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Hyperhomocysteinemia (HHcy) is associated with all-cause mortality in some disease states. However, the correlation between HHcy and the risk of mortality in the general population has rarely been researched. We aimed to evaluate the association between HHcy and all-cause and cause-specific mortality among adults in the United States. This study analyzed data from the National Health and Nutrition Examination Survey database (1999–2002 survey cycle). A multivariable Cox regression model was built to evaluate the correlation between HHcy and all-cause and cause-specific mortality. Smooth curve fitting was used to analyze their dose-dependent relationship. A total of 8,442 adults aged 18–70 years were included in this study. After a median follow-up period of 14.7 years, 1,007 (11.9%) deaths occurred including 197 cardiovascular disease (CVD)-related deaths, 255 cancer-related deaths, and 58 respiratory disease deaths. The participants with HHcy had a 93% increased risk of all-cause mortality (hazard ratio [HR], 1.93; 95% confidence interval [CI)], 1.48–2.51), 160% increased risk of CVD mortality (HR, 2.60; 95% CI, 1.52–4.45), and 82% increased risk of cancer mortality (HR, 1.82; 95% CI, 1.03–3.21) compared to those without HHcy. For unmeasured confounding, E-value analysis proved to be robust. In conclusion, HHcy was associated with high risk of all-cause and cause-specific (CVD, cancer) mortality among adults aged below 70 years.
The selection of high-quality sperms is critical to intracytoplasmic sperm injection, which accounts for 70–80% of in vitro fertilization (IVF) treatments. So far, sperm screening is usually performed manually by clinicians. However, the performance of manual screening is limited in its objectivity, consistency, and efficiency. To overcome these limitations, we have developed a fast and noninvasive three-stage method to characterize morphology of freely swimming human sperms in bright-field microscopy images using deep learning models. Specifically, we use an object detection model to identify sperm heads, a classification model to select in-focus images, and a segmentation model to extract geometry of sperm heads and vacuoles. The models achieve an F1-score of 0.951 in sperm head detection, a z-position estimation error within ±1.5 μm in in-focus image selection, and a Dice score of 0.948 in sperm head segmentation, respectively. Customized lightweight architectures are used for the models to achieve real-time analysis of 200 frames per second. Comprehensive morphological parameters are calculated from sperm head geometry extracted by image segmentation. Overall, our method provides a reliable and efficient tool to assist clinicians in selecting high-quality sperms for successful IVF. It also demonstrates the effectiveness of deep learning in real-time analysis of live bright-field microscopy images.
The subduction model of the Neo-Tethys during the Early Cretaceous has always been a controversial topic, and the scarcity of Early Cretaceous magmatic rocks in the southern part of the Gangdese batholith is the main cause of this debate. To address this issue, this article presents new zircon U–Pb chronology, zircon Hf isotope, whole-rock geochemistry and Sr–Nd isotope data for the Early Cretaceous quartz diorite dykes with adakite affinity in Liuqiong, Gongga. Zircon U–Pb dating of three samples yielded ages of c. 141–137 Ma, indicating that the Liuqiong quartz diorite was emplaced in the Early Cretaceous. The whole-rock geochemical analysis shows that the Liuqiong quartz diorite is enriched in large-ion lithophile elements (LILEs) and light rare-earth elements (LREEs) and is depleted in high-field-strength elements (HFSEs), which are related to slab subduction. Additionally, the Liuqiong quartz diorite has high SiO2, Al2O3 and Sr contents, high Sr/Y ratios and low heavy rare-earth element (HREE) and Y contents, which are compatible with typical adakite signatures. The initial 87Sr/86Sr values of the Liuqiong adakite range from 0.705617 to 0.705853, and the whole-rock ϵNd(t) values vary between +5.78 and +6.24. The zircon ϵHf(t) values vary from +11.5 to +16.4. Our results show that the Liuqiong adakite magma was derived from partial melting of the Neo-Tethyan oceanic plate (mid-ocean ridge basalt (MORB) + sediment + fluid), with some degree of subsequent peridotite interaction within the overlying mantle wedge. Combining regional data, we favour the interpretation that the Neo-Tethyan oceanic crust was subducted at a low angle beneath the Gangdese during the Early Cretaceous.
This paper, in allusion to the limitations of traditional transfer alignment methods based on the external measurement equipment or the empirical model of angular deformation, proposes a rapid and accurate transfer alignment method without relying on the empirical angular deformation model. Firstly, the relationship between the actual angular deformation and the angular velocities measured by the gyroscopes in the master and slave inertial navigation systems (INSs) is derived to roughly estimate the angular deformation. Secondly, according to the error characteristics of gyroscopes, the error model of angular deformation is established. Thirdly, expanding the angular deformation error instead of the installation error angle, flexure angle and flexure angle rate into the state vector, a low-order transfer alignment filtering model independent of the empirical angular deformation model is established. The proposed method not only gets rid of the dependence on an empirical angular deformation model, but also realises the rapid and accurate initial alignment of the slave INS without adding any external measurement equipment. The simulations and experiments evidence the validity of the proposed transfer alignment method.
The association between executive dysfunction, brain dysconnectivity, and inflammation is a prominent feature across major psychiatric disorders (MPDs), schizophrenia, bipolar disorder, and major depressive disorder. A dimensional approach is warranted to delineate their mechanistic interplay across MPDs.
This single site study included a total of 1543 participants (1058 patients and 485 controls). In total, 1169 participants underwent diffusion tensor and resting-state functional magnetic resonance imaging (745 patients and 379 controls completed the Wisconsin Card Sorting Test). Fractional anisotropy (FA) and regional homogeneity (ReHo) assessed structural and functional connectivity, respectively. Pro-inflammatory cytokine levels [interleukin (IL)-1β, IL-6, and tumor necrosis factor-α] were obtained in 325 participants using blood samples collected with 24 h of scanning. Group differences were determined for main measures, and correlation and mediation analyses and machine learning prediction modeling were performed.
Executive deficits were associated with decreased FA, increased ReHo, and elevated IL-1β and IL-6 levels across MPDs, compared to controls. FA and ReHo alterations in fronto-limbic-striatal regions contributed to executive deficits. IL-1β mediated the association between FA and cognition, and IL-6 mediated the relationship between ReHo and cognition. Executive cognition was better predicted by both brain connectivity and cytokine measures than either one alone for FA-IL-1β and ReHo-IL-6.
Transdiagnostic associations among brain connectivity, inflammation, and executive cognition exist across MPDs, implicating common neurobiological substrates and mechanisms for executive deficits in MPDs. Further, inflammation-related brain dysconnectivity within fronto-limbic-striatal regions may represent a transdiagnostic dimension underlying executive dysfunction that could be leveraged to advance treatment.
Ammannia multiflora Roxb. is a dominant broadleaf weed that is a serious problem in southern China rice fields, and acetolactate synthase (ALS)-inhibiting herbicides have been used for its control for more than 20 years. Excessive reliance on ALS-inhibiting herbicides has led to herbicide resistance in A. multiflora. In this study, 10 A. multiflora populations from the Jiangsu Province of China were collected, and the resistance levels and target site–resistance mechanisms to ALS-inhibiting herbicides bensulfuron-methyl and penoxsulam were investigated. The dose–response assays showed that eight populations evolved resistance to bensulfuron-methyl (9.1- to 90.9-fold) and penoxsulam (5.0- to 103.1-fold). Amplification of ALS genes indicated that there were three ALS genes (AmALS1, AmALS2, and AmALS3) in A. multiflora. Sequence analysis revealed amino acid mutations at Pro-197 in either AmALS1 (Pro-197-Ala, Pro-197-Ser, and Pro-197-His) or AmALS2 (Pro-197-Ser and Pro-197-Arg) in resistant populations, and no mutations were found in AmALS3. Moreover, two independent mutations (Pro-197-Ala in AmALS1 and Pro-197-Ser in AmALS2 or Pro-197-Ala in AmALS1 and Pro-197-Arg in AmALS2) coexisted in two resistant populations, respectively. In addition, the auxin mimic herbicides MCPA and florpyrauxifen-benzyl, the photosystem II inhibitor bentazon, and the protoporphyrinogen oxidase inhibitor carfentrazone-ethyl can effectively control the resistant A. multiflora populations. Our study demonstrates the wide prevalence of ALS inhibitor–resistant A. multiflora populations in Jiangsu Province and the diversity of Pro-197 mutations in ALS genes and provides alternative herbicide options for controlling resistant A. multiflora populations.
Little is known about how sociodemographic and clinical factors affect the caregiving burden of persons with schizophrenia (PwSs) with transition in primary caregivers.
This study aimed to examine the predictive effects of sociodemographic and clinical factors on the caregiving burden of PwSs with and without caregiver transition from 1994 to 2015 in rural China.
Using panel data, 206 dyads of PwSs and their primary caregivers were investigated in both 1994 and 2015. The generalised linear model approach was used to examine the predictive effects of sociodemographic factors, severity of symptoms and changes in social functioning on the caregiving burden with and without caregiver transition.
The percentages of families with and without caregiver transition were 38.8% and 61.2%, respectively. Among families without caregiver transition, a heavier burden was significantly related to a larger family size and more severe symptoms in PwSs. Deteriorated functioning of ‘social activities outside the household’ and improved functioning of ‘activity in the household’ were protective factors against a heavy caregiving burden. Among families with caregiver transition, younger age, improved marital functioning, deteriorated self-care functioning, and better functioning of ‘social interest or concern’ were significant risk factors for caregiving burden.
The effects of sociodemographic and clinical correlates on the caregiving burden were different among families with and without caregiver transition. It is crucial to explore the caregiver arrangement of PwSs and the risk factors for burden over time, which will facilitate culture-specific family interventions, community-based mental health services and recovery.
Athetis lepigone Möschler (Lepidoptera, Noctuidae) is a common maize pest in Europe and Asia. However, there is no long-term effective management strategy is available yet to suppress its population. Adults rely heavily on olfactory cues to locate their optimal host plants and oviposition sites. Pheromone-binding proteins (PBPs) are believed to be responsible for recognizing and transporting different odorant molecules to interact with receptor membrane proteins. In this study, the ligand-binding specificities of two AlepPBPs (AlepPBP2 and AlepPBP3) for sex pheromone components and host plant (maize) volatiles were measured by fluorescence ligand-binding assay. The results demonstrated that AlepPBP2 had a high affinity with two pheromones [(Z)-7-dodecenyl acetate, Ki = 1.11 ± 0.1 μM, (Z)-9-tetradecenyl acetate, Ki = 1.32 ± 0.15 μM] and ten plant volatiles, including (-)-limonene, α-pinene, myrcene, linalool, benzaldehyde, nonanal, 2-hexanone, 3-hexanone, 2-heptanone and 6-methyl-5-hepten-2-one. In contrast, we found that none of these chemicals could bind to AlepPBP3. Our results clearly show no significant differences in the functional characterization of the binding properties between AlepPBP2 and AlepPBP3 to sex pheromones and host plant volatiles. Furthermore, molecular docking was employed for further detail on some crucial amino acid residues involved in the ligand-binding of AlepPBP2. These findings will provide valuable information about the potential protein binding sites necessary for protein-ligand interactions which appear as attractive targets for the development of novel technologies and management strategies for insect pests.
Bladder cancer is the most common malignant tumour of the urinary system that is characterised by significant intra-tumoural heterogeneity. While large-scale sequencing projects have provided a preliminary understanding of tumour heterogeneity, these findings are based on the average signals obtained from the pooled populations of diverse cells. Recent advances in single-cell sequencing (SCS) technologies have been critical in this regard, opening up new ways of understanding the nuanced tumour biology by identifying distinct cellular subpopulations, dissecting the tumour microenvironment, and characterizing cellular genomic mutations. By integrating these novel insights, SCS technologies are expected to make powerful and meaningful changes to the current diagnosis and treatment of bladder cancer through the identification and usage of novel biomarkers as well as targeted therapeutics. SCS can discriminate complex heterogeneity in a large population of tumour cells and determine the key molecular properties that influence clinical outcomes. Here, we review the advances in single-cell technologies and discuss their applications in cancer research and clinical practice, with a specific focus on bladder cancer.
Due to less light scattering and a better signal-to-noise ratio in deep imaging, two-photon fluorescence microscopy (TPFM) has been widely used in biomedical photonics since its advent. However, optical aberrations degrade the performance of TPFM in terms of the signal intensity and the imaging depth and therefore restrict its application. Here, we introduce adaptive optics based on the genetic algorithm to detect the distorted wavefront of the excitation laser beam and then perform aberration correction to optimize the performance of TPFM. By using a spatial light modulator as the wavefront controller, the correction phase is obtained through a signal feedback loop and a process of natural selection. The experimental results show that the signal intensity and imaging depth of TPFM are improved after aberration correction. Finally, the method was applied to two-photon fluorescence lifetime imaging, which helps to improve the signal-to-noise ratio and the accuracy of lifetime analysis. Furthermore, the method can also be implemented in other experiments, such as three-photon microscopy, light-sheet microscopy, and super-resolution microscopy.
To improve mobile robot positioning accuracy in building environments and construct structural three-dimensional (3D) maps, this paper proposes a stereo visual-inertial odometry (VIO) system based on structural lines and points belonging to lines. The 2-degree-of-freedom (DoF) spatial structural lines based on the Manhattan world assumption are used to establish visual measurement constraints. The property of point belonging to a line (PPBL) is used to initialize the structural lines and establish spatial distance-residual constraints between point and line landmarks in the reconstructed 3D map. Compared with the 4-DoF spatial straight line, the 2-DoF structural line reduces the variables to be estimated and introduces the orientation information of scenes to the VIO system. The utilization of PPBL makes the proposed system fully exploit the prior geometric information of environments and then achieves better performance. Tests on public data sets and real-world experiments show that the proposed system can achieve higher positioning accuracy and construct 3D maps that better reflect the structure of scenes than existing VIO approaches.
Metabolically healthy obesity (MHO) might be an alternative valuable target in obesity treatment. We aimed to assess whether alternative Mediterranean (aMED) diet and Dietary Approaches to Stop Hypertension (DASH) diet were favourably associated with obesity and MHO phenotype in a Chinese multi-ethnic population. We conducted this cross-sectional analysis using the baseline data of the China Multi-Ethnic Cohort study that enrolled 99 556 participants from seven diverse ethnic groups. Participants with self-reported cardiometabolic diseases were excluded to eliminate possible reverse causality. Marginal structural logistic models were used to estimate the associations, with confounders determined by directed acyclic graph (DAG). Among 65 699 included participants, 11·2 % were with obesity. MHO phenotype was present in 5·7 % of total population and 52·7 % of population with obesity. Compared with the lowest quintile, the highest quintile of DASH diet score had 23 % decreased odds of obesity (OR = 0·77, 95 % CI 0·71, 0·83, Ptrend < 0·001) and 27 % increased odds of MHO (OR = 1·27, 95 % CI 1·10, 1·48, Ptrend = 0·001) in population with obesity. However, aMED diet showed no obvious favourable associations. Further adjusting for BMI did not change the associations between diet scores and MHO. Results were robust to various sensitivity analyses. In conclusion, DASH diet rather than aMED diet is associated with reduced risk of obesity and presents BMI-independent metabolic benefits in this large population-based study. Recommendation for adhering to DASH diet may benefit the prevention of obesity and related metabolic disorders in Chinese population.
Extensive magmatism in NE China, eastern Central Asian Orogenic Belt, has produced multi-stage granitic plutons and accompanying W mineralization. The Narenwula complex in the southwestern Great Xing’an Range provides important insights into the petrogenesis, geodynamic processes and relationship with W mineralization. The complex comprises granodiorites, monzogranites and granite porphyry. Mafic microgranular enclaves are common in the granodiorites, and have similar zircon U–Pb ages as their host rocks (258.5–253.9 Ma), whereas the W-bearing granitoids yield emplacement ages of 149.8–148.1 Ma. Permian granodiorites are I-type granites that are enriched in large-ion lithophile elements and light rare earth elements, and depleted in high field strength elements and heavy rare earth elements. Both the mafic microgranular enclaves and granodiorites have nearly identical zircon Hf isotopic compositions. The results suggest that the mafic microgranular enclaves and granodiorites formed by the mixing of mafic and felsic magmas. W-bearing granitoids are highly fractionated A-type granites, enriched in Rb, Th, U and Pb, and depleted in Ba, Sr, P, Ti and Eu. They have higher W concentrations and Rb/Sr ratios, and lower Nb/Ta, Zr/Hf and K/Rb ratios than the W-barren granodiorites. These data and negative ϵHf(t) values (–6.0 to –2.1) suggest that they were derived from the partial melting of ancient lower crust and subsequently underwent extreme fractional crystallization. Based on the regional geology, we propose that the granodiorites were generated in a volcanic arc setting related to the subduction of the Palaeo-Asian Ocean, whereas the W-bearing granitoids and associated deposits formed in a post-orogenic extensional setting controlled by the Mongol–Okhotsk Ocean and Palaeo-Pacific Ocean tectonic regimes.
This work reports experimental observation and theoretical explanation of the dynamics and morphology of a droplet passing through a soap film. During the process, the film undergoes four sequential responses: (1) film deformation upon droplet impact; (2) drop–film detachment; (3) coalescence of the film shell with the drop; (4) peel-off of the film shell. Physical models and the corresponding analytical expressions are developed to reveal the underlying physics for the observed four responses. It is identified that the film is an elongated catenoid under continuous stretch by the droplet, and that they separate at the fixed height of 5.8 times of the droplet radius while the detach point is located at the centre of the height. After separation, the droplet is wrapped with a film shell, which is then punctured by the ring tip of the converging surface wave at the impacting Weber number range of [45, 225]. The film shell then coalesces with the droplet, falls off with a fixed velocity and is eventually ejected as a bubble leaving the droplet with a transplanted surface of the soap solution.
This study examined the pattern of medical utilization and the distribution of comorbidities shortly before death among adolescents who died from suicide and compared these data with those of living controls.
From Taiwan's National Health Insurance Research Database, this study identified adolescents aged 10–19 years who died from suicide (n = 935) between 1 January 2000, and 31 December 2016, by linking each patient with the national mortality database. The researchers conducted a nested case–control study through risk set sampling, and for each case, 20 age- and sex-matched controls (n = 18 700) were selected from the general population. The researchers applied conditional logistic regression to investigate differences in medical utilization and physical and psychiatric comorbidities between cases and controls.
Cases had a higher proportion of contact with the psychiatric department but a similar proportion of contact with any non-psychiatric medical department within 1 year before suicide compared with controls. There were 18.6% of adolescent suicide victims who only had contacted with a psychiatric department 3 months before suicide. Moreover, cases had a higher proportion of contact with non-psychiatric services within 3 months before suicide, particularly with emergency, surgery, and internal medicine departments. Cases had higher risks of several psychiatric disorders and physical illnesses, including heart diseases, pneumonia, and ulcer disease, than did controls.
The findings of increased medical utilization and higher risks of physical and psychiatric comorbidities in adolescent suicide victims are crucial for developing specific interventions to prevent suicide in this population.
The effects of chordwise deformation and the half-amplitude asymmetry on the hydrodynamic performance and vortex dynamics of batoid fish have been numerically investigated, in which the two parameters were represented by the wavenumber ($W$) and the ratio of the half-amplitude above the longitudinal axis to that below ($HAR$). Fin kinematics were prescribed based on biological data. Simulations were conducted using the immersed boundary method. It was found that moderate chordwise deformation enhances the thrust, saves the power and increases the efficiency. A large $HAR$ can also increase thrust performance. By using the derivative-moment transformation theory at several subdomains to capture the local vortical structures and a force decomposition, it was shown that, at high Strouhal numbers ($St$), the tip vortex is the main source of thrust, whereas the leading-edge vortex (LEV) and trailing-edge vortex weaken the thrust generation. However, at lower $St$, the LEV would enhance the thrust. The least deformation ($W=0$) leads to the largest effective angle of attack, and thus the strongest vortices. However, moderate deformation ($W=0.4$) has an optimal balance between the performance enhancement and the opposite effect of different local structures. The performance enhancement of $HAR$ was also due to the increase of the vortical contributions. This work provides a new insight into the role of vortices and the force enhancement mechanism in aquatic swimming.
Cancer remains the leading cause of death worldwide, and metastasis is still the major cause of treatment failure for cancer patients. Epithelial–mesenchymal transition (EMT) has been shown to play a critical role in the metastasis cascade of epithelium-derived carcinoma. Tumour microenvironment (TME) refers to the local tissue environment in which tumour cells produce and live, including not only tumour cells themselves, but also fibroblasts, immune and inflammatory cells, glial cells and other cells around them, as well as intercellular stroma, micro vessels and infiltrated biomolecules from the nearby areas, which has been proved to widely participate in the occurrence and progress of cancer. Emerging and accumulating studies indicate that, on one hand, mesenchymal cells in TME can establish ‘crosstalk’ with tumour cells to regulate their EMT programme; on the other, EMT-tumour cells can create a favourable environment for their own growth via educating stromal cells. Recently, our group has conducted a series of studies on the interaction between tumour-associated macrophages (TAMs) and colorectal cancer (CRC) cells in TME, confirming that the interaction between TAMs and CRC cells mediated by cytokines or exosomes can jointly promote the metastasis of CRC by regulating the EMT process of tumour cells and the M2-type polarisation process of TAMs. Herein, we present an overview to describe the current knowledge about EMT in cancer, summarise the important role of TME in EMT, and provide an update on the mechanisms of TME-induced EMT in CRC, aiming to provide new ideas for understanding and resisting tumour metastasis.
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.
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.
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.
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.