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Studies have demonstrated that bullying victimization is a risk factor for depressive symptoms; however, little is known about the underlying processes that may mediate or moderate this relationship. To address this research gap, this study examined the mediating effects of personal and general belief in a just world (BJW) and the moderating effect of classroom-level victimization on the relationship between bullying victimization and depressive symptoms. Using a short-term longitudinal design, two-wave data were obtained from 2,551 Chinese adolescents (initial age = 12.99 ± 0.61, 52.2% boys) from 47 classes over 6 months. The results indicated that Time 1 personal BJW mediated the relationship between Time 1 bullying victimization and Time 2 depressive symptoms. Furthermore, the mediating effect of Time 1 personal BJW was moderated by Time 1 classroom-level victimization; this effect was stronger for adolescents in classrooms with low levels of victimization. These findings contribute to our understanding of how and when bullying victimization impacts youth depressive symptoms. Education practitioners should pay special attention to personal BJW in victimized adolescents, especially when classroom-level victimization is low.
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INTRODUCTION: Bullying victimization and aggression are frequent phenomena among adolescents and have been linked to various mental health problems. Although the correlation between bullying victimization and aggression is well-documented, the direction between the two has been debated. Moreover, the underlying mechanism through which victimization influences aggression or vice versa has gained little attention. The current study used data across two-time points to address this gap and explore the reciprocal relationships between victimization and aggression. The mediating role of teacher justice and related gender differences were also examined. METHODS: A total of 2462 Chinese adolescents (50.9% boys; Mage = 13.95 years, SD = 0.60) completed measures on two occasions in 1 year with 6-month assessment intervals. Structural equation modeling was used to examine the longitudinal relations among the variables. RESULTS: Results found that bullying victimization significantly and positively predicted both reactive and proactive aggression over time among the total sample. Reactive aggression significantly positively predicted victimization, while proactive aggression negatively predicted victimization in boys. Furthermore, teacher justice mediated the relationships between victimization and both functions of aggression. Mediation was gender-specific, with a significant mediating effect on girls. CONCLUSIONS: The results reveal the violent cycle of bullying victimization and aggression and underscore the role of teacher justice in this process. These findings have important implications for targeted interventions.
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Bullying , Vítimas de Crime , Masculino , Feminino , Humanos , Adolescente , Grupo Associado , Agressão/psicologia , Bullying/psicologia , Vítimas de Crime/psicologia , Fatores SexuaisRESUMO
INTRODUCTION: Internet addiction has garnered growing attention in recent years, and peer victimization plays a major contributor to adolescents' Internet addiction. However, little is known about the mediating and moderating mechanisms in the association between peer victimization and Internet addiction. Guided by cognitive behavioral model and worldview verification model, this study examined a moderated mediation model in which anger rumination at Time 1 (T1) mediated the association between peer victimization at T1 and Internet addiction at Time 2 (T2), and this mediation effect was moderated by T1 social dominance orientation (SDO). METHODS: A short-term longitudinal design was adopted, incorporating two measurement occasions (with approximately 6-month intervals). Participants were 2597 adolescents (51.5% male, Mage = 13.9, SD = 0.60) from seven secondary schools in Zhengzhou City, China. All participants were invited to complete the self-reported questionnaires assessing peer victimization, anger rumination, SDO at T1 (December 2015) and Internet addiction at T2 (June 2016), respectively. A short-term longitudinal moderated mediation model was conducted to analyze the association between variables. RESULTS: The results showed that T1 peer victimization was positively associated with T2 Internet addiction in which association was mediated by T1 anger rumination. T1 SDO moderated the associations between T1 peer victimization and T1 anger rumination and this effect was stronger with lower levels of SDO. In terms of gender differences, SDO moderated the associations between peer victimization and anger rumination only for boys. CONCLUSIONS: Results highlight that anger rumination is a potential mechanism explaining how peer victimization is related to Internet addiction and that this relation may be moderated by SDO.
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Bullying , Vítimas de Crime , Humanos , Masculino , Adolescente , Feminino , Transtorno de Adição à Internet , Bullying/psicologia , Grupo Associado , Ira , Vítimas de Crime/psicologia , InternetRESUMO
Although non-suicidal self-injury (NSSI) and depressive symptoms often co-occur, as well as display distinct profiles in different genders, few studies examined the gender-specific profiles and transitions of NSSI and depressive symptoms among adolescents and the role of bullying victimization on their profiles and transitions. This study examined the profiles and transitions of NSSI and depressive symptoms for Chinese adolescent boys and girls separately, along with the predictive role of bullying victimization in subgroup memberships and transitions. A total of 3510 adolescents (52.9% boy, M age = 13.36, SD = 0.50) participated in two waves of the study over six months. The results indicated that four and three profiles identified for girls and boys separately. Adolescents in at-risk profiles showed varying degrees of transition. Adolescents with more bullying victimization were more likely to belong or transition to at-risk profiles for both genders, and bullying victimization exacerbated girls transitioning into co-occurring high profile but not in boys. The findings indicate distinct profile and transition patterns of NSSI and depressive symptoms, as well as different risk role of bullying victimization on their profiles and transitions in boys and girls, highlighting the importance of gender differences in understanding co-occurring and transitional nature of NSSI and depressive symptoms and the risk role of bullying victimization, informing effective strategies for prevention and intervention.
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Bullying , Vítimas de Crime , Comportamento Autodestrutivo , Humanos , Masculino , Adolescente , Feminino , Depressão/epidemiologia , Comportamento Autodestrutivo/epidemiologia , Fatores SexuaisRESUMO
Although loneliness and depressive symptoms are particularly prominent among migrant children and often occur simultaneously, little is known about the co-occurring and transitional nature of loneliness and depressive symptoms among migrant children, and the role of bullying victimization on their profiles and transitions. This study examined the profiles and transitions of loneliness and depressive symptoms among migrant children using latent profile analysis and latent transition analysis, as well as how bullying victimization predicted their profile memberships and transitions. A total of 692 migrant children (55.3% males, Mage = 9.41, SD = 0.55, range = 8 to 12 years old at T1) participated in both two waves of the study over six months. The results indicated that low profile (59.2%), moderate profile (22.0%), moderately high profile (14.3%), and high profile (4.5%) were identified at Time 1; low profile (69.4%), predominantly loneliness profile (16.8%), predominantly depressive symptoms profile (6.5%), and high profile (7.3%) were identified at Time 2. Migrant children in at-risk profiles displayed varying degrees of transition. Migrant children experiencing more bullying victimization were more likely to belong or transition to at-risk profiles. The findings highlight the importance of subgroup differences considerations in understanding the co-occurring and transitional nature of loneliness and depressive symptoms, as well as the predictive role of bullying victimization, informing effective strategies for prevention and intervention.
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Bullying , Vítimas de Crime , Migrantes , Masculino , Humanos , Criança , Feminino , Solidão , DepressãoRESUMO
C-Alkyl glycosides and glycoproteins exist in natural products and are prized for their role as carbohydrate mimics in drug design. However, a practical strategy that merges glycosyl donors with readily accessible reagents, derived from abundant carboxylic acid and amine feedstocks, is yet to be conceived. Herein, we show that a nickel catalyst promotes C-C coupling between glycosyl halides and aliphatic acids or primary amines (converted into redox-active electrophiles in one step), in the presence of Hantzsch ester and LiI (or Et3 N) under blue LED illumination to deliver C-alkyl glycosides with high diastereoselectivity. Mechanistic studies support the photoinduced formation of alkyl radicals that react with a glycosyl nickel species generated in situ to facilitate cross-coupling. Through this manifold, innate CO2 H and NH2 motifs embedded within amino acids and oligopeptides are selectively capped and functionalized to afford glycopeptide conjugates through late-stage glycosylation.
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Glicopeptídeos , Níquel , Níquel/química , Glicosídeos/química , Carboidratos , Aminas , CatáliseRESUMO
Stereoselective C-glycosylation reactions are increasingly gaining attention in carbohydrate chemistry because they enable glycosyl precursors, readily accessible as anomeric mixtures, to converge to a single diastereomeric product. However, controlling the stereochemical outcome through transition-metal catalysis remains challenging, and methods that leverage bench-stable heteroaryl glycosyl sulfone donors to facilitate glycosylation are rare. Herein, we show two complementary nonprecious metal catalytic systems, based on iron or nickel, which are capable of promoting efficient C-C coupling between heteroaryl glycosyl sulfones and aromatic nucleophiles or electrophiles through distinct mechanisms and modes of activation. Diverse C-aryl glycosides were secured with excellent selectivity, scope, and functional-group compatibility, and reliable access to both α and ß isomers was possible for key sugar residues.
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Metal-catalyzed C-H glycosylation reactions with glycosyl chloride donors have emerged as a useful strategy for the synthesis of C-glycosides. Previously, palladium and nickel complexes were reported to catalyze C-H glycosylation reactions using amide-linked bidentate auxiliaries. Herein, a ruthenium-catalyzed ortho C-H glycosylation reaction of arenes with various glycosyl chloride donors using a monodentate pyridine directing group is developed. Preliminary mechanistic studies indicated that two-electron oxidative addition and reductive elimination of ruthenocycle intermediate led to the glycosylation products.
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Cloretos , Rutênio , Catálise , Glicosilação , PiridinasRESUMO
C-Acyl glycosides are versatile intermediates to natural products and medicinally relevant entities. Conventional cross-coupling strategies to secure these molecules often relied on two-component manifolds in which a glycosyl precursor is coupled with an acyl donor (pre-synthesized or generated in situ) under transition metal or dual catalysis to forge a C-C bond. Here, we disclose a three-component Ni-catalyzed reductive regime that facilitates the chemoselective union of glycosyl halides, organoiodides and commercially available isobutyl chloroformate as a CO surrogate. The method tolerates multiple functionalities and the resulting products are obtained in high diastereoselectivities. Theoretical calculations provide a mechanistic rationale for the unexpectedly high chemoselectivity of sequential cross-electrophile couplings. This approach enables the expeditious assembly of difficult-to-synthesize C-acyl glycosides, as well as late-stage keto-glycosylation of oligopeptides.
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Glicosídeos , Níquel , Níquel/química , Catálise , Glicosídeos/química , GlicosilaçãoRESUMO
Parental involvement in adolescents' learning has been linked to high academic achievement, yet few studies have examined its reverse relationship at the same time and the potential mechanisms that underly these associations. To address this research gap, this study investigated the reciprocal relationship between parental involvement and academic achievement as well as the mediating role of adolescents' academic engagement among Chinese adolescents. In addition, the current study explored whether these relationships varied by gender. Using a longitudinal design, a total of 2381 secondary school students (48.8% girls, Mage = 13.38 ± 0.59) participated in the study. The results found significant positive directional effects from academic achievement to parental involvement among total sample, but not vice versa. The cross-lagged effect from academic achievement to parental involvement only existed among adolescent girls. Bootstrap analyses in the total sample revealed that parental involvement was related to academic achievement through the indirect effects of adolescents' behavioral engagement. In terms of gender differences, behavioral engagement totally mediated the path from academic achievement to parental involvement for boys, while no significant mediation effect was found for girls. These results have provided empirical evidence of the evocative role of adolescents' academic characteristics on parenting behaviors and the double-edged effect of parental involvement on adolescents' academic performance, they also suggest that further research is needed to explore effective and appropriate ways for parents to get involved in adolescents' learning in order to promote their children's academic achievement.
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Sucesso Acadêmico , Adolescente , Criança , Escolaridade , Feminino , Humanos , Masculino , Relações Pais-Filho , Poder Familiar , PaisRESUMO
C-vinyl glycosides are an important class of carbohydrates and pose a unique synthetic challenge. A new strategy has been developed for stereoselective synthesis of C-vinyl glycosides via Pd-catalyzed directed C-H glycosylation of alkenes with glycosyl chloride donors using an easily removable bidentate auxiliary. Both the γ C-H bond of allylamines and the δ C-H bond of homoallyl amine substrates can be glycosylated in high efficiency and with excellent regio- and stereoselectivity. The resulting C-vinyl glycosides can be further converted to a variety of C-alkyl glycosides with high stereospecificity. These reactions offer a broadly applicable method to streamline the synthesis of complex C-vinyl glycosides from easily accessible starting materials.
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BACKGROUND Since the use of human umbilical cord Wharton's Jelly derived mesenchymal stromal cells (hWJ-MSCs) to treat sarcopenia has not been explored, we studied the effects of hWJ-MSCs in aged male C57BL/6J mice with sarcopenia induced by hindlimb suspension, and explored the potential mechanism. MATERIAL AND METHODS Hindlimb suspension was used to induce sarcopenia in 24-month-old C57BL/6J mice and green fluorescent protein-tagged hWJ-MSCs and controls were transplanted into mice via tail vein or local intramuscular injection. After hWJ-MSC transplantation, changes in whole body muscle strength and endurance, gastrocnemius muscle weight and myofiber cross-sectional area (CSA) were studied. Proliferation of skeletal muscle stem cell, apoptosis, and chronic inflammation were also investigated. RESULTS We demonstrated that whole body muscle strength and endurance, gastrocnemius muscle mass, and CSA were significantly increased in hWJ-MSC-transplanted mice than in controls (P<0.05). In hWJ-MSC-transplanted mice, apoptotic myonuclei was reduced, and BrdU and Pax-7 expression indices of gastrocnemius muscles were increased (P<0.05). Tumor necrosis factor (TNF)-α and interleukin (IL)-6 were downregulated, and IL-4 and IL-10 were upregulated (P<0.05). CONCLUSIONS hWJ-MSCs may ameliorate sarcopenia in aged male C57BL/6J mice induced by hindlimb suspension, and this may be via activation of resident skeletal muscle satellite cells, reduction of apoptosis, and less chronic inflammation.
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Células-Tronco Mesenquimais/fisiologia , Sarcopenia/terapia , Geleia de Wharton/fisiologia , Animais , Apoptose , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Elevação dos Membros Posteriores , Humanos , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Camundongos , Camundongos Endogâmicos C57BL , Cordão Umbilical/metabolismo , Cordão Umbilical/fisiologia , Geleia de Wharton/citologiaRESUMO
This study aimed to investigate the phenomenon of mitochondrial apoptosis and autophagy in the process of adipose-derived stromal cell (ADSC) differentiation into astrocytes for 48 h, 7 days, 14 days, and 21 days. Immunocytochemistry and Western blotting indicated that the expression of GFAP reached a peak on the 7th day (P < 0.05). The expression of Bcl-2 was decreased (P < 0.05), but Bax, Cyt-c, and LC3 increased with time and reached a maximum on the 14th day (P < 0.05). TEM was used to observe the ultrastructure of mitochondria, apoptosis, and autophagy. An MTT assay indicated that the number of surviving cells decreased. During ADSC differentiation into astrocytes, the effect of Bcl-2 inhibition on apoptosis decreased, whereas mitochondrial apoptosis and autophagy were enhanced; however, this selective autophagy could not eliminate all the damaged mitochondria, leading to mitochondrial apoptosis.
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Tecido Adiposo/citologia , Astrócitos/citologia , Mitocôndrias/fisiologia , Células Estromais/citologia , Tecido Adiposo/metabolismo , Adulto , Apoptose/fisiologia , Proteínas Reguladoras de Apoptose/metabolismo , Astrócitos/metabolismo , Autofagia/fisiologia , Diferenciação Celular/fisiologia , Sobrevivência Celular/fisiologia , Células Cultivadas , Humanos , Proteínas de Membrana/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Mitocôndrias/metabolismo , Células Estromais/metabolismoRESUMO
Although research has indicated the association between child abuse and non-suicidal self-injury (NSSI), few studies have examined their relationship in a particular sample of Chinese rural-to-urban migrant adolescents who tend to experience parental abuse and engage in NSSI. More importantly, factors moderating the relationship between child abuse and migrant adolescents' NSSI have been understudied. To address this issue, this study aimed to examine whether beliefs about adversity and family socioeconomic status (SES) moderated the longitudinal relationship between child abuse and NSSI in a sample of Chinese migrant adolescents. 308 Chinese rural-to-urban migrant adolescents (aged 10-14; 138 boys) completed the two-wave survey. Self-reported questionnaires regarding child abuse, NSSI, beliefs about adversity, and family SES were used. Results showed that child abuse was significantly positively related to NSSI a year later. Moreover, the interaction of child abuse, beliefs about adversity, and family SES was significant. Specifically, for migrant adolescents with low SES, positive beliefs about adversity played a protective role in the association between child abuse and NSSI; while for those with high SES, such beliefs showed vulnerability. Findings underscore the importance of considering multiple resilient factors simultaneously by examining beliefs about adversity and SES as the moderating mechanisms in the association between child abuse and NSSI. Findings also emphasize the significance of developing differential interventions targeting NSSI in abused Chinese migrant adolescents. Positive beliefs about adversity are important in buffering the negative effect of child abuse for migrant adolescents with low SES. For those with high SES, special attention should be given to the interactive impact of child abuse, beliefs about adversity, and family SES.
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Maus-Tratos Infantis , Comportamento Autodestrutivo , Migrantes , Adolescente , Criança , Humanos , Masculino , Maus-Tratos Infantis/estatística & dados numéricos , Comportamento Autodestrutivo/epidemiologia , Classe Social , Migrantes/psicologia , Migrantes/estatística & dados numéricos , Feminino , China/etnologiaRESUMO
The healthy context paradox is defined as the phenomenon that victims' psychological adjustment worsens in a context with a lower rate of victimization. The unexpected pattern was primarily confirmed in children and adolescents from western societies, and it is unclear whether classroom-level victimization could moderate the link between peer victimization and psychological adjustment in the Chinese cultural context, where Confucian philosophies and collectivism are highly valued. Furthermore, most existing research used a single method to assess peer victimization. The current study attempted to examine classroom-level peer victimization as a moderator in the association between individual-level peer victimization and depression, self-esteem, and well-being among 2613 Chinese seventh graders (1237 girls, Mage = 13.00±.61) from 47 classrooms (Mclassroom size = 55.60, range from 45 to 65) using both self-reported and peer-reported information on peer victimization. At the individual level, the results revealed that both self- and peer-reported victimization were positively related to depression and negatively related to self-esteem and well-being. Most importantly, consistent with past findings documenting the healthy context paradox, self-reported victimized youth experienced a higher level of depression and lower level of self-esteem and well-being in classrooms where the overall level of victimization was relatively low. However, the healthy context paradox was not replicated in the nominated data of peer victimization. These results confirmed the healthy context paradox in Chinese culture to some extent. The findings emphasize the importance of measuring peer victimization from multiple sources and suggest there is a need for additional support to victimized middle school students where the classroom context was relatively healthy.
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Bullying , Vítimas de Crime , Feminino , Criança , Humanos , Adolescente , População do Leste Asiático , Bullying/psicologia , Grupo Associado , Ajustamento Emocional , Vítimas de Crime/psicologiaRESUMO
RATIONALE: Previous research investigating the comorbidity of loneliness and social anxiety symptoms in population samples has relied on latent variable modeling in which averaged scores representing dimensions were derived from observed symptoms. Studies have not examined how loneliness and social anxiety co-occur at the symptom level or their relations with peer relationships. OBJECTIVE: This study examined the comorbidity of loneliness and social anxiety and the role of peer relationships (i.e., the number of reciprocated friends, friendship quality, and bullying victimization) in adolescents' co-occurring network using a large sample of Chinese adolescents. METHODS: We performed a network analysis in a sample of Chinese adolescents (N = 2601, 51.6% male, M age = 13.9 years, SD = 0.60). Participants completed self-report measures of loneliness, social anxiety, bullying victimization, and friendship quality as well as peer nomination measures of the number of reciprocated friends. RESULTS: Network analysis revealed that feeling ridiculed, fear of being rejected, having difficulty asking others to do things together, and feeling left out at school were essential bridge symptoms in the co-occurrence of loneliness and social anxiety. Bullying victimization had more positive associations with symptoms of social anxiety, and friendship quality had more negative associations with symptoms of loneliness. CONCLUSIONS: The findings provide preliminary evidence for the comorbidity of loneliness and social anxiety symptoms in adolescents. The results also highlight the potential importance of targeting peer relationships in the prevention and intervention of loneliness and social anxiety symptoms. The combination of longitudinal networks and interventions on bridge symptoms may provide further insight into the development of the links between peer relationships, loneliness, and social anxiety symptoms.
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Medo , Solidão , Adolescente , Masculino , Humanos , Feminino , Emoções , Comorbidade , Ansiedade/epidemiologiaRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors that threaten human health; thus, the establishment of an animal model with clinical features similar to human hepatocellular carcinoma is of important practical significance. METHODS: Taking advantage of the novel microcarrier-6, human HCC cells were injected into immunocompetent mice to establish a novel human HCC patient-derived xenograft (PDX) model. Primary HCC cells were isolated from fresh hepatocellular carcinoma tissues, which were subsequently co-cultured with microcarrier-6 to construct a three-dimensional tumor cell culture model in vitro. The HCC-microcarrier complex was implanted into mice by subcutaneous inoculation, and the tumor formation time, tumor formation rate, and pathological manifestation were recorded. Changes of immune parameters in mice were detected by flow cytometry. RESULTS: The success rate was 60% (6/10) in the establishment of hepatocellular carcinoma PDX mouse model, and the total tumor formation rate of the tumor-forming model is 90-100%. H&E staining and immunohistochemical experiments indicate that the model well retained the characteristics of the primary tumor. Interestingly, M2 macrophages in tumor-bearing mice increased significantly, and the levels of CD4+ T cells were significantly reduced. CONCLUSIONS: Through the application of the microcarrier-6 in immunocompetent mice, we successfully established a novel human HCC PDX model, which can be used to better study and further elucidate the occurrence and pathogenic mechanism of HCC, improve the predictability of toxicity and drug sensitivity in HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Xenoenxertos , Ensaios Antitumorais Modelo de Xenoenxerto , Técnicas de Cocultura , Linhagem Celular TumoralRESUMO
BACKGROUND: The need to retrieve or classify protein molecules using structure or sequence-based similarity measures underlies a wide range of biomedical applications. Traditional protein search methods rely on a pairwise dissimilarity/similarity measure for comparing a pair of proteins. This kind of pairwise measures suffer from the limitation of neglecting the distribution of other proteins and thus cannot satisfy the need for high accuracy of the retrieval systems. Recent work in the machine learning community has shown that exploiting the global structure of the database and learning the contextual dissimilarity/similarity measures can improve the retrieval performance significantly. However, most existing contextual dissimilarity/similarity learning algorithms work in an unsupervised manner, which does not utilize the information of the known class labels of proteins in the database. RESULTS: In this paper, we propose a novel protein-protein dissimilarity learning algorithm, ProDis-ContSHC. ProDis-ContSHC regularizes an existing dissimilarity measure dij by considering the contextual information of the proteins. The context of a protein is defined by its neighboring proteins. The basic idea is, for a pair of proteins (i, j), if their context N(i) and N(j) is similar to each other, the two proteins should also have a high similarity. We implement this idea by regularizing dij by a factor learned from the context N(i) and N(j).Moreover, we divide the context to hierarchial sub-context and get the contextual dissimilarity vector for each protein pair. Using the class label information of the proteins, we select the relevant (a pair of proteins that has the same class labels) and irrelevant (with different labels) protein pairs, and train an SVM model to distinguish between their contextual dissimilarity vectors. The SVM model is further used to learn a supervised regularizing factor. Finally, with the new Supervised learned Dissimilarity measure, we update the Protein Hierarchial Context Coherently in an iterative algorithm--ProDis-ContSHC.We test the performance of ProDis-ContSHC on two benchmark sets, i.e., the ASTRAL 1.73 database and the FSSP/DALI database. Experimental results demonstrate that plugging our supervised contextual dissimilarity measures into the retrieval systems significantly outperforms the context-free dissimilarity/similarity measures and other unsupervised contextual dissimilarity measures that do not use the class label information. CONCLUSIONS: Using the contextual proteins with their class labels in the database, we can improve the accuracy of the pairwise dissimilarity/similarity measures dramatically for the protein retrieval tasks. In this work, for the first time, we propose the idea of supervised contextual dissimilarity learning, resulting in the ProDis-ContSHC algorithm. Among different contextual dissimilarity learning approaches that can be used to compare a pair of proteins, ProDis-ContSHC provides the highest accuracy. Finally, ProDis-ContSHC compares favorably with other methods reported in the recent literature.
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Algoritmos , Inteligência Artificial , Bases de Dados de Proteínas , Proteínas/química , Modelos Químicos , Proteínas/classificação , Proteínas/isolamento & purificaçãoRESUMO
Introduction: Non-dystrophic myotonias (NDMs) are skeletal muscle ion channelopathies caused by CLCN1 or SCN4A mutations. This study aimed to describe the clinical, myopathological, and genetic analysis of NDM in a large Chinese cohort. Methods: We reviewed the clinical manifestations, laboratory results, electrocardiogram, electromyography, muscle biopsy, genetic analysis, treatment, and follow-up of 20 patients (from 18 families) with NDM. Results: Cases included myotonia congenita (MC, 17/20) and paramyotonia congenita (PMC, 3/20). Muscle stiffness and hypertrophy, grip and percussion myotonia, and the warm-up phenomenon were frequently observed in MC and PMC patients. Facial stiffness, eye closure myotonia, and cold sensitivity were more common in PMC patients and could be accompanied by permanent weakness. Nine MC patients and two PMC patients had cardiac abnormalities, mainly manifested as cardiac arrhythmia, and the father of one patient died of sudden cardiac arrest. Myotonic runs in electromyography were found in all patients, and seven MC patients had mild myopathic changes. There was no difference in muscle pathology between MC and PMC patients, most of whom had abnormal muscle fiber type distribution or selective muscle fiber atrophy. Nineteen CLCN1 variants were found in 17 MC patients, among which c.795T>G (p.D265E) was a new variant, and two SCN4A variants were found in three PMC patients. The patients were treated with mexiletine and/or carbamazepine, and the symptoms of myotonia were partially improved. Conclusions: MC and PMC have considerable phenotypic overlap. Genetic investigation contributes to identifying the subtype of NDM. The muscle pathology of NDM lacks specific changes.
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The agricultural non-point source pollution (ANPSP) load in Guangdong province is very large and has a serious impact on the regional ecological environment. Inventory analysis was used to assess and analyze the temporal and spatial variation characteristics of the ANPSP load of Guangdong province during 1999-2019, and the sources of ANPSP were discussed, as well as the relationship between them. The results showed that, during the past 20 years, the total ANPSP pollution loads of Guangdong province decreased by 6.08%, and the pollution loads of chemical oxygen demand (COD), total nitrogen (TN), and total phosphorus (TP) increased by -11.88%, 4.99%, and 26.17%, respectively. The input intensity of chemical fertilizers and pesticides increased by 112.19% and 60.38%, respectively. The Pearl River Delta had the highest ANPSP loads in Guangdong province, followed by those in northern, western, and eastern Guangdong. Livestock and poultry breeding were the main sources of COD, the total percent fertilizers and livestock and poultry breeding were the main sources of TN, and livestock and poultry breeding and aquaculture were the main sources of TP. In addition, the contribution of pollutants discharged from aquaculture showed an obvious increasing trend. There were certain differences in the pollution sources in different regions. In western Guangdong, northern Guangdong, and eastern Guangdong, livestock and poultry breeding were the main sources of COD and TP, and fertilizer was the main source of TN; by contrast in the Pearl River Delta, aquaculture had become the main source of TN and TP pollution loads. The correlation results showed that the decline in the total ANPSP in Guangdong province was mainly due to the increase in high urbanization rate and the decrease in the proportion of rural population. In general, there were stage changes in the time and differences in spatial characteristics and sources of ANPSP in Guangdong province. A combination of comprehensive treatment and targeted pollution treatment should be adopted, and fertilizer reduction measures and pollution treatment in the aquaculture should be strengthened in an all-around way, focusing on strengthening the treatment of pollution from aquaculture in the Pearl River Delta region and the treatment of rural life pollution in northern Guangdong.