ABSTRACT
Intrinsically disordered proteins (IDPs) participate in various biological processes. Interactions involving IDPs are usually dynamic and are affected by their inherent conformation fluctuations. Comprehensive characterization of these interactions based on current techniques is challenging. Here, we present GSALIDP, a GraphSAGE-embedded LSTM network, to capture the dynamic nature of IDP-involved interactions and predict their behaviors. This framework models multiple conformations of IDP as a dynamic graph, which can effectively describe the fluctuation of its flexible conformation. The dynamic interaction between IDPs is studied, and the data sets of IDP conformations and their interactions are obtained through atomistic molecular dynamic (MD) simulations. Residues of IDP are encoded through a series of features including their frustration. GSALIDP can effectively predict the interaction sites of IDP and the contact residue pairs between IDPs. Its performance in predicting IDP interactions is on par with or even better than the conventional models in predicting the interaction of structural proteins. To the best of our knowledge, this is the first model to extend the protein interaction prediction to IDP-involved interactions.
ABSTRACT
BACKGROUND: Childhood sexual abuse (CSA) is a severe global problem associated with alcohol use disorder (AUD). Previous studies have confirmed this relationship; however, there is a lack of research on the disease burden of AUD attributable to CSA. OBJECTIVE: To analyze global spatiotemporal trends and differences in the disease burden of AUD attributable to CSA and its relationship with age, sex, and the sociodemographic index (SDI). PARTICIPANTS AND SETTING: Data from the Global Burden of Disease 2019 Public Database. METHODS: Summary exposure value (SEV) was used to evaluate CSA. Disability-adjusted life year (DALY), years lived with disability (YLD), years of life lost (YLL), and their annual rates of change were used to evaluate disease burden. Cluster analysis based on Ward's method was used to examine the global burden associated with age, sex, and SDI. A 95 % uncertainty intervals (UI), excluding 0, was considered statistically significant. RESULTS: In 2019, 1.63 million (95 % UI 0.23-3.90 million) DALYs of AUD were caused by CSA and the age-standardized rates (ASRs) of DALY was 19.77 (95 % UI 2.78-47.46) globally. Annual rates of change in DALY of people over 65 years of age increased from 1990 to 2019 in all regions except the High-middle SDI regions. The ASRs of DALY of females in High SDI regions, were always at a much higher level than other SDI regions, and showed an upward trend from 1990 to 2019 (DALY 1990: 20.38 [95 % UI 2.87-47.77], 2019: 23.61 [95 % UI 3.55-54.94]). CONCLUSIONS: Substantial geographical differences were observed in the burden of AUD attributable to CSA. The level of CSA exposure was inconsistent with the related burden of AUD in different regions according to the sociodemographic index. The burden of disease increased in the elderly population and in females in high sociodemographic index regions.
Subject(s)
Alcoholism , Child Abuse, Sexual , Global Burden of Disease , Global Health , Humans , Female , Global Burden of Disease/trends , Male , Adult , Young Adult , Middle Aged , Adolescent , Child , Alcoholism/epidemiology , Global Health/statistics & numerical data , Child Abuse, Sexual/statistics & numerical data , Aged , Sex Factors , Socioeconomic Factors , Sociodemographic Factors , Disability-Adjusted Life Years/trends , Cost of Illness , Age FactorsABSTRACT
INTRODUCTION: Suicide and early alcohol use initiation are public health concerns. Previous studies have explored the associations between age of alcohol use initiation and suicidal behaviors, which progresses from ideation to action. Distinguishing between the various associations can help gain a deeper understanding of suicidal behaviors and aid in developing social suicide prevention strategies. METHODS: The study utilized the Youth Risk Behavior Survey to investigate this association. A total of 17 209 students were finally included in the study. Conditional suicidal behaviors included no suicidal behavior (NS), suicidal ideation without a plan or attempt (SINPA), suicide plan without an attempt (SPNA) and suicide attempt (SA). RESULTS: Among 17 209 students, the prevalence of suicidal ideation, suicide plan, and suicide attempt were 21.4%, 17.3%, and 11.1%, respectively. Moreover, 15.2% of the students used alcohol before age 13, whereas 31.7% of students used alcohol at age 13 or older. Compared to NS, students using alcohol showed significant associations with SA (OR = 2.34, p < .001; OR = 1.29, p < .01), SPNA (OR = 1.68, p < .001; OR = 1.19, p < .05) and SINPA (OR = 1.55, p < .001; OR = 1.40, p < .001). Comparing with SINPA and SNPA, students using alcohol before age 13 were associated with SA (OR = 1.61, p < .001; OR = 1.46, p < .001), whereas those using alcohol at or after the age 13 were not associated with SA (OR = 0.98, p > .05; OR = 1.09, p > .05). DISCUSSION: This study demonstrated that early alcohol use initiation was significantly associated with suicide attempts among students with suicidal ideations or plans.
Subject(s)
Suicidal Ideation , Suicide, Attempted , Humans , Adolescent , Suicide Prevention , Surveys and Questionnaires , Students , Risk Factors , PrevalenceABSTRACT
Background: Bipolar disorder is identified as a cause of severe damage to the physical, psychological and social functioning of adolescents and young adults. Aims: The aim of this study is to ascertain the trends in the burden of bipolar disorder among individuals aged 10-24 years at global, regional and national levels from 1990 to 2019. Methods: The data analysed in this study were from the Global Burden of Diseases 2019. The numbers, rates per 100â 000 population, average annual percentage changes (AAPCs) of incidence, prevalence and years lived with disability (YLDs) of bipolar disorder are reported at the global, regional and national levels among individuals aged 10-24 years. Global trends by age, sex and Social Development Index (SDI) were further analysed. Results: Globally, the incidence of bipolar disorder among adolescents and young adults increased from 79.21 per 100 000 population (95% uncertainty interval (UI): 58.13 to 105.15) in 1990 to 84.97 per 100 000 population (95% UI: 61.73 to 113.46) in 2019, AAPC 0.24 (95% confidence interval (CI): 0.22 to 0.26). In the past three decades, there has been an increase in incidence, prevalence and YLDs in both males and females. The largest increase in incidence between 1990 and 2019 was observed in those aged 20-24 years old (from 51.76 per 100 000 population (95% UI: 26.81 to 87.20) in 1990 to 58.37 per 100 000 population (95% UI: 30.39 to 98.55) in 2019; AAPC 0.42 (95% CI: 0.38 to 0.47)). By the SDI quintile, the largest increase in incidence was observed in the middle SDI; however, the high SDI countries had the highest incidence. Regionally, the largest increase in incidence was observed in southern Latin America. At the national level, the most pronounced increase in the incidence was in Greenland. Conclusions: The global increase in incidence among adolescents and young adults between 1990 and 2019 indicates that strategies to improve their mental health still need to be emphasised.
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Seventeen undescribed sesquiterpene-alkaloid hybrids (liriogerphines E-U, 1-17) were isolated and identified during a further phytochemical investigation on the branches and leaves of Chinese tulip tree (Liriodendron chinense), a rare medicinal and ornamental plant endemic to China. These unique heterodimers are conjugates of germacranolide-type sesquiterpenoids with structurally diverse alkaloids [i.e., aporphine- (1-15), proaporphine- (16), and benzyltetrahydroisoquinoline-type (17)] via the formation of a C-N bond. The previously undescribed structures were elucidated by comprehensive spectroscopic data analyses and electronic circular dichroism calculations. Such a class of sesquiterpene-alkaloid hybrids presumably biosynthesized via an aza-Michael addition is quite rare from terrestrial plants. In particular, the sesquiterpene-benzyltetrahydroisoquinoline hybrid skeleton has never been reported until the present study. All the isolates were evaluated for their cytotoxic effects against a small panel of leukemia cell lines (Raji, Jeko-1, Daudi, Jurkat, MV-4-11 and HL-60), and some of them exhibited considerable activities.
Subject(s)
Alkaloids , Antineoplastic Agents , Liriodendron , Sesquiterpenes , Liriodendron/chemistry , Alkaloids/chemistry , Plant Leaves/chemistry , Sesquiterpenes/chemistry , Molecular StructureABSTRACT
Annexins exist widely in plants as multigene families and play critical roles in stress responses and a range of cellular processes. This study provides a comprehensive account of the cloning and functional characterization of the rice annexin gene OsAnn5. The findings reveal that a cold stress treatment at the seedling stage of rice induced OsAnn5 expression. GUS staining assay indicated that the expression of OsAnn5 was non tissue-specific and was detected in almost all rice tissues. Subcellular localization indicated that OsAnn5-GFP (green fluorescent protein) signals were found in the endoplasmic reticulum apparatus. Compared with wild type rice, knocking out OsAnn5 using the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR associated proteins) mediated genome editing resulted in sensitivity to cold treatments. These results indicate that OsAnn5 is involved in cold stress tolerance at the seedling stage.
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Background: Workplace violence (WPV) had always been the focus of attention in all walks of lives, especially in the health fields. Previous studies had shown it adversely affected mental health for healthcare workers. In addition, both sleep quality and physical activity were supported to have impact on mental health. However, the mechanism of sleep quality and physical activity influence the association between WPV and mental health had not been explored, so the purpose of this paper was to explore this mechanistic link among workplace violence, sleep quality, physical activity, and mental health in Chinese health technicians. Methods: Cross-sectional study was conducted in 3 cities of China, totally 3426 valid questionnaires were collected. WPV, physical activity, and social-demographic variables were evaluated. The Pittsburgh Sleep Quality Index and the Kessler Psychological Distress Scale were used to measure sleep quality and mental health. Descriptive analysis, univariate analysis, Pearson correlation, and moderated mediation analysis were used to estimate prevalence of WPV, association between WPV and mental health, and the role of sleep quality and physical activity on association between WPV and mental health. Results: The prevalence of WPV was 52.2% among Chinese health technicians. After controlling social-demographic and work-related variables, sleep quality partially mediated the effect of WPV on mental health (indirect effect=0.829). Physical activity moderated the relationship between WPV and sleep quality (ß=0.235, p=0.013), but not find the moderating role between WPV and mental health (ß=0.140, p=0.474), and between sleep quality and mental health (ß=0.018, p=0.550). Conclusion: The rate of WPV among health technicians remained at an alarming level. Sleep quality and physical activity could mitigate the adverse effect of WPV on mental health. In the future, we could improve sleep quality and encourage health technicians to engage physical activity to decrease the negative effect of WPV on mental health.
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Microvascular reconstruction is essential for peripheral nerve repair. S-Propargyl-cysteine (SPRC), the endogenous hydrogen sulfide (H2S) donor, has been reported to promote angiogenesis. The aim of this study is to utilize the pro-angiogenic ability of SPRC to support peripheral nerve repair and to explore the potential mechanisms. The effects and mechanisms of SPRC on angiogenesis and peripheral nerve repair were examined under hypoxic condition by establishing a sciatic nerve crushed injury model in mice and rats, and a hypoxia model in human umbilical vascular endothelial cells (HUVECs) in vitro. We found that SPRC accelerated the function recovery of the injured sciatic nerve and alleviated atrophy of the gastrocnemius muscle in mice. It facilitated the viability of Schwann cells (SCs), the outgrowth and myelination of regenerated axons, and angiogenesis in rats. It enhanced the viability, proliferation, adhesion, migration, and tube formation of HUVECs under hypoxic condition. SPRC activated sirtuin1 (SIRT1) expression by promoting the production of endogenous H2S, and SIRT1 negatively regulated Notch signaling in endothelial cells (ECs), thereby promoting angiogenesis. Collectively, our study has provided important evidence that SPRC has an effective role in peripheral nerve repair through microvascular reconstruction, which could be a potentially effective medical therapy for peripheral nerve injury.
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Liriogerphines A-D (1-4, respectively), an unprecedented class of hybrids of germacranolide-type sesquiterpenoids and aporphine-type alkaloids, were isolated from the rare medicinal plant Liriodendron chinense. Their structures were elucidated by comprehensive spectroscopic analyses combined with electronic circular dichroism calculations and X-ray crystallographic data. Biosynthetically, an aza-Michael addition reaction is proposed to be involved in the assemblies of this class of hybrids. Compound 4 exhibited cytotoxicity against leukemia cells via inducing apoptosis and inhibiting Bcl-2 expression.
Subject(s)
Alkaloids , Antineoplastic Agents , Liriodendron , Sesquiterpenes , Alkaloids/chemistry , Alkaloids/pharmacology , China , Molecular Structure , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , TreesABSTRACT
Closely associated with type 2 diabetes mellitus (T2DM), hepatic steatosis and cardiac hypertrophy resulting from chronic excess intake can exacerbate insulin resistance (IR). The current study aims to investigate the pharmacological effects of hirsutine, one indole alkaloid isolated from Uncaria rhynchophylla, on improving hepatic and cardiac IR, and elucidate the underlying mechanism. T2DM and IR in vivo were established by high-fat diet (HFD) feeding for 3 months in C57BL/6 J mice. In vitro IR models were induced by high-glucose and high-insulin (HGHI) incubation in HepG2 and H9c2 cells. Hirsutine administration for 8 weeks improved HFD-induced peripheral hyperglycemia, glucose tolerance and IR by OGTT and ITT assays, and simultaneously attenuated hepatic steatosis and cardiac hypertrophy by pathological observation. The impaired p-Akt expression was activated by hirsutine in liver and heart tissues of HFD mice, and also in the models in vitro. Hirsutine exhibited the effects on enhancing glucose consumption and uptake in IR cell models via activating phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which was blocked by PI3K inhibitor LY294002. Moreover, the effect of hirsutine on promoting glucose uptake and GLUT4 expression in HGHI H9c2 cells was also prevented by Compound C, an inhibitor of AMP-activated protein kinase (AMPK). Enhancement of glycolysis might be another factor of hirsutine showing its effects on glycemic control. Collectively, it was uncovered that hirsutine might exert beneficial effects on regulating glucose homeostasis, thus improving hepatic and cardiac IR, and could be a promising compound for treating diet-induced T2DM.
Subject(s)
Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 2 , Fatty Liver , Insulin Resistance , Alkaloids , Animals , Cardiomegaly/metabolism , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Diet, High-Fat/adverse effects , Fatty Liver/metabolism , Glucose/metabolism , Liver , Mice , Mice, Inbred C57BL , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , UncariaABSTRACT
OBJECTIVE: To analyze the compositions of the essential oil from the rhizome of Curcuma aromatica in Guangxi. METHODS: The essential oil from the rhizome of Curcuma aromatica was extrated by steam distillation and analysed by GC-MS. RESULTS: 50 chemical constituents accounting for 93.11% of total content were identified. CONCLUSION: The main components are eucalyptol (53.86%), neocurdione (9.89%), linalool (4.24%), camphor (3.14%), alpha-terpineol (2.94%) and germacrone (2.89%).
Subject(s)
Curcuma/chemistry , Cyclohexanols/analysis , Monoterpenes/analysis , Oils, Volatile/chemistry , Plants, Medicinal/chemistry , Cyclohexane Monoterpenes , Cyclohexanols/chemistry , Cyclohexenes/analysis , Cyclohexenes/chemistry , Distillation/methods , Eucalyptol , Gas Chromatography-Mass Spectrometry , Monoterpenes/chemistry , Oils, Volatile/isolation & purification , Plant Oils/chemistry , Plant Oils/isolation & purification , Rhizome/chemistry , SteamABSTRACT
The response of two carbide derived carbons (CDCs) films to NH(3), N(2)O, and room air is investigated by four probe resistance at room temperature and pressures up to 760 Torr. The two CDC films were synthesized at 600 (CDC-600) and 1000 degrees C (CDC-1000) to vary the carbon morphology from completely amorphous to more ordered, and determine the role of structure, surface area, and porosity on sensor response. Sensor response time followed kinetic diameter and indicated a more ordered carbon structure slowed response due to increased tortuosity caused by the formation of graphitic layers at the particle fringe. Steady state sensor response was greater for the less-ordered material, despite its decreased surface area, decreased micropore volume, and less favorable surface chemistry, suggesting carbon structure is a stronger predictor of sensor response than surface chemistry. The lack of correlation between adsorption of the probe gases and sensor response suggests chemical interaction (charge transfer) drive sensor response within the material; N(2)O response, in particular, did not follow simple adsorption behavior. Based on Raman and FTIR characterization, carbon morphology (disorder) appeared to be the determining factor in overall sensor response, likely due to increased charge transfer between gases and carbon defects of amorphous or disordered regions. The response of the amorphous CDC-600 film to NH(3) was 45% without prior oxidation, showing amorphous CDCs have promise as chemical sensors without additional pretreatment common to other carbon sensors.
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OBJECTIVE: To compare therapeutic effects of electroacupuncture (EA) treatment and medication on acute gouty arthritis (AGA), so as to search for a therapeutic method for treatment of gout with renal insufficiency. METHODS: Ninety cases of AGA were randomly divided into an EA group, an allopurinol group and a probenecid group, 30 cases in each group. The EA group were treated by EA at Sanyinjiao (SP 6), Fenglong (ST 40), Yinlingquan (SP 9), once a day; the allopurinol group by oral administration of Allopurinol, twice a day, 100 mg each time and the probenecid group by oral administration of Probenecid, twice daily, 0.25 g each time. Contents of blood uric acid (BUA) and urinary uric acid (UUA) in each group were detected. RESULTS: In all groups, there were significant differences in BUA and UUA levels before and after treatment (P < 0.01). There was no significant difference between the EA group and the allopurinol group in blood uric acid level after treatment (P > 0.05) and there was no significant difference between the EA group and the probenecid group in the urinary innary uric acid level (P > 0.05). Comparison of therapeutic effects among the 3 groups indicated that the mean rank was 56.23 in the EA group, 43.17 in the allopurinol group and 37.10 in the probenecid group, indicating that the therapeutic effect in the EA group was better than that in the allopurinol group, and the allopurinol group was better than that in the probenecid group. CONCLUSION: EA can reduce the production of uric acid and promote the excretion of uric acid and has a better treatment effect. And there are no harmful effects on renal function. EA is an effective therapeutic method for treatment of gout with renal insufficiency.