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Abstract Background and objectives Congenital heart defect (CHD) is one of the most common birth defects. The aim of this cohort study was to evaluate the prevalence of chromosomal abnormalities and the clinical utility of chromosomal microarray analysis (CMA) in fetuses with different types of CHD, aiming to assist genetic counseling and clinical decision-making. Methods In this study, 642 fetuses with CHD were enrolled from a single center over a six-year period (2017–2022). Both conventional karyotyping and CMA were performed simultaneously on these fetuses. Results The diagnostic yield of CMA in fetuses with CHD in our study was 15.3% (98/642). Our findings revealed a significant increase in the diagnostic yield of CMA compared to karyotyping in fetuses with CHD. Among CHD subgroups, the diagnostic yields were high in complex CHD (34.9%), conotruncal defects (28.6%), right ventricular outflow tract obstructive defects (RVOTO) (25.9%), atrioventricular septal defects (AVSD) (25.0%) and left ventricular outflow tract obstructive defects (LVOTO) (24.1%), while those in other CHD (10.6%) and septal defects (10.9%) were relatively low. The overall detection rate of clinically significant chromosomal abnormalities was significantly higher in the non-isolated CHD group compared to the isolated CHD group (33.1% vs. 9.9%, P

Abstract Modulation of scattering in random lasers (RLs) by magnetic fields has attracted much attention due to its rich physical insights. We fabricate magnetic gain polymer optical fiber to generate RLs. From macroscopic experimental phenomena, with the increase of the magnetic field strength, the magnetic transverse photocurrent exists in disordered multiple scattering of RLs and the emission intensity of RLs decreases, which is the experimental observation of photonic Hall effect (PHE) and photonic magnetoresistance (PMR) in RLs. At the microscopic level, based on the field dependence theory of magnetic disorder in scattered nanoparticles and the replica symmetry breaking theory, the magnetic-induced transverse diffusion of photons reduces the scattering disorder, and then decreases the intensity fluctuation disorder of RLs. Our work establishes a connection between the above two effects and RLs, visualizes the influence of magnetic field on RL scattering at the microscopic level, which is crucial for the design of RLs.

Abstract Northeast China is the main food production base of China. Extreme precipitation (EP) events can seriously impact agricultural production and socioeconomics, but the understanding of EP in Northeast China is still limited. In this study, using the non-stationary generalized extreme value (GEV) model, we investigate the trend and potential risk of EP in Northeast China during 1959–2017, especially in early and mid-summer (periods of high frequency of EP). Then, the relationships between EP and large-scale circulation over Northeast China in early and mid-summer are analyzed separately. The EP in Northeast China mainly presents positive trends in early summer but negative trends in mid-summer. Meanwhile, the EP with all the return periods presents apparently increasing trends in early summer, corresponding to more frequent EP events. Nevertheless, in mid-summer, the EP with 2-year return period decreases with location parameter, and the EP with 20-year, 50-year, and 100-year return periods slightly increases with scale parameter. The EP with 2-year return period occurs frequently in Liaoning Province, while the EP with 100-year return period is more likely to occur in Jilin Province and Heilongjiang Province. Moreover, the increase of the EP in early summer is mainly influenced by the northeast cold vortex; the effect of cold air on the EP is stronger in mid-summer, giving a clear explanation why the EP in mid-summer does not increase significantly. Overall, the outcomes of this study would be beneficial for the disaster prevention and mitigation in Northeast China.

Abstract Background Chronic obstructive pulmonary disease (COPD) contributes to the incidence and prognosis of lung cancer. The presence of COPD significantly increases the risk of lung squamous cell carcinoma (LSCC). COPD may promote an immunosuppressive microenvironment in LSCC by regulating the expression of immune‐inhibitory factors in T cells, although the mechanisms remain unclear. In this study, we aimed to decipher the tumour microenvironment signature for LSCC with COPD at a single‐cell level. Methods We performed single‐cell RNA sequencing on tumour tissues from LSCC with or without COPD, then investigated the features of the immune and tumour cells. We employed multiple techniques, including multispectral imaging, flow cytometry, tissue microarray analysis, survival analysis, co‐culture systems and in vitro and in vivo treatment experiments, to validate the findings obtained from single‐cell analyses. Results LSCC with COPD showed increased proportions of tumour‐associated macrophages (TAMs) and higher levels of CD8+ T cell exhaustion molecules, which contributed to an immunosuppressive microenvironment. Further analysis revealed a critical cluster of CD74+ tumour cells that expressed both epithelial and immune cell signatures, exhibited a stronger capacity for tumorigenesis and predicted worse overall survival. Notably, migration inhibitory factor (MIF) secreted by TAMs from LSCC with COPD may promote the activation of CD74. MIF‐CD74 may interact with CD8+ T cells and impair their anti‐tumour activity by regulating the PI3K‐STAT3‐programmed cell death‐1 ligand 1 signalling pathway, facilitating tumour proliferation and immune evasion. Conclusions Our comprehensive picture of the tumour ecosystem in LSCC with COPD provides deeper insights into relevant immune evasion mechanisms and potential targets for immunotherapy. Highlight Our results demonstrated higher proportions of tumour‐associated macrophages (TAMs) and higher levels of exhaustion molecules in CD8+ T cells in the microenvironment of LSCC with COPD. CD74+tumour cells were associated with poor disease prognosis. Migration inhibitory factor (MIF)‐CD74 may interact with CD8+ T cells and impair their anti‐tumour activity by regulating the PI3K‐STAT3‐PD‐L1 signalling pathway, facilitating immune evasion.

Improving the nitrogen and phosphorus removal rates and efficiently controlling membrane fouling are the keys to fully exploiting the applicability of anaerobic membrane bioreactor (AnMBR) process in high-concentration wastewater treatment. To that purpose, an integrated reactor composed of an anaerobic ceramic membrane bioreactor and N anaerobic fluidized bed (AnCMBR-AFB) was built and pollutant removal efficiency, nitrogen and phosphorus recovery characteristics, and membrane pollution features of this integrated reactor were investigated. The results revealed that the integrated reactor had good pollutant removal efficiency, with turbidity, chromaticity, and UV254 average values of the effluent being 0.470 NTU, 0.011 A, and 0.057 cm−1, respectively, and the average CODCr removal rate was 80%. The nitrogen and phosphorus recoveries were significantly higher than the nitrogen and phosphorus removal rates of conventional AnMBR at 23.20 ± 1.17% and 43.34 ± 1.54%, respectively. Microscopic analysis revealed the formation of magnesium ammonium phosphate (MAP) crystals on the carrier's surface, and friction between the carrier and the membrane surface could delay membrane fouling while allowing the contaminated membrane surface to retain significant roughness. Membrane fouling was mostly brought on by amides and saturated hydrocarbons, and inorganic metal ions also played a role to some extent. HIGHLIGHTS Pollutant removal during the operation of the AnCMBR-AFB-integrated reactor.; The AnCMBR-AFB-integrated reactor recovers nitrogen and phosphorus by the MAP crystallization process higher than AnMBR.; Membrane fouling is decreased by the friction between the fluidized carrier and the ceramic membrane.;

Abstract The compaction quality of subgrade filler strongly affects subgrade settlement. The main objective of this research is to analyze the macro- and micro-mechanical compaction characteristics of subgrade filler based on the real shape of coarse particles. First, an improved Viola–Jones algorithm is employed to establish a digitalized 2D particle database for coarse particle shape evaluation and discrete modeling purposes of subgrade filler. Shape indexes of 2D subgrade filler are then computed and statistically analyzed. Finally, numerical simulations are performed to quantitatively investigate the effects of the aspect ratio (AR) and interparticle friction coefficient (μ) on the macro- and micro-mechanical compaction characteristics of subgrade filler based on the discrete element method (DEM). The results show that with the increasing AR, the coarse particles are narrower, leading to the increasing movement of fine particles during compaction, which indicates that it is difficult for slender coarse particles to inhibit the migration of fine particles. Moreover, the average displacement of particles is strongly influenced by the AR, indicating that their occlusion under power relies on particle shapes. The displacement and velocity of fine particles are much greater than those of the coarse particles, which shows that compaction is primarily a migration of fine particles. Under the cyclic load, the interparticle friction coefficient μ has little effect on the internal structure of the sample; under the quasi-static loads, however, the increase in μ will lead to a significant increase in the porosity of the sample. This study could not only provide a novel approach to investigate the compaction mechanism but also establish a new theoretical basis for the evaluation of intelligent subgrade compaction.

This paper aims to explore the coarse-grained rearrangement (CGR) phenomenon and its effect on the mechanical behaviors of high-speed railway graded aggregate (HRGA) materials during vibratory compaction. Firstly, the evolution of CGR is characterized by the analysis of mechanical behaviors and migration of the coarse grains in the HRGA materials. Then, a new indicator, the fraction of horizontally deflected coarse grains Hr, is proposed to evaluate the CGR, which increases with the rearrangement degree during vibratory compaction. Finally, using the discrete element method (DEM), the evolution of macro and micro mechanical properties of HRGA materials with different Hr-values (Hr = 0, 0.2, 0.4, 0.6, 0.8, and 1.0) are analyzed based on triaxial compression tests. The numerical results show that the shear strength of the assembly firstly increases with Hr and then reaches a plateau when Hr ≥ 0.6, which can be considered as the vibratory compaction steady state. For the microscopic behaviors, with Hr increasing, the enhanced interlocking between coarse particles makes it more difficult for them to rotate, leading to an increased proportion of sliding contact. Moreover, the effectiveness of the state of Hr = 0.6 was validated by the X-ray computed tomography (X-CT) scanning test. This research is expected to provide microscopic insights into the formation of internal structures for HRGA materials during vibratory compaction and provide a new method to assess the compaction quality of gravel fillers.

The essence of vibratory compaction of high-speed railway graded aggregate (HRGA) materials lies in both internal particle rearrangement and breakage. However, there is a research gap on the level of particle rearrangement and breakage effects on the vibratory compaction characteristics. A novel index, the breakage contribution rate Cb, was proposed to quantify the contribution level of particle breakage to vibratory compaction characteristics based on theoretical derivation. Additionally, the relationship between the gradation, maximum dry density (MDD) and Cb was established using a high-performance machine learning (ML) model. Finally, the impact of Cb on vibratory compaction characteristics under different compaction conditions, including vibration parameters, container size, and sample thickness, was explored through laboratory vibratory compaction tests (LVCTs). The results show that the Cb is better predicted by the PSO-ANN-ML model (the comprehensive evaluation index in the testing set is 4.028). Under different compaction conditions, Cb has a significant important effect on determining the actual dry density (ADD). When Cb> 8.8%, it may lead to over-compaction, which has a negative effect on the overall quality of the compacted structure. Based on the analysis of Cb and ADD, it is recommended that the vibratory frequency should be set to the inherent frequency of the sample, while the ratio of excitation force to static load should be controlled at 1.8. The ratio of the container diameter and the sample thickness to the maximum particle size of the sample should be controlled at 4.4 and 3.5, respectively. The breakage contribution rate index proposed in the study has significant implications for the control of compaction quality and the understanding of the compaction mechanism.

ABSTRACTGestational diabetes mellitus (GDM) is characterized by the development of hyperglycemia and insulin resistance during the second or third trimester of pregnancy, associated with considerable risks to both the mother and developing fetus. Although emerging evidence suggests an association between the altered gut microbiota and GDM, remarkably little is known about the microbial and metabolic mechanisms that link the dysbiosis of the gut microbiota to the development of GDM. In this study, a metagenome-wide association study and serum metabolomics profiling were performed in a cohort of pregnant women with GDM and pregnant women with normal glucose tolerance (NGT). We identified gut microbial alterations associated with GDM and linked to the changes in circulating metabolites. Blood metabolite profiles revealed that GDM patients exhibited a marked increase in 2-hydroxybutyric acid and L-alpha-aminobutyric acid, but a decrease in methionine sulfoxide, allantoin, and dopamine and dopaminergic synapse, when compared with those in NGT controls. Short-chain fatty acid-producing genera, including Faecalibacterium, Prevotella, and Streptococcus, and species Bacteroides coprophilus, Eubacterium siraeum, Faecalibacterium prausnitzii, Prevotella copri, and Prevotella stercorea, were significantly reduced in GDM patients relative to those in NGT controls. Bacterial co-occurrence network analysis revealed that pro-inflammatory bacteria were over-represented as the core species in GDM patients. These microbial and metabolic signatures are closely associated with clinical parameters of glucose metabolism in GDM patients and NGT controls. In conclusion, we identified circulating dopamine insufficiency, imbalanced production of SCFAs, and excessive metabolic inflammation as gut microbiota-driven multiple parallel hits linked to GDM development. This work might explain in part the mechanistic link between altered gut microbiota and GDM pathogenesis, and suggest that gut microbiota may serve as a promising target to intervene in GDM.

The land surface of a watershed acts as a large reservoir, with its catchment water storage capacity (CWSC) influencing rainfall-runoff relationship. Estimating CWSC at global grid scale is challenging due to calibration complexity, limited spatial continuity, and data scarcity. To address this, a deep learning-based approach incorporates spatial reconstruction and temporal transfer for capturing spatio-temporal variations in watershed characteristics. The study focuses on the Global Runoff Data Centre dataset and presents a grid-based hydrological model. Findings demonstrate accurate identification of CWSC distribution, with the model achieving an R ^2 of 0.92 and the runoff Kling–Gupta efficiency of 0.71 during validation. According to the CMIP6 projections, the global CWSC is anticipated to undergo a significant increase at a rate of 1.7 mm per decade under the SSP5-8.5 emission scenario. Neglecting spatio-temporal CWSC variability globally overestimates climate change’s impact on runoff, potentially reducing the projected long-term increase by up to 41%.

Diabetes patients need to monitor blood glucose all year round. In this article, a novel scheme is proposed for blood glucose detection. The proposed sensor is based on a U-shaped microfiber prepared using hydrogen-oxygen flame-heating technology, and then 3-aminopropyltriethoxysilane (APTES) and glucose oxidase (GOD) are successively coated on the surface of the U-shaped microfiber via a coating technique. The glucose reacts with the GOD of the sensor surface to produce gluconic acid, which changes the effective refractive index and then shifts the interference wavelength. The structure and morphology of the sensor were characterized via scanning electron microscope (SEM) and confocal laser microscopy (CLM). The experimental results show that the sensitivity of the sensor is as high as 5.73 nm/(mg/mL). Compared with the glucose sensor composed of the same material, the sensitivity of the sensor increased by 329%. The proposed sensor has a broad application prospect in blood glucose detection of diabetic patients due to the advantages of miniaturization, high sensitivity, and good stability.

Abstract Daily inflow forecasting is of vital importance in reservoir economic operation. In the context of hydrometeorological forecasting, the effectiveness of the data‐driven models has been demonstrated as bias correctors for physically‐based models or direct forecasting models. However, existing studies only highlight the performance improvements provided by the data‐driven model, lacking a comprehensive investigation on whether the data‐driven model should be used as bias correctors or direct forecasting models. This study constructs long short‐term memory (LSTM)‐based preprocessing and postprocessing techniques for a hydrological model, which are tested by linear scaling preprocessing and autoregressive (AR) postprocessing models. The integrated model is compared with the LSTM‐only model. The Shuibuya and Zuojiang reservoirs in China are selected as case studies. Results indicate that: (1) LSTM‐based bias correctors are effective in both preprocessing and postprocessing and (2) the integrated model is comparable to the LSTM‐only model when trained with four or more years of data, while it is better than the LSTM‐only model when trained with less data. These findings demonstrate that data‐driven methods can effectively correct the bias in physically‐based model output, and integrating the physical and data‐driven models is useful in improving multi‐step ahead reservoir inflow forecasting if limited data can be obtained.

Floquet topological insulators (FTIs) have richer topological properties than static systems. In this work, we designed different domain wall (DW) structures consisting of a Floquet photonic lattice with opposite helical directions. We investigated the existence and types of edge states in three shared coupling structures and the impact of these shared coupling structures on edge states. When two opposite helical lattices share a straight waveguide array coupling, the edge states are localized on the straight waveguide. When two opposite helical lattices share a clockwise (or anticlockwise) helical waveguide array coupling, the DWs consist of zigzag and bearded edges, but the positions of the zigzag and bearded edges of the shared clockwise waveguide array are different from those of the shared anticlockwise waveguide array. The slope and transmission rate of the edge states both vary with the degree of coupling between the shared waveguides. The characteristics of these edge states, such as transmission speed and band gap width, are also affected by the incidence angle, modulation phase factor, and helical radii, and the methods for controlling the edge states in different shared coupling structures are provided. This will help deepen our understanding of how topological structures influence the electronic and photonic properties of materials. This could also lead to combining topology with metasurface-based structured light, which would highlight many novel properties with great application potential for various fields, such as imaging, metrology, communication, quantum information processing, and light–matter interaction.

Abstract There are many kinds of materials or methods used to make optical microcavities, and they have many different geometric structures. And electrospinning technique has become a very convenient and easy one to prepare polymer fiber. Based on this situation, PM597-doped polymer solution was prepared into high-performance fibers with different diameters by electrospinning technology in our work. In order to better study the temperature sensing of polymer fiber whispering gallery mode, we have placed it on two different substrates with gold and aluminum. A 532 nm pulsed laser beam was used to excite a single fiber in the radial direction, then the whispering gallery mode (WGM) laser was observed and the distribution of WGM was determined by theoretical calculations. The threshold of samples on aluminum substrate is 0.4 μJ. In addition, it is found that the samples on aluminum substrate performed better in temperature sensing, and the value is 0.13 nm/°C. As a result, WGM polymer fiber microcavities on aluminum substrate made by electrospinning technology have very broad development prospects in biosensing, optical pump lasers and other applications.

BackgroundNitrous oxide (N2O) is an increasingly popular recreational drug. N2O irreversibly disturbs the metabolism of vitamin B12, resulting in a functional deficiency. Vitamin B12 is vital for myelin synthesis and its deficiency primarily produces neurological complications. Inhaling N2O is more common and neurological complications are more evident than before.Case presentationWe report a young man who developed progressive limb numbness and unsteady walking after N2O abuse. The dominant diagnosis was subacute combined degeneration of the spinal cord (SCD). The patient was admitted to the hospital and given adenosylcobalamin treatment, but his symptoms progressed significantly from before and he developed acute cognitive impairment. After methylprednisolone combined with vitamin B12 treatment, symptoms significantly improved.ConclusionClinicians need to understand the presentation and treatment of SCD caused by N2O abuse. When symptoms progress despite conventional vitamin B12 therapy, the combination of methylprednisolone and vitamin B12 may be considered.

To evaluate the performance of expanded non-invasive prenatal testing (expanded noninvasive prenatal testing, NIPT-Plus) in screening for fetal chromosomal abnormalities includes aneuploidies and copy number variations, a total of 23,116 pregnant women with a singleton pregnancy were recruited for NIPT-Plus. Screening positive results were verified by karyotype analysis and chromosomal microarray analysis after amniocentesis. A total of 264 pregnancies (1.14%) were positive results as predicted by NIPT-Plus, including 233 aneuploidies and 31 copy number variations. Following genetic counseling, 233 (88.26%) pregnant women underwent invasive prenatal diagnosis and 136 were verified as true positives, comprising 72 common trisomies (T21, T18, T13), 47 sex chromosomal abnormalities two rare autosomal aneuploidies (RATs) and 15 copy number variations The positive predictive value for common trisomies, SCAs, RATs and CNVs were 68.57%, 68.12%, 6.67% and 51.72%, respectively. Pregnant women with screen-positive results for common trisomies have higher rates of invasive prenatal diagnosis and pregnancy termination than those with positive results for SCAs, RATs, and CNVs. NIPT-Plus showed a good performance in detecting common trisomies, SCAs and also contributed to detecting pathogenic CNVs, but higher accuracy was required in the detection of RATs. In summary, this study provides a reference for the clinical application of NIPT-Plus for screening fetal chromosomal abnormalities in this region. Therefore, we suggest that NIPT-Plus could be widely used in clinical screening for fetal chromosomal abnormalities in combination with prenatal diagnosis and genetic counseling.

Background: Hyperphenylalaninemia (HPA) is the most common inborn error in amino acid metabolism. It can be primarily classified into phenylalanine hydroxylase (PAH) deficiency and tetrahydrobiopterin (BH4) deficiency. BH4 deficiency (BH4D) is caused by genetic defects in enzymes involved in the biosynthesis and regeneration of BH4. 6-pyruvoyl-tetrahydropterin synthase (PTPS/PTS), which is encoded by the PTS gene, participates in the biosynthesis of BH4. PTPS deficiency (PTPSD) is the major cause of BH4D. In this study, we investigated that the prevalence of BH4D in Jiangxi province was approximately 12.5 per 1,000,000 live births (69/5,541,627). Furthermore, the frequency of BH4D was estimated to be 28.8% (69/240) in the HPA population of Jiangxi. In this study, we aimed to characterize the mutational spectrum of the PTS gene in patients with PTPSD from Jiangxi province.Method: Newborn screening data of Jiangxi province from 1997 to 2021 were analyzed and 53 families with PTPSD were enrolled for the analysis of the PTS gene variants by Sanger sequencing.Results: 106 variants were identified in 106 alleles of 53 patients with PTPSD, including 13 types of variants reported previously, and two novel variants (c.164-36A>G and c.146_147insTG). The predominant variant was c.259C>T (47.2%), followed by c.84-291A>G (19.8%), c.155A>G (8.5%), c.286G>A (6.6%) and c.379C>T (4.7%).Conclusion: The results of this study can not only provide guidance for the molecular diagnosis and genetic counseling in cases of PTPS deficiency but also enrich the PTS mutation database.

Dietary and symbiotic bacteria can exert powerful influence on metazoan lipid metabolism. Recent studies have emerged that microbiota have a role in animal obesity and related health disorders, but the mechanisms by which bacteria influence lipid storage in their host are unknown. To reduce the complexity of the relationship between gut microbiota and the host, Caenorhabditis elegans (C. elegans) has been chosen as a model organism to study interspecies interaction. Here, we demonstrate that feeding C. elegans with an opportunistic pathogenic bacterium Stenotrophomonas maltophilia (S. maltophilia) retards growth and promotes excessive neutral lipid storage. Gene expression analysis reveals that dietary S. maltophilia induces a lipogenic transcriptional response that includes the SREBP ortholog SBP-1, and fatty acid desaturases FAT-6 and FAT-7. Live imaging and ultrastructural analysis suggest that excess neutral lipid is stored in greatly expanded lipid droplets (LDs), as a result of enhanced endoplasmic reticulum (ER)-LD interaction. We also report that loss of function mutations in dpy-9 in C. elegans confers resistance to S. maltophilia. Dietary S. maltophilia induces supersized LDs by enhancing lipogenesis and ER-LD contacts in C. elegans. This work delineates a new model for understanding microbial regulation of metazoan physiology.

Abstract Background Long noncoding RNA NEAT1 has been implicated in glioma progression. However, the effect of NEAT1 on glycolysis of glioma cell and the potential mechanism remain unclear. Methods In vitro experiments, including CCK-8, colony formation, ECAR, and lactate detection assays were performed to evaluate the effect of NEAT1 on proliferation and glycolysis of glioma cell. RNA pulldown and RIP assays were performed to identify the interaction between NEAT1 and PGK1. Truncated mutation of NEAT1 and PGK1 was used to confirm the specific interactive domains between NEAT1 and PGK1. Animal studies were performed to analyze the effect of NEAT1/PGK1 on glioma progression. Results NEAT1 knockdown significantly suppressed the proliferation and glycolysis of glioma cells. NEAT1 could specifically interact with PGK1, which promotes PGK1 stability. Hairpin A of NEAT1 is essential for interaction with M1 domain of PGK1. Depletion of NEAT1 markedly inhibited tumor growth in mice, while PGK1 could reverse this effect. Higher expression of NEAT1 was associated with poor overall survival of GBM patients. Conclusions NEAT1 over expression promotes glioma progression through stabilizing PGK1. NEAT1/PGK1 axis is a candidate therapeutic target for glioma treatment.

Circular RNA (circRNA) is a unique type of endogenous RNA. It does not have free 3 ′or 5′ ends, but forms covalently closed continuous rings. Rheumatoid arthritis (RA) is a common chronic autoimmune joint disease, characterized by chronic inflammation of the joint synovial membrane, joint destruction, and the formation of pannus. Although the pathogenesis of rheumatoid arthritis remains incompletely understood, a growing amount of research shows that circRNA has a close relationship with RA. Researchers have found that abnormally expressed circRNAs may be associated with the occurrence and development of RA. This article reviews the inflammatory immune, functions, mechanisms, and values of the circRNAs in RA to provide new ideas and novel biomarkers for the diagnosis and treatment of RA.

Background and PurposeInfantile neuroaxonal dystrophy (INAD) is a subtype of PLA2G6-Associated Neurodegeneration (PLAN) with an age of early onset and severe clinical phenotypes of neurodegeneration. Individuals affected with INAD are characterized by rapid progressive psychomotor deterioration, neuroregression, and hypotonia followed by generalized spasticity, optic atrophy, and dementia. In this case, we aimed to identify the underlying causative genetic factors of a Chinese family with two siblings who presented with walking difficulty and inability to speak. We provided a prenatal diagnosis for the family and information for the prevention of this genetic disease.MethodsRetrospective clinical information and magnetic resonance imaging (MRI) findings of the proband were collected. Trio-whole exome sequencing (WES) including the proband and his parents was performed to explore the genetic causes, while Sanger sequencing was subsequently used to validate the variants identified by Trio-WES in the pedigree. Furthermore, prenatal molecular genetic diagnosis was carried out through amniocentesis to investigate the status of pathogenic mutations in the fetus by Sanger sequencing at an appropriate gestational age.ResultsThe two siblings were both clinically diagnosed with rapid regression in psychomotor development milestones. Brain MRI showed cerebellar atrophy and typical bilaterally symmetrical T2/FLAIR hyperintense signal changes in periventricular areas, indicating periventricular leukomalacia, and myelin sheath dysplasia. Trio-WES revealed two heterozygous variants in PlA2G6 associated with clinical manifestations in the proband: a novel maternally inherited variant c.217C>T (p.Gln73*) and a previously reported paternally inherited recurrent pathogenic variant c.1894C>T (p.Arg632Trp). These two heterozygous mutations were also detected in the younger brother who had similar clinical features as the proband. The novel variant c.217C>T was classified as “pathogenic (PVS1 + PM2 + PP3),” while the variant c.1894C>T was “pathogenic” (PS1 + PM1 + PM2 + PM3 + PP3) based on the latest American College of Medical Genetics and Genomics (ACMG) guidelines on sequence variants. Combining the molecular evidence and clinical phenotypes, the diagnosis of INAD was established for the two affected siblings. The two variants that were identified were considered the causative mutations for INAD in this family. Prenatal diagnosis suggested compound heterozygous mutations of c.217C>T and c.1894C>T in the fetus, indicating a high risk of INAD, and the parents chose to terminate the pregnancy.ConclusionWe identified a novel pathogenic mutation that broadens the mutation spectrum of PLA2G6 and will provide clues for the molecular diagnosis of INAD. Furthermore, our study has helped to elucidate the causative genetic factors of this Chinese family with INAD effectively and efficiently by using the emerging Trio-WES strategy and providing precise genetic counseling for this family.

Abstract Irrigation is the dominant section of human water use, exerting essential impacts on hydrological processes and water resources. To more realistically simulate irrigation processes in water‐rich regions, an irrigation scheme is incorporated into a land surface‐hydrological model. It calculates the irrigation water requirement according to meteorological conditions, cropping area and growing stage, and root‐zone soil moisture, and determines the irrigation water withdrawal based on the available water resources as well as describing water extraction and irrigation processes in the model. The coupled model is applied to the Yangtze River Basin (YRB) in China, and verified using the observed daily river discharge from 1987 to 1990, evapotranspiration and irrigation amounts from 1999 to 2003. The results first show that the model can well reproduce hydrological processes within the basin, and the simulated irrigation largely agrees with the observation, in terms of annual irrigation and its spatial pattern. Second, inclusion of irrigation processes allows the model to better estimate evapotranspiration, with relative biases decreased from about −10% to −3%. It is also found that in comparison to arid/semi‐arid areas, although presenting a less effect on river discharge and groundwater, the irrigation in the YRB significantly alters hydrological processes through water redistribution. The irrigation‐induced evapotranspiration increment and runoff decrease indicate a shift in the surface water and energy balance, implying a potential effect on the atmosphere. Therefore, representing irrigation processes properly is important, particularly for understanding the coupling effect of the nature‐human system and improving the hydrological prediction accuracy.

Study region: Qingjiang cascade reservoir, China. Study focus: Reservoirs regulate the natural streamflow to utilize water resources comprehensively. How to mine the existing massive reservoir operation data to describe human operation behaviors is a challenge. To address this issue, a data-driven method, Long short-term memory (LSTM), was used to simulate the reservoir outflow by inputting historical information. The physics-guided LSTM model, shortly named PG-LSTM, was formulated by using synthetic flood samples and physical constraints of water balance, boundary, and monotonicity. New hydrological insights: (1) PG-LSTM can reproduce historical outflow with seasonal variations, or predict outflow without lags, (2) knowledge of reservoir operations can guide LSTM with the reduction of negative flow occurrence and the accurate identification of operation behaviors under extreme hydrological conditions, (3) specifically, compared with conventional LSTM, gradient boosting regression tree and conventional reservoir operation, PG-LSTM can improve the Nash-Sutcliffe efficiency of cascade reservoir during the test period from 0.50, 0.20, and 0.17 to 0.54 in the reproduction scenario, and from 0.84, 0.26, and 0.17 to 0.85 in the prediction scenario with five-fold cross-validation method. The PG-LSTM is helpful to describe human operation behaviors of reservoirs.

In this study, a unique 0-D/2-D Ti3C2 structure was assembled by salt-etching Ti3C2 nanodots out of their parent 2-D Ti3C2 nanosheets. The strong quantum confinement in finite-sized nanodots and concomitant nanodents endowed this structure with a gradient bandgap. UV–Vis diffuse reflectance spectrum revealed the bandgap energies of the coated nanodots and inner nanosheets were 2.82 and 2.40 eV, respectively. Accordingly, the 0-D/2-D Ti3C2 was fairly sensitive to sunlight and could efficiently degrade MB, MeB and RhB dyes in contaminated water under solar illumination. Photocatalytic experiments evidenced that less dye adsorption would induce higher removal ratio of the dye. Moreover, cyclic removal experiments showed the photodegradation efficiency of 0-D/2-D Ti3C2 could still exceed 60% after the fifth cycle for MB, MeB and RhB dyes.

With advances in artificial intelligence, machine learning-based models such as long short-term memory (LSTM) models have shown much promise in forecasting long-term runoff by mapping pathways between large-scale climate patterns and catchment runoff responses without considering physical processes. The recognition of key factors plays a vital role and thus affects the performance of the model. However, there is no conclusion on which recognition algorithm is the most suitable. To address this issue, an LSTM model combined with two attention mechanisms both in the input and hidden layers, namely AT-LSTM, is proposed for long-term runoff forecasting at Yichang and Pingshan stations in China. The added attention mechanisms automatically assign weights to 130 climate phenomenon indexes, avoiding the use of subjectively set recognition algorithms. Results show that the AT-LSTM model outperforms the Pearson’s correlation based LSTM model in terms of four evaluation metrics for monthly runoff forecasting. Further, the set indirect runoff prediction method verifies that the AT-LSTM model also performs effectively in precipitation and potential evapotranspiration forecasting, and the indirect runoff prediction is inferior to the AT-LSTM model to establish a direct link between climate factors and runoff. Finally, four key factors related to runoff are identified by the attention mechanism and their impacts on runoff are analyzed on intra- and inter-annual scales. The proposed AT-LSTM model can effectively improve the accuracy of long-term forecasting and identify the dynamic influence of input factors.

Medium-low-speed maglevs are increasingly used in the urban rail transit industry because of their advantages, such as low noise and low energy consumption. In this study, a finite element analysis of the responses of the subgrade that supports a medium-low-speed maglev structure under a dynamic maglev load is presented. First, the finite element analysis considers a low-lying structure with different elastic moduli. Then, the attenuation laws of the dynamic stress and dynamic deformation for different depth ranges of the subgrade under the rail beam are analyzed. In addition, the magnitude of the influence of the dynamic load is clarified. The results lead to a recommendation of a base bed thickness of 1.5 m, graded gravel or group A filler as the surface layer of filler, and gravel soil as the bottom layer. This study provides theoretical support for the construction design of a subgrade structure under the rail beam of a low-lying maglev line.

Study region: Upper Yangtze River Basin, China. Study focus: The intensification of climate change and human activities leads to non-stationarity of hydrological processes. Previous studies mainly focus on monthly hydrological or Budyko models. However, it is a challenge that catchment hydrological responses to human activities for daily hydrological models. This study aims to evaluate anthropogenic impacts on water yield of the upper Yangtze River Basin by representing the Xinanjiang model parameters as functions of socio-economic factors. New hydrological insights: The hydrological parameters WM (soil water storage capacity) and KE (ratio of potential evaporation to pan evaporation) increased in 1976–2000, while the parameter B (non-homogeneity of the soil water storage capacity) declined. It is further demonstrated that the population and the drainage area of reservoirs have the greatest impact on B and WM, respectively. Their linear functional form is validated to be effective for improving streamflow simulation. These findings can help understand the non-stationarity of the rainfall-runoff relationship due to increasing human development and contribute to adaptive development strategies for future water resource management.

Traditional analytical methods for thalassemia screening are needed to process complicated and time-consuming sample pretreatment. In recent decades, ambient mass spectrometry (MS) approaches have been proven to be an effective analytical strategy for direct sample analysis. In this work, we applied ambient MS with wooden-tip electrospray ionization (WT-ESI) for the direct analysis of raw human blood samples that were pre-identified by gene detection. A total of 319 whole blood samples were investigated in this work, including 100 α-thalassemia carriers, 67 β-thalassemia carriers, and 152 control healthy samples. Only one microliter of raw blood sample was directly loaded onto the surface of the wooden tip, and then five microliters of organic solvent and a high voltage of +3.0 kV were applied onto the wooden tip to generate spray ionization. Multiply charged ions of human hemoglobin (Hb) were directly observed by WT-ESI-MS from raw blood samples. The signal ratios of Hb chains were used to characterize two main types of thalassemia (α and β types) and healthy control blood samples. Our results suggested that the ratios of charged ions to Hb chains being at +13 would be an indicator for β-thalassemia screening.

Very few studies have focused on diatomaceous earth slopes along high-speed railways, and the special properties of diatomaceous earth under alternating dry and wet conditions are unknown. This paper studies diatomaceous earth in the Shengzhou area, through which the newly built Hangzhou–Taizhou high-speed railway passes, and the basic physical and hydraulic properties of diatomaceous earth are analyzed by indoor test methods. A convenient, efficient, and controllable high-speed railway slope artificial rainfall simulation system is designed, and in situ comprehensive monitoring and fissure observation are performed on site to analyze the changes in various diatomaceous soil slope parameters under rainfall infiltration, and to explore the cracking mechanisms of diatomaceous earth under alternating dry and wet conditions. The results indicate extremely poor hydrophysical properties of diatomaceous earth in the Shengzhou area; the disintegration resistance index values of natural diatomaceous earth samples subjected to dry and wet cycles are 1.8–5.6%, and the disintegration is strong. Comprehensive indoor tests and water content monitoring show that natural diatomaceous earth has no obvious influence when it contacts water, but it disintegrates and cracks under alternating dry and wet conditions. The horizontal displacement of both slope types mainly occurs within 0.75–2.75 m of the surface layer, indicating shallow surface sliding; after testing, natural slope crack widths of diatomaceous earth reach 10–25 mm, and their depths reach 40–60 cm. To guarantee safety during high-speed railway engineering construction, implementing proper protection for diatomaceous earth slopes is recommended.

With the development of the refining industry, the treatment of refinery wastewater has become an urgent problem. In this study, a ceramic membrane (CM) was combined with Fenton-activated carbon (AC) adsorption to dispose of refinery wastewater. The effect of the combined process was analyzed using excitation–emission matrix (EEM), ultraviolet-visible (UV-vis) and Fourier transform infrared spectroscopies (FTIR). Compared with direct filtration, the combined process could significantly improve the removal of organic pollution, where the removal rate of the COD and TOC could be 70% and the turbidity removal rate was above 97%. It was found that the effluent could meet the local standards. In this study, the membrane fouling was analyzed for the impact of the pretreatment on the membrane direction. The results showed that Fenton-AC absorption could effectively alleviate membrane fouling. The optimal critical flux of the combined process was increased from 60 to 82 L/(m2·h) compared with direct filtration. After running for about 20 d, the flux remained at about 55 L/(m2·h) and the membrane-fouling resistance was only 1.2 × 1012 m−1. The Hermia model revealed that cake filtration was present in the early stages of the combined process. These results could be of great use in improving the treatment efficiency and operation cycle of refinery wastewater.