageamento por Ressonância Magnética , Humanos , Encéfalo , Mapeamento Encefálico , Cognição
12.
Neurosci Bull ; 38(5): 533-547, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34988911

RESUMO

People as third-party observers, without direct self-interest, may punish norm violators to maintain social norms. However, third-party judgment and the follow-up punishment might be susceptible to the way we frame (i.e., verbally describe) a norm violation. We conducted a behavioral and a neuroimaging experiment to investigate the above phenomenon, which we call the "third-party framing effect". In these experiments, participants observed an anonymous perpetrator deciding whether to keep her/his economic benefit while exposing a victim to a risk of physical pain (described as "harming others" in one condition and "not helping others" in the other condition), then they had a chance to punish that perpetrator at their own cost. Our results showed that the participants were more willing to execute third-party punishment under the harm frame compared to the help frame, manifesting a framing effect. Self-reported anger toward perpetrators mediated the relationship between empathy toward victims and the framing effect. Meanwhile, activation of the insula mediated the relationship between mid-cingulate cortex activation and the framing effect; the functional connectivity between these regions significantly predicted the size of the framing effect. These findings shed light on the psychological and neural mechanisms of the third-party framing effect.


Assuntos
Neuroimagem , Punição , Empatia , Feminino , Giro do Cíngulo , Humanos , Dor , Punição/psicologia
13.
Neuroimage ; 238: 118249, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34116146

RESUMO

Previous behavioral studies have shown that sharing painful experiences can strengthen social bonds and promote mutual prosociality, yet the neural mechanisms underlying this phenomenon remain unclear. We hypothesized that sharing a painful experience induces brain-to-brain synchronization and mutual empathy for each other's pain between pain-takers and pain-observers, which then leads to enhanced social bonding. To test this hypothesis, we adopted an electroencephalographic (EEG) hyper-scanning technique to assess neuronal and behavioral activity during a Pain-Sharing task in which high- or low-intensity pain stimulation was randomly delivered to one participant of a dyad on different experimental trials. Single-brain analysis showed that sensorimotor α-oscillation power was suppressed more when expecting high-intensity pain than when expecting low-intensity pain similarly for self-directed or partner-directed pain. Dual-brain analysis revealed that expecting high-intensity pain induced greater brain-to-brain synchronization of sensorimotor α-oscillation phases between pain-takers and pain-observers than did expecting low-intensity pain. Mediation analysis further revealed that brain-to-brain synchronization of sensorimotor α-oscillations mediated the effects of pain-stimulation intensity on mutual affective sharing for partner-directed pain. This mutual affective empathy during the task predicted the social bonding, as indexed by prosocial inclinations measured after the task. These results support the hypothesis that sharing a painful experience triggers emotional resonance between pairs of individuals through brain-to-brain synchronization of neuronal α-oscillations recorded over the sensorimotor cortex, and this emotional resonance further strengthens social bonds and motivates prosocial behavior within pairs of individuals.


Assuntos
Encéfalo/fisiopatologia , Empatia/fisiologia , Dor/fisiopatologia , Adolescente , Eletroencefalografia , Emoções , Feminino , Humanos , Masculino , Dor/psicologia , Comportamento Social , Adulto Jovem
14.
Cereb Cortex ; 31(11): 5121-5130, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34148081

RESUMO

The present study combined a novel hypothetical investment game with functional magnetic resonance imaging to examine how moral conflict biases our real decision preference when it is not obvious or explicitly presented. Investment projects were chosen based on their prior subjective morality ratings to fit into 2 categories: a high level of moral conflict (HMC) or a low level of moral conflict (LMC). Participants were instructed to invest high or low amounts of capital into different projects. Behavioral and neural responses during decision making were recorded and compared. Behaviorally, we observed a significant decision bias such that investments were lower for HMC projects than for LMC projects. At the neural level, we found that moral conflict-related activity in the anterior cingulate cortex (ACC) was higher in the HMC condition than in the LMC condition and that reward-related activity in bilateral striatum was lower. Dynamic causal modeling further suggested that the moral conflict detected in the ACC influenced final decisions by modulating the representation of subjective value through the ACC's connection to the reward system.


Assuntos
Mapeamento Encefálico , Giro do Cíngulo , Mapeamento Encefálico/métodos , Tomada de Decisões/fisiologia , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiologia , Humanos , Imageamento por Ressonância Magnética/métodos , Princípios Morais , Recompensa
15.
Cancer Immunol Res ; 8(5): 632-647, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32127389

RESUMO

Oncolytic virotherapy can lead to systemic antitumor immunity, but the therapeutic potential of oncolytic viruses in humans is limited due to their insufficient ability to overcome the immunosuppressive tumor microenvironment (TME). Here, we showed that locoregional oncolytic virotherapy upregulated the expression of PD-L1 in the TME, which was mediated by virus-induced type I and type II IFNs. To explore PD-1/PD-L1 signaling as a direct target in tumor tissue, we developed a novel immunotherapeutic herpes simplex virus (HSV), OVH-aMPD-1, that expressed a single-chain variable fragment (scFv) against PD-1 (aMPD-1 scFv). The virus was designed to locally deliver aMPD-1 scFv in the TME to achieve enhanced antitumor effects. This virus effectively modified the TME by releasing damage-associated molecular patterns, promoting antigen cross-presentation by dendritic cells, and enhancing the infiltration of activated T cells; these alterations resulted in antitumor T-cell activity that led to reduced tumor burdens in a liver cancer model. Compared with OVH, OVH-aMPD-1 promoted the infiltration of myeloid-derived suppressor cells (MDSC), resulting in significantly higher percentages of CD155+ granulocytic-MDSCs (G-MDSC) and monocytic-MDSCs (M-MDSC) in tumors. In combination with TIGIT blockade, this virus enhanced tumor-specific immune responses in mice with implanted subcutaneous tumors or invasive tumors. These findings highlighted that intratumoral immunomodulation with an OV expressing aMPD-1 scFv could be an effective stand-alone strategy to treat cancers or drive maximal efficacy of a combination therapy with other immune checkpoint inhibitors.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Herpesvirus Humano 1/imunologia , Células Supressoras Mieloides/imunologia , Neoplasias/terapia , Terapia Viral Oncolítica/métodos , Receptores Imunológicos/antagonistas & inibidores , Anticorpos de Cadeia Única/farmacologia , Animais , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Imunomodulação , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Nus , Neoplasias/imunologia , Microambiente Tumoral/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Oncoimmunology ; 9(1): 1726168, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32117591

RESUMO

Oncolytic viruses represent a promising therapeutic modality, but they have yet to live up to their therapeutic potential. Safety and efficacy concerns impel us to identify least toxic oncolytic agents that would generate durable and multifaceted anti-tumor immune responses to disrupt the tumors. Here we describe a rational engineered oncolytic herpes virus (OVH) that is a selective killer for targeting tumors, has strong safety records, induces complete regression of tumors in multiple tumor models, and elicits potent antitumor immunity. By far, the potential of OVs in promoting the tumor antigen-specific humoral immune responses remains obscure. In this study, we found that effective treatment by OVH induced immunogenic cell death, which facilitates to elicit humoral immune responses. Depletion experiments revealed that B cells were required for maximal antitumor efficacy of oncolytic immunotherapy. Both serum transfer and antibody treatment experiments revealed that endogenous oncolysis-induced antigen-targeting therapeutic antibodies can lead to systemic tumor regression. Our data demonstrate that tumor-targeting immune modulatory properties confer oncolytic OVH virotherapy as potent immunotherapeutic cancer vaccines that can generate specific and efficacious antitumor humoral responses by eliciting endogenous tumor antigen-targeting therapeutic antibodies in situ, resulting in an efficacious and tumor-specific therapeutic effect.


Assuntos
Vacinas Anticâncer , Terapia Viral Oncolítica , Vírus Oncolíticos , Antígenos de Neoplasias , Imunoterapia , Vírus Oncolíticos/genética
17.
Soc Cogn Affect Neurosci ; 14(7): 747-757, 2019 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-31236566

RESUMO

Predictability has been suggested to modulate both the anticipation and perception of self-pain. Considering the overlapping neural circuits between self-pain and other-pain perceptions, the present study investigated how the predictability of forthcoming pain modulates the anticipation and perception of self-pain and other-pain. We used a balanced, within-participant experimental design in which a visual cue indicating the recipient, intensity and predictability of an upcoming painful electrical stimulation was presented before its delivery. Subjective ratings and electroencephalography activities to the anticipation and perception of self-pain and other-pain were recorded and compared between certain and uncertain conditions. Results showed that predictability affected the perception of self-pain and other-pain in a similar manner such that the differences in behavioral ratings and event-related potentials to high-intensity and low-intensity pain were significantly reduced when the intensity was uncertain. The strengths of predictability-induced modulation of self-pain and other-pain perceptions were positively correlated with each other. Furthermore, predictability also modulated the anticipation of both self-pain and other-pain such that pre-stimulus high-frequency α-oscillation power at sensorimotor electrodes contralateral to the stimulation side was maximally suppressed when anticipating certain high-intensity pain. These findings demonstrate that predictability-induced modulation on pain anticipation and perception was similarly applied to both self-pain and other-pain.


Assuntos
Percepção da Dor/fisiologia , Incerteza , Adulto , Estimulação Elétrica , Eletroencefalografia , Potenciais Evocados/fisiologia , Feminino , Humanos , Masculino , Dor , Medição da Dor
18.
Biol Reprod ; 101(1): 223-234, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31004475

RESUMO

Sulforaphane (SFN), a dietary isothiocyanate that is mainly found in cruciferous vegetables, possesses anti-oxidative and anticancer activity and modulates inflammation. However, little is known about the role of SFN in obesity-related male reproductive defects. The present study aimed to investigate the effects of SFN on high-fat diet (HFD)-induced male spermatogenic impairment and further clarify the possible underlying mechanisms. In this study, 8-week-old mice were randomly divided into four groups. Mice were fed a normal diet or an HFD with or without SFN supplementation. Sulforaphane was subcutaneously injected at a dose of 0.5 mg/kg 5 days/week for 4 weeks beginning 8 weeks after initiation of the HFD. The results demonstrated that SFN could protect against HFD-induced reproductive dysfunction in male mice. Moreover, SFN also improved reproductive ability, as demonstrated by an increased pregnancy rate and decreased embryo resorption rate in comparison to the corresponding HFD group. We also observed a decrease in apoptosis and an attenuation of endoplasmic reticulum (ER) stress after SFN treatment. In vitro studies of mouse and human sperm samples also revealed that SFN protects against the palmitic acid-induced reduction in sperm viability and motility by inhibiting ER stress in an AMP-activated protein kinase (AMPK)-dependent manner. AMPK-dependent ER stress attenuation by SFN was further confirmed using AMPK knockout mice. Taken together, these data show that SFN protects against HFD-induced male reproductive dysfunction by inhibiting ER stress and apoptosis. These findings may be helpful for identifying new therapeutic methods to treat male infertility.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Infertilidade Masculina/etiologia , Infertilidade Masculina/prevenção & controle , Isotiocianatos/farmacologia , Espermatogênese/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/genética , Adulto , Animais , Estudos de Casos e Controles , Células Cultivadas , Humanos , Infertilidade Masculina/patologia , Infertilidade Masculina/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/complicações , Obesidade/patologia , Obesidade/fisiopatologia , Sêmen/efeitos dos fármacos , Sêmen/fisiologia , Análise do Sêmen/métodos , Espermatogênese/fisiologia , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Espermatozoides/fisiologia , Sulfóxidos
19.
Mater Sci Eng C Mater Biol Appl ; 101: 614-618, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31029354

RESUMO

Here we report a simple and low-cost colorimetric assay for ultrasensitive detection of copper (II) ions (Cu2+) based on pH-dependent formation of plasmonic MoO3-x nanosheets. The reaction between ascorbic acid (AA) and Cu2+ gives birth to hydrogen ions, which remarkably promotes the reduction of MoO3 nanosheets by AA to form oxygen vacancies-rich MoO3-x nanosheets that increase the free carrier concentration, generating a strong local surface plasmon resonance (LSPR) absorption. The Cu2+-triggered LSPR is utilized for development of the colorimetric assay. Under the optimal experimental conditions, this colorimetric assay can be used for selective detection of Cu2+, and the limit of detection is 0.8 nM, which is lower than that of most of the reported methods. Additionally, the present colorimetric assay has also been successfully employed for Cu2+ determination in real serum and human hair samples with satisfactory recoveries ranging from 96% to 108%.


Assuntos
Colorimetria/métodos , Cobre/química , Nanopartículas Metálicas/química , Molibdênio/química , Concentração de Íons de Hidrogênio
20.
Front Neurosci ; 13: 1432, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32038139

RESUMO

"Social mindfulness" refers to being thoughtful of others and considering their needs before making decisions, and can be characterized by low-cost and subtle gestures. The present study compared the behavioral and neural responses triggered by observing others' socially mindful/unmindful choices and how these responses were modulated by the social status of the agency. At the behavioral level, observing socially mindful choices made observers feel better, rate the actors as more likable, and behave more cooperatively than did observing socially unmindful choices. Analysis of event-related potentials in the brain revealed that compared with socially unmindful choices, mindful choices elicited more negative feedback-related negativity (FRN). Notably, while this effect of social mindfulness was only significant when the actor's social status was medium and high, it was undetectable when the actor's social status was low. These results demonstrate that the social mindfulness of others can be rapidly detected and processed, as reflected by FRN, even though it does not seem to receive further, more elaborate evaluation. These findings indicated that low-cost cooperative behaviors such as social mindfulness can also be detected and appreciated by our brain, which may result in better mood and more cooperative behaviors in the perceivers. Besides, the perception of social mindfulness is sensitive to important social information, such as social status.

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