ACC SYNTHASE4 inhibits gibberellin biosynthesis and FLOWERING LOCUS T expression during citrus flowering.

Flowering is an essential process in fruit trees. Flower number and timing have a substantial impact on the yield and maturity of fruit. Ethylene and gibberellin (GA) play vital roles in flowering, but the mechanism of coordinated regulation of flowering in woody plants by GA and ethylene is still unclear. In this study, a lemon (Citrus limon L. Burm) 1-aminocyclopropane-1-carboxylic acid synthase gene (CiACS4) was overexpressed in Nicotiana tabacum and resulted in late flowering and increased flower number. Further transformation of citrus revealed that ethylene and starch content increased, and soluble sugar content decreased in 35S:CiACS4 lemon. Inhibition of CiACS4 in lemon resulted in effects opposite to that of 35S:CiACS4 in transgenic plants. Overexpression of the CiACS4-interacting protein ETHYLENE RESPONSE FACTOR3 (CiERF3) in N. tabacum resulted in delayed flowering and more flowers. Further experiments revealed that the CiACS4-CiERF3 complex can bind the promoters of FLOWERING LOCUS T (CiFT) and GOLDEN2-LIKE (CiFE) and suppress their expression. Moreover, overexpression of CiFE in N. tabacum led to early flowering and decreased flowers, and ethylene, starch, and soluble sugar contents were opposite to those in 35S:CiACS4 transgenic plants. Interestingly, CiFE also bound the promoter of CiFT. Additionally, GA3 and 1-aminocyclopropanecarboxylic acid (ACC) treatments delayed flowering in adult citrus, and treatment with GA and ethylene inhibitors increased flower number. ACC treatment also inhibited the expression of CiFT and CiFE. This study provides a theoretical basis for the application of ethylene to regulate flower number and mitigate the impacts of extreme weather on citrus yield due to delayed flowering.

Cardiac forces regulate zebrafish heart valve delamination by modulating Nfat signaling.

In the clinic, most cases of congenital heart valve defects are thought to arise through errors that occur after the endothelial-mesenchymal transition (EndoMT) stage of valve development. Although mechanical forces caused by heartbeat are essential modulators of cardiovascular development, their role in these later developmental events is poorly understood. To address this question, we used the zebrafish superior atrioventricular valve (AV) as a model. We found that cellularized cushions of the superior atrioventricular canal (AVC) morph into valve leaflets via mesenchymal-endothelial transition (MEndoT) and tissue sheet delamination. Defects in delamination result in thickened, hyperplastic valves, and reduced heart function. Mechanical, chemical, and genetic perturbation of cardiac forces showed that mechanical stimuli are important regulators of valve delamination. Mechanistically, we show that forces modulate Nfatc activity to control delamination. Together, our results establish the cellular and molecular signature of cardiac valve delamination in vivo and demonstrate the continuous regulatory role of mechanical forces and blood flow during valve formation.

Interrogation of 3d Transition Bimetallic Nanocrystal Nucleation and Growth Using In Situ Electron Microscope and Synchrotron X-ray Techniques.

Understanding the nucleation and growth mechanism of 3d transition bimetallic nanocrystals (NCs) is crucial to developing NCs with tailored nanostructures and properties. However, it remains a significant challenge due to the complexity of 3d bimetallic NCs formation and their sensitivity to oxygen. Here, by combining in situ electron microscopy and synchrotron X-ray techniques, we elucidate the nucleation and growth pathways of Fe-Ni NCs. Interestingly, the formation of Fe-Ni NCs emerges from the assimilation of Fe into Ni clusters together with the reduction of Fe-Ni oxides. Subsequently, these NCs undergo solid-state phase transitions, resulting in two distinct solid solutions, ultimately dominated by γ-Fe3Ni2. Furthermore, we deconvolve the interplays between local coordination and electronic state concerning the growth temperature. We directly visualize the oxidation-state distributions of Fe and Ni at the nanoscale and investigate their changes. This work may reshape and enhance the understanding of nucleation and growth in atomic crystallization.

Pre-intervention myocardial stress is a good predictor of aortic valvoluplasty outcome for fetal critical aortic stenosis and evolving HLHS.

Fetal critical aortic stenosis with evolving hypoplastic left heart syndrome (CAS-eHLHS) causes biomechanical and functional aberrations, leading to a high risk of progression to hypoplastic left heart syndrome (HLHS) at birth. Fetal aortic valvuloplasty (FAV) can resolve outflow obstruction and may reduce progression risk. However, it is currently difficult to accurately predict which patients will respond to the intervention and become functionally biventricular (BV) at birth, as opposed to becoming functionally univentricular (UV). This prediction is important for patient selection, parental counselling, and surgical planning. Therefore, we investigated whether biomechanics parameters from pre-FAV image-based computations could robustly distinguish between CAS-eHLHS cases with BV or UV outcomes in a retrospective cohort. To do so we performed image-based finite element biomechanics modelling of nine CAS-eHLHS cases undergoing intervention and six healthy fetal control hearts, and found that a biomechanical parameter, peak systolic myofibre stress, showed a uniquely large difference between BV and UV cases, which had a larger magnitude effect than echocardiography parameters. A simplified equation was derived for quick and easy estimation of myofibre stress from echo measurements via principal component analysis. When tested on a retrospective cohort of 37 CAS-eHLHS cases, the parameter outperformed other parameters in predicting UV versus BV outcomes, and thus has a high potential of improving outcome predictions, if incorporated into patient selection procedures. Physiologically, high myocardial stresses likely indicate a healthier myocardium that can withstand high stresses and resist pathological remodelling, which can explain why it is a good predictor of BV outcomes. KEY POINTS: Predicting the morphological birth outcomes (univentricular versus biventricular) of fetal aortic valvuloplasty for fetal aortic stenosis with evolving HLHS is important for accurate patient selection, parental counselling and management decisions. Computational simulations show that a biomechanics parameter, pre-intervention peak systolic myofibre stress, is uniquely robust in distinguishing between such outcomes, outperforming all echo parameters. An empirical equation was developed to quickly compute peak systolic myofibre stress from routine echo measurements and was the best predictor of outcomes among a wide range of parameters tested.

Role of tissue biomechanics in the formation and function of myocardial trabeculae in zebrafish embryos.

Cardiac trabeculae are uneven ventricular muscular structures that develop during early embryonic heart development at the outer curvature of the ventricle. Their biomechanical function is not completely understood, and while their formation is known to be mechanosensitive, it is unclear whether ventricular tissue internal stresses play an important role in their formation. Here, we performed imaging and image-based cardiac biomechanics simulations on zebrafish embryonic ventricles to investigate these issues. Microscopy-based ventricular strain measurements show that the appearance of trabeculae coincided with enhanced deformability of the ventricular wall. Image-based biomechanical simulations reveal that the presence of trabeculae reduces ventricular tissue internal stresses, likely acting as structural support in response to the geometry of the ventricle. Passive ventricular pressure-loading experiments further reveal that the formation of trabeculae is associated with a spatial homogenization of ventricular tissue stiffnesses in healthy hearts, but gata1 morphants with a disrupted trabeculation process retain a spatial stiffness heterogeneity. Our findings thus suggest that modulating ventricular wall deformability, stresses, and stiffness are among the biomechanical functions of trabeculae. Further, experiments with gata1 morphants reveal that a reduction in fluid pressures and consequently ventricular tissue internal stresses can disrupt trabeculation, but a subsequent restoration of ventricular tissue internal stresses via vasopressin rescues trabeculation, demonstrating that tissue stresses are important to trabeculae formation. Overall, we find that tissue biomechanics is important to the formation and function of embryonic heart trabeculation. KEY POINTS: Trabeculations are fascinating and important cardiac structures and their abnormalities are linked to embryonic demise. However, their function in the heart and their mechanobiological formation processes are not completely understood. Our imaging and modelling show that tissue biomechanics is the key here. We find that trabeculations enhance cardiac wall deformability, reduce fluid pressure stresses, homogenize wall stiffness, and have alignments that are optimal for providing load-bearing structural support for the heart. We further discover that high ventricular tissue internal stresses consequent to high fluid pressures are needed for trabeculation formation through a rescue experiment, demonstrating that myocardial tissue stresses are as important as fluid flow wall shear stresses for trabeculation formation.

Detection of Helicobacter pylori Infection in Human Gastric Fluid Through Surface-Enhanced Raman Spectroscopy Coupled With Machine Learning Algorithms.

Diagnostic methods for Helicobacter pylori infection include, but are not limited to, urea breath test, serum antibody test, fecal antigen test, and rapid urease test. However, these methods suffer drawbacks such as low accuracy, high false-positive rate, complex operations, invasiveness, etc. Therefore, there is a need to develop simple, rapid, and noninvasive detection methods for H. pylori diagnosis. In this study, we propose a novel technique for accurately detecting H. pylori infection through machine learning analysis of surface-enhanced Raman scattering (SERS) spectra of gastric fluid samples that were noninvasively collected from human stomachs via the string test. One hundred participants were recruited to collect gastric fluid samples noninvasively. Therefore, 12,000 SERS spectra (n = 120 spectra/participant) were generated for building machine learning models evaluated by standard metrics in model performance assessment. According to the results, the Light Gradient Boosting Machine algorithm exhibited the best prediction capacity and time efficiency (accuracy = 99.54% and time = 2.61 seconds). Moreover, the Light Gradient Boosting Machine model was blindly tested on 2,000 SERS spectra collected from 100 participants with unknown H. pylori infection status, achieving a prediction accuracy of 82.15% compared with qPCR results. This novel technique is simple and rapid in diagnosing H. pylori infection, potentially complementing current H. pylori diagnostic methods.

Exploring functional genes' correlation with (S)-equol concentration and new daidzein racemase identification.

With its estrogenic activity, (S)-equol plays an important role in maintaining host health and preventing estrogen-related diseases. Exclusive production occurs through the transformation of soy isoflavones by intestinal bacteria, but the reasons for variations in (S)-equol production among different individuals and species remain unclear. Here, fecal samples from humans, pigs, chickens, mice, and rats were used as research objects. The concentrations of (S)-equol, along with the genetic homology and evolutionary relationships of (S)-equol production-related genes [daidzein reductase (DZNR), daidzein racemase (DDRC), dihydrodaidzein reductase (DHDR), tetrahydrodaidzein reductase (THDR)], were analyzed. Additionally, in vitro functional verification of the newly identified DDRC gene was conducted. It was found that approximately 40% of human samples contained (S)-equol, whereas 100% of samples from other species contained (S)-equol. However, there were significant variations in (S)-equol content among the different species: rats > pigs > chickens > mice > humans. The distributions of the four genes displayed species-specific patterns. High detection rates across various species were exhibited by DHDR, THDR, and DDRC. In contrast, substantial variations in detection rates among different species and individuals were observed with respect to DZNR. It appears that various types of DZNR may be associated with different concentrations of (S)-equol, which potentially correspond to the regulatory role during (S)-equol synthesis. This enhances our understanding of individual variations in (S)-equol production and their connection with functional genes in vitro. Moreover, the newly identified DDRC exhibits higher potential for (S)-equol synthesis compared to the known DDRC, providing valuable resources for advancing in vitro (S)-equol production. IMPORTANCE: (S)-equol ((S)-EQ) plays a crucial role in maintaining human health, along with its known capacity to prevent and treat various diseases, including cardiovascular diseases, metabolic syndromes, osteoporosis, diabetes, brain-related diseases, high blood pressure, hyperlipidemia, obesity, and inflammation. However, factors affecting individual variations in (S)-EQ production and the underlying regulatory mechanisms remain elusive. This study examines the association between functional genes and (S)-EQ production, highlighting a potential correlation between the DZNR gene and (S)-EQ content. Various types of DZNR may be linked to the regulation of (S)-EQ synthesis. Furthermore, the identification of a new DDRC gene offers promising prospects for enhancing in vitro (S)-EQ production.

Mechanism of Xing 9 ling tablet candy for alcoholic liver disease based on network pharmacology.

Xing 9 Ling tablet candy (X9LTC) effectively treats alcoholic liver disease (ALD), but its potential mechanism and molecular targets remain unstudied. We aimed to address this gap using network pharmacology. Furthermore, high-performance liquid chromatography (HPLC) and database analysis revealed a total of 35 active ingredients and 311 corresponding potential targets of X9LTC. Protein interaction analysis revealed PTGS2, JUN, and FOS as its core targets. Enrichment analysis indicated that chemical carcinogenesis-receptor activation, IL-17 and TNF signaling pathway were enriched by multiple core targets, which might be the main pathway of action. Further molecular docking validation showed that the core targets had good binding activities with the identified compounds. Animal experiments showed that X9LTC could reduce the high expression of ALT, AST and TG in the serum of ALD mice, alleviate the lesions in liver tissues, and reverse the high expression of PTGS2, JUN, and FOS proteins in the liver tissues. In this study, we established a method for the determination of X9LTC content for the first time, and predicted its active ingredient and mechanism of action in treating ALD, providing theoretical basis for further research.

Characterization, expressional and evolutionary analysis of five fish-specific CCRs (CCR4La, CCR4Lc, CCR12a1, CCR12a2, and CCR12b) in largemouth bass (Micropterus salmoides).

CC chemokine receptors (CCRs), the numbers of the G protein-coupled receptor (GPCR) superfamily, had crucial roles in treating infection, inflammation, and tissue damage by binding to their ligands. In this study, five fish-specific CCRs, namely CCR4La, CCR4Lc, CCR12a1, CCR12a2, and CCR12b, were identified in largemouth bass (Micropterus salmoides). The correction of nomenclatures of these CCRs were confirmed by phylogenetic analysis, structural analysis and genomic synteny analysis. Following 1 × 106 CFU/mL and 1 × 107 CFU/mL Edwardsiella piscicida infection, these five CCRs were significantly induced in spleen of largemouth bass, indicating their important roles in the immune response against bacterial infection. Selection pressure analysis revealed that CCR4La, CCR4Lc, CCR12a1, and CCR12a2 underwent negative selection pressure, whereas CCR12b experienced positive selection pressure. Robust selection site detection methods identified that positive selected sites of CCR4La, CCR4Lc, CCR12a1, and CCR12a2 mainly distributed in their extracellular regions, which involved in ligand binding and pathogen interaction. Similarly, the positive selected sites of CCR12b were also located in its extracellular regions. The accuracy of the pressure selected sites were also validated by molecular docking analysis. The potential ligands for these five CCRs were identified by molecular docking analysis, with finding that CCL3 and CCL5 might be the ligands of largemouth bass CCR4La/Lc, and CCL5, CCL8, CCL7, CCL13 and CCL26 might be that of largemouth bass CCR12a1/a2/b. Our results provided basis for elucidating the functions of chemokine-receptor complex in largemouth bass.

Polycyclic polyprenylated acylphloroglucinols (PPAPs) from Garcinia oblongifolia and their antitumoractivity.

Two new polycyclic polyprenylated acylphloroglucinols, along with four previously known compounds, were isolated and identified from the fruits of Garcinia oblongifolia. The structures of these compounds were elucidated through a combination of spectroscopic techniques, including MS, UV, IR, and 1D/2D NMR, as well as their chemical properties. Additionally, the cytotoxic activities of compounds 1‒6 against the H134B cell line were evaluated using the MTT assay, revealing that compounds 1 and 2 exhibit promising antitumor activity.

[Correlations Between the Expression of MicroRNA-155 and Suppressor of Cytokine Signaling 1 in Colonic Mucosal Tissue and Disease Severity in Patients With Ulcerative Colitis].

Objective To explore the relationship between the expression levels of microRNA-155 (miR-155) and suppressor of cytokine signaling 1 (SOCS1) in the colonic mucosal tissue of patients with ulcerative colitis (UC) and the severity of the disease.Methods A total of 130 UC patients admitted to the Second Affiliated Hospital of Hebei North University from September 2021 to June 2023 were selected.According to the modified Mayo score system,the patients were assigned into an active stage group (n=85) and a remission stage group (n=45).According to the modified Truelove and Witts classification criteria,the UC patients at the active stage were assigned into a mild group (n=35),a moderate group (n=30),and a severe group (n=20).A total of 90 healthy individuals who underwent colonoscopy for physical examination or those who had normal colonoscopy results after single polypectomy and excluded other diseases were selected as the control group.The colonic mucosal tissues of UC patients with obvious lesions and the colonic mucosal tissue 20 cm away from the anus of the control group were collected.The levels of miR-155 and SOCS1 mRNA in tissues were determined by fluorescence quantitative PCR,and the expression of SOCS1 protein in tissues was determined by immunohistochemistry.The correlations of the levels of miR-155 and SOCS1 mRNA in the colonic mucosal tissue with the modified Mayo score of UC patients were analyzed.The values of the levels of miR-155 and SOCS1 mRNA in predicting the occurrence of severe illness in the UC patients at the active stage were evaluated.Results Compared with the control group and the remission stage group,the active stage group showed up-regulated expression level of miR-155,down-regulated level of SOCS1 mRNA,and decreased positive rate of SOCS1 protein in the colonic mucosal tissue (all P<0.001).The expression level of miR-155 and modified Mayo score in colonic mucosal tissues of UC patients at the active stage increased,while the mRNA level of SOCS1 was down-regulated as the disease evolved from being mild to severe (all P<0.001).The modified Mayo score was positively correlated with the miR-155 level and negative correlated with the mRNA level of SOCS1 in colonic mucosal tissues of UC patients (all P<0.001).The high miR-155 level (OR=2.762,95%CI=1.284-5.944,P=0.009),low mRNA level of SOCS1 (OR=2.617,95%CI=1.302-5.258,P=0.007),and modified Mayo score≥12 points (OR=3.232,95%CI=1.450-7.204,P=0.004) were all risk factors for severe disease in the UC patients at the active stage.The area under curve of miR-155 combined with SOCS1 mRNA in predicting severe illness in the UC patients at the active stage was 0.920.Conclusions The expression levels of miR-155 and SOCS1 mRNA were correlated with the disease severity in the UC patients at the active stage.The combination of the two indicators demonstrates good performance in predicting the occurrence of severe illness in UC patients at the active stage.

[Extraction process optimization and link evaluation of Reyanning Mixture based on quality by design idea].

Reyanning Mixture is one of the superior Chinese patent medicine varieties of "Qin medicine". Based on the idea of quality by design(QbD), the extraction process of the Reyanning Mixture was optimized. The caffeic acid, polydatin, resveratrol, and emodin were used as critical quality attributes(CQAs). The material-liquid ratio, extraction temperature, and extraction time were taken as critical process parameters(CPPs) by the Plackett-Burman test. The mathematical model was established by the star design-effect surface method, and the design space was constructed and verified. The optimal extraction process of the Reyanning Mixture was obtained as follows: material-liquid ratio of 11.84 g·mL~(-1), extraction temperature at 81 ℃, and two extractions. A partial least-square(PLS) quantitative model for CQAs was established by using near-infrared spectroscopy(NIRS) combined with high-performance liquid chromatography(HPLC) under the optimal extraction process. The results showed that the correlation coefficients of the correction set(R_c) and validation set(R_p) of the quantitative models of four CQAs were more than 0.9. The root mean square error of the correction set(RMSEC) were 0.744, 6.71, 3.95, and 1.53 µg·mL~(-1), respectively, and the root mean square error of the validation set(RMSEP) were 0.709, 5.88, 2.92, and 1.59 µg·mL~(-1), respectively. Therefore, the optimized extraction process of the Reyanning Mixture is reasonable, feasible, stable, and reliable. The NIRS quantitative model has a good prediction, which can be used for the rapid content determination of CQAs during extraction. They can provide an experimental basis for the process research and quality control of Reyanning Mixture.

Age Estimation by Machine Learning and CT-Multiplanar Reformation of Cranial Sutures in Northern Chinese Han Adults.

OBJECTIVES: To establish age estimation models of northern Chinese Han adults using cranial suture images obtained by CT and multiplanar reformation (MPR), and to explore the applicability of cranial suture closure rule in age estimation of northern Chinese Han population. METHODS: The head CT samples of 132 northern Chinese Han adults aged 29-80 years were retrospectively collected. Volume reconstruction (VR) and MPR were performed on the skull, and 160 cranial suture tomography images were generated for each sample. Then the MPR images of cranial sutures were scored according to the closure grading criteria, and the mean closure grades of sagittal suture, coronal sutures (both left and right) and lambdoid sutures (both left and right) were calculated respectively. Finally taking the above grades as independent variables, the linear regression model and four machine learning models for age estimation (gradient boosting regression, support vector regression, decision tree regression and Bayesian ridge regression) were established for northern Chinese Han adults age estimation. The accuracy of each model was evaluated. RESULTS: Each cranial suture closure grade was positively correlated with age and the correlation of sagittal suture was the highest. All four machine learning models had higher age estimation accuracy than linear regression model. The support vector regression model had the highest accuracy among the machine learning models with a mean absolute error of 9.542 years. CONCLUSIONS: The combination of skull CT-MPR and machine learning model can be used for age estimation in northern Chinese Han adults, but it is still necessary to combine with other adult age estimation indicators in forensic practice.

Clinical care pathway to detect advanced liver disease in patients with type 2 diabetes through automated fibrosis score calculation and electronic reminder messages: a randomised controlled trial.

OBJECTIVE: We aimed to test the hypothesis that automated fibrosis score calculation and electronic reminder messages could increase the detection of advanced liver disease in patients with type 2 diabetes. DESIGN: In this pragmatic randomised controlled trial at five general medical or diabetes clinics in Hong Kong and Malaysia, we randomly assigned patients in a 1:1 ratio to the intervention group with Fibrosis-4 index and aspartate aminotransferase-to-platelet ratio index automatically calculated based on routine blood tests, followed by electronic reminder messages to alert clinicians of abnormal results, or the control group with usual care. The primary outcome was the proportion of patients with increased fibrosis scores who received appropriate care (referred for hepatology care or specific fibrosis assessment) within 1 year. RESULTS: Between May 2020 and Oct 2021, 1379 patients were screened, of whom 533 and 528 were assigned to the intervention and control groups, respectively. A total of 55 out of 165 (33.3%) patients with increased fibrosis scores in the intervention group received appropriate care, compared with 4 of 131 (3.1%) patients in the control group (difference 30.2% (95% CI 22.4% to 38%); p<0.001). Overall, 11 out of 533 (2.1%) patients in the intervention group and 1 out of 528 (0.2%) patients in the control group were confirmed to have advanced liver disease (difference 1.9% (95% CI 0.61% to 3.5%); p=0.006). CONCLUSION: Automated fibrosis score calculation and electronic reminders can increase referral of patients with type 2 diabetes and abnormal fibrosis scores at non-hepatology settings. TRIAL REGISTRATION NUMBER: NCT04241575.

Characteristics of white matter alterations along fibres in patients with bulimia nervosa: A combined voxelwise and tractography study.

Accumulating evidence supports the hypothesis that white matter (WM) abnormalities are involved in the pathophysiology of bulimia nervosa (BN); however, findings from in vivo neuroimaging studies have been inconsistent. We aimed to investigate the possible brain WM alterations, including WM volume and microstructure, in patients with BN. We recruited 43 BN patients and 31 healthy controls (HCs). All participants underwent structural and diffusion tensor imaging. Differences in WM volume and microstructure were evaluated using voxel-based morphometry, tract-based spatial statistics, and automated fibre quantification analysis. Compared with HCs, BN patients showed significantly decreased fractional anisotropy in the middle part of the corpus callosum (nodes 31-32) and increased mean diffusivity in the right cranial nerve V (CN V) (nodes 27-33 and nodes 55-88) and vertical occipital fasciculus (VOF) (nodes 58-85). Moreover, we found decreased axial diffusivity in the right inferior fronto-occipital fasciculus (node 67) and increased radial diffusivity in the CN V (nodes 22-34 and nodes 52-89) and left VOF (nodes 60-66 and nodes 81-85). Meanwhile, WM microstructural changes were correlated with patients' clinical manifestations. We did not find any significant differences in WM volume and the main WM fibre bundle properties between BN patients and HCs. Taken together, these findings provide that BN shows significant brain WM reorganization, but primarily in microstructure (part of WM fibre bundle), which is not sufficient to cause changes in WM volume. The automated fibre quantification analysis could be more sensitive to detect the subtle pathological changes in a point or segment of the WM fibre bundle.

Relapse risk revealed by degree centrality and cluster analysis in heroin addicts undergoing methadone maintenance treatment.

BACKGROUND: Based on hubs of neural circuits associated with addiction and their degree centrality (DC), this study aimed to construct the addiction-related brain networks for patients diagnosed with heroin dependence undertaking stable methadone maintenance treatment (MMT) and further prospectively identify the ones at high risk for relapse with cluster analysis. METHODS: Sixty-two male MMT patients and 30 matched healthy controls (HC) underwent brain resting-state functional MRI data acquisition. The patients received 26-month follow-up for the monthly illegal-drug-use information. Ten addiction-related hubs were chosen to construct a user-defined network for the patients. Then the networks were discriminated with K-means-clustering-algorithm into different groups and followed by comparative analysis to the groups and HC. Regression analysis was used to investigate the brain regions significantly contributed to relapse. RESULTS: Sixty MMT patients were classified into two groups according to their brain-network patterns calculated by the best clustering-number-K. The two groups had no difference in the demographic, psychological indicators and clinical information except relapse rate and total heroin consumption. The group with high-relapse had a wider range of DC changes in the cortical-striatal-thalamic circuit relative to HC and a reduced DC in the mesocorticolimbic circuit relative to the low-relapse group. DC activity in NAc, vACC, hippocampus and amygdala were closely related with relapse. CONCLUSION: MMT patients can be identified and classified into two subgroups with significantly different relapse rates by defining distinct brain-network patterns even if we are blind to their relapse outcomes in advance. This may provide a new strategy to optimize MMT.

Evolutionary trade-off between innate and acquired immune defences in birds.

BACKGROUND: The development, maintenance, and use of immune defences are costly. Therefore, animals face trade-offs in terms of resource allocation within their immune system and between their immune system and other physiological processes. To maximize fitness, evolution may favour investment in one immunological defence or subsystem over another in a way that matches a species broader life history strategy. Here, we used phylogenetically-informed comparative analyses to test for relationships between two immunological components. Natural antibodies and complement were used as proxies for the innate branch; structural complexity of the major histocompatibility complex (MHC) region was used for the acquired branch. RESULTS: We found a negative association between the levels of natural antibodies (i.e., haemagglutination titre) and the total MHC gene copy number across the avian phylogeny, both at the species and family level. The family-level analysis indicated that this association was apparent for both MHC-I and MHC-II, when copy numbers within these two MHC regions were analysed separately. The association remained significant after controlling for basic life history components and for ecological traits commonly linked to pathogen exposure. CONCLUSION: Our results provide the first phylogenetically robust evidence for an evolutionary trade-off within the avian immune system, with a more developed acquired immune system (i.e., more complex MHC architecture) in more derived bird lineages (e.g., passerines) being accompanied by an apparent downregulation of the innate immune system.

Curcumin ameliorates pulmonary fibrosis progression by inhibiting the fibrotic process of lung fibroblasts.

The objective of this study was to analyze the effect of curcumin (Cur) on pulmonary fibrosis (PF), so as to provide new clinical evidence for future PF treatment. To achieve these goals, the researchers set up bought human lung fibroblasts MRC-5 as a control group without treatment, a model group for PF cell modeling, and an intervention group for Cur intervention after PF modeling. Cell proliferation capacity and cellular TGF-ß1, α-SMA, Collagen I, Collagen III, Bax, N-cadherin and E-cadherin protein expression were determined. The results show that markedly enhanced cell proliferation capacity and TGF-ß1, α-SMA, Collagen I and Collagen III protein levels were observed in the model group, while the cell activity and fibrosis degree in the intervention group were significantly decreased compared with the model group (P<0.05). In addition, the intervention group exhibited lower N-cadherin and Bax with higher E-cadherin than the model group (P<0.05). In addition, the team found that the inflammatory response and oxidative stress were also more significantly improved in the intervention group (P<0.05). These experimental results tell us that Cur can ameliorate the fibrotic process of PF by inhibiting the activity of MRC-5.

Group Model Building on causes and interventions for falls in Singapore: insights from a systems thinking approach.

BACKGROUND: Falls in older adults are the result of a complex web of interacting causes, that further results in other physical, emotional, and psychological sequelae. A conceptual framework that represents the reciprocal dynamics of these causal factors can enable clinicians, researchers, and policymakers to clarify goals in falls intervention in older adults. METHODS: A Group Model Building (GMB) exercise was conducted with researchers and clinicians from academic units and public healthcare institutes in Singapore. The aim of the exercise was to produce a shared visual representation of the causal structure for falls and engage in discussions on how current and future falls intervention programmes can address falls in the older adults, especially in the Asian context. It was conducted in four steps: 1) Outlining and prioritising desirable patient outcomes, 2) Conceptual model building, 3) Identifying key intervention elements of effective falls intervention programmes, 4) Mapping of interventions to outcomes. This causal loop diagram (CLD) was then used to generate insights into the current understanding of falls causal relationships, current efforts in falls intervention in Singapore, and used to identify gaps in falls research that could be further advanced in future intervention studies. RESULTS: Four patient outcomes were identified by the group as key in falls intervention: 1) Falls, 2) Injurious falls, 3) Fear of falling, and 4) Restricted mobility and life space. A CLD of the reciprocal relationships between risk factors and these outcomes are represented in four sub-models: 1) Fear of falling, 2) Injuries associated with falls, 3) Caregiver overprotectiveness, 4) Post-traumatic stress disorder and psychological resilience. Through this GMB exercise, the group gained the following insights: (1) Psychological sequelae of falls is an important falls intervention outcome. (2) The effects of family overprotectiveness, psychological resilience, and PTSD in exacerbating the consequences of falls are not well understood. (3) There is a need to develop multi-component falls interventions to address the multitude of falls and falls related sequelae. CONCLUSION: This work illustrates the potential of GMB to promote shared understanding of complex healthcare problems and to provide a roadmap for the development of more effective preventive actions.

Comparative study on ignition delay time and burning rate of modified double-base propellant and fuel-rich propellant.

With the higher requirements of various tactical and technical indicators of the weapon systems, the current research on the ignition and combustion characteristics of different types of solid propellants is not comprehensive. In more complex and harsh environmental conditions, the pressure affects the ignition and combustion characteristics. Therefore, the paper studies the ignition and combustion characteristics of the modified double-base propellants (MDB propellants) and fuel-rich propellants (FR propellants) under low-pressure environment. Combining experiment and theory, the ignition delay time and burning rate of two kinds of solid propellants are compared and analyzed at low pressure by the laser ignition experimental device. The results displayed that the burning flames of the FR and MDB propellant presented evident V-shape and cylindrical, respectively. The flame brightness decreased with the decrease in pressure. With the increase of pressure and heat flux, the ignition delay time of the MDB propellant and the FR propellant decreased. By comparison, Model 2 of the ignition delay time was more effective for the estimation of the ignition delay time of the FR propellant. The experimental results are compared with the three burning rate models, which are the Vielle formula (Model 1), Summerfield formula (Model 2), and B-number burning rate formula (Model 3). The results showed the burning rate was more in accord with Model 3.