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BACKGROUND: Triple-negative breast cancer (TNBC) is recognized as the most aggressive and immunologically infiltrated subtype of breast cancer. A high circulating neutrophil-to-lymphocyte ratio (NLR) is strongly linked to a poor prognosis among patients with breast cancer, emphasizing the critical role of neutrophils. Although the involvement of neutrophils in tumor metastasis is well documented, their interactions with primary tumors and tumor cells are not yet fully understood. METHODS: Clinical data were analyzed to investigate the role of neutrophils in breast cancer. In vivo mouse model and in vitro co-culture system were used for mechanism researches. Blocking experiments were further performed to identify therapeutic agents against TNBC. RESULTS: TNBC cells secreted GM-CSF to sustain the survival of mature neutrophils and upregulated CD11b expression. Through CD11b, neutrophils specifically binded to ICAM1 on TNBC cells, facilitating adhesion. Transcriptomic sequencing combined with human and murine functional experiments revealed that neutrophils, through direct CD11b-ICAM1 interactions, activated the MAPK signaling pathway in TNBC cells, thereby enhancing tumor cell invasion and migration. Atorvastatin effectively inhibited ICAM1 expression in tumor cells, and tumor cells with ICAM1 knockout or treated with atorvastatin were unresponsive to neutrophil activation. The MAPK pathway and MMP9 expression were significantly inhibited in the tumor tissues of TNBC patients treated with atorvastatin. CONCLUSIONS: Targeting CD11b-ICAM1 with atorvastatin represented a potential clinical approach to reduce the malignant characteristics of TNBC.
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Antígeno CD11b , Adesão Celular , Molécula 1 de Adesão Intercelular , Neutrófilos , Neoplasias de Mama Triplo Negativas , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Neutrófilos/metabolismo , Humanos , Animais , Antígeno CD11b/metabolismo , Antígeno CD11b/genética , Feminino , Molécula 1 de Adesão Intercelular/metabolismo , Molécula 1 de Adesão Intercelular/genética , Camundongos , Linhagem Celular Tumoral , Progressão da Doença , Movimento CelularRESUMO
Real-time fMRI (rt-fMRI) neurofeedback (NF) training is a novel non-invasive technique for volitional brain modulation. Given the important role of the anterior insula (AI) in human cognitive and affective processes, it has become one of the most investigated regions in rt-fMRI studies. Most rt-fMRI insula studies employed emotional recall/imagery as the regulation strategy, which may be less effective for psychiatric disorders characterized by altered emotional processing. The present study thus aimed to examine the feasibility of a novel interoceptive strategy based on heartbeat detection in rt-fMRI guided AI regulation and its associated behavioral changes using a randomized double-blind, sham feedback-controlled between-subject design. 66 participants were recruited and randomly assigned to receive either NF from the left AI (LAI) or sham feedback from a control region while using the interoceptive strategy. N = 57 participants were included in the final data analyses. Empathic and interoceptive pre-post training changes were collected as behavioral measures of NF training effects. Results showed that participants in the NF group exhibited stronger LAI activity than the control group with LAI activity being positively correlated with interoceptive accuracy following NF training, although there were no significant increases of LAI activity over training sessions. Importantly, ability of LAI regulation could be maintained in a transfer session without feedback. Successful LAI regulation was associated with strengthened functional connectivity of the LAI with cognitive control, memory and learning, and salience/interoceptive networks. The present study demonstrated for the first time the efficacy of a novel regulation strategy based on interoceptive processing in up-regulating LAI activity. Our findings also provide proof of concept for the translational potential of this strategy in rt-fMRI AI regulation of psychiatric disorders characterized by altered emotional processing.
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Imageamento por Ressonância Magnética , Neurorretroalimentação , Humanos , Imageamento por Ressonância Magnética/métodos , Neurorretroalimentação/métodos , Emoções/fisiologia , Encéfalo/fisiologia , Empatia , Mapeamento Encefálico/métodosRESUMO
Phenylalanine ammonia-lyase is one of the most widely studied enzymes in the plant kingdom. It is a crucial pathway from primary metabolism to significant secondary phenylpropanoid metabolism in plants, and plays an essential role in plant growth, development, and stress defense. Although PAL has been studied in many actual plants, only one report has been reported on potato, one of the five primary staple foods in the world. In this study, 14 StPAL genes were identified in potato for the first time using a genome-wide bioinformatics analysis, and the expression patterns of these genes were further investigated using qRT-PCR. The results showed that the expressions of StPAL1, StPAL6, StPAL8, StPAL12, and StPAL13 were significantly up-regulated under drought and high temperature stress, indicating that they may be involved in the stress defense of potato against high temperature and drought. The expressions of StPAL1, StPAL2, and StPAL6 were significantly up-regulated after MeJa hormone treatment, indicating that these genes are involved in potato chemical defense mechanisms. These three stresses significantly inhibited the expression of StPAL7, StPAL10, and StPAL11, again proving that PAL is a multifunctional gene family, which may give plants resistance to multiple and different stresses. In the future, people may improve critical agronomic traits of crops by introducing other PAL genes. This study aims to deepen the understanding of the versatility of the PAL gene family and provide a valuable reference for further genetic improvement of the potato.
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Fenilalanina Amônia-Liase , Solanum tuberosum , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Humanos , Fenilalanina Amônia-Liase/genética , Fenilalanina Amônia-Liase/metabolismo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas/metabolismo , Solanum tuberosum/metabolismoRESUMO
BACKGROUND: Amyotrophic lateral sclerosis (ALS), one of the motor neuron diseases, appears to be caused by genetic and environmental risk factors. However, the influence of Pro34Ser variant of CHCHD10 gene in increasing risk of ALS remains indeterminate. This study conducted a meta-analysis to establish the association between Pro34Ser variant of CHCHD10 gene and risk of ALS. METHODS: PubMed, Web of Science, and Embase databases were systematically searched for genome-wide association studies or case-control studies published up to March 28, 2020, on the association between Pro34Ser variant and risk of ALS. Data from eligible studies were extracted and analyzed. RESULTS: Twelve case-control studies involving 7442 patients with sporadic ALS and 75,371 controls were analyzed. The Pro34Ser variant was not associated with increased risk of ALS disease based on fixed-effects meta-analysis (Pro34Ser-positive vs Pro34Ser-negative: OR 1.23, 95% CI 0.90 to 1.69, P = 0.201). CONCLUSION: Existing evidence suggests that Pro34Ser variant in CHCHD10 is not associated with risk of ALS, particularly in Caucasian participants. However, our results ought to be validated using large, well-designed studies, especially in Asian and African populations.
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Esclerose Lateral Amiotrófica , Esclerose Lateral Amiotrófica/epidemiologia , Esclerose Lateral Amiotrófica/genética , Povo Asiático , Estudos de Casos e Controles , Estudo de Associação Genômica Ampla , Humanos , Proteínas Mitocondriais/genética , População BrancaRESUMO
AIMS AND OBJECTIVES: To investigate the effect of a short-term Balint group on the improvement in communication ability and self-efficacy of pre-examination and triage nurses during coronavirus disease 2019 (COVID-19). BACKGROUND: Working on the front lines of COVID-19 has brought unprecedented psychological stress on pre-examination and triage nurses. Nurse-patient communication ability and the level of self-efficacy are both significant for nurses' psychosomatic health and work input. However, limited empirical evidence exists regarding nurse-patient communication and self-efficacy and specific psychological intervention effects. DESIGN: Cross-sectional research fulfilling the completed checklist of items that should be included in reports of cross-sectional studies (Appendix S1). METHODS: Nurses (n = 41) in the first layer of pre-examination and triage were engaged in a Balint group activity twice a week for two weeks. They were assessed with the General Self-Efficacy Scale (GSES) pre- and postintervention, and a nurse-patient communication survey form was developed for further postintervention evaluation. The sample was recruited from a class A third-grade hospital in Sichuan, China. RESULTS: Most of the subjects reported improvement in nurse-patient communication, increased cooperation between patients and their families, and a decreased missed examination rate after the intervention. Moreover, the total mean score of the GSES of nurses after the intervention was increased, but the difference was not statistically significant. The scores of all items in the GSES were improved, and the scores increase for item 4 (I am confident that I can effectively deal with any unexpected event) was statistically significant. CONCLUSIONS: During the COVID-19 pandemic, a short-term Balint group activity can improve the communication ability and self-efficacy level of front-line nurses to some extent. RELEVANCE TO CLINICAL PRACTICE: This information may provide some theoretical support for the development of early psychological interventions during major epidemic situations.
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COVID-19/enfermagem , Relações Enfermeiro-Paciente , Autoeficácia , Adulto , COVID-19/epidemiologia , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Melhoria de Qualidade , SARS-CoV-2 , Inquéritos e Questionários , Triagem/organização & administraçãoRESUMO
OBJECTIVE: Macrophages are among the most abundant cells in the colon tumour microenvironment, and there is a close relationship among monocytes, macrophages and the gut microbiota. Alterations in the gut microbiota are involved in tumour development, but the underlying mechanisms remain unclear. We aim to elucidate the temporal changes in macrophage subsets and functions, and how these dynamics are regulated by microbial cues in the initiation of colitis-associated cancer. DESIGN: A mouse model of colitis-associated tumourigenesis was established to determine macrophage dynamics. The role of monocyte-like macrophage (MLM) was confirmed by targeting its chemotaxis. The effects of the gut microbiota were assessed by antibiotic treatment and faecal microbiota transplantation. RESULTS: A selective increase in MLMs was observed in the initial stages of colitis-associated cancer, with an enhanced secretion of inflammatory cytokines. MLM accumulation was regulated by CCL2 expression of colonic epithelial cells, which was influenced by bacteria-derived lipopolysaccharide (LPS). LPS further stimulated interleukin 1ß production from MLMs, inducing interleukin-17-producing T-helper cell activation to promote inflammation. These observations were also supported by altered microbial composition associated with human colitis and colorectal cancer, evolving transcriptional signature and immune response during human colitis-associated tumourigenesis. CONCLUSIONS: The gut microbiota uses LPS as a trigger to regulate MLM accumulation in a chemokine-dependent manner and generate a precancerous inflammatory milieu to facilitate tumourigenesis.
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BACKGROUND AND AIMS: Decreased adiponectin (APN) level has been indicated to be associated with depression. In the present study, we aimed to investigate whether serum APN could predict poststroke depression (PSD) at 3 months in patients with acute ischemic stroke. METHOD: Patients with first-ever ischemic stroke and hospitalized within 24 hours of symptoms onset were enrolled prospectively during March 2017 to September 2017. Serum APN level was measured at admission by enzyme-linked immunosorbent assay. Neuropsychological evaluations were performed at the 3-month follow-up. PSD was diagnosed using the Chinese version of the Structured Clinical Interview for DSM-IV. The association between APN level and predict PSD was analyzed by binary logistic regression analysis. RESULTS: Of the 255 acute ischemic stroke patients included, the median (interquartile range) APN level was 5.4 (3.0-7.5) µg/mL. PSD was observed in 69 patients, which accounted for 27.1% (95% confidence interval, 24.3%-29.9%) of the cohort. Patients with PSD showed lower level of APN (3.5 [2.5-6.3] µg/mL versus 6.2 [3.5-8.0] µg/mL, Pâ¯=â¯.001) at admission. Univariate logistic regression analysis indicated that patients with APN level in the first tertile compared with the third tertile were more likely to have PSD (odds ratio, 3.550; 95% confidence interval, 1.732-7.276; Pâ¯=â¯.008). The association remained significant even after multivariable adjustment for potential confounders. CONCLUSIONS: This study demonstrated that decreased APN level at admission might be associated with PSD in patients after acute ischemic stroke.
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Adiponectina/sangue , Isquemia Encefálica/sangue , Isquemia Encefálica/psicologia , Depressão/sangue , Depressão/psicologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/psicologia , Idoso , Biomarcadores/sangue , Isquemia Encefálica/diagnóstico , Depressão/diagnóstico , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Admissão do Paciente , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Fatores de TempoRESUMO
Plant growth and morphogenesis largely benefit from cell elongation and expansion and are normally regulated by environmental stimuli and endogenous hormones. Auxin, as one of the most significant plant growth regulators, controls various phases of plant growth and development. The PIN-FORMED (PIN) gene family of trans-membrane proteins considered as auxin efflux carriers plays a pivotal role in polar auxin transport and then mediates the growth of different plant tissues. In this study, the phylogenetic relationship and structural compositions of the PIN gene family in 19 plant species covering plant major lineages from algae to angiosperms were identified and analyzed by employing multiple bioinformatics methods. A total of 155 PIN genes were identified in these species and found that representative of the PIN gene family in algae came into existence and rapidly expanded in angiosperms (seed plants). The phylogenetic analysis indicated that the PIN proteins could be divided into 14 distinct clades, and the origin of PIN proteins could be traced back to the common ancestor of green algae. The structural analysis revealed that two putative types (canonical and noncanonical PINs) existed among the PIN proteins according to the length and the composition of the hydrophilic domain of the protein. The expression analysis of the PIN genes exhibited inordinate responsiveness to auxin (IAA) and ABA both in shoots and roots of Solanum tuberosum. While the majority of the StPINs were up-regulated in shoot and down-regulated in root by the two hormones. The majority of PIN genes had one or more putative auxin responses and ABA-inducible response elements in their promoter regions, respectively, implying that these phytohormones regulated the expression of StPIN genes. Our study emphasized the origin and expansion of the PIN gene family and aimed at providing useful insights for further structural and functional exploration of the PIN gene family in the future.
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Evolução Biológica , Regulação da Expressão Gênica de Plantas , Proteínas de Membrana Transportadoras/metabolismo , Solanum tuberosum/metabolismo , Transporte Biológico , Ácidos Indolacéticos/metabolismo , Proteínas de Membrana Transportadoras/química , Proteínas de Membrana Transportadoras/genética , Desenvolvimento Vegetal , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas/metabolismo , Conformação Proteica , Análise de Sequência de Proteína , Solanum tuberosum/fisiologiaRESUMO
Lateral organ boundaries domain (LBD) proteins belong to a particular class of transcription factors of lateral organ boundary (LOB) specific domains that play essential roles in plant growth and development. However, a potato phylogenetic analysis of the LBD family has not been fully studied by scholars and researchers. In this research, bioinformatics methods and the growth of potatoes were used to identify 43 StLBD proteins. We separated them into seven subfamilies: Ia, Ib, Ic, Id, Ie, IIa and IIb. The number of amino acids encoded by the potato LBD family ranged from 94 to 327. The theoretical isoelectric point distribution ranged from 4.16 to 9.12 Kda, and they were distributed among 10 chromosomes. The results of qRT-PCR showed that the expression levels of StLBD2-6 and StLBD3-5 were up-regulated under drought stress in the stem. The expression levels of StLBD1-5 and StLBD2-6 were down-regulated in leaves. We hypothesized that StLBD1-5 was down-regulated under drought stress, and that StLBD2-6 and StLBD3-5 up-regulation might help to maintain the normal metabolism of potato and enhance the potatoes' resistance to drought.
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Família Multigênica/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Solanum tuberosum/genética , Fatores de Transcrição/genética , Proteínas de Arabidopsis/genética , Mapeamento Cromossômico , Análise por Conglomerados , Secas , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Família Multigênica/fisiologia , Filogenia , Folhas de Planta/crescimento & desenvolvimento , Proteínas de Plantas/metabolismo , Domínios Proteicos/genética , RNA-Seq , Solanum tuberosum/crescimento & desenvolvimento , Solanum tuberosum/metabolismo , Estresse Fisiológico , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: Heat shock proteins (Hsps) are essential components in plant tolerance mechanism under various abiotic stresses. Hsp20 is the major family of heat shock proteins, but little of Hsp20 family is known in potato (Solanum tuberosum), which is an important vegetable crop that is thermosensitive. RESULTS: To reveal the mechanisms of potato Hsp20s coping with abiotic stresses, analyses of the potato Hsp20 gene family were conducted using bioinformatics-based methods. In total, 48 putative potato Hsp20 genes (StHsp20s) were identified and named according to their chromosomal locations. A sequence analysis revealed that most StHsp20 genes (89.6%) possessed no, or only one, intron. A phylogenetic analysis indicated that all of the StHsp20 genes, except 10, were grouped into 12 subfamilies. The 48 StHsp20 genes were randomly distributed on 12 chromosomes. Nineteen tandem duplicated StHsp20s and one pair of segmental duplicated genes (StHsp20-15 and StHsp20-48) were identified. A cis-element analysis inferred that StHsp20s, except for StHsp20-41, possessed at least one stress response cis-element. A heatmap of the StHsp20 gene family showed that the genes, except for StHsp20-2 and StHsp20-45, were expressed in various tissues and organs. Real-time quantitative PCR was used to detect the expression level of StHsp20 genes and demonstrated that the genes responded to multiple abiotic stresses, such as heat, salt or drought stress. The relative expression levels of 14 StHsp20 genes (StHsp20-4, 6, 7, 9, 20, 21, 33, 34, 35, 37, 41, 43, 44 and 46) were significantly up-regulated (more than 100-fold) under heat stress. CONCLUSIONS: These results provide valuable information for clarifying the evolutionary relationship of the StHsp20 family and in aiding functional characterization of StHsp20 genes in further research.
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Genoma de Planta , Proteínas de Choque Térmico HSP20/genética , Proteínas de Plantas/genética , Solanum tuberosum/genética , Transcriptoma , Mapeamento Cromossômico , Cromossomos de Plantas , Secas , Duplicação Gênica , Regulação da Expressão Gênica de Plantas , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Família Multigênica , Filogenia , Regiões Promotoras Genéticas , Solanum tuberosum/crescimento & desenvolvimento , Estresse FisiológicoRESUMO
Rewilding abandoned farmlands provides a nature-based climate solution via carbon (C) offsetting; however, the C-cycle-climate feedback in such restored ecosystems is poorly understood. Therefore, we conducted a 2-year field experiment in Loess Plateau, China, to determine the impacts of warming (â¼1.4 °C) and altered precipitation (±25 %, ±50 %, and ambient), alone or in concert on soil C pools and associated C fluxes. Experimental warming significantly enhanced soil respiration without affecting the ecosystem net C uptake and soil C storage; these variables tended to increase along the manipulated precipitation gradient. Their interactions increased ecosystem net C uptake (synergism) but decreased soil respiration and soil C accumulation (antagonism) compared with a single warming or altered precipitation. Additionally, most variables related to the C cycle tended to be more responsive to increased precipitation, but the ecosystem net C uptake responded intensely to warming and decreased precipitation. Overall, ecosystem net C uptake and soil C storage increased by 94.4 % and 8.2 %, respectively, under the warmer-wetter scenario; however, phosphorus deficiency restricted soil C accumulation under these climatic conditions. By contrast, ecosystem net C uptake and soil C storage decreased by 56.6 % and 13.6 %, respectively, when exposed to the warmer-drier climate, intensifying its tendency toward a C source. Therefore, the C sink function of semiarid abandoned farmland was unsustainable. Our findings emphasize the need for management of post-abandonment regeneration to sustain ecosystem C sequestration in the context of climate change, aiding policymakers in the development of C-neutral routes in abandoned regions.
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Ciclo do Carbono , Mudança Climática , Solo , China , Solo/química , Ecossistema , Fazendas , Carbono/análise , Agricultura/métodos , Monitoramento AmbientalRESUMO
Background: SARS-CoV-2, first identified in Wuhan, China, in December 2019, has been gradually spreading worldwide since 2020. The relationship between SARS-CoV-2 infection and psychotic disorders has received much attention, and several studies have described the direct/indirect mechanisms of its effects on the brain, but no mechanism has been found to explain recurrent episodes of COVID-19-related psychotic symptoms. Case: We report the case of an 18-year-old female patient with no family or personal psychotic disorder history with multiple hospital admissions with symptoms such as disorganized speech and behavior, hyperactivity, restlessness, and impulsive aggression during the COVID-19 recovery period. Relevant tests revealed longitudinal changes such as persistent IL-6 and IL-10 elevation, abnormal discharges on EEG, and brain and hippocampal MRI abnormal signals. The patient was treated with antipsychotics, MECT, combination therapy of hormones and antivirals, then discharged after multiple treatment rounds. Conclusion: The case presented here outlines the possibility that the COVID-19 recovery period may be a critical period for acute psychotic episodes and that the patient's recurrent psychotic symptoms may be associated with neuro-immuno-endocrine dysfunction mediated by sustained cytokine synthesis, further causing structural and functional brain damage. Routine psychiatric evaluation and related screening should be performed at all stages of the illness to better identify, prevent, and effectively intervene in psychiatric disorders following COVID-19. Because many outcomes require long-term assessment, a clearer understanding of the impact of the COVID-19 epidemic on mental health is likely to emerge in the future.
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Background: Breast squamous cell carcinoma (SCC) is an uncommon and highly aggressive variant of metaplastic breast cancer. Despite its rarity, there is currently no consensus on treatment guidelines for this specific subtype. Previous studies have demonstrated that chemotherapy alone has limited efficacy in treating breast SCC. However, the potential for targeted therapy in combination with chemotherapy holds promise for future treatment options. Case presentation: In this case report, we present a patient with advanced HER2-positive breast SCC, exhibiting a prominent breast mass, localized ulcers, and metastases in the lungs and brain. Our treatment approach involved the administration of HER2-targeted drugs in conjunction with paclitaxel, resulting in a sustained control of tumor growth. Conclusion: This case represents a rare occurrence of HER2-positive breast SCC, with limited available data on the efficacy of previous HER2-targeted drugs in treating such patients. Our study presents the first application of HER2-targeted drugs in this particular case, offering novel therapeutic insights for future considerations. Additionally, it is imperative to conduct further investigations to assess the feasibility of treatment options in a larger cohort of patients.
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Wang, Luyao, Bo Zhou, Chenghui Yang, Shuya Pan, Yulan Huang, and Jinyu Wang. The effect of ultrahigh altitude on the mental health of civil servants in western China based on propensity score matching. High Alt Med Biol. 24:193-200, 2023. Objective: This study aims to analyze the net effect of ultrahigh altitude on the mental health of civil servants in western China after adjusting for sociodemographic factors. Methods: A cross-sectional study was performed to survey the mental health of 2,939 civil servants working at an altitude of more than 1,500 m in 13 areas of the Tibetan Qiang Autonomous Prefecture of Ngawa using the Insomnia Severity Index Questionnaire, 7-item Generalized Anxiety Disorder Scale, and Patient Health Questionnaire-9. Ultrahigh altitude refers to an area above 3,500 m above sea level, which may have an impact on the sleep and mood of residents. Therefore, our research was divided into two groups based on altitude (ultrahigh altitude >3,500 m; high altitude = 1,500-3,400 m). Propensity score matching (PSM) was used to control for sociodemographic factors and compare the differences in mental health between the two groups. Results: After kernel matching, the mean bias of the covariates was reduced from 21.6 to 1.8. The severity of insomnia, depression, and anxiety in civil servants at ultrahigh altitudes was still significantly greater than that in civil servants at high altitudes after controlling for sociodemographic factors, and the average treatment effects on the treated were 1.39, 1.35, and 0.80, respectively; the results were significant (α < 0.01). PSM regression analysis further showed that for every 100 m increase in altitude, the severity of anxiety, depression, and insomnia increased by 0.042 points (p < 0.001), 0.063 points (p < 0.001), and 0.070 points (p < 0.001), respectively, all of which were higher than those obtained with ordinary least squares regression. Conclusion: Ultrahigh altitude significantly increases the severity of insomnia, depression, and anxiety after adjusting for sociodemographic factors.
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Saúde Mental , Distúrbios do Início e da Manutenção do Sono , Humanos , Altitude , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Estudos Transversais , Pontuação de Propensão , China/epidemiologiaRESUMO
OBJECTIVE: Multiple studies have indicated that electroconvulsive therapy (ECT) could increase brain-derived neurotrophic factor (BDNF) concentrations in patients with different mental disorders. The aim of this synthesis was to evaluate post-ECT BDNF concentrations in patients with various mental disorders. METHODS: The Embase, PubMed and Web of Science databases were systematically searched for studies in English comparing BDNF concentrations before and after ECT through 11/2022. We extracted the pertinent information from the included studies and evaluated their quality. The standardized mean difference (SMD) with a 95% confidence interval (CI) was calculated to quantify BDNF concentration differences. RESULTS: In total, 35 studies assessed BDNF concentrations in 868 and 859 patients pre and post-ECT treatment, respectively. Post-ECT-treatment BDNF concentrations were significantly higher than the pretreatment concentrations (Hedges'g = -0.50, 95% CI (-0.70, -0.30), heterogeneity I2 = 74%, p < 0.001). The analysis that combined both ECT responders and non-responders demonstrated a marked increase in total BDNF levels subsequent to ECT treatment (Hedges'g = -0.27, 95% CI (-0.42, -0.11), heterogeneity I2 = 40%, p = 0.0007). CONCLUSION: Irrespective of the effectiveness of ECT, Our study shows that peripheral BDNF concentrations increase significantly after the entire course of ECT, which may enhance our comprehension of the interplay between ECT treatment and BDNF levels. However, BDNF concentrations were not associated with the effectiveness of ECT, and abnormal concentrations of BDNF may be linked to the pathophysiological process of mental illness, necessitating more future research.
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Eletroconvulsoterapia , Transtornos Mentais , Humanos , Fator Neurotrófico Derivado do Encéfalo , Transtornos Mentais/terapiaRESUMO
BACKGROUND: Chronic stress promotes most hallmarks of cancer through impacting the malignant tissues, their microenvironment, immunity, lymphatic flow, etc. Existing studies mainly focused on the roles of stress-induced activation of systemic sympathetic nervous system and other stress-induced hormones, the organ specificity of chronic stress in shaping the pre-metastatic niche remains largely unknown. This study investigated the role of chronic stress in remodeling lung pre-metastatic niche of breast cancer. METHODS: Breast cancer mouse models with chronic stress were constructed by restraint or unpredictable stress. Expressions of tyrosine hydroxylase, vesicular acetylcholine transporter (VAChT), EpCAM and NETosis were examined by immunofluorescence and confocal microscopy. mRNA and protein levels of choline acetyltransferase (ChAT), VAChT, and peptidylarginine deiminase 4 were detected by qRT-PCR and Western blotting, respectively. Immune cell subsets were analyzed by flow cytometry. Acetylcholine (ACh) and chemokines were detected by ELISA and multi chemokine array, respectively. ChAT in lung tissues from patients was examined by immunohistochemistry. RESULTS: Breast cancer-bearing mice suffered chronic stress metastasized earlier and showed more severe lung metastasis than did mice in control group. VAChT, ChAT and ChAT+ epithelial cells were increased significantly in lung of model mice undergone chronic stress. ACh and chemokines especially CXCL2 in lung culture supernatants from model mice with chronic stress were profoundly increased. Chronic stress remodeled lung immune cell subsets with striking increase of neutrophils, enhanced NETosis in lung and promoted NETotic neutrophils to capture cancer cells. ACh treatment resulted in enhanced NETosis of neutrophils. The expression of ChAT in lung tissues from breast cancer patients with lung metastasis was significantly higher than that in patients with non-tumor pulmonary diseases. CONCLUSIONS: Chronic stress promotes production of CXCL2 that recruits neutrophils into lung, and induces pulmonary epithelial cells to produce ACh that enhances NETosis of neutrophils. Our findings demonstrate for the first time that chronic stress induced epithelial cell derived ACh plays a key role in remodeling lung pre-metastatic niche of breast cancer.
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Neoplasias da Mama , Neoplasias Pulmonares , Humanos , Camundongos , Animais , Feminino , Acetilcolina/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Pulmão , Células Epiteliais/metabolismo , Quimiocinas , Microambiente TumoralRESUMO
Major depressive disorder (MDD) patients demonstrate abnormal neural activation even after complete remission. Many task-related functional magnetic resonance imaging (fMRI) studies have focused on changes in brain function in individuals with remitted MDD (rMDD). We conducted a meta-analysis of these studies to explore differences in brain activation between patients with rMDD and healthy controls (HCs). Our meta-analysis included 13 studies, encompassing 18 experiments, 304 rMDD patients and 321 HCs. Patients with rMDD showed increased neural activation in the left inferior parietal gyrus and right fusiform gyrus and decreased neural activation in the left superior frontal gyrus, right middle temporal gyrus and right Heschl gyrus. Meta-regression analysis revealed that patient age and the number of depressive episodes were negatively associated with brain activity in the left superior frontal gyrus. Our findings suggest abnormal brain function, especially in areas involved in cognitive function, emotion regulation and perception, in rMDD patients; alterations of these regions may be the primary or secondary neurophysiological mechanisms underlying MDD and provide potential neuroimaging targets for early screening.
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Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Mapeamento Encefálico , Encéfalo , Imageamento por Ressonância Magnética/métodos , Cognição/fisiologiaRESUMO
Auxin is the only plant hormone that exhibits transport polarity mediated by three families: auxin resistant (AUX) 1/like AUX1 (LAX) influx carriers, pin-formed (PIN) efflux carriers, and ATP-binding cassette B (ABCB) influx/efflux carriers. Extensive studies about the biological functions of auxin transporter genes have been reported in model plants. Information regarding these genes in potato remains scarce. Here, we conducted a comprehensive analysis of auxin transporter gene families in potato to examine genomic distributions, phylogeny, co-expression analysis, gene structure and subcellular localization, and expression profiling using bioinformatics tools and qRT-PCR analysis. From these analyses, 5 StLAXs, 10 StPINs, and 22 StABCBs were identified in the potato genome and distributed in 10 of 18 gene modules correlating to the development of various tissues. Transient expression experiments indicated that three representative auxin transporters showed plasma membrane localizations. The responsiveness to auxin and auxin transport inhibitors implied their possible roles in mediating intercellular auxin homoeostasis and redistribution. The differential expression under abscisic acid and abiotic stresses indicated their specific adaptive mechanisms regulating tolerance to environmental stimuli. A large number of auxin-responsive and stress-related cis-elements within their promoters could account for their responsiveness to diverse stresses. Our study aimed to understand the biological significance of potato auxin transporters in hormone signaling and tolerance to environmental stresses.
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Phospholipase D (PLD) is the most important phospholipid hydrolase in plants, which can hydrolyze phospholipids into phosphatidic acid (PA) and choline. When plants encounter low temperature, drought and high salt stress, phospholipase D and its products play an important role in regulating plant growth and development and coping with stress. In this study, 16 members of StPLD gene family were identified in potato genome, which were distributed in α, ß, δ, and ζ subfamilies, and their expression patterns under salt, high temperature, drought, and ABA stress were detected by qRT-PCR method. Gene expression analysis showed that the expression of StPLD genes in potato was upregulated and downregulated to varying degrees under the four stresses, indicating that the PLD gene family is involved in the interaction of potato plant hormones and abiotic stress signals. Chromosome distribution showed that StPLD gene was unevenly distributed on 8 chromosomes, and only one pair of tandem repeat genes was found. All StPLD promoters contain hormone and stress-related cis-regulatory elements to respond to different stresses. Structural analysis showed that StPLD genes in the same subgroup had a similar exon-intron structure. Our study provides a valuable reference for further research of the function and structure of PLD gene.
RESUMO
Angiogenesis is an essential physiological process and hallmark of cancer. Currently, antiangiogenic therapy, mostly targeting the vascular endothelial growth factor (VEGF)/VEGFR2 signaling axis, is commonly used in the clinic for solid tumors. However, antiangiogenic therapies for breast cancer patients have produced limited survival benefits since cancer cells rapidly resistant to anti-VEGFR2 therapy. We applied the low-dose and high-dose VEGFR2 mAb or VEGFR2-tyrosine kinase inhibitor (TKI) agents in multiple breast cancer mouse models and found that low-dose VEGFR2 mAb or VEGFR2-TKI achieved good effects in controlling cancer progression, while high-dose treatment was not effective. To further investigate the mechanism involved in regulating the drug resistance, we found that high-dose anti-VEGFR2 treatment elicited IL17A expression in γδ T cells via VEGFR1-PI3K-AKT pathway activation and then promoted N2-like neutrophil polarization, thus inducing CD8+ T cell exhaustion to shape an immunosuppressive microenvironment. Combining anti-VEGFR2 therapy with immunotherapy such as IL17A, PD-1 or Ly-6G mAb therapy, which targeting the immunomodulatory axis of "γδT17 cells-N2 neutrophils" in vivo, showed promising therapeutic effects in breast cancer treatment. This study illustrates the potential mechanism of antiangiogenic therapy resistance in breast cancer and provides synergy treatment for cancer.