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Recently, anticancer peptides (ACPs) have emerged as unique and promising therapeutic agents for cancer treatment compared with antibody and small molecule drugs. In addition to experimental methods of ACPs discovery, it is also necessary to develop accurate machine learning models for ACP prediction. In this study, features were extracted from the three-dimensional (3D) structure of peptides to develop the model, compared to most of the previous computational models, which are based on sequence information. In order to develop ACPs with more potency, more selectivity and less toxicity, the model for predicting ACPs, hemolytic peptides and toxic peptides were established by peptides 3D structure separately. Multiple datasets were collected according to whether the peptide sequence was chemically modified. After feature extraction and screening, diverse algorithms were used to build the model. Twelve models with excellent performance (Acc > 90%) in the ACPs mixed datasets were used to form a hybrid model to predict the candidate ACPs, and then the optimal model of hemolytic peptides (Acc = 73.68%) and toxic peptides (Acc = 85.5%) was used for safety prediction. Novel ACPs were found by using those models, and five peptides were randomly selected to determine their anticancer activity and toxic side effects in vitro experiments.
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Antineoplásicos , Bases de Dados de Proteínas , Aprendizado de Máquina , Neoplasias/tratamento farmacológico , Peptídeos , Células A549 , Sequência de Aminoácidos , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Células HeLa , Hemólise/efeitos dos fármacos , Humanos , Células MCF-7 , Neoplasias/metabolismo , Neoplasias/patologia , Peptídeos/química , Peptídeos/genética , Peptídeos/farmacologia , OvinosRESUMO
AIMS: Gatekeeper training (GKT) is an important suicide prevention strategy. Studies have evaluated the effectiveness of GKT in different populations, often neglecting family and friends who play a vital role in caring for people with suicide risk. This review evaluated GKT programs targeting family and friends to determine their effectiveness in this specific population. METHODS: Academic databases were searched for studies on GKT programs. Programs involving family and friends caring for people with suicide risk were assessed for any impact on knowledge, self-efficacy, attitudes, and suicide prevention skills. RESULTS: Seventeen studies were reviewed. GKT showed significant gains on outcomes of interest. Three studies targeted family and friends, with one involving them in program creation and conduction and another adjusting the program after their input. CONCLUSIONS: GKT programs have potentially positive effects on family and friends caring for people with suicide risk. Few programs address the specific needs of this group, and programs adapted specifically for them are scarce. Future program development recommendations are discussed.
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Amigos , Prevenção do Suicídio , Humanos , Desenvolvimento de Programas , AutoeficáciaRESUMO
Increasing preclinical and clinical studies revealed that many tumor models had resistance to anti-VEGF-A and anti-VEGF-R2 therapies. Studies have shown that simultaneously blocked DLL4-Notch and VEGF signaling pathways can synergistically inhibit density and function of tumor blood vessels and reduce tumor growth rate. We successfully developed a bispecific monoclonal antibody (named HB-32) that targeting both human DLL4 and human VEGF. HB-32 showed high binding affinity to VEGF and DLL4. Furthermore, HB-32 inhibited proliferation, migration and tube formation of HUVEC. Finally, in vivo xenograft studies demonstrated that HB-32 inhibited proliferation of breast cancer cells (MDA-MB-231) and induced tumor cell apoptosis more efficiently than an anti-VEGF antibody or anti-DLL4 antibody alone. These findings indicate that our bispecific antibody provide a potential treatment for breast cancer.
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Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Anticorpos Monoclonais/farmacologia , Antineoplásicos/farmacologia , Proteínas de Ligação ao Cálcio/antagonistas & inibidores , Neoplasias Mamárias Experimentais/irrigação sanguínea , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/isolamento & purificação , Antineoplásicos/administração & dosagem , Antineoplásicos/isolamento & purificação , Proteínas de Ligação ao Cálcio/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Feminino , Células HEK293 , Humanos , Injeções Subcutâneas , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Nus , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Mitochondrial dysfunctions are responsible for myocardial injury upon ischemia/reperfusion (I/R), and mitochondrial E3 ubiquitin ligase 1 (Mul1) plays an important role in maintaining mitochondrial functions. This study aims to explore the function of Mul1 in myocardial I/R injury and the underlying mechanisms. The Sprague-Dawley rat hearts were subjected to 1 h of ischemia plus 3 h of reperfusion, which showed the I/R injury (increase in infarct size and creatine kinase release) and the elevated total and mitochondrial protein levels of Mul1 and p53 accompanied by the enhanced interactions between Mul1 and p53 as well as p53 and small a ubiquitin-like modifier (SUMO1). Consistently, hypoxia/reoxygenation (H/R) treated cardiac (H9c2) cells displayed cellular injury (apoptosis and necrosis), upregulation of total and mitochondrial protein levels of Mul1 and p53, and enhanced interactions between p53 and SUMO1 concomitant with mitochondrial dysfunctions (an increase in mitochondrial membrane potential and reactive oxygen species production with a decrease in ATP production); these phenomena were attenuated by knockdown of Mul1 expression. Based on these observations, we conclude that a novel role of Mul1 has been identified in the myocardial mitochondria, where Mul1 stabilizes and activates p53 through its function of SUMOylation following I/R, leading to p53-mediated mitochondrial dysfunction and cell death.
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Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Regulação para Cima , Trifosfato de Adenosina/metabolismo , Animais , Linhagem Celular , Técnicas de Silenciamento de Genes , Masculino , Potencial da Membrana Mitocondrial , Proteínas Mitocondriais/deficiência , Proteínas Mitocondriais/genética , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/patologia , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina-Proteína Ligases/deficiência , Ubiquitina-Proteína Ligases/genéticaRESUMO
In order to investigate the compositions and wet deposition fluxes of trace elements and rare earth elements (REEs) in the precipitation of the southeastern edge of the Tibetan Plateau, 38 precipitation samples were collected from March to August in 2012 in an urban site of Lijiang city in the Mt. Yulong region. The concentrations of most trace elements and REEs were higher during the non-monsoon season than during the monsoon season, indicating that the lower concentrations of trace elements and REEs observed during monsoon had been influenced by the dilution effect of increased precipitation. The concentrations of trace elements in the precipitation of Lijiang city were slightly higher than those observed in remote sites of the Tibetan Plateau but much lower than those observed in the metropolises of China, indicating that the atmospheric environment of Lijiang city was less influenced by anthropogenic emissions, and, as a consequence, the air quality was still relatively good. However, the results of enrichment factor and principal component analysis revealed that some anthropogenic activities (e.g., the increasing traffic emissions from the rapid development of tourism) were most likely important contributors to trace elements, while the regional/local crustal sources rather than anthropogenic activities were the predominant contributors to the REEs in the wet deposition of Lijiang city. Our study was relevant not only for assessing the current status of the atmospheric environment in the Mt. Yulong region, but also for specific management actions to be implemented for the control of atmospheric inputs and the health of the environment for the future.
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Poluentes Atmosféricos/análise , Monitoramento Ambiental , Metais Terras Raras/análise , Neve/química , Oligoelementos/análise , China , Cidades , TibetRESUMO
Invasive papillary carcinoma is a rare form of breast cancer that is more likely to occur in postmenopausal women. Previous studies have been limited to case reports and small retrospective studies, leading to low awareness of this type of tumor and difficult clinical management. According to the available literature, invasive papillary carcinoma exhibits unique pathological features and biological behaviors. Invasive papillary carcinoma is mostly luminal type, with a low rate of lymph node metastasis, which underlies its favorable prognosis. The effectiveness of adjuvant therapy in reducing tumor burden and improving prognosis in patients with invasive papillary carcinoma remains uncertain. Due to the rarity of the lesion, conducting prospective clinical trials is impractical. The use of biological models, such as organoids, can help alleviate the impact of the scarcity of this condition on research. In addition, invasive papillary carcinoma is affected by specific genomic events, and more extensive studies of gene expression profiling may provide molecular-level insights to make optimal therapeutic decisions.
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Invasive papillary carcinoma (IPC) of the breast is a rare form of cancer. The current report documents a case of IPC characterized by a large tumor size and skin involvement. Surgical exploration revealed no evidence of axillary lymph node metastasis in breast cancer. Due to financial constraints, the patient opted solely for anastrozole endocrine therapy at a dosage of 1 mg/day for a period of 5 years post-surgery, foregoing other treatments such as radiotherapy and chemotherapy. Since discharge, 2.5 years have passed, during which the patient has been followed up via phone every 3 months, showing a good prognosis. A literature review indicated that IPC is prevalent amongst the elderly population and can be misdiagnosed due to its morphological, cytomorphological and immunophenotypic overlap with other types of papillary neoplasms. This tumor exhibits a more favorable prognosis compared with IDC, primarily attributed to its advantageous gene and molecular expression patterns, coupled with its decreased invasiveness. Despite limited evidence-based research on the treatment of IPC, the present case report, albeit with limitations, underscores the importance of avoiding over-treatment and suggests the feasibility of combining surgery with endocrine therapy for IPC.
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Retinoblastoma (RB) is a type of pediatric solid tumor in the fundus. The lack of precision therapies combined with the difficulty of delivering small interfering RNA (siRNA) into the eyes means that there is currently no nucleic acid-based therapy for RB in clinical practice. Here, we reported on anti-GD2 and glutathione-responsive spherical nucleic acids (SNAs), loaded with siRNA and the inhibitor NVP-CGM097, which jointly blocked the oncogenic factor n in RB cells (Y79 and WERI-RB-1). The SNAs were formed through the self-assembly of bifunctional cholesterol amphiphiles containing aptamers that specifically targeted GD2-positive RB cells, allowing for the formation of an SNA with a dense DNA shell. The aptamer/siRNA component functioned both as a carrier and a payload, enhancing the specific recognition and delivery of both components and constituting an active agent for MDM2 regulation. Following SNA endocytosis by RB cells, siRNA and NVP-CGM097 were released from the SNA particles by glutathione, which synergistically blocked the MDM2-p53 pathway, increasing p53 protein content and inducing cell apoptosis. This study showed a potent antitumor effect following intravitreal injection of SNAs in Y79 tumor-bearing mice through clinical manifestation and tumor pathological analysis. In hematological analysis and hepatotoxicity assays, SNAs were safer for mice than melphalan, the favored drug for treating RB in clinical practice. Our results illustrated the potential of intravitreally injected SNAs as a precision medicine for treating RB.
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Aptâmeros de Nucleotídeos , Proteínas Proto-Oncogênicas c-mdm2 , RNA Interferente Pequeno , Retinoblastoma , Animais , Humanos , Camundongos , Apoptose/efeitos dos fármacos , Aptâmeros de Nucleotídeos/farmacologia , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/antagonistas & inibidores , Neoplasias da Retina/tratamento farmacológico , Neoplasias da Retina/patologia , Neoplasias da Retina/metabolismo , Neoplasias da Retina/genética , Retinoblastoma/tratamento farmacológico , Retinoblastoma/patologia , Retinoblastoma/metabolismo , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Endogâmicos ICR , FemininoRESUMO
Primary familial brain calcification (PFBC), also known as Fahr's disease, is a central nervous system calcium deposition disorder with symmetrical basal ganglia calcification. Most PFBC cases are caused by SLC20A2 gene variant. We report a Chinese female patient with PFBC and dopamine-responsive parkinsonism who had motor fluctuations and dyskinesia and recovered effectively after symptomatic medication adjustment. A novel heterozygous missense variant was found by whole-exome sequencing and proven harmful by family validation and genetic analysis. This example expands the phenotype of SLC20A2-associated PFBC patients and shows the clinical efficacy of dopaminergic replacement treatment.
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In recent years, studies have shown that low-dose supplemental infrared (IR) irradiation exhibits systemic anti-inflammatory effects. The gut microbiota is increasingly recognized as a potential mediator of these effects due to its role in regulating host metabolism and inflammatory responses. To investigate the role of gut microbiota diversity and metabolite changes in the mechanism of light-emitting diodes (LED) infrared's anti-inflammatory action, we conducted IR irradiation on mice. Serum inflammatory cytokines were measured using ELISA, and fecal samples were subjected to metagenomic, untargeted, and targeted metabolomic analyses. Our results demonstrated a significant increase in the anti-inflammatory cytokine IL-10 in the IR group, accompanied by a declining trend in pro-inflammatory cytokines. Gut microbiome analysis revealed distinct alterations in composition and functional genes between the groups, including the enrichment of beneficial bacteria like various species of Parabacteroides and Akkermansia muciniphila in the IR group. Notably, the IR group exhibited enrichment in carbohydrate metabolism pathways and a reduction in DNA damage and repair pathways. Furthermore, targeted metabolomic analysis highlighted a notable increase in short-chain fatty acids (SCFAs), including butyric acid and isobutyric acid, which positively correlated with the abundance of several beneficial bacteria. These findings suggest a potential interplay between gut microbiota-derived SCFAs and the anti-inflammatory response. In conclusion, our study provides comprehensive insights into the changes in gut microbiota species and functions associated with IR irradiation. Moreover, we emphasize the significance of altered SCFAs levels in the IR group, which may contribute to the observed anti-inflammatory effects. Our findings contribute valuable evidence supporting the role of low-dose infrared light irradiation as an anti-inflammatory therapy.
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Cancer immunotherapy has been developed to improve therapeutic effects for patients by activating the innate immune stimulator of interferon gene (STING) pathway. However, most patients cannot benefit from this therapy, mainly due to the problems of excessively low immune responses and lack of tumor specificity. Herein, we report a solution to these two problems by developing a bifunctional platform of black phosphorus quantum dots (BPQDs) for STING agonists. Specifically, BPQDs could connect targeted functional groups and regulate surface zeta potential by coordinating metal ions to increase loading (over 5 times) while maintaining high universality (7 STING agonists). The controlled release of STING agonists enabled specific interactions with their proteins, activating the STING pathway and stimulating the secretion release of immunosuppressive factors by phosphorylating TBK1 and IFN-IRF3 and secreting high levels of immunostimulatory cytokines, including IL-6, IFN-α, and IFN-ß. Moreover, the immunotherapy was enhanced was enhanced mild photothermal therapy (PTT) of BPQDs platform, producing enough T cells to eliminate tumors and prevent tumor recurrence. This work facilitates further research on targeted delivery of small-molecule immune drugs to enhance the development of clinical immunotherapy.
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Imunoterapia , Proteínas de Membrana , Fósforo , Pontos Quânticos , Pontos Quânticos/química , Fósforo/química , Imunoterapia/métodos , Animais , Proteínas de Membrana/agonistas , Humanos , Camundongos , Linhagem Celular Tumoral , Citocinas/metabolismo , Terapia Fototérmica/métodos , Camundongos Endogâmicos C57BL , Sistemas de Liberação de Medicamentos , FemininoRESUMO
BACKGROUND: Identifying neuroimaging biomarkers of antidepressant response may help guide treatment decisions and advance precision medicine. AIMS: To examine the relationship between anhedonia and functional neurocircuitry in key reward processing brain regions in people with major depressive disorder receiving aripiprazole adjunct therapy with escitalopram. METHOD: Data were collected as part of the CAN-BIND-1 study. Participants experiencing a current major depressive episode received escitalopram for 8 weeks; escitalopram non-responders received adjunct aripiprazole for an additional 8 weeks. Functional magnetic resonance imaging (on weeks 0 and 8) and clinical assessment of anhedonia (on weeks 0, 8 and 16) were completed. Seed-based correlational analysis was employed to examine the relationship between baseline resting-state functional connectivity (rsFC), using the nucleus accumbens (NAc) and anterior cingulate cortex (ACC) as key regions of interest, and change in anhedonia severity after adjunct aripiprazole. RESULTS: Anhedonia severity significantly improved after treatment with adjunct aripiprazole.There was a positive correlation between anhedonia improvement and rsFC between the ACC and posterior cingulate cortex, ACC and posterior praecuneus, and NAc and posterior praecuneus. There was a negative correlation between anhedonia improvement and rsFC between the ACC and anterior praecuneus and NAc and anterior praecuneus. CONCLUSIONS: Eight weeks of aripiprazole, adjunct to escitalopram, was associated with improved anhedonia symptoms. Changes in functional connectivity between key reward regions were associated with anhedonia improvement, suggesting aripiprazole may be an effective treatment for individuals experiencing reward-related deficits. Future studies are required to replicate our findings and explore their generalisability, using other agents with partial dopamine (D2) agonism and/or serotonin (5-HT2A) antagonism.
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Lithium-ion capacitors (LICs) are emerging as one of the most advanced hybrid energy storage devices, however, their development is limited by the imbalance of the dynamics and capacity between the anode and cathode electrodes. Herein, anthracite was proposed as the raw material to prepare coal-based, nitrogen-doped porous carbon materials (CNPCs), together with being employed as a cathode and anode used for dual-carbon lithium-ion capacitors (DC-LICs). The prepared CNPCs exhibited a folded carbon nanosheet structure and the pores could be well regulated by changing the additional amount of g-C3N4, showing a high conductivity, abundant heteroatoms, and a large specific surface area. As expected, the optimized CNPCs (CTK-1.0) delivered a superior lithium storage capacity, which exhibited a high specific capacity of 750 mAh g-1 and maintained an excellent capacity retention rate of 97% after 800 cycles. Furthermore, DC-LICs (CTK-1.0//CTK-1.0) were assembled using the CTK-1.0 as both cathode and anode electrodes to match well in terms of internal kinetics and capacity simultaneously, which displayed a maximum energy density of 137.6 Wh kg-1 and a protracted lifetime of 3000 cycles. This work demonstrates the great potential of coal-based carbon materials for electrochemical energy storage devices and also provides a new way for the high value-added utilization of coal materials.
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In order to extend the shelf life of refrigerating raw lamb by inhibiting the growth of microorganisms, preventing the oxidation of fat and protein, and absorbing the juice outflow of lamb during storage, an active packaging system based on plastic/gelatin bilayer film with essential oil was developed in this study. Three kinds of petroleum-derived plastic films, oriented polypropylene (OPP), polyethylene terephthalate, and polyethylene, were coated with gelatin to make bilayer films for lamb preservation. The results showed significant improvement in the mechanical properties, oxygen, moisture, and light barriers of the bilayer films compared to the gelatin film. The OPP/gelatin bilayer film was selected for further experiments because of its highest acceptance by panelists. If the amount of juice outflow was less than 350% of the mass of the gelatin layer, it was difficult for the gelatin film to separate from lamb. With the increase in essential oil concentration, the water absorption capacity decreased. The OPP/gelatin bilayer films with 20% mustard or 10% oregano essential oils inhibited the growth of bacteria in lamb and displayed better mechanical properties. Essential oil decreased the brightness and light transmittance of the bilayer films and made the film yellow. In conclusion, our results suggested that the active packaging system based on OPP/gelatin bilayer film was more suitable for raw lamb preservation than single-layer gelatin film or petroleum-derived plastic film, but need further study, including minimizing the amount of essential oil, enhancing the mechanical strength of the gelatin film after water absorption.
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BACKGROUND: Suicidal ideation is highly prevalent in Major Depressive Disorder (MDD). However, the factors determining who will transition from ideation to attempt are not established. Emerging research points to suicide capability (SC), which reflects fearlessness of death and increased pain tolerance, as a construct mediating this transition. This Canadian Biomarker Integration Network in Depression study (CANBIND-5) aimed to identify the neural basis of SC and its interaction with pain as a marker of suicide attempt. METHODS: MDD patients (n = 20) with suicide risk and healthy controls (n = 21) completed a self-report SC scale and a cold pressor task measuring pain threshold, tolerance, endurance, and intensity at threshold and tolerance. All participants underwent a resting-state brain scan and functional connectivity was examined for 4 regions: anterior insula (aIC), posterior insula (pIC), anterior mid-cingulate cortex (aMCC) and subgenual anterior cingulate cortex (sgACC). RESULTS: In MDD, SC correlated positively with pain endurance and negatively with threshold intensity. Furthermore, SC correlated with the connectivity of aIC to the supramarginal gyrus, pIC to the paracingulate gyrus, aMCC to the paracingulate gyrus, and sgACC to the dorsolateral prefrontal cortex. These correlations were stronger in MDD compared to controls. Only threshold intensity mediated the correlation between SC and connectivity strength. LIMITATIONS: Resting-state scans provided an indirect assessment of SC and the pain network. CONCLUSIONS: These findings highlight point to a neural network underlying SC that is associated with pain processing. This supports the potential clinical utility of pain response measurement as a method to investigate markers of suicide risk.
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Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Imageamento por Ressonância Magnética , Canadá , Giro do Cíngulo/diagnóstico por imagem , Dor/diagnóstico por imagemRESUMO
Objectives: Cranial magnetic resonance imaging (MRI) could be a crucial tool for the assessment for neurological symptoms in patients with Wilson's disease (WD). Diffusion-weighted imaging (DWI) hyperintensity reflects the acute brain injuries, which mainly occur in specific brain regions. Therefore, this study aimed to develop a weighted cranial DWI scale for patients with WD, with special focus on specific brain regions. Materials and methods: In total, 123 patients with WD were enrolled, 118 of whom underwent 1.5 T-MRI on admission. The imaging score was calculated as described previously and depended on the following sequences: one point was acquired when abnormal intensity occurred in the T1, T2, and fluid-attenuation inversion recovery sequences, and two points were acquired when DWI hyperintensity were found. Consensus weighting was conducted based on the symptoms and response to treatment. Results: Intra-rater agreement were good (r = 0.855 [0.798-0.897], p < 0.0001). DWI hyperintensity in the putamen was a high-risk factor for deterioration during de-copper therapy (OR = 8.656, p < 0.05). The high-risk factors for readmission for intravenous de-copper therapies were DWI hyperintensity in the midbrain (OR = 3.818, p < 0.05) and the corpus callosum (OR = 2.654, p < 0.05). Both scoring systems had positive correlation with UWDRS scale (original semi-quantitative scoring system, r = 0.35, p < 0.001; consensus semi-quantitative scoring system, r = 0.351, p < 0.001.). Compared to the original scoring system, the consensus scoring system had higher correlations with the occurrence of deterioration (OR = 1.052, 95%CI [1.003, 1.0103], p < 0.05) and readmission for intravenous de-copper therapy (OR = 1.043, 95%CI [1.001, 1.086], p < 0.05). Conclusion: The predictive performance of the consensus semi-quantitative scoring system for cranial MRI was improved to guide medication, healthcare management, and prognosis prediction in patients with WD. For every point increase in the neuroimaging score, the risk of exacerbations during treatment increased by 5.2%, and the risk of readmission to the hospital within 6 months increased by 4.3%.
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Anhedonia is a prevalent symptom across many psychiatric disorders. The contemporary scope of anhedonia across various models includes interest, reward anticipation, motivation, effort expenditure, reward valuation, expectation, pleasure, satiation, and learning. In order to further elucidate the impact of anhedonia on treatment outcomes, quality of life, as well as brain function, validated tools to probe the various facets of anhedonia are necessary. This chapter evaluates assessment tools for anhedonia in clinical populations and in animals. Subjective clinical scales have been in use for decades, and as the construct of anhedonia evolved, contemporary scales were developed to integrate these new concepts. Clinical scales are useful for understanding the subjective experience of anhedonia but do not account for objective aspects of anhedonia, including implicit learning. Behavioral tasks that probe responses to rewarding stimuli have been useful to fill this gap and to delineate the specific brain processes underlying facets of anhedonia. Although there have been translational challenges in the assessments of anhedonia and reward deficits from preclinical to clinical (and vice versa), the multifaceted clinical scales and reward tasks provide valuable insights into the conceptualization of anhedonia and its neural basis across psychiatric disorders.
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Anedonia , Transtornos Mentais , Anedonia/fisiologia , Animais , Humanos , Motivação , Qualidade de Vida , RecompensaRESUMO
BACKGROUND: Growing evidence suggests cognitive deficits may represent neurocognitive markers with predictive utility in identifying those at risk for suicide. Characterizing these deficits may offer the opportunity to develop targeted interventions. AIM: The aim of this systematic qualitative review is to provide a synthesis of the published data on neurocognition in suicide ideators and attempters in order to clarify which neurocognitive targets may be most relevant to address using cognitive-based psychotherapeutic strategies in patients at risk for suicide. RESULTS: A total of 63 studies met criteria for inclusion. The most consistent findings were in depressed suicide attempters, where deficits in executive subdomains of inhibition, selective attention and decision-making, as well as in working memory, were identified. In contrast, no clear pattern of neurocognitive deficits emerged from studies in suicide ideators across diagnoses. CONCLUSIONS: More studies are needed to clarify the role of cognitive deficits in specific subtypes of individuals at risk for suicide. The findings are discussed in the context of promising research on cognitive remediation and other psychological interventions.
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Transtornos Cognitivos , Suicídio , Cognição , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/psicologia , Humanos , Ideação Suicida , Tentativa de Suicídio/psicologiaRESUMO
[This corrects the article on p. 2387 in vol. 10, PMID: 32905508.].
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Mountainous alpine ecosystems are sensitive to global change, where soil nutrient content would potentially vary under current climate change background, and thus possibly influence the activity of nitrifiers and denitrifiers, as well as N2O emissions. However, within mountainous alpine ecosystems, the potential variation of soil nutrients under current global change and the consequence to N2O emission from nitrification and denitrification are still unclarified, hampering a comprehensive understanding of the feedback mechanisms between the nitrogen cycle and climate change. In order to fill this knowledge gap, we selected alpine grasslands at three different elevations and investigated the distribution and environmental drivers of nitrifiers and denitrifiers. The results showed that the lowest elevation site tended to have higher total phosphorus (TP) accumulation within the topsoil. The abundance of functional groups, emission of CO2 and N2O, and the N2O/CO2 ratio showed a decreasing trend along elevation. TP was the greatest influence on denitrifier composition (nosZ/narG and nirS/nirK ratios) and considerably influenced nitrifier composition (AOA/AOB ratio), and was significantly correlated to the N2O/CO2 ratio. In microcosms of soils from the highest elevation site, TP addition decreased the ratios of nosZ/narG, nirS/nirK, and AOA/AOB, and increased N2O/CO2 ratio and N2O emission, thus contributing to positive climate change feedback. This study indicates the potential for change within the nitrifier and denitrifier communities under current climate change, and highlights the role TP plays in governing nitrification and denitrification in mountainous alpine ecosystems.