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Direct numerical simulations are performed to explore the evolution behaviour of the turbulent/non-turbulent interface (TNTI) in a temporally evolving turbulent plane jet, using the evolution equation for the TNTI surface area. A novel algorithm is used to calculate the surface area of the TNTI and entrainment flux. It is shown that the surface area remains relatively constant, which leads to the mean entrainment velocity being inversely proportional to the square root of time. On average, the effects of the stretching and curvature/viscous terms on the TNTI area roughly counterbalance each other, while the curvature/inviscid term associated with vortex stretching is virtually zero. More specifically, the stretching term contributes to the production of the surface area, while the curvature/viscous term is associated with a destruction in the surface area. The local effect of the curvature/viscous term exhibits high spatial intermittency with small-scale extreme/intense events, whereas the effect of the large-scale stretching term is more continuous. To shed light on the contribution of curvature/viscous term to the evolution of the surface area, we decompose it into three components. The effect of the curvature/normal diffusion term (the curvature/viscous dissipation term) in the bulging regions (the valley regions) mainly contributes to the production of the area. The continuous decrease of the average mean curvature is associated with the production of the bulging regions and the destruction of the valley regions. Finally, although the entrainment velocity is mainly dominated by the normal diffusion effect, all three components related to the viscous effect are indispensable to the production and destruction of the TNTI area. This numerical study contributes to a better understanding of the evolution of the TNTI area.
Timing of food intake is an emerging aspect of nutrition; however, there is a lack of research accurately assessing food timing in the context of the circadian system. The study aimed to investigate the relation between food timing relative to clock time and endogenous circadian timing with adiposity and further explore sex differences in these associations among 151 young adults aged 18–25 years. Participants wore wrist actigraphy and documented sleep and food schedules in real time for 7 consecutive days. Circadian timing was determined by dim-light melatonin onset (DLMO). The duration between last eating occasion and DLMO (last EO-DLMO) was used to calculate the circadian timing of food intake. Adiposity was assessed using bioelectrical impedance analysis. Of the 151 participants, 133 were included in the statistical analysis finally. The results demonstrated that associations of adiposity with food timing relative to circadian timing rather than clock time among young adults living in real-world settings. Sex-stratified analyses revealed that associations between last EO-DLMO and adiposity were significant in females but not males. For females, each hour increase in last EO-DLMO was associated with higher BMI by 0·51 kg/m2 (P = 0·01), higher percent body fat by 1·05 % (P = 0·007), higher fat mass by 0·99 kg (P = 0·01) and higher visceral fat area by 4·75 cm2 (P = 0·02), whereas non-significant associations were present among males. The findings highlight the importance of considering the timing of food intake relative to endogenous circadian timing instead of only as clock time.
To ascertain whether psychotherapies combined with medication are more efficacious than those without medication and determine which combinations yield the best results.
Methods:
We conducted a network meta-analysis of randomised controlled trials (RCTs) comparing behavioural activation (BA), psychoanalytic/psychodynamic psychotherapy (DYN), interpersonal psychotherapy (IPT), individual face-to-face cognitive behavioural therapy (CBT (ftf)), group cognitive behavioural therapy (gCBT), and computerised or internet cognitive behavioural therapy (iCBT) with each other, or with treatment-as-usual (TAU) and wait list control (WLC) among adults formally diagnosed with depression. The psychotherapy arms were categorised as either psychotherapy alone or psychotherapy combined with medication (+ p). Treatment efficacy was assessed based on depression severity. We used a random-effects model to conduct a pairwise meta-analysis.
Results:
A total of 100 RCTs with 9,873 participants were included. The most common treatment was CBT (ftf) alone. All treatment arms were compared with TAU. Most psychotherapies combined with medication were superior to psychotherapy alone. In the subgroup analyses according to the baseline severity of depression, most psychotherapies combined with medication were more effective than psychotherapy alone in moderate-to-severe depression, whereas in mild depression, such differences were not observed. Among psychotherapies with medication, gCBT + p was significantly more effective than TAU and other psychotherapies in both the main and subgroup analyses.
Conclusion:
The efficacy of depression treatment varied depending on the severity of the depressive condition. Notably, gCBT + p was identified as the most effective approach for treating adult depression.
Perinatal malnutrition is a critical cause of diseases in offspring. Based on the different rates of organ development, we hypothesised that malnutrition at varying early life stages would have a differential impact on cardiovascular disease in middle-aged and older adults. This study sought to assess the long-term impact of exposure to the 1959–1961 Great Chinese Famine (GCF) during early developmental periods on risks of cardiovascular diseases in the late middle-aged offspring. A total 6, 662 individuals, born between 1958 and 1964, were divided into six groups according to the birth date. The generalised line model was used to control age and estimate differences with 95% confidence interval (CI) in blood pressure. Binary logistic regression was applied to evaluate the association between famine exposure and cardiovascular diseases. Compared to the unexposed late middle-aged persons, blood pressure was elevated in the entire gestation exposure group, regardless of postnatal exposure to GCF. Increased blood pressure was also found in the female offspring exposed to GCF during early and middle gestation. The early-childhood exposure was associated with the risk of bradycardia in the offspring. The risks of vertebral artery atherosclerosis were elevated in GCF famine-exposed groups except first trimester exposed group. The chronic influence of GCF in early life periods was specific to the developmental timing window, sexesand organs, suggesting an essential role of interactions among multiple factors and prenatal malnutrition in developmentally “programming” cardiovascular diseases.
MicroRNAs (miRNAs) play important roles in regulating salt tolerance in Dongxiang wild rice (DXWR, Oryza rufipogon Griff.). The development of salt-responsive miRNA-simple sequence repeat (SSR) markers will significantly bolster research on DXWR, providing novel tools for exploring salt-tolerant genetic resources and advancing the development of salt-tolerant rice varieties. In the present study, a total of 137 miRNA-SSR markers were successfully developed, specifically derived from miRNAs responsive to salt stress in DXWR. Subsequently, a subset of 20 markers was randomly selected for validation across three distinct DXWR populations, along with 35 modern rice varieties. Notably, 13 of these markers exhibited remarkable polymorphism. The polymorphic markers collectively amplified 52 SSR loci, averaging four alleles per locus. The polymorphism information content values associated with these loci spanned from 0.23 to 0.70, with a mean value of 0.49. Particularly noteworthy is the miR162a-SSR marker, which demonstrated distinct allelic patterns and holds potential as a diagnostic marker for discriminating the salt-tolerant rice varieties from the non-tolerant varieties. This study provides a valuable tool for genetic analysis and precision breeding, facilitating the identification and utilization of valuable salt-tolerant genetic resources.
Aphis spiraecola Patch is one of the most economically important tree fruit pests worldwide. The pyrethroid insecticide lambda-cyhalothrin is commonly used to control A. spiraecola. In this 2-year study, we quantified the resistance level of A. spiraecola to lambda-cyhalothrin in different regions of the Shaanxi province, China. The results showed that A. spiraecola had reached extremely high resistance levels with a 174-fold resistance ratio (RR) found in the Xunyi region. In addition, we compared the enzymatic activity and expression level of P450 genes among eight A. spiraecola populations. The P450 activity of A. spiraecola was significantly increased in five regions (Xunyi, Liquan, Fengxiang, Luochuan, and Xinping) compared to susceptible strain (SS). The expression levels of CYP6CY7, CYP6CY14, CYP6CY22, P4504C1-like, P4506a13, CYP4CZ1, CYP380C47, and CYP4CJ2 genes were significantly increased under lambda-cyhalothrin treatment and in the resistant field populations. A L1014F mutation in the sodium channel gene was found and the mutation rate was positively correlated with the LC50 of lambda-cyhalothrin. In conclusion, the levels of lambda-cyhalothrin resistance of A. spiraecola field populations were associated with P450s and L1014F mutations. Our combined findings provide evidence on the resistance mechanism of A. spiraecola to lambda-cyhalothrin and give a theoretical basis for rational and effective control of this pest species.
Modification of the surfaces of montmorillonite (Mnt) by organic molecules is an effective method for improving their affinity toward non-aqueous substances, and has resulted in extensive industrial applications as rheological control agents, drilling fluids, and other functional materials used in applications ranging from environmental remediation to coatings. The present study reviewed recent progress in organo-modification of Mnt, and provides state-of-the-art insights into proposed modification mechanisms and the peculiar functionalities of the resulting organo-montmorillonite (OMnt). Several routes have been employed to modify Mnt, including ion exchange with organic ions, surface adsorption, and grafting of organics. Commonly used organic modifiers include cationic, anionic, zwitterionic, non-ionic, and polymeric species. Organo-modification is driven by multiple interactions: van der Waals forces, cation exchange, electrostatic interaction, hydrogen bonds, and ion–dipole interaction. OMnt, in general, exhibits synergistic and/or antagonistic effects when used in oil-based drilling fluids, environmental remediation, or layered silicate/polymer nanocomposites. The detailed mechanisms of non-ionic and zwitterionic modification of Mnt remain unclear. This literature survey suggests that future work should emphasize deeper understanding of interactions between the Mnt and the organic modifiers, and meanwhile expand the applications of OMnt into catalysis, drug carriers, and the biomedical field.
Assess turnaround time (TAT) and cost-benefit of on-site C. auris screening and its impact on length of stay (LOS) and costs compared to reference laboratories.
Design:
Before-and-after retrospective cohort study.
Setting:
Large-tertiary medical center.
Methods:
We validated an on-site polymerase chain reaction-based testing platform for C. auris and retrospectively reviewed hospitalized adults who screened negative before and after platform implementation. We constructed multivariable models to assess the association of screening negative with hospital LOS/cost in the pre and postimplementation periods. We adjusted for confounders such as demographics and indwelling device use, and compared TATs for all samples tested.
Results:
The sensitivity and specificity of the testing platform were 100% and 98.11%, respectively, compared to send-out testing. The clinical cohort included 287 adults in the pre and 1,266 postimplementation period. The TAT was reduced by more than 2 days (3 (interquartile range (IQR): 2.0, 7.0) vs 0.42 (IQR: 0.24, 0.81), p < 0.001). Median LOS was significantly lower in the postimplementation period; however, this was no longer evident after adjustment. In relation to total cost, the time period had an effect of $6,965 (95% CI: −$481, $14,412); p = 0.067) on reducing the cost. The median adjusted total cost per patient was $7,045 (IQR: $3,805, $13,924) less in the post vs the preimplementation period.
Conclusions:
Our assessment did not find a statistically significant change in LOS, nevertheless, on-site testing was not cost-prohibitive for the institution. The value of on-site testing may be supported if an institutional C. auris reduction strategy emphasizes faster TATs.
The aim of this study was to investigate the prevalence of anemia in twin pregnancies and the influence of anemia on maternal and neonatal outcomes. This retrospective study included twin pregnant women who delivered in a tertiary hospital in China from January 2018 to December 2018. Patients were divided by WHO criteria (hemoglobin <11.0 g/dL): the anemic and nonanemic groups. Patients with anemia were further classified as recovered or unrecovered subgroup after oral iron therapy. Maternal and neonatal outcomes in women carrying twins were compared using Student’s t test and the chi-squared test or the Fisher exact test. Univariable and multivariable logistic regression models were used to determine the association of maternal and neonatal characteristics with anemia. Linear regression analysis was used to estimate mean birth weight and gestational week. The prevalence of anemia was 42.6% (182/427) in twin pregnancies. The anemic group had higher rates of low 1-minute Apgar score (4.4% vs. 1.8%, p = .028), perinatal death (1.9% vs. 0.2%, p = .012) and neonatal intensive care unit (NICU) admission (27.2% vs. 20.2%, p = .017; adjusted OR, 1.478; 95% CI [1.07, 2.044]). The recovered subgroup had lower NICU admission rate (13.5% vs. 30.3%, p = .006; OR, 0.388; 95% CI [0.186, 0.809]), higher gestational week and birth weight (β, 0.954 week; 95% CI [0.114, 1.794] and β, 171.01 g; 95% CI [9.894, 332.126] respectively). The prevalence of anemia in twin gestation is high. Anemia is associated with adverse neonatal outcomes, and correction of anemia significantly improved the pregnancy outcomes.
This paper presents a low-cost, accurate indoor positioning system that integrates image acquisition and processing and data-driven modeling algorithms for robotics research and education. Multiple overhead cameras are used to obtain normalized image coordinates of ArUco markers, and a new procedure is developed to convert them to the camera coordinate frame. Various data-driven models are proposed to establish a mapping relationship between the camera and the world coordinates. One hundred fifty data pairs in the camera and world coordinates are generated by measuring the ArUco marker at different locations and then used to train and test the data-driven models. With the model, the world coordinate values of the ArUco marker and its robot carrier can be determined in real time. Through comparison, it is found that a straightforward polynomial regression outperforms the other methods and achieves a positioning accuracy of about 1.5 cm. Experiments are also carried out to evaluate its feasibility for use in robot control. The developed system (both hardware and algorithms) is shared as an open source and is anticipated to contribute to robotic studies and education in resource-limited environments and underdeveloped regions.
In this study, the length scaling for the boundary layer separation induced by two incident shock waves is experimentally and analytically investigated. The experiments are performed in a Mach 2.73 flow. A double-wedge shock generator with two deflection angles ($\alpha _1$ and $\alpha _2$) is employed to generate two incident shock waves. Two deflection angle combinations with an identical total deflection angle are adopted: ($\alpha _1 = 7^\circ$, $\alpha _2 = 5^\circ$) and ($\alpha _1 = 5^\circ$, $\alpha _2 = 7^\circ$). For each deflection angle combination, the flow features of the dual-incident shock wave–turbulent boundary layer interactions (dual-ISWTBLIs) under five shock wave distance conditions are examined via schlieren photography, wall-pressure measurements and surface oil-flow visualisation. The experimental results show that the separation point moves downstream with increasing shock wave distance ($d$). For the dual-ISWTBLIs exhibiting a coupling separation state, the upstream interaction length ($L_{int}$) of the separation region approximately linearly decreases with increasing $d$, and the decrease rate of $L_{int}$ with $d$ increases with the second deflection angle under the condition of an identical total deflection angle. Based on control volume analysis of mass and momentum conservations, the relation between $L_{int}$ and $d$ is analytically determined to be approximately linear for the dual-ISWTBLIs with a coupling separation region, and the slope of the linear relation obtained analytically agrees well with that obtained experimentally. Furthermore, a prediction method for $L_{int}$ of the dual-ISWTBLIs with a coupling separation region is proposed, and the relative error of the predicted $L_{int}$ in comparison with the experimental result is $\sim$10 %.
Objectives: Rapid and accurate screening for carbapenemase-producing organism (CPOs) in hospitalized patients is critical for infection control and prevention. The Xpert Carba-R assay is designed for rapid detection of CPOs, but 1 assay is usually conducted for only 1 sample. We evaluated a pooling strategy for CPO screening using the Xpert Carba-R assay. Methods: Swab sets containing 2 swabs were collected from 415 unique patients at Peking University People’s Hospital. One swab was used for the pooling test, in which 5 swabs from different patients were mixed in 1 sample treatment solution. The prevalence of CPOs in the hospital (5.3%) predicted that 5:1 pooling was most economical. As the reference method, the other swab was tested by culture using sequencing. Results: Of 415 samples, 383 were CPO negative using the pooling test strategy and 31 were positive. All samples that were negative by pooling were negative by culture and sequencing. Among the 31 positive samples identified by the pooling strategy, 26 were positive by culture and sequencing (including 24 samples with 1 targeted gene and 2 samples with double targeted genes, 1 NDM+/IMP+ and 1 VIM+/IMP+), and 5 were negative. Overall, 198 tests were conducted in the study, and 217 were saved compared with testing individually. The efficiency of the pooling strategy was 215%. The overall sensitivity was 1 (95% CI, 0.840–1), the specificity was 0.987 (95% CI, 0.968–0.995), the accuracy was 0.987 (95% CI, 0.970–0.996), positive predictive value was 0.838 (95% CI, 0.655–0.939), and the negative predictive value was 1 (95% CI, 0.988–1). Conclusions: The pooling strategy using the Xpert Carba-R assay showed good potential in screening CPO with good sensitivity and a significantly lower cost.
Objectives: The number of lung transplants is increasing year by year in China and globally. With the widespread use of donation after brainstem death (DBD) donor lungs and donation after circulatory death (DCD) donor lungs, donor-derived infection (DDI) poses a major challenge in lung transplantation. Using donor lungs infected or colonized with carbapenem-resistant Enterobacteriaceae (CRE) may have serious implications in lung-transplant recipients. Currently, traditional microbial culture along with antimicrobial susceptibility testing cannot fully meet the need for rapid and accurate diagnosis of CRE infection in a donor before organ harvest. Methods: The Xpert Carba-R device (Cepheid, Sunnyvale, CA) was used to detect and differentiate Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), Verona integron-encoded metallo-β-lactamase (VIM), active-on-imipenem (IMP), and OXA-48 carbapenemase genotypes in bronchial lavage fluid from donor lungs before organ harvest. Positive detection of 1 or more of these genotypes indicated a potentially CRE-infected donor lung, and these organs were removed from the lung transplantation cohort. Donor lungs negative for all KPC, NDM, VIM, IMP, and OXA-48 genotypes determined by the Xpert Carba-R device were used for lung transplantation. The incidence of CRE-associated DDI and infection-related complications were compared in the Xpert Carba-R screening group and an historic control group. Results: In this study, 21 donor lungs were tested with the Xpert Carba-R device to detect and differentiate carbapenemase genotypes. Among them, 4 were positive for 1 or more carbapenemase genotypes and were discarded, and the remaining 17 donor lungs showing no carbapenemase gene presence were used for lung transplantation. No CRE-associated DDI occurred in these 17 lung-transplant recipients. Conclusions: Rapid and accurate detection of the carbapenemase gene in donor lungs at the point of care before transplantation using the Xpert Carba-R device reduced the risk of CRE-associated DDI in lung-transplant recipients.
The purpose of this study was to analyse the clinical characteristics of patients with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) PCR re-positivity after recovering from coronavirus disease 2019 (COVID-19). Patients (n = 1391) from Guangzhou, China, who had recovered from COVID-19 were recruited between 7 September 2021 and 11 March 2022. Data on epidemiology, symptoms, laboratory test results and treatment were analysed. In this study, 42.7% of recovered patients had re-positive result. Most re-positive patients were asymptomatic, did not have severe comorbidities, and were not contagious. The re-positivity rate was 39%, 46%, 11% and 25% in patients who had received inactivated, mRNA, adenovirus vector and recombinant subunit vaccines, respectively. Seven independent risk factors for testing re-positive were identified, and a predictive model was constructed using these variables. The predictors of re-positivity were COVID-19 vaccination status, previous SARs-CoV-12 infection prior to the most recent episode, renal function, SARS-CoV-2 IgG and IgM antibody levels and white blood cell count. The predictive model could benefit the control of the spread of COVID-19.
Circulating n-3 PUFA, which integrate endogenous and exogenous n-3 PUFA, can be better used to investigate the relationship between n-3 PUFA and disease. However, studies examining the associations between circulating n-3 PUFA and colorectal cancer (CRC) risk were limited, and the results remained inconclusive. This case–control study aimed to examine the association between serum n-3 PUFA and CRC risk in Chinese population. A total of 680 CRC cases and 680 sex- and age-matched (5-year interval) controls were included. Fatty acids were assayed by GC. OR and 95 % CI were calculated using multivariable logistic regression after adjustment for potential confounders. Higher level of serum α-linolenic acid (ALA), docosapentaenoic acid (DPA), DHA, long-chain n-3 PUFA and total n-3 PUFA were associated with lower odds of CRC. The adjusted OR and 95 % CI were 0·34 (0·24, 0·49, Pfor trend < 0·001) for ALA, 0·57 (0·40, 0·80, Pfor trend < 0·001) for DPA, 0·48 (0·34, 0·68, Pfor trend < 0·001) for DHA, 0·39 (0·27, 0·56, Pfor trend < 0·001) for long-chain n-3 PUFA and 0·31 (0·22, 0·45, Pfor trend < 0·001) for total n-3 PUFA comparing the highest with the lowest quartile. However, there was no statistically significant association between EPA and odds of CRC. Analysis stratified by sex showed that ALA, DHA, long-chain n-3 PUFA and total n-3 PUFA were inversely associated with odds of CRC in both sexes. This study indicated that serum ALA, DPA, DHA, long-chain n-3 PUFA and total n-3 PUFA were inversely associated with odds of having CRC in Chinese population.
The question of whether narcissists are more creative than peers has attracted much scholarly attention in both psychology and organizational management sciences. Drawing from social cognitive theory, we theorized that the relationship between narcissism and creativity could be explained by individual creative self-efficacy, which depends on one's direct and vicarious experiences of creativity. Drawing from trait activation theory, we further proposed organizational valuing of creativity as a key contextual moderator that determines whether narcissism facilitates or inhibits creative self-efficacy and, in turn, creativity. We suggest that high organizational valuing of creativity will energize narcissists to put their attention and effort into both direct and vicarious experiences of creativity, enhancing their creative self-efficacy and creativity. We tested our conceptual model through a field study with data collected from 269 full-time employees working in 86 work teams. The empirical results provided support for the social cognitive explanation for the positive relationship between narcissism and creativity in the context of high organizational valuing of creativity. Our study not only resolved prior debates on the relationship between narcissism and creativity but also provided direct empirical support for social cognitive theory and the person-in-context interactionist perspective of creativity research.
This study aimed to determine the ideal pacing site in children by comparing the postoperative ventricular synchrony in children with left bundle branch area pacing and those with right ventricular septal pacing.
Methods:
This retrospective study included children with complete atrioventricular block who underwent permanent pacemaker implantation from March 2019 to August 2021. Patients were grouped according to their ventricular pacing site, the left bundle branch area pacing group and the right ventricular septal pacing group. Two-dimensional speckle tracking echocardiography was used to evaluate the ventricular synchrony.
Results:
Forty-eight children (median age, 2.7 years; interquartile range, 1.7–4.6 years) were included. The paced QRS duration in the left bundle branch area pacing group was significantly narrower than that in the right ventricular septal pacing group (100.2 ± 9.3 versus 115.4 ± 15.1 ms, p = 0.001). The median follow-up duration was 1.5 years (interquartile range, 1–2 years). At the last follow-up, the average capture threshold of the ventricular electrode in the left bundle branch area pacing group was lower than that in the right ventricular septal pacing group (0.79 ± 0.18 versus 1.20 ± 0.56 V, p = 0.008). The left ventricular intraventricular synchrony parameters in the left bundle branch area pacing group were better than those in the right ventricular septal pacing group (e.g. standard deviation of the time to peak longitudinal strain, 37.4 ± 4.3 versus 46.6 ± 8.2 ms, p = 0.000). The average interventricular mechanical delay time in the left bundle branch area pacing group was significantly shorter than that in the right ventricular septal pacing group (36.4 ± 14.2 versus 52.5 ± 22.7 ms, p = 0.016).
Conclusion:
Compared with right ventricular septal pacing, left bundle branch area pacing in children produces a narrower QRS duration and better pacing and ventricular synchrony parameters postoperatively.
Plasma jets are widely investigated both in the laboratory and in nature. Astrophysical objects such as black holes, active galactic nuclei and young stellar objects commonly emit plasma jets in various forms. With the availability of data from plasma jet experiments resembling astrophysical plasma jets, classification of such data would potentially aid in not only investigating the underlying physics of the experiments but also the study of astrophysical jets. In this work we use deep learning to process all of the laboratory plasma images from the Caltech Spheromak Experiment spanning two decades. We found that cosine similarity can aid in feature selection, classify images through comparison of feature vector direction and be used as a loss function for the training of AlexNet for plasma image classification. We also develop a simple vector direction comparison algorithm for binary and multi-class classification. Using our algorithm we demonstrate 93 % accurate binary classification to distinguish unstable columns from stable columns and 92 % accurate five-way classification of a small, labelled data set which includes three classes corresponding to varying levels of kink instability.
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.