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Genetic mutations of fused in sarcoma (FUS) causing amyotrophic lateral sclerosis (ALS) may disrupt mRNA splicing events. For example, the FUS c.1394-2delA variant was reported in two western ALS patients, but its molecular mechanism is unclear. In this study, we aim to investigate FUS splice site mutations in Chinese ALS patients.
Methods:
Sanger sequencing was used to identify FUS splicing mutations in Chinese ALS patients. We combined a deep learning tool (SpliceAI), RNA sequencing, and RT-PCR/RT-qPCR to analyze the effect of FUS c.1394-2delA mutation on RNA splicing and expression. AlphaFold was used to predict the protein structure of mutant FUS. In transfected cell lines, we used immunofluorescence to assess cytoplasmic mislocalization of mutant FUS protein.
Results:
We identified a de novo FUS splice acceptor site mutation (c.1394-2delA, p. Gly466Valfs*14) in one Chinese sporadic ALS patient, which is linked to exon 14 skipping, and upregulated total FUS mRNA expression. The FUS splice site mutation was predicted to be translated into a truncated protein product at C-terminal. In vitro studies revealed that the FUS mutation increased cytoplasmic mislocalization in both HEK293T and SH-SY5Y cells.
Conclusions:
We identified a de novo FUS splicing mutation (c.1394-2delA, p. Gly466Valfs*14) in 1 out of 233 Chinese ALS patients. It caused abnormal RNA splicing, upregulated gene expression, truncated FUS translation, and cytosolic mislocalization. Our findings suggested that FUS splice site mutation is rare in Chinese ALS patients and extended our knowledge of molecular mechanisms of the FUS c.1394-2delA mutation.
Studies of ‘food globalisation’ have traced the dispersal of cereals across prehistoric Eurasia. The degree to which these crops were accompanied by knowledge of soil and water preparation is less well known, however. The authors use stable isotope and archaeobotanical analyses to trace long-term trends in cultivation practices on the Loess Plateau (6000 BC–AD 1900). The results indicate that ancient farmers cultivated grains originating in South-west Asia and used distinct strategies for different species. Barley was integrated into pre-existing practices, while wheat was grown using novel soil and water management strategies. These distinct approaches suggest that the spread of prehistoric crops and knowledge about them varied by local context.
We report that vertical vibration with small amplitude and high frequency can tame convective heat transport in Rayleigh–Bénard convection in a turbulent regime. When vertical vibration is applied, a dynamically averaged ‘anti-gravity’ results that stabilizes the thermal boundary layer and inhibits the eruption of thermal plumes. This eventually leads to the attenuation of the intensity of large-scale mean flow and a significant suppression of turbulent heat transport. Accounting for both the thermally led buoyancy and the vibration-induced anti-gravitational effects, we propose an effective Rayleigh number that helps to extend the Grossmann–Lohse theory to thermal vibrational turbulence. The prediction of the reduction on both the Nusselt and Reynolds numbers obtained by the extended model is found to agree well with the numerical data. In addition, vibrational influences on the mean flow structure and the temporal evolution of Nusselt and Reynolds numbers are investigated. The non-uniform characteristic of vibration-induced ‘anti-gravity’ is discussed. The present findings provide a powerful basis for studying thermal vibrational turbulence and put forward a novel strategy for actively controlling thermal turbulence.
Treatment non-response and recurrence are the main sources of disease burden in major depressive disorder (MDD). However, little is known about its neurobiological mechanism concerning the brain network changes accompanying pharmacotherapy. The present study investigated the changes in the intrinsic brain networks during 6-month antidepressant treatment phase associated with the treatment response and recurrence in MDD.
Methods
Resting-state functional magnetic resonance imaging was acquired from untreated patients with MDD and healthy controls at baseline. The patients' depressive symptoms were monitored by using the Hamilton Rating Scale for Depression (HAMD). After 6 months of antidepressant treatment, patients were re-scanned and followed up every 6 months over 2 years. Traditional statistical analysis as well as machine learning approaches were conducted to investigate the longitudinal changes in macro-scale resting-state functional network connectivity (rsFNC) strength and micro-scale resting-state functional connectivity (rsFC) associated with long-term treatment outcome in MDD.
Results
Repeated measures of the general linear model demonstrated a significant difference in the default mode network (DMN) rsFNC change before and after the 6-month antidepressant treatment between remitters and non-remitters. The difference in the rsFNC change over the 6-month antidepressant treatment between recurring and stable MDD was also specific to DMN. Machine learning analysis results revealed that only the DMN rsFC change successfully distinguished non-remitters from the remitters at 6 months and recurring from stable MDD during the 2-year follow-up.
Conclusion
Our findings demonstrated that the intrinsic DMN connectivity could be a unique and important target for treatment and recurrence prevention in MDD.
It has been suggested that added sugar intake is associated with non-alcoholic fatty liver disease (NAFLD). However, previous studies only focused on sugar-sweetened beverages; the evidence for associations with total added sugars and their sources is scarce. This study aimed to examine the associations of total added sugars, their physical forms (liquid vs. solid), and food sources with risk of NAFLD among adults in Tianjin, China. We used data from 15,538 participants, free of NAFLD, other liver diseases, cardiovascular disease, cancer, or diabetes at baseline (2013-2018 years). Added sugar intake was estimated from a validated 100-item food frequency questionnaire. NAFLD was diagnosed by ultrasonography after exclusion of other causes of liver diseases. Multivariable Cox proportional hazards models were fitted to calculate hazards ratios (HRs) and corresponding 95% confidence intervals (CIs) for NAFLD risk with added sugar intake. During a median follow-up of 4.2 years, 3,476 incident NAFLD cases were documented. After adjusting for age, sex, body mass index and its change from baseline to follow-up, lifestyle factors, personal and family medical history, and overall diet quality, the multivariable HRs (95% CIs) of NAFLD risk were 1.18 (1.06, 1.32) for total added sugars, 1.20 (1.08, 1.33) for liquid added sugars, and 0.96 (0.86, 1.07) for solid added sugars when comparing the highest quartiles of intake with the lowest quartiles of intake. In this prospective cohort of Chinese adults, higher intakes of total added sugars and liquid added sugars, but not solid added sugars, were associated with a higher risk of NAFLD.
We aimed to examine the association between the quantity and quality of dietary fat in early pregnancy and gestational diabetes mellitus (GDM) risk. In total, 1477 singleton pregnant women were included from Sichuan Provincial Hospital for Women and Children, Southwest China. Dietary information was collected by a 3-d 24-h dietary recall. GDM was diagnosed based on the results of a 75-g, 2-h oral glucose tolerance test at 24–28 gestational weeks. Log-binomial models were used to estimate relative risks (RR) and 95% CI. The results showed that total fat intake was positively associated with GDM risk (Q4 v. Q1: RR = 1·40; 95 % CI 1·11, 1·76; Ptrend = 0·001). This association was also observed for the intakes of animal fat and vegetable fat. After stratified by total fat intake (< 30 %E v. ≥ 30 %E), the higher animal fat intake was associated with higher GDM risk in the high-fat group, but the moderate animal fat intake was associated with reduced risk of GDM (T2 v. T1: RR = 0·65; 95 % CI 0·45, 0·96) in the normal-fat group. Vegetable fat intake was positively associated with GDM risk in the high-fat group but not in the normal-fat group. No association between fatty acids intakes and GDM risk was found. In conclusion, total fat, animal and vegetable fat intakes were positively associated with GDM risk, respectively. Whereas when total fat intake was not excessive, higher intakes of animal and vegetable fat were likely irrelevant with increased GDM risk, even the moderate animal fat intake could be linked to lower GDM risk.
The purpose of this study is to realize virtual interaction and manipulation control of a hexacopter based on hand gesture recognition from a designed data glove, to provide an intuitive and visual real-time simulation system for flight control algorithm verification and external control equipment testing. First, the hand gesture recognition from a designed data glove is studied, which can recognize different actions, such as mobile ready, grab, loosen, landing, take-off, and hover. Then, the design of virtual simulation system for hexacopter capture is completed, with the model design of hexacopter and manipulator, and the simulation software design with
$CoppeliaSim$
. Finally, virtual simulation experiment of hexacopter grasping and virtual flight control experiment based on data glove are tested, respectively, and quantitatively described. The overall recognition rate is 84.3%, indicating that the data glove produced has the ability to recognize gestures, but its recognition performance is not superior. In gesture recognition, the recognition rate of static gestures is relatively higher than that of dynamic gestures. Among the static gestures, the hover gesture has the highest recognition rate. The average correct rate of static gestures can reach 94%. The lowest recognition rate of dynamic gestures is upward movement, and the average recognition rate of dynamic gestures is 76.1%. The research can be used to remotely operate hexacopter using a data glove in the future and improve the control performance through virtual interaction and manipulation simulation before actual application.
Prospective cohort studies linking organ meat consumption and nonalcoholic fatty liver disease (NAFLD) are limited, especially in Asian populations. This study aimed to prospectively investigate the association between organ meat consumption and risk of NAFLD in a general Chinese adult population. This prospective cohort study included a total of 15,568 adults who were free of liver disease, cardiovascular disease, and cancer at baseline. Dietary information was collected at baseline using a validated food frequency questionnaire. NAFLD was diagnosed by abdominal ultrasound after excluding other causes related to chronic liver disease. Cox proportional regression models were used to assess the association between organ meat consumption and risk of NAFLD. During a median of 4.2 years of follow-up, we identified 3,604 incident NAFLD cases. After adjusting for demographic characteristics, lifestyle factors, vegetable, fruit, soft drink, seafood, and red meat consumption, the multivariable hazard ratios (95% confidence intervals) for incident NAFLD across consumption of organ meat were 1.00 (reference) for almost never, 1.04 (0.94, 1.15) for tertile 1, 1.08 (0.99, 1.19) for tertile 2, and 1.11 (1.01, 1.22) for tertile 3, respectively (P for trend <0.05). Such association did not differ substantially in the sensitivity analysis. Our study indicates that organ meat consumption was related to a modestly higher risk of NAFLD among Chinese adults. Further investigations are needed to confirm this finding.
Peanut shell plays key roles in protecting the seed from diseases and pest infestation but also in the processing of peanut and is an important byproduct of peanut production. Most studies on peanut shell have focused on the utilization of its chemical applications, but the genetic basis of shell-related traits is largely unknown. A panel of 320 peanut (Arachis hypogaea) accessions including var. hypogaea, var. vulgaris, var. fastigiata and var. hirsuta was used to study the genetic basis of two physical and five microstructure-related traits in peanut shell. Significant phenotypic differences were revealed among the accessions of var. hypogaea, var. hirsuta, var. vulgaris and var. fastigiata for mechanical strength, thickness, three sclerenchymatous layer projections and main cell shape of the sclerenchymatous layer. We identified 10 significant single nucleotide polymorphisms (SNPs) through genome-wide association study (P < 5.0 × 10−6) combining the shell-related traits and high-quality SNPs. In total, 192 genes were located in physical proximity to the significantly associated SNPs, and 11 candidate genes were predicted related to their potential contribution to the development and structure of the peanut shell. All SNPs were detected on the B genome demonstrating the biased contribution of the B genome for the phenotypical make-up of peanut. Exploring the newly identified candidate genes will provide insight into the molecular pathways that regulate peanut shell-related traits and provide valuable information for molecular marker-assisted breeding of an improved peanut shell.
The aim of the present study was to compare the rate of preterm birth (PTB) and growth from birth to 18 years between twins conceived by in vitro fertilization (IVF) and twins conceived by spontaneous conception (SC) in mainland China. The retrospective cohort study included 1164 twins resulting from IVF and 25,654 twins conceived spontaneously, of which 494 from IVF and 6338 from SC were opposite-sex twins. PTB and low birth weight (LBW), and growth, including length/height and weight, were compared between the two groups at five stages: infancy (0 year), toddler period (1–2 years), preschool (3–5 years), primary or elementary school (6–11 years), and adolescence (10–18 years). Few statistically significant differences were found for LBW and growth between the two groups after adjusting for PTB and other confounders. Twins born by IVF faced an increased risk of PTB compared with those born by SC (adjusted odds ratio [aOR] 8.21, 95% confidence interval [CI] [3.19, 21.13], p < .001 in all twins and aOR 10.12, 95% CI [2.32, 44.04], p = .002 in opposite-sex twins). Twins born by IVF experienced a similar growth at five stages (0–18 years old) when compared with those born by SC. PTB risk, however, is significantly higher for twins conceived by IVF than those conceived by SC.
Chronic inflammation exerts pleiotropic effects in the aetiology and progression of chronic obstructive pulmonary disease (COPD). Glucosamine is widely used in many countries and may have anti-inflammatory properties. We aimed to prospectively evaluate the association of regular glucosamine use with incident COPD risk and explore whether such association could be modified by smoking in the UK Biobank cohort, which recruited more than half a million participants aged 40–69 years from across the UK between 2006 and 2010. Cox proportional hazards models with adjustment for potential confounding factors were used to calculate hazard ratios (HR) as well as 95 % CI for the risk of incident COPD. During a median follow-up of 8·96 years (interquartile range 8·29–9·53 years), 9016 new-onset events of COPD were documented. We found that the regular use of glucosamine was associated with a significantly lower risk of incident COPD with multivariable adjusted HR of 0·80 (95 % CI, 0·75, 0·85; P < 0·001). When subgroup analyses were performed by smoking status, the adjusted HR for the association of regular glucosamine use with incident COPD were 0·84 (0·73, 0·96), 0·84 (0·77, 0·92) and 0·71 (0·62, 0·80) among never smokers, former smokers and current smokers, respectively. No significant interaction was observed between glucosamine use and smoking status (Pfor interaction = 0·078). Incident COPD could be reduced by 14 % to 84 % through a combination of regular glucosamine use and smoking cessation.
Nutritional Risk Screening index is a standard tool to assess nutritional risk, but epidemiological data are scarce on controlling nutritional status (CONUT) as a prognostic marker in acute haemorrhagic stroke (AHS). We aimed to explore whether the CONUT may predict a 3-month functional outcome in AHS. In total, 349 Chinese patients with incident AHS were consecutively recruited, and their malnutrition risks were determined using a high CONUT score of ≥ 2. The cohort patients were divided into high-CONUT (≥ 2) and low-CONUT (< 2) groups, and primary outcomes were a poor functional prognosis defined as the modified Rankin Scale (mRS) score of ≥ 3 at post-discharge for 3 months. Odds ratios (OR) with 95 % confidence intervals (CI) for the poor functional prognosis at post-discharge were estimated by using a logistic analysis with additional adjustments for unbalanced variables between the high-CONUT and low-CONUT groups. A total of 328 patients (60·38 ± 12·83 years; 66·77 % male) completed the mRS assessment at post-discharge for 3 months, with 172 patients at malnutrition risk at admission and 104 patients with a poor prognosis. The levels of total cholesterol and total lymphocyte counts were significantly lower in high-CONUT patients than low-CONUT patients (P = 0·012 and < 0·001, respectively). At 3-month post discharge, there was a greater risk for the poor outcome in the high-CONUT compared with the low-CONUT patients at admission (OR: 2·32, 95 % CI: 1·28, 4·17). High-CONUT scores independently predict a 3-month poor prognosis in AHS, which helps to identify those who need additional nutritional managements.
In China, the indications of paliperidone extended in schizophrenia adolescents (12-17 years) was approved by National Medical Products Administration (NMPA) in 2017. But, the utilization of paliperidone in this group needs to be further investigated.
Objectives
To assess paliperidone utilization in schizophrenia adolescents.
Methods
The study employed the electronic medical records (EMRs) database from a psychiatry specialized hospital (PH) and a general hospital (GH), respectively. General information, including birth date, gender, visit date, diagnosis (inpatient and outpatient) with ICD-10 coding, drug characterize, prescription date and dosage, was de-identified and standardized for analysis. Schizophrenia adolescents (ICD-10: F20.x) received at least one prescription of paliperidone between 2018 and 2019 were included in this study. Index date was defined as the date of first identified paliperidone prescription. The patients were followed up until the end of 2019 with the last record, or upon reaching 18 years. The database was analyzed based on days of supply, administration frequency, and daily dose.
Results
Overall, 112 and 117 eligible patients were included in the present study from PH and GH, respectively. The median drug supply was 179.0 days and 44.0 days, respectively, during which median number of prescriptions patients received was 6.0 and 3.0. Paliperidone was mostly initiated alone (57.1% and 88.9%) with frequency of once daily (97.3% and 88.9%), and the median of average daily dose during follow-up was 5.7 mg/day and 6.0 mg/day, respectively.
Conclusions
The duration of paliperidone usage was very different in two hospitals, but the dosages in both hospitals were generally agreed with prescribing information.
Fruit intake may influence gestational diabetes mellitus (GDM) risk. However, prospective evidence remains controversial and limited. The current study aimed to investigate whether total fruit and specific fruit intake influence GDM risk.
Design:
A prospective cohort study was conducted. Dietary information was collected by a 3-d 24-h dietary recall. All participants underwent a standard 75-g oral glucose tolerance test at 24–28 gestational weeks. Log-binomial models were used to estimate the association between fruit intake and GDM risk, and the results are presented as relative risks (RR) and 95 % CI.
Setting:
Southwest China.
Participants:
Totally, 1453 healthy pregnant women in 2017.
Results:
Total fruit intake was not associated with lower GDM risk (RR of 1·03 (95 % CI 0·83, 1·27) (Ptrend = 0·789)). The RR of GDM risk was 0·73 for the highest anthocyanin-rich fruit intake quartile compared with the lowest quartile (95 % CI 0·56, 0·93; Ptrend = 0·015). A higher grape intake had a linear inverse association with GDM risk (Q4 v. Q1: RR = 0·65; 95 % CI 0·43, 0·98; Ptrend = 0·044), and after further adjustment for anthocyanin intake, the inverse association tended to be non-linear (Q4 v. Q1: RR = 0·65; 95 % CI 0·44, 0·98; Ptrend = 0·079). However, we did not find an association between glycaemic index-grouped fruit, glycaemic load-grouped fruit or other fruit subtype intake and GDM risk.
Conclusions:
In conclusion, specific fruit intake (particularly anthocyanin-rich fruit and grapes) but not total fruit intake was inversely associated with GDM risk.
We aimed to examine the association between low-carbohydrate diet (LCD) scores during the first trimester and gestational diabetes mellitus (GDM) risk in a Chinese population. A total of 1455 women were included in 2017. Dietary information during the first trimester was collected by 24-h dietary recalls for 3 d. The overall, animal and plant LCD scores, which indicated adherence to different low-carbohydrate dietary patterns, were calculated. GDM was diagnosed based on the results of a 75-g, 2-h oral glucose tolerance test at 24–28 weeks gestation. Log-binomial models were used to estimate relative risks (RR) and 95 % CI. The results showed that the multivariable-adjusted RR of GDM from the lowest to the highest quartiles of the overall LCD score were 1·00 (reference), 1·15 (95 % CI 0·92, 1·42), 1·30 (95 % CI 1·06, 1·60) and 1·24 (95 % CI 1·01, 1·52) (P = 0·026 for trend). Multivariable-adjusted RR (95 % CI) of GDM from the lowest to the highest quartiles of the animal LCD score were 1·00 (reference), 1·20 (95 % CI 0·96, 1·50), 1·41 (95 % CI 1·14, 1·73) and 1·29 (95 % CI 1·04, 1·59) (P = 0·002 for trend). After additional adjustment for gestational weight gain before GDM diagnosis, the association of the overall LCD score with GDM risk was non-significant, while the association of animal LCD score with GDM risk remained significant. In conclusion, a low-carbohydrate dietary pattern characterised by high animal fat and protein during the first trimester is associated with an increased risk of GDM in Chinese women.
The Yangtze Block in South China constitutes an important Precambrian landmass in the present East Asian continent. The Neoproterozoic sedimentary successions of the Hengdan Group in the NW Yangtze Block record essential information for deciphering the Neoproterozoic tectonics along the NW margin. However, its depositional age, provenance and tectonic properties remain uncertain. Here, a combined analysis of detrital zircon U–Pb dating and geochemistry is performed on representative samples from the Hengdan Group. Concordant dating results of samples from the bottom and upper parts constrain the maximum depositional age at c. 720 Ma. Detrital zircon age patterns of samples reveal a uniformly pronounced age peak at c. 915–720 Ma, which is consistent with the magmatic pulses in domains at the NW end of the Yangtze Block. In addition, these samples display left-sloping post-Archaean Australian shale (PAAS)-normalized rare-earth element patterns and variable trace element patterns, resembling sediments accumulated in a basin related to an active continental margin geodynamic setting. Provenance analysis reveals that the main sources featured intermediate to felsic components, which experienced rapid erosion and sedimentation. These integrated new investigations, along with previous compilations, indicate that the Hengdan Group might have been deposited in a fore-arc basin controlled by subduction beneath the Bikou Terrane. Thus, such interpretation further supports proposals for subduction-related tectonics along the western margin of the Yangtze Block during the early Neoproterozoic.
Early replacement of a new central venous catheter (CVC) may pose a risk of persistent or recurrent infection in patients with a catheter-related bloodstream infection (CRBSI). We evaluated the clinical impact of early CVC reinsertion after catheter removal in patients with CRBSIs.
Methods:
We conducted a retrospective chart review of adult patients with confirmed CRBSIs in 2 tertiary-care hospitals over a 7-year period.
Results:
To treat their infections, 316 patients with CRBSIs underwent CVC removal. Among them, 130 (41.1%) underwent early CVC reinsertion (≤3 days after CVC removal), 39 (12.4%) underwent delayed reinsertion (>3 days), and 147 (46.5%) did not undergo CVC reinsertion. There were no differences in baseline characteristics among the 3 groups, except for nontunneled CVC, presence of septic shock, and reason for CVC reinsertion. The rate of persistent CRBSI in the early CVC reinsertion group (22.3%) was higher than that in the no CVC reinsertion group (7.5%; P = .002) but was similar to that in the delayed CVC reinsertion group (17.9%; P > .99). The other clinical outcomes did not differ among the 3 groups, including rates of 30-day mortality, complicated infection, and recurrence. After controlling for several confounding factors, early CVC reinsertion was not significantly associated with persistent CRBSI (OR, 1.59; P = .35) or 30-day mortality compared with delayed CVC reinsertion (OR, 0.81; P = .68).
Conclusions:
Early CVC reinsertion in the setting of CRBSI may be safe. Replacement of a new CVC should not be delayed in patients who still require a CVC for ongoing management.