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Background The cell wall plays crucial roles in establishing the morphology of plant cells and defense response to biotic and abiotic stresses. The plant COBRA protein family plays an important role in secondary cell wall biosynthesis and the orientation of cell expansion, which have been extensively studied in Arabidopsis thaliana, maize, rice, etc., but no systematic studies were conducted in wheat. Methods and Results In this study, the full-length sequence of TaCOBLs was obtained by homology cloning from wheat, and a conserved motif analysis confirmed that TaCOBLs belonged to the COBRA protein family. qRT-PCR results showed that the TaCOBL transcripts were induced by abiotic stresses, including cold, drought, salinity, and abscisic acid (ABA). Two haplotypes of TaCOBL-5B (Hap5B-a and Hap5B-b), harboring one indel (----/TATA) in the 5’ flanking region (-550 bp), were found on chromosome 5BS. A co-dominant marker, Ta5BF/Ta5BR, was developed based on the polymorphism of the two TaCOBL-5B haplotypes. Significant correlations between the two TaCOBL-5B haplotypes and cold resistance were observed under four environmental conditions. Conclusion Hap5B-a, a favored haplotype acquired during wheat polyploidization, may positively contribute to enhanced cold resistance in wheat. Based on the promoter activity analysis, the Hap5B-a promoter containing a TATA-box was more active than that of Hap5B-b without the TATA-box under low temperature. Our study provides valuable information indicating that the TaCOBL genes are associated with cold response in wheat.

Objectives We aimed to evaluate the risk factors for moderate-to-severe bronchopulmonary dysplasia (BPD) and focus on discussing its relationship with the duration of initial invasive mechanical ventilation (IMV) in very preterm neonates less than 32 weeks of gestational age (GA). Methods We performed a prospective cohort study involving infants born at 23–31 weeks of GA who were admitted to 47 different neonatal intensive care unit (NICU) hospitals in China from January 2018 to December 2021. Patient data were obtained from the Sina-northern Neonatal Network (SNN) Database. Results We identified 6538 very preterm infants, of whom 49.5% (3236/6538) received initial IMV support, and 12.6% (823/6538) were diagnosed with moderate-to-severe BPD symptoms. The median duration of initial IMV in the moderate-to-severe BPD group was 26 (17–41) days, while in the no or mild BPD group, it was 6 (3–10) days. The incidence rate of moderate-to-severe BPD and the median duration of initial IMV were quite different across different GAs. Multivariable logistic regression analysis showed that the onset of moderate-to-severe BPD was significantly associated with the duration of initial IMV [adjusted odds ratio (AOR): 1.97; 95% confidence interval (CI): 1.10–2.67], late-onset neonatal sepsis (LONS), and patent ductus arteriosus (PDA). Conclusion In this multicenter cohort study, the duration of initial IMV was still relatively long in very premature infants, and the longer duration of initial IMV accounts for the increased risk of moderate-to-severe BPD.

Background The long-term use of visual display terminals (VDT) is linked to an increased risk of dry eye disease (DED). Numerous studies have indicated that ocular mucins play a vital role in the pathogenesis of DED. Therefore, we aimed to evaluate (1) whether mRNA levels of membrane-associated mucins (MAMs), including MUC1, MUC4, MUC16, and MUC20, as well as MUC5AC are altered in conjunctival cells of VDT users with and without DED and (2) the relationship between mucin levels and subjective and objective tests of DED in VDT users. Methods Seventy-nine VDT users were enrolled and divided into DED (n = 53) and control (n = 26) groups. All participants were evaluated for parameters of DED using the Ocular Surface Disease Index (OSDI) questionnaire, tear breakup time (TBUT), corneal fluorescein staining (CFS), lissamine green (LG) staining, and tear meniscus height (TMH). Based on the conjunctival impression cytology (CIC) method, differences in MUC1, MUC4, MUC16, MUC20, and MUC5AC mRNA expression levels were observed between the DED and control groups, and between symptomatic and asymptomatic participants. Results The DED group showed significantly decreased MUC1, MUC16, and MUC20 expressions (all P Conclusion VDT users with an increased frequency of ocular discomfort or a diagnosis of DED had a decreased MUC1, MUC16 and MUC20 mRNA expression in their conjunctival cells. MAMs deficiency in the conjunctival epithelium may be one of the mechanisms leading to tear film instability and DED in VDT users.

To evaluate binocular visual function after unilateral and bilateral implantation of segmented refractive multifocal intraocular lenses (MIOLs). This prospective comparative pilot study included patients who underwent SBL-3 (Lenstec; + 3.00 D) implantation at Peking University Third Hospital. Patients were divided into two groups (monocular or binocular surgery). Thirty-two patients with emmetropic presbyopic contralateral eyes and 49 patients with bilateral SBL-3 implantation within a week between eyes were included in the unilateral SBL-3 and bilateral groups, respectively. At 3-month follow-up, the main outcomes were binocular uncorrected distant, intermediate, and near visual acuity (UDVA, UIVA, and UNVA). Secondary outcomes included binocular best-corrected visual acuity at all distances, defocus curve, contrast sensitivity, photic phenomena, spectacle independence, patient satisfaction, and National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) score. The essential perceptual phenomena constituting binocular vision, simultaneous perception, fusion, and stereopsis were also evaluated. Both groups showed similar binocular UDVA and UIVA, but UNVA was significantly better in the bilateral group (0.07 ± 0.07 versus 0.12 ± 0.07, P = 0.008). Better binocular defocus curve at intermediate to near focal points, higher percentage of spectacle independence at near distance, and NEI-VFQ-25 near activity scores were observed in the bilateral group. No significant differences in contrast sensitivity, photic phenomena, overall satisfaction, other NEI-VFQ-25 subscales, fusional amplitude, and stereoacuity were found between groups. Unilateral implantation of segmented refractive MIOL provided desirable distant visual acuity and high patient satisfaction, but inferior intermediate and near visual outcomes compared with bilateral implantation.

The plenoptic imaging technique provides a promising approach to the non-invasive three-dimensional measurement, especially for the high-temperature combustion diagnosis. We establish a light-field convolution imaging model for diffusion flame in this work, considering the radiation transfer process inside the diffusion flame and the light transfer process inside the focused plenoptic camera together. The radiation transfer process is described by the radiation transfer equation and solved by the generalized source multi-flux method. Wave optics theory is adopted to describe the light transfer process, combining Fresnel diffraction and the phase conversion of the lens. The flame light-field image is obtained by the light-field convolution imaging model and adopted as the measurement signal to reconstruct three-dimensional temperature field. The inverse problem of temperature reconstruction is solved by the least square QR decomposition method. The simulative temperature reconstruction work is conducted, including the inverse analysis, the uncertainty analysis, and the measurement noise influence. All the results show that the proposed measurement method is available to reconstruct three-dimensional temperature with satisfactory accuracy and acceptable uncertainty. Both symmetric and asymmetric distributed temperature fields are investigated, and the reconstructed results prove the validity and universality of the measurement method.

Background To assess and compare the efficacy, safety, accuracy, predictability and visual quality of a diffractive trifocal intraocular lens (IOL) and a refractive rotationally asymmetric bifocal IOL in eyes with axial myopia. Methods This prospective cohort study enrolled patients with implantation of the diffractive trifocal IOL or the refractive bifocal IOL. Eyes were divided into four groups according to the IOL implanted and axial length. Manifest refraction, uncorrected and corrected visual acuity at far, intermediate and near distances, prediction error of spherical equivalent (SE), contrast sensitivity and aberrations were evaluated three months after surgery. Results In total, 80 eyes of 80 patients were included: 20 eyes in each group. Three months postoperatively, the corrected distance visual acuity of two trifocal groups were significantly better than the axial myopia bifocal group (P = 0.007 and 0.043). There was no significant difference of postoperative SE (P = 0.478), but the SE predictability of the trifocal IOL was better, whether in axial myopia groups (P = 0.015) or in control groups (P = 0.027). The contrast sensitivity was similar among four groups. The total aberration, higher order aberration and trefoil aberration of bifocal groups were significantly higher (all P Conclusions The diffractive trifocal IOL and the refractive bifocal IOL both provided good efficacy, accuracy, predictability and safety for eyes with axial myopia. By contrast, the trifocal IOL had a better performance in corrected distance visual acuity and visual quality. Trial registration The study was retrospectively registered and posted on clinicaltrials.gov at 12/02/2020 (NCT04265846).

Background Appropriate sizing of the implantable collamer lens (ICL) and accurate prediction of the vault are crucial prior to surgery. However, sometimes, the vault value is higher or lower than predicted, necessitating reoperation. The present study aimed to develop neural networks for improving predictions of vault values following ICL implantation based on preoperative biometric data. Methods This retrospective study included 137 eyes of 74 patients with ICLs. Linear regression and neural network analyses were used to examine the relationship between vault values at the 6-month follow-up and preoperative parameters (e.g., ICL characteristics and biometrics). Results Linear regression analysis revealed that vault values were correlated with five variables: ICL size, anterior chamber depth (ACD), angle-to-angle (ATA), white-to-white (WTW), and lens thickness (LT) (adjusted R2 = 0.411). Inclusion of more input variables was associated with better performance in the neural network analysis. The degree of fit when all 11 variables were included in the neural network model was close to 1 (R2 = 0.98). R2 values for the quaternary neural network model enrolling four input variables (ICL size, ATA, ACD, and LT) reached 0.90. Conclusions A neural network equation including the ICL size and biometric parameters of the anterior segment (ATA, ACD, and LT) can be used to predict the postoperative vault, aiding in the selection of an appropriate ICL size and reducing the need for reoperation after surgery.

The spatiotemporal distribution of phthalate acid esters (phthalates, PAEs) in wastewater treatment plants (WWTPs) in China was studied. The concentration of PAEs in influent and effluent increased from 2009 to 2016, indicating that the exposure level of PAEs in China increased continuously. Although the concentration of PAEs in sewage sludge in China ranged from 33.3 to 298 ug/g, there was no obvious spatial distribution pattern. Among the 19 PAE homologues, DEHP, DnBP, and DIBP were the most abundant phthalates detected in wastewater and sludge. Ecological risk assessment confirmed that there was a high chronic and acute risk of DIBP in effluent since 2015. Therefore, this study highlights the need for further studies on the exposure and toxicology of DIBP. Dietary intake accounted for more than 98% of the total risk, indicating that the risk of sludge application in agricultural land was much higher than that in nonagricultural land. The results from this study will provide valuable information for the safe disposal of sludge and wastewater.

Information transmission in underwater conditions cannot depend on various media, thus an Autonomous Underwater Vehicle (AUV) is imperative to assist divers with conducting underwater operations and information transmission. However, little work has been done to promote the interaction between AUV and divers. To help resolve this issue, this paper proposes a method to help the navigation guidance of AUV by predicting the divers’ headings. In this work, the visual method is chosen to estimate pose of divers since it can adapt to complex underwater environment conditions at a lower cost than other methods. The contour information is used to obtain the keypoints of the diver which are input into the Long-Short Term Memory Network to predict the headings. The dataset which redefines the skeleton of divers in our work is original and open for future researches. Compared with the original method, the accuracy of pose estimation on this dataset is 85 $$\%$$ , an increase of 9 $$\%$$ , and with a small error of diver’s heading prediction, which indicates that our method can obtain competitive prediction results.

Background Many surgical options have been described to manage post-tubercular kyphosis, but the standard approach for treating severe post-tubercular angular kyphosis in children has not been established yet. The present study was performed to evaluate the safety and efficacy of deformed complex vertebral osteotomy (DCVO) for the treatment of severe thoracic post-tubercular angular kyphosis (> 70°) in children. Methods Deformed complex vertebrae indicated that multiple deformed and fused vertebrae were usually involved with two or more vertebral bodies and the partial or total fusion of many segments' facet joints and intervertebral discs. Thus, DCVO indicated that a wider posterior wedge-shaped and three-column osteotomy was performed within deformed complex vertebrae to correct a more extensive range of angles. From 2010 to 2017, 15 children who suffered from severe thoracic post-tubercular angular kyphosis underwent DCVO. Deformed complex vertebrae involved two vertebral bodies in 9 patients and three vertebral bodies in 6 patients. The Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) were assessed preoperatively and at the final follow up. This was a retrospective study analysing the outcome after grade 4/5 spinal osteotomies in deformed complex vertebrae. Results The mean duration of surgery was 239 ± 37.81 min. The average period of follow-up was 31.6 ± 6.98 months. The preoperative mean kyphosis of deformed complex vertebrae was 83.39° ± 9.04°; the mean thoracic kyphosis (TK) and lumbar lordosis (LL) were 81.09° ± 8.51° and 80.51° ± 7.64°, respectively; the mean sagittal vertical axis (SVA) was 3.83 cm ± 1.43 cm. The postoperative mean kyphosis of deformed complex vertebrae was reduced to 19.98° ± 2.47° (P P P p = 0.982, p = 0.604, p = 0.754). Complicated with neural dysfunction preoperatively, 5 Frankel's grade D cases showed complete neurological recovery at final follow up. VAS score reduced from 3.6 ± 1.18 to 0.87 ± 0.64 (P P Conclusions DCVO was an individualized osteotomy for treating severe thoracic post-tubercular angular kyphosis in children and could be safe and effective in reducing the incidence of complications and significantly improving kyphosis correction.

Background Pyogenic vertebral osteomyelitis (PVO), which is a potentially life-threatening condition and is associated with significant morbidity and mortality, is a cause of back pain that can lead to neurologic deficits if not diagnosed in time and effectively treated. The objective of this study is to compare the efficacy of posterior single-segment and short-segment fixation combined with one-stage posterior debridement and fusion for the treatment of mono-segmental lumbar or lumbosacral PVO. Methods Charts of all patients with mono-segmental lumbar or lumbosacral PVO were treated by single-stage posterior debridement, bone graft fusion, and pedicle screw fixation from April 2012 to January 2016. All patients were divided into two groups: sinlge-segment fixation (Group A, n = 31) and short-segment fixation (Group B, n = 36). These patients were followed up for a minimum of five years. The clinical efficacy was evaluated and compared on average operation time, blood loss, visual analog scale (VAS), erythrocyte sedimentation rate (ESR), C-Reactive protein (CRP), neurological function recovery and local lordotic angle. Results All 67 patients were completely cured during the follow-up. All patients had significant improvement of neurological condition and pain relief at the final follow-up. The VAS was 7.1 ± 0.7 in group A and 7.2 ± 0.6 in group B pre-operatively, which decreased to 2.1 ± 0.6 and 2.0 ± 0.7, respectively, at three months after surgery, then reduced to 0.4 ± 0.5 and 0.5 ± 0.5, respectively, at the final follow-up. ESR, CRP returned to normal limits in all patients 3 months after surgery. The mean blood loss and operation time in group A were less than that in group B (P P P P Conclusion Posterior-only debridement, interbody graft using titanium mesh cage, posterior single-segment instrumentation and fusion represent a safe and effective treatment option for selected patients with mono-segmental lumbar and lumbosacral PVO. This approach may preserve more lumbar normal motor units with less blood loss and operation time when compared with that of short-segment fixation. But short-segment fixation was superior to the single-segment fixation in the correction of kyphosis.

Working in collaboration with an Autonomous Underwater Vehicle is a new working method for divers. Using gestures to give instructions for the diver is a simple and effective mode of underwater human–robot interaction (HRI). In this paper, a gestures tracking method for under human–robot interaction based on fuzzy control is proposed. Firstly, four object recognition algorithms in terms of gesture recognition are compared. YOLO V4-tiny was an extremely high performance, as the gesture area recognition algorithm. We propose a model based on Siamese Network for gesture classification. A gesture tracking method based on fuzzy control is proposed, analyzing the image from AUV front camera to establish a 3D fuzzy rule set. This method can realize the self-regulation of AUV and keep the diver's gestures in the camera view. The experiment result shows the efficiency of the proposed method.

For the interaction between marine robots and divers in the underwater environment, a method of diver’s gesture recognition and segmentation is proposed. This method first uses the progressive growing training method to optimize the generative adversarial networks, generating high-resolution images with complex content. Then, we use the generative adversarial network model as a data augmentation method and generate high-resolution images. We make the masks of gestures in the new dataset and use the mask R-CNN algorithm for gesture recognition and gesture segmentation. The experimental results show that the generating data improves the accuracy of several object recognition algorithms but cannot completely replace the original data and the mean average precision of gesture recognition is 0.85. The visualization shows the validity and weakness of segmentation.

Objectives We aimed to assess the clinical value of multimodal photoacoustic/ultrasound (PA/US) articular imaging scores, a novel imaging method which can reflect the micro-vessels and oxygenation level of inflamed joints of rheumatoid arthritis (RA). Methods Seven small joints were examined by the PA/US imaging system. A 0–3 scoring system was used to semi-quantify the PA and power-Doppler (PD) signals, and the sums of PA and PD scores (PA-sum and PD-sum scores) of the seven joints were calculated. The relative oxygen saturation (SO2) values of the inflamed joints were measured and classified into 3 PA+SO2 patterns. The correlations between the PA/US imaging scores and the disease activity scores were assessed. Results Thirty-one patients of RA and a total of 217 joints were examined using the PA/US system. The PA-sum had high positive correlations with the standard clinical scores of RA (DAS28 [ESR] ρ = 0.754, DAS28 [CRP] ρ = 0.796, SDAI ρ = 0.836, CDAI ρ = 0.837, p < 0.001), which were superior to the PD-sum (DAS28 [ESR] ρ = 0.651, DAS28 [CRP] ρ = 0.676, SDAI ρ = 0.716, CDAI ρ = 0.709, p < 0.001). For the patients with high PA-sum scores, significant differences between hypoxia and hyperoxia were identified in pain visual analog score (p = 0.020) and patient’s global assessment (p = 0.026). The PA+SO2 patterns presented moderate and high correlation with PGA (ρ = 0.477, p = 0.0077) and VAS pain score (ρ = 0.717, p < 0.001). Conclusion The PA scores have significant correlations with standard clinical scores for RA, and the PA+SO2 patterns are also related with clinical scores that reflect pain severity. PA may have clinical potential in evaluating RA. Key Points • Multimodal photoacoustic/ultrasound imaging is a novel method to assess micro-vessels and oxygenation of local lesions. • Significant correlations between multimodal imaging parameters and clinical scores of RA patients were verified. • The multimodal PA/US system can provide objective imaging parameters, including PA scores of micro-vessels and relative SO2value, as a supplementary to disease activity evaluation.

Autonomous underwater vehicle (AUV) plays an important role in ocean research and exploration. The underwater environment has a great influence on AUV control and human–robot interaction, since underwater environment is highly dynamic with unpredictable fluctuation of water flow, high pressure and light attenuation. The traditional control model contains a large number of parameters, which is not effective and produces errors frequently. The proposal of fuzzy control addressed this issue to a certain extent. It applies fuzzy variables to the controller, which replace the values in an interval. In addition to the controller, underwater human–robot interaction is also difficult. Divers cannot speak or show any facial expressions underwater. The buttons on the AUV also need to overcome the huge water pressure. In this paper, we proposed a method to recognize the gesture instructions and apply it to the fuzzy control of AUV. Our contribution is the gesture recognition framework for the human–robot interaction, including the gesture detection network and the algorithm for the control of AUV. The experiment result shows the efficiency of the proposed method.

Substantial quantities of openly dumped slag contribute to the absence of recovery and utilization of valuable metals as well as potential environmental pollution to water and soil. Owing to the excessively high arsenic content present in iron extracted from copper smelting slag, we propose a new arsenic removal process in this paper. The results indicate that arsenic sulfides in copper smelting slag can be significantly removed at 1100 °C in an N2 atmosphere, leading to a 0.15% residual arsenic content. Furthermore, undecomposed arsenate in the slag can be reduced in an N2–CO atmosphere. During a coal-based direct reduction process, under optimal conditions, the removal efficiency of arsenic is relatively low. Subsequently, under optimal conditions, the arsenic content drops significantly from 0.18 to 0.080%. This new removal process engenders lower arsenic content in iron extracted from slag than the standards of pig iron and direct reduced iron in steelmaking.

Standard plenoptic camera can be used to capture multi-dimensional radiation information of high temperature luminous flame to reconstruct the temperature distribution. In this study, a novel method for reconstructing three-dimensional temperature field is proposed. This method is based on the optical tomography combined with standard plenoptic camera. The flame projection information from different planes is contained in one radiation image. In this model, we introduced the effective concept of the nearest neighbor method in the frequency domain to strip the interference of redundant information in the projection and to realize three-dimensional deconvolution. The flame emission intensity received by the pixels on the charge-coupled device sensor can be obtained according to the optical tomographic model. The temperature distributions of the axisymmetric and non-axisymmetric flames can be reconstructed by solving the mathematical model with the nearest neighbor method. The numerical results show that three-dimensional temperature fields of high temperature luminous flames can be retrieved, proving the validity of the proposed method.

This paper investigates the long-term monthly, seasonal, and annual trends of climatic variables, snow cover extent, and discharge in Langtang Basin, Central Himalayas. The Mann-Kendall test with variance corrections is used to detect the trend, and Sen’s slope estimator is calculated to quantify the trend. The innovative trend analysis, a graphical method for trend detection, is applied, and the results are compared. The snow cover extent for the study area was derived from moderate resolution imaging spectroradiometer (MODIS) satellite images. The result suggests that there is a significant increasing trend for mean temperature and minimum temperature, while no remarkable trend is identified for maximum temperature. Similarly, precipitation shows a rising trend for all seasons except winter. Snow cover is a major source of fresh water for the region and is depleting at an alarming rate. River discharge, augmented by snowmelt and high rainfall, is upsurging. In summary, this study portrays the links of climatic variables with snow cover and river discharge. The outcome of this study will be useful for understanding the climate change status in the Central Himalayas and sustainably managing the watershed.

Operators’ ordering is often employed in almost all calculations of quantum optics. In this paper by virtue of differentiation within ordered product of operators we put forward general differential formalism of normally and anti-normally ordering Bose operators, which seems neat and concise

The boundary emissivity, thermal conductivity, and boundary time-varying heat flux in the participating media are retrieved in this work. In the forward model, the coupled radiation-conduction heat transfer in the participating medium is resolved by the finite volume method combined with discrete ordinates method. The inverse model utilizes the temperature signals at the appropriate position of the medium as the known information and uses the unscented Kalman filter (UKF) as an optimization tool to reconstruct the boundary emissivity, thermal conductivity, and boundary time-varying heat flux. It is found that when the emissivity, thermal conductivity, and boundary time-varying heat flux are reconstructed simultaneously, only the temperature information of two locations is required. The influence of the measurement noise, sampling interval, absorption coefficient, process noise covariance, measurement noise covariance on the accuracy and stability of the retrieval results is investigated in detail. All the reconstruction results indicate that the UKF technique is effective and robust for estimating the photothermal parameters and boundary condition of the radiation-conduction heat transfer problems.

Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC50 between 1.2 and 4.3 μM, depending on viruses or cells, and selective index (SI) in 15–83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1–9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2–25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity.

Progressive loss of neurons in a specific brain area is one of the manifestations of Alzheimer’s disease (AD). Much effort has been devoted to investigating brain atrophy and AD. However, the causal relationship between cortical structure and AD is not clear. We conducted a bidirectional two-sample Mendelian randomization analysis to investigate the causal relationship between cortical structure (surface area and thickness of the whole cortex and 34 cortical regions) and AD risk. Genetic variants used as instruments came from a large genome-wide association meta-analysis of cortical structure (33,992 participants of European ancestry) and AD (AD and AD-by-proxy, 71,880 cases, 383,378 controls). We found suggestive associations of the decreased surface area of the temporal pole (OR (95% CI): 0.95 (0.9, 0.997), p = 0.04), and decreased thickness of cuneus (OR (95% CI): 0.93 (0.89, 0.98), p = 0.006) with higher AD risk. We also found a suggestive association of vulnerability to AD with the decreased surface area of precentral (β (SE): –43.4 (21.3), p = 0.042) and isthmus cingulate (β (SE): –18.5 (7.3), p = 0.011). However, none of the Bonferroni-corrected p values of the causal relationship between cortical structure and AD met the threshold. We show suggestive evidence of an association of the atrophy of the temporal pole and cuneus with higher AD risk. In the other direction, there was a suggestive causal relationship between vulnerability to AD and the decreased surface area of the precentral and isthmus cingulate. Our findings shed light on the associations of cortical structure with the occurrence of AD.

Background: Environmental factors are associated with human longevity, but their specificity and causality remain mostly unclear. By integrating the innovative “exposome” concept developed in the field of environmental epidemiology, this study aims to determine the components of exposome causally linked to longevity using Mendelian randomization (MR) approach. Methods: A total of 4587 environmental exposures extracting from 361,194 individuals from the UK biobank, in exogenous and endogenous domains of exposome were assessed. We examined the relationship between each environmental factor and two longevity outcomes (i.e., surviving to the 90th or 99th percentile age) from various cohorts of European ancestry. Significant results after false discovery rates correction underwent validation using an independent exposure dataset. Findings: Out of all the environmental exposures, seven age-related diseases and pathological conditions were causally associated with lower odds of longevity, including coronary atherosclerosis (odds ratio=0·0012, 95% confidence interval [0·0002, 0·0096], P=2·0×10-10), widely defined ischaemic heart disease (0·0028, [0·0001, 0·066], P=0·0003), Alzheimer’s disease (0·80, [0·72, 0·89], P=3·0×10-5), hypertension (0·17, [0·11, 0·25], P=1·4×10-17), diabetes (0·016, [0·0034, 0·079], P=3·1×10-7), high cholesterol (0·14, [0·058, 0·36], P=3·4×10-5), and venous thromboembolism (0·90, [0·83, 0·98], P=0·004). Five physiological properties and lifestyles were identified to affect longevity. Among them, higher body mass index, greater body fat, and previously smoking hand-rolled cigarettes were adversely associated with longevity. While faster walking pace and higher education attainment were positively associated with longevity. Interpretation: The present study highlights several targets for achieving longevity, including management of cardiometabolic factors, Alzheimer’s disease, venous thromboembolism, smoking, and advancement of physical activity, educational attainment, and overall health. Our results warrant further studies to elucidate the underlying mechanisms of these reported causal associations. Funding Statement: This study was supported by grants from the National Natural Science Foundation of China (91849126), the National Key R&D Program of China (2018YFC1314700), Shanghai Municipal Science and Technology Major Project (No.2018SHZDZX01), ZJLab, Shanghai Center for Brain Science and Brain-Inspired Technology, Tianqiao and Chrissy Chen Institute, and the State Key Laboratory of Neurobiology and Frontiers Center for Brain Science of Ministry of Education, Fudan University. Declaration of Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Ethics Approval Statement: This study is based on publicly available summarized data. Individual studies within each genomewide association study received approval from a relevant institutional review board, and informed consent was obtained from participants or from a caregiver, legal guardian, or other proxy.