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Abstract Methylmalonic acidemia (MMA) is the most common inborn organic acidemia, presenting multisystemic complications. Uric acid may have neurotoxic or neuroprotective effects due to its antioxidant or pro-inflammatory properties; however, its role in MMA brain injury remains unclear. We examined the correlation between the serum uric acid levels and brain imaging features of MMA. Data were collected from a cross-sectional study of 216 patients with MMA and 216 healthy matched controls aged 0–5 years in China. Serum uric acid levels were measured, and magnetic resonance imaging and computed tomography findings were retrieved from hospital records. Overall, 74.1% patients had brain abnormalities. Patients in the MMA group with abnormal brain imaging had higher serum uric acid levels than those in the MMA normal brain imaging and control groups. The area under the curve of serum uric acid was 0.74, 0.91, and 0.93 for MMA diagnosis with abnormal brain images, basal ganglia changes, and globus pallidus changes, respectively. Higher serum uric acid levels were independently associated with abnormal brain images. Children aged

Abstract Background Isolated methylmalonic acidemia, an autosomal recessive disorder of propionate metabolism, is usually caused by mutations in the methylmalonyl-CoA mutase gene (mut-type). Because no universal consensus was made on whether mut-type methylmalonic acidemia should be included in newborn screening (NBS), we aimed to compare the outcome of this disorder detected by NBS with that detected clinically and investigate the influence of NBS on the disease course. Design & methods In this study, 168 patients with mut-type methylmalonic acidemia diagnosed by NBS were compared to 210 patients diagnosed after disease onset while NBS was not performed. Clinical data of these patients from 7 metabolic centers in China were analyzed retrospectively, including initial manifestations, biochemical metabolites, the responsiveness of vitamin B12 therapy, and gene variation, to explore different factors on the long-term outcome. Results By comparison of the clinically-diagnosed patients, NBS-detected patients showed younger age at diagnosis, less incidence of disease onset, better responsiveness of vitamin B12, younger age at start of treatment, lower levels of biochemical features before and after treatment, and better long-term prognosis (P

Lung cancer is the malignant tumor with the highest incidence and mortality rate worldwide. For lung adenocarcinoma, identifying specific gene mutations, fusions, and giving corresponding targeted drugs can greatly improve the survival time of the patients. Among them, anaplastic lymphoma kinase (ALK) fusion occurs in 3%-7% of non-small cell lung cancer (NSCLC). In clinical practice, a variety of detection methods can be used to determine the ALK fusion status, but false negative test results are possible. This paper retrospectively analyzed the diagnosis and treatment of a patient with lung adenocarcinoma, judged the ALK fusion status by various detection methods. Among them, immunohistochemistry (IHC)(Ventana D5F3), RNA based next-generation sequencing (RNA-based NGS) confirmed positive echinoderm microtubule associated protein like 4 (EML4)-ALK fusion, while DNA-based NGS was negative. This paper analyzed the detection methods of ALK fusion, in order to clarify which detection method is the most accurate and simple to choose in different clinical cases and guide the subsequent treatment.

The cerebral lymphatic drainage plays an important role in the occurrence and development of central nervous system diseases. Recent studies have shown that cerebral lymphatic drainage is regulated by circadian rhythm and anesthesia state; however, the regulating mechanism is still unclear. In this study, we used the second near-infrared region in vivo imaging to explore the regulation of cerebral lymphatic drainage in mice at different states. At first, by injection of a tracer at different times, we confirmed that the drainage of the meningeal lymphatic system was the fastest at zeitgeber time 2, while the internal flow of the glymphatic system was the slowest. Under anesthesia with isoflurane, administration of dexmedetomidine, an anesthetic that inhibits norepinephrine (NE) release, enabled mice to enter the stage of non-rapid eye movement sleep, at which time the influx of the glymphatic system increased, the efflux of the meningeal lymphatic system decreased, and the clearance rate of the brain parenchyma decreased. However, following the exogenous NE supplement, mice quickly changed from a non-rapid eye movement stage into an awake state with the meningeal lymphatic drainage retrieval. The results showed whether the drainage of the glymphatic system and meningeal lymphatic vessels, or parenchymal clearance, has made rapid adjustments based on sleep status that is regulated by NE. This study reveals that the NE-regulated sleep–wake cycle is a powerful regulator of cerebral lymphatic drainage and provides a potential therapeutic target for related central nervous system diseases.

Abstract Meningeal lymphatic vessels (mLVs) have been shown to be involved in amyloid beta (Aβ) clearance, which is considered as a potential therapeutic target for Alzheimer’s disease (AD). In this study, based on the superficial spatial distribution of mLVs, a near-infrared light is employed to modulate lymphatic drainage, significantly improving cognition of both aged and AD (5xFAD and APP/PS1) mice, and alleviating AD-associated pathology by reducing Aβ deposition, neuroinflammation and neuronal damage. Furthermore, transmission electron microscopy imaging and RNA sequencing data indicate amelioration of mitochondrial metabolism and cellular junction of meningeal lymphatic endothelial cells (mLECs) by light modulation. These studies collectively suggest that near-infrared light treatment can improve cognitive function by strengthening scavenging ability of mLVs through restoring mLEC function. In conclusion, lymphatic drainage potentiation by light promotes pathological remission and cognitive enhancement in aging and AD mouse models, which offers a potential amelioration strategy for neurodegenerative diseases.

Abstract Background Pitt–Hopkins syndrome (PTHS) is a neurodevelopmental disorder that remains underdiagnosed and its clinical presentations and mutation profiles in a diverse population are yet to be evaluated. This retrospective study aims to investigate the clinical and genetic characteristics of Chinese patients with PTHS. Methods The clinical, biochemical, genetic, therapeutic, and follow-up data of 47 pediatric patients diagnosed with PTHS between 2018 and 2021 were retrospectively analyzed. Results The Chinese PTHS patients presented with specific facial features and exhibited global developmental delay of wide severity range. The locus heterogeneity of the TCF4 gene in the patients was highlighted, emphasizing the significance of genetic studies for accurate diagnosis, albeit no significant correlations between genotype and phenotype were observed in this cohort. The study also reports the outcomes of patients who underwent therapeutic interventions, such as ketogenic diets and biomedical interventions. Conclusions The findings of this retrospective analysis expand the phenotypic and molecular spectra of PTHS patients. The study underscores the need for a long-term prospective follow-up study to assess potential therapeutic interventions.

The integrated Fabry-Perot (FP) interferometers structure based on four core fiber (FCF) and a helical phase-modulation microdisk (HPMD) structure is proposed. The HPMD is designed to generate π/2 phase difference between adjacent fiber cores at the end face of the FCF. Four extrinsic FP cavities are formed by the HPMD and another reflected mirror perpendicular to the fiber. The quadrature phase demodulation theory is derived and the FP cavities length can be directly calculated by the reflected intensity of the FCF. The crosstalk effect between the four cores is analyzed. In addition, the simulation results also show that the structure has strong anti-interference ability to temperature fluctuations, the sensitivity of phase difference and temperature is only 0.009 °/K. The results of phase demodulation show that the demodulation effect is better when the thickness of the phase disk is 765 nm, and the mean relative error is 0.58%. The influence of machining error of FCF on demodulation results is also analyzed. The phase demodulation relative error is 0.65% when the alignment mismatch is reach 100 μm.

Abstract To analyze the independent risk factors for recurrent bleeding and death within 1 year after endoscopic treatment of esophagogastric varices hemorrhage (EGVB) in patients with liver cirrhosis, and to validate the predictive value of ALBI score for recurrent bleeding and death within 1 year after endoscopic treatment of EGVB in patients with liver cirrhosis. A total of 338 patients with EGVB who received endoscopic treatment for the first time in the Department of Gastroenterology, First Affiliated Hospital of Nanchang University from January 1, 2016 to March 1, 2020 were selected. A database was established to analyze the patients’ demographic data, surgical variables and postoperative outcomes. All patients were contacted and followed up to verify the predictive value of ALBI score for recurrent bleeding and mortality. 130 patients had rebleeding within 1 year after surgery (38.5%). 66 patients died within 1 year after surgery (19.5%). Patients with ALBI grade 3 had significantly higher rebleeding and mortality rates than those with grades 1 and 2. The AUC was used to compare the predictive value of the four scores for rebleeding and mortality within one year after endoscopic surgery. Both ALBI scores had the largest AUC. The ALBI score has certain predictive value for rebleeding and mortality within 1 year after endoscopic therapy in patients with cirrhotic EGVB.

Cardiac hypertrophy is characterized by an increased volume of individual cardiomyocytes rather than an increase in their number. Myocardial hypertrophy due to pathological stimuli encountered by the heart, which reduces pressure on the ventricular walls to maintain cardiac function, is known as pathological hypertrophy. This eventually progresses to heart failure. Certain varieties of regulated cell death (RCD) pathways, including apoptosis, pyroptosis, ferroptosis, necroptosis, and autophagy, are crucial in the development of pathological cardiac hypertrophy. This review summarizes the molecular mechanisms and signaling pathways underlying these RCD pathways, focusing on their mechanism of action findings for pathological cardiac hypertrophy. It intends to provide new ideas for developing therapeutic approaches targeted at the cellular level to prevent or reverse pathological cardiac hypertrophy.

In this paper, a new type of harmonic injection permanent magnet shape optimization method is proposed to suppress the torque ripple of surface-mounted permanent magnet synchronous motor. The sinusoidal waveform shaping of the axial section of the permanent magnet is added with the third harmonic shaping, and the sine wave and the third harmonic are derived. The optimal ratio is 6:1. The permanent magnet no shaping, sinusoidal shaping and sinusoidal combined third harmonic shaping are compared. The results show that the sinusoidal combined third harmonic shaping design can effectively suppress the torque ripple of the surface mounted permanent magnet synchronous motor and obtain a relatively large output torque. At the same time, a method of using permanent magnet segmentation to approximately equivalently replace sine combined with third harmonic shaping design is proposed, which effectively saves the manufacturing cost of permanent magnets and provides design and research ideas for more economical and effective optimization of surface-mounted permanent magnet motors.

Because of its simple structure, large torque and high efficiency, permanent magnet synchronous motor of low speed and high torque is widely adopted in many fields. In this paper, a 394.5kW mining low-speed high-torque permanent magnet synchronous motor (LSHTPMSM) is regarded as the study object. According to the physical model, a three-dimensional equivalent heat transfer temperature field calculation model of the motor is built to simulate the temperature distribution of the motor under rated conditions. In terms of the serious issue of stator winding temperature increase of permanent magnet synchronous motor of low speed and high torque, the heat conduction optimization of the end of the stator winding is studied, which enhances the heat dissipation effect of the stator end winding, effectively reduces its temperature increase and temperature gradient with the winding in the slot, and improves the practical efficiency and service life of the motor. Finally, the motor temperature rise test platform is constructed for the verification of the feasibility of the optimization scheme, which provides a reference direction for the heat dissipation optimization of permanent magnet synchronous motor of low speed and high torque.

Transportation resilience, as a component of city sustainability, plays a crucial role in the daily management and emergency response of urban road systems. With coastal cities becoming increasingly vulnerable to typhoons, rainstorms, and other disasters, it is essential to assess the resilience of urban road transportation in a refined and differentiated approach. Existing resilience assessment methods often overlook significant biases, neglecting the dynamic response of road traffic and non-stationary characteristics of traffic systems. To address these limitations, we develop a quantitative resilience assessment method for urban road transportation during rainfall that is based on the improved Resilience Triangle. The method is applied to DiDi urban traffic speed and meteorological data of Shenzhen, China, from April to September 2018, with a focus on Typhoon Mangkhut as an extreme weather case. By analyzing transportation resilience variations across road densities, road hierarchies, and rainfall scenarios, we found that road densities and rainfall intensities explain resilience variations better than road hierarchies. Specifically, as accumulative precipitation exceeds 100 mm, a substantial surge in loss of performance is observed. Typhoon rainfalls result in a greater loss in urban road traffic compared to general rainfalls. The results offer valuable insights for urban road planning, traffic emergency management, and transportation resilience construction in the face of increasingly severe weather challenges.

Alpine wetland degradation threatens riparian biodiversity and ecological balance. Our study, conducted in July 2020 along the northern and eastern shores of Qinghai Lake, seeks to unravel the impacts of such degradation on plant species dominance and ecological niches, using advanced network analysis methods to explore the dynamics and survival strategies of plant species. We applied a space-to-time method to delineate three wetland degradation stage: a healthy swamp wetland, a slightly degraded wet meadow, and a degraded dry meadow. Six representative sampling points were chosen. At each point, three sample lines were randomly established, radiating outward from the center of the lake wetland, with each stage of degradation meticulously examined through three replicates to assess the plant communities in terms of species composition, plant height, coverage, and abundance. The results indicated: Species such as Kobresia tibetica and Leymus secalinus exhibit remarkable abundance across various stages of wetland degradation, indicating a robust tolerance to these conditions. This observation, coupled with the complexity of plant community structures in degrading wetlands, suggests that such intricacy cannot be solely attributed to the dominance of particular species. Instead, it is the result of a diverse array of species adapting to fluctuating water levels, which promotes increased species richness. Despite the prominence of species that exhibit rapid growth and reproduction, the ecological significance of less abundant species in contributing to the community’s complexity is also notable. Changes in habitat conditions due to wetland degradation facilitate both competitive and cooperative interactions among species, highlighting the dynamic nature of these ecosystems. Our analysis shows no significant linear relationship between the ecological niche overlap values and niche widths of plant species. However, the strategies employed by dominant species for competition and resource acquisition, as observed in the ecological niche overlap networks, underscore the adaptive capacity of plant communities. These insights underscore the need for tailored restoration strategies to conserve the biodiversity of alpine lake riparian ecosystems. This research not only sheds light on the resilience and adaptability of ecosystems in the Qinghai-Tibetan Plateau but also offers valuable lessons for the conservation of similar habitats worldwide. Our findings underscore the need for tailored restoration strategies to conserve the biodiversity of alpine lake riparian ecosystems. This research not only sheds light on the resilience and adaptability of ecosystems in the Qinghai-Tibetan Plateau but also offers valuable lessons for the conservation of similar habitats worldwide.

Vissers-Bodmer Syndrome, an autosomal dominant disease, is a neurodevelopmental disorder characterized by global developmental delay, intellectual disability, hypotonia and autistic features with a highly variable phenotype. It is caused by variants in the CCR4-NOT transcription complex, subunit 1 gene (CNOT1). However, the pathophysiologic mechanism of the Vissers-Bodmer Syndrome remains unclear. Notably, this syndrome has not been previously reported in the Chinese. In this study, we utilized whole exome sequencing to identify three novel variants in the CNOT1 gene, encompassing one frameshift variant and two missense variants, in three Chinese patients mainly presenting with developmental delay, intellectual disability and/or autism. Interestingly, three patients exhibited novel manifestations including spina bifida occulta, horse-shoe kidney and café-au-lait spot. The frameshift variant, p.Gly172Alafs*5, occurring de novo, leading to a premature stop codon in the protein, was classified into pathogenic. Two missense variants c.3451A > G (p.Asn1151Asp) and c.557C > T (p.Ser186Phe) were predicted to be deleterious by multiple prediction algorithms with high conservation among a variety of species. Additionally, three-dimensional structure modeling and predicting indicated the substitution of the mutated amino acids would decrease the stability of CNOT1 protein. Given that CNOT1 is a relatively novel disease gene, we evaluated the gene-disease validity following ClinGen Standard Operating Procedure. The existing evidence substantiates a “Definitive” level of gene-disease relationship. The genetic findings provide a reliable basis for the genetic counseling of the family reproduction. Moreover, our results expand the genetic and phenotypic spectrum of CNOT1-related Vissers-Bodmer Syndrome.

Multimedia technology holds paramount importance in driving innovation within vocational education, significantly influencing learning satisfaction. Its integration facilitates dynamic and interactive learning environments, catering to diverse learning styles and preferences. Moreover, multimedia technology enables educators to simulate real-world scenarios, providing practical and hands-on training opportunities. This aspect is particularly valuable in vocational education, where practical skills and application are required. The paper investigates the impact of multimedia technology in enhancing learning satisfaction within innovative vocational education. It delves into the utilization of multimedia tools and their correlation with learner satisfaction, exploring how these technologies augment engagement and comprehension in vocational training. The primary data from 515 students of vocational colleges of China has been collected and regression analysis is applied for empirical analysis. The findings of the study highlight that multimedia technology has positive relationship with innovative vocational education and learning outcome. The findings contribute valuable insights for policymakers regarding significant role multimedia plays in fostering enhanced learning experiences and overall satisfaction among vocational learners.

Introduction: Intrauterine adhesions (IUA), also known as Asherman's syndrome, is caused by trauma to the pregnant or non-pregnant uterus, which leads to damaged endometrial basal lining and partial or total occlusion of the uterine chambers, resulting in abnormal menstruation, infertility, or recurrent miscarriage. The essence of this syndrome is endometrial fibrosis. And there is no effective treatment for IUA to stimulate endometrial regeneration currently. Recently, menstrual blood-derived stem cells (MenSCs) have been proved to hold therapeutic promise in various diseases, such as myocardial infarction, stroke, diabetes, and liver cirrhosis.Methods: In this study, we examined the effects of MenSCs on the repair of uterine adhesions in a rat model, and more importantly, promoted such therapeutic effects via a xeno-free VitroGel MMP carrier.Results: This combined treatment reduced the expression of inflammatory factors, increased the expression of anti-inflammatory factors, restricted the area of endometrial fibrosis, diminished uterine adhesions, and partially restored fertility, showing stronger effectiveness than each component alone and almost resembling the sham group.Discussion: Our findings suggest a highly promising strategy for IUA treatment.

In this paper, a 20kW vehicle built-in permanent magnet synchronous motor is taken as an example, and a magnetic barrier structure is added to the rotor of the motor to solve the uneven saturation problem of the rotor side magnetic bridge. This structure improves the air-gap flux density waveform of the motor by influencing the internal magnetic flux path of the motor rotor, thus improving the sine of the no-load back EMF waveform of the motor and reducing the torque ripple of the motor. At the same time, Taguchi method is used to optimize the structural parameters of the added magnetic barrier. In order to facilitate the analysis of its uneven saturation phenomenon and improve the optimization effect, a simple equivalent magnetic network (EMN) model considering the uneven saturation of rotor magnetic bridge is established in this paper, and the initial values of optimization factors are selected based on this model. Finally, the no-load back EMF waveform distortion rate, torque ripple and output torque of the optimized motor are compared and analyzed, and the influence of magnetic barrier structure parameters on the electromagnetic performance of the motor is also analyzed. The results show that the optimized motor can not change the output torque of the motor as much as possible on the basis of reducing the waveform distortion rate of no-load back EMF and torque ripple.

Leakage in water supply pipelines remains a significant challenge. It leads to resource and economic waste. Researchers have developed several leak detection methods, including the use of embedded sensors and pressure prediction. The former approach involves pre-installing detectors inside pipelines to detect leaks. This method allows for the precise localization of leak points. The stability is compromised because of the wireless signal strength. The latter approach, which relies on pressure measurements to predict leak events, does not achieve precise leak point localization. To address these challenges, in this paper, a coherent optical time-domain reflectometry (φ-OTDR) system is employed to capture vibration signal phase information. Subsequently, two pre-trained neural network models based on CNN and Resnet18 are responsible for processing this information to accurately identify vibration events. In an experimental setup simulating water pipelines, phase information from both leaking and non-leaking pipe segments is collected. Using this dataset, classical CNN and ResNet18 models are trained, achieving accuracy rates of 99.7% and 99.5%, respectively. The multi-leakage point experiment results indicate that the Resnet18 model has better generalization compared to the CNN model. The proposed solution enables long-distance water-pipeline precise leak point localization and accurate vibration event identification.

Earthquakes are environmental disturbances affecting ecosystem functioning, health, and biodiversity, but their potential impacts on plant–soil interface are still poorly understood. In this study, grassland habitats in areas near and away from the seismo-fault in Madou, a region typical of alpine conditions on the Qinghai–Tibetan Plateau, were randomly selected. The impacts of earthquake on soil properties and plant nutrient content in the short term were emphasized, and their potential relationships with community diversity and productivity were examined. According to the findings of the study, the Maduo earthquake led to a decrease in soil nutrient content in alpine grassland ecosystems, especially soil TC, TN, TP, TCa, AP, AK, NH4+-N, and SOC, and inhibited the absorption of N, Ca, and Mg nutrients by plants. In addition, the diversity and productivity of communities were affected by both direct and indirect earthquake pathways. The negative impacts of seismic fracture on soil structure had the most significant direct impact on plant community diversity. Earthquakes also indirectly reduced community productivity by reducing the soil N content and inhibiting the absorption of plant nutrients. Our findings suggested that earthquakes could potentially decrease the stability of the alpine grassland ecosystem on the QTP by affecting nutrient availability at the plant–soil interface.

Abstract Background Orthodontic tooth movement (OTM), a process of alveolar bone remodelling, is induced by mechanical force and regulated by local inflammation. Bone marrow-derived mesenchymal stem cells (BMSCs) play a fundamental role in osteogenesis during OTM. Macrophages are mechanosensitive cells that can regulate local inflammatory microenvironment and promote BMSCs osteogenesis by secreting diverse mediators. However, whether and how mechanical force regulates osteogenesis during OTM via macrophage-derived exosomes remains elusive. Results Mechanical stimulation (MS) promoted bone marrow-derived macrophage (BMDM)-mediated BMSCs osteogenesis. Importantly, when exosomes from mechanically stimulated BMDMs (MS-BMDM-EXOs) were blocked, the pro-osteogenic effect was suppressed. Additionally, compared with exosomes derived from BMDMs (BMDM-EXOs), MS-BMDM-EXOs exhibited a stronger ability to enhance BMSCs osteogenesis. At in vivo, mechanical force-induced alveolar bone formation was impaired during OTM when exosomes were blocked, and MS-BMDM-EXOs were more effective in promoting alveolar bone formation than BMDM-EXOs. Further proteomic analysis revealed that ubiquitin carboxyl-terminal hydrolase isozyme L3 (UCHL3) was enriched in MS-BMDM-EXOs compared with BMDM-EXOs. We went on to show that BMSCs osteogenesis and mechanical force-induced bone formation were impaired when UCHL3 was inhibited. Furthermore, mothers against decapentaplegic homologue 1 (SMAD1) was identified as the target protein of UCHL3. At the mechanistic level, we showed that SMAD1 interacted with UCHL3 in BMSCs and was downregulated when UCHL3 was suppressed. Consistently, overexpression of SMAD1 rescued the adverse effect of inhibiting UCHL3 on BMSCs osteogenesis. Conclusions This study suggests that mechanical force-induced macrophage-derived exosomal UCHL3 promotes BMSCs osteogenesis by targeting SMAD1, thereby promoting alveolar bone formation during OTM. Graphical Abstract

Antimicrobial photodynamic therapy (aPDT) is a non-pharmacological antimicrobial regimen based on light, photosensitizer and oxygen. It has become a potential method to inactivate multidrug-resistant bacteria. However, limited by the delivery of photosensitizer (PS) in biofilm, eradicating biofilm-associated infections by aPDT remains challenging. This study aimed to explore the feasibility of combining ultrasonic irradiation with aPDT to enhance the efficacy of aPDT against methicillin-resistant staphylococcus aureus (MRSA) biofilm. A cationic benzylidene cyclopentanone photosensitizer with much higher selectivity to bacterial cells than mammalian cells were applied at the concentration of 10 μM. 532 nm laser (40 mW/cm2, 10 min) and 1 MHz ultrasound (500 mW/cm2, 10 min, simultaneously with aPDT) were employed against MRSA biofilms in vitro. In addition to combined with ultrasonic irradiation and aPDT, MRSA biofilms were treated with laser irradiation only, photosensitizer only, ultrasonic irradiation only, ultrasonic irradiation and photosensitizer, and aPDT respectively. The antibacterial efficacy was determined by XTT assay, and the penetration depth of PS in biofilm was observed using a photoluminescence spectrometer and a confocal laser scanning microscopy (CLSM). In addition, the viability of human dermal fibroblasts (WS-1 cells) after the same treatments mentioned above and the uptake of P3 by WS-1 cells after ultrasonic irradiation were detected by CCK-8 and CLSM in vitro. Results showed that the percent decrease in metabolic activity resulting from the US + aPDT group (75.76%) was higher than the sum of the aPDT group (44.14%) and the US group (9.88%), suggesting synergistic effects. Meanwhile, the diffusion of PS in the biofilm of MRSA was significantly increased by 1 MHz ultrasonic irradiation. Ultrasonic irradiation neither induced the PS uptake by WS-1 cells nor reduced the viability of WS-1 cells. These results suggested that 1 MHz ultrasonic irradiation significantly enhanced the efficacy of aPDT against MRSA biofilm by increasing the penetration depth of PS. In addition, the antibacterial efficacy of aPDT can be enhanced by ultrasonic irradiation, the US + aPDT treatment demonstrated encouraging in vivo antibacterial efficacy (1.73 log10 CFU/mL reduction). In conclusion, the combination of aPDT and 1 MHz ultrasound is a potential and promising strategy to eradicate biofilm-associated infections of MRSA.

Laser absorption spectroscopy for gas sensing basically employs an air pump located at the gas cell probe to draw in ambient gases, and the on-site gas sample is subsequently delivered for laboratory non-real-time analysis. In this study, an in situ all-fiber remote gas sensing strategy is proposed. The anti-resonant hollow-core fiber (AR-HCF) is used as the sensing fiber, and a 20 m middle-hole eccentric-core fiber (MH-ECF) is used as the conducting fiber. The remote ambient gases can be inhaled into the AR-HCF as a result of the negative pressure transmitted through the MH-ECF when pumping gas at the interface of the MH-ECF. Since the real-time monitoring of greenhouse gas emissions in industrial processes holds immense significance in addressing global climate change, the detection of CO2 is achieved with the TDLAS-WMS method, and the gas sensing performance of an all-fiber remote gas sensing structure (RGS) is experimentally validated. The response time t90 under the pumping condition is about 456 s, which is about 30 times faster than that of free diffusion. Allan deviation results for more than one hour of continuous monitoring indicate that the lowest detection limit for the all-fiber RGS is 0.0373% when the integration time is 184 s. The all-fiber remote gas sensing strategy also possesses the benefits of being applicable to multiplex, hazardous gas environment passive monitoring.

Hybrid excitation synchronous motor has the advantages of uniform and adjustable electromagnetic field, wide speed range and high power density. It has broad application prospects in new energy electric vehicles, wind power generation and other fields. This paper introduces the basic structure of hybrid excitation motor with modular stator, and analyzes the operation principle of hybrid excitation motor. The cooling structure of the water-cooled plate is designed, and the effects of the thickness of the water-cooled plate and the number of water channels in the water-cooled plate on the heat dissipation capacity of the water-cooled plate are analyzed by theoretical and computational fluid dynamics methods. The effects of different water cooling plate structures on water velocity, pressure drop, water pump power consumption and heat dissipation capacity were compared and analyzed. The influence of different inlet flow velocity on the maximum temperature rise of each part of the motor is analyzed, and the temperature of each part of the motor under the optimal water flow is analyzed. The influence of the traditional spiral water jacket cooling structure and the water-cooled plate cooling structure on the maximum temperature rise of the motor components is compared and analyzed. The results show that the water-cooled plate cooling structure is more suitable for the modular stator motor studied in this paper. Based on the water-cooled plate cooling structure, the air-water composite cooling structure is designed, and the effects of the air-water composite cooling structure and the water-cooled plate cooling structure on the maximum temperature rise of each component of the motor are compared and analyzed. The results show that the maximum temperature rise of each component of the motor is reduced under the air-water composite cooling structure.

In order to obtain better torque performance of high-speed interior permanent magnet motor(HSIPMM) and solve the problem that electromagnetic optimization design is seriously limited by its mechanical strength, a complete optimization design method is proposed in this paper. The object of optimization design is a 15kW, 20000r/min HSIPMM whose permanent magnets in rotor is segmented. Eight structural dimensions are selected as its optimization variables. After design of experiment(DOE), multiple surrogate models are fitted, a set of surrogate models with minimum error is selected by using error evaluation indexes to optimize, the NSGA-II algorithm is used to get the optimal solution. The optimal solution is verified by load test on a 15kW, 20000 r/min HSIPMM prototype. This paper can be used as a reference for the optimization design of HSIPMM.

Hybrid excitation motor is a combination of permanent magnet motor and electric excitation motor, which can flexibly adjust the air gap magnetic field. At present, the traditional silicon steel sheet core material is widely used, but this material limits the further reduction of stator iron loss. In this paper, a new type of hybrid excitation synchronous motor with modular stator structure based on amorphous alloy material is proposed. The design power is 1kW, and the speed is 3000rpm. By placing the armature winding and electric excitation winding in the stator slot, the slip ring and brush are avoided, and the reliability of the motor is improved. The rotor adopts staggered magnetic pole structure, which has strong flux adjusting ability. The core loss is greatly reduced by using amorphous alloy. Firstly, the structure and working principle of the new motor are given; Secondly, the size parameters of the motor are given, and the principle of flux adjustment is verified and analyzed by three-dimensional finite element(3D-FEM); Finally, through theoretical analysis of the influence factors of the magnetic adjustment ability and 3D-FEM finite element computation, the flux adjustment ability and the torque lifting at low speed are verified, and the advantages of the motor are verified.

Aiming at the problem of temperature rise of mine flameproof outer rotor permanent magnet synchronous motor, based on the fluid structure coupling method, the temperature distribution of motor under three cooling schemes of air cooling and water cooling are calculated respectively. For the structure I air cooling system, the influence of different number of heat sink on the maximum temperature rise and pressure drop of fluid channel is analyzed, and the parameters of heat sink are optimized. For the structure II air cooling system, the influence of setting fillet at the turn back of the fluid channel on the head loss in the fluid domain of the motor is analyzed, and the influence of different fillet radius on the head loss and the maximum temperature rise in the fluid domain is obtained. For the structure II water cooling system, the influence of different water flow speed on the maximum temperature rise of the motor is analyzed, and the influence of different assembly clearance of modular stator teeth and yoke on the maximum temperature rise of the motor is analyzed. The cooling effect and temperature rise distribution characteristics of the three cooling schemes are compared and analyzed. Finally, a water-cooled prototype is manufactured, and the temperature rise experiment is carried out, and the influence of the thermal deformation of fluid channel, stator yoke and stator teeth on the maximum temperature of the motor is analyzed. The results show that the calculated temperature field after considering the thermal deformation is closer to the experimental value, which verifies the accuracy of the calculation results, It also provides a reference for the selection and design of the cooling structure of the same type of PMSM electric roller.

Piglet weaning is an important stage in production where changes in the environment and diet can cause problems such as intestinal inflammation and diarrhea. Vitamin A is an essential nutrient for human and animal growth and has immunomodulatory and inflammatory effects. A large body of literature has previously reported on the use of vitamin A in piglet production, so our experiment added different concentrations of vitamin A (0, 1100, 2200, 4400, 8800, and 17,600 IU/kg) to weaned piglet diets to study the effects of different doses on growth performance, intestinal barrier, inflammation, and flora in weaned piglets. We selected 4400 IU/kg as the optimum concentration of vitamin A in relation to average daily weight gain, feed intake, feed-to-weight ratio, and diarrhea rate, and subsequently tested the inflammatory factors, immunoglobulin content, antioxidant levels, and intestinal flora of weaned piglets. Results: We observed that the diarrhea rate of weaned piglets was significantly lower after the addition of 4400 IU/kg of vitamin A to the diet (p < 0.05). A control group and a 4400 IU/kg VA group were selected for subsequent experiments. We found that after the addition of vitamin A, the serum CAT level of weaned piglets increased significantly, the expression of Claudin-1 in the jejunum and ileum increased significantly, the expression of Occludin gene in the jejunum increased significantly, the expression of IL-5 and IL-10 in the ileum increased significantly (p < 0.05), and the expression of IL-4, IL-5, and IL-10 in the ileum increased significantly (p < 0.05). Meanwhile, in the colonic flora of vitamin A-added weaned piglets, the relative abundance of Actinobacteria and Erysipelotrichales decreased significantly, while the relative abundance of Bacteroidales increased significantly (p < 0.05). The results of this study indicated that vitamin A at 4400 IU/kg reduces diarrhea in weaned piglets by increasing antioxidant levels, increasing intestinal tight junction protein gene expression, and regulating colonic gut microbiota.

Abstract Facility location selection plays a critical role in the planning of logistics networks. It selects the addresses of facility nodes from a candidate set of locations to optimise multiple targets such as transportation efficiency and economic cost considering the practical constraints of the real world. Thus, it is often formulated as a combinational optimisation problem, which is solved by either mixed integer programing algorithms or heuristic methods. However, these approaches are limited by several issues such as a high computational cost and weak generalisation flexibility. In this work, a novel hierarchical clustering framework is proposed for facility location selection, which can flexibly support a wide variety of optimisation targets and the combinations of multiple practical constraints that are vital in the real logistics scenarios. Beyond the original hierarchical clustering algorithm, it incorporates a looking‐forward mechanism that alleviates the ‘greedy trap’ by utilising global information. These advantages enable the proposed method to generate reliable solutions with high time efficiency. As demonstrated by the experimental results on real JD Logistics data, the proposed method outperforms the widely adopted GGA and VNS algorithms. It also has a much lower computation cost compared to the SCIP solver, while the quality of solutions are within an acceptable range.

BackgroundProline-rich transmembrane protein 2 (PRRT2) plays an important role in the central nervous system and mutations in the gene are implicated in a variety of neurological disorders. This study aimed to summarize the clinical characteristics and gene expression analysis of neurological diseases related to the PRRT2 gene and explore the clinical characteristics, therapeutic effects, and possible pathogenic mechanisms of related diseases.MethodsWe enrolled 10 children with PRRT2 mutation-related neurological diseases who visited the Children's Hospital affiliated with the Shanghai Jiaotong University School of Medicine/Shanghai Children's Hospital between May 2017 and February 2022. Video electroencephalography (VEEG), cranial imaging, treatment regimens, gene results, and gene expression were analyzed. Genetic testing involved targeted sequencing or whole-exome genome sequencing (WES). We further analyzed the expression and mutation conservation of PRRT2 and synaptosome-associated protein 25 (SNAP25) in blood samples using quantitative polymerase chain reaction (qPCR) and predicted the protein structure. Summary analysis of the reported gene maps and domains was also performed.ResultsTen children with PRRT2 gene mutations were analyzed, and 4 mutations were identified, consisting of 2 new (c.518A > C, p.Glu173 Ala; c.879 + 112G > A, p.?) and two known (c. 649 dup, p. Arg217Profs * 8; c. 649 del, p. Arg217Glufs * 12) mutations. Among these mutations, one was de novo(P6), and three could not be determined because one parent refused genetic testing. The clinical phenotypes were paroxysmal kinesigenic dyskinesia (PKD), benign familial infantile epilepsy (BFIE), epilepsy, infantile spasms, and intellectual disability. The qPCR results showed that PRRT2 gene expression levels were significantly lower in children and parent carriers than the control group. The SNAP25 gene expression level of affected children was significantly lower (P ≤ 0.001) than that of the control group. The mutation sites reported in this study are highly conserved in different species. Among the various drugs used, oxcarbazepine and sodium valproate were the most effective. All 10 children had a good disease prognosis, and 8 were completely controlled with no recurrence, whereas 2 had less severe and fewer seizures.ConclusionMutation of PRRT2 led to a significant decrease in its protein expression level and that of SNAP25, suggesting that the mutant protein may lead to the loss of its function and that of related proteins. This mutation site is highly conserved in most species, and there was no significant correlation between specific PRRT2 genotypes and clinical phenotypes. Asymptomatic carriers also have decreased gene expression levels, suggesting that more factors are involved.

The importance of work stress on newcomers’ organizational socialization has been a topic of substantial interest. However, the impact mechanism of different stressors on newcomers’ organizational socialization is still in the early stages of theory development. This study, based on the theory of the dual work stress model, explored how to challenge stressors and hindrance stressors impact newcomers’ organizational socialization via the mediation of job crafting. Based on the empirical data from 247 newcomers, we found that challenge stressors positively affected newcomers’ organizational socialization; on the contrary, hindrance stressors would result in negative influences. In addition, leader-member exchange enhanced the positive effect of challenge stressors on newcomers’ job crafting and further moderated the indirect influence of challenge stressors on newcomers’ organizational socialization via job crafting. These findings provide a practical guide for organizations to apply stress management and promote newcomers’ socialization.

Pathogenic variants in the nuclear receptor superfamily 4 group A member 2 (NR4A2) cause an autosomal dominant neurodevelopmental disorder with or without seizures. Here, we described two patients presenting with developmental delay, language impairment, and attention-deficit hyperactivity disorder. Trio-based whole exome sequencing revealed two novel heterozygous variants, c.1541-2A > C and c.915C > A, in NR4A2. Both variants were identified as de novo and confirmed by Sanger sequencing. In vitro functional analyses were performed to assess their effects on expression of mRNA or protein. The canonical splicing variant c.1541-2A > C caused aberrant splicing, leading to the retention of intron 7 and a truncated protein due to an early termination codon within intron 7 with decreased protein expression, while the variant c.915C > A was shown to result in a shorter protein with increased expression level unexpectedly. The clinical and genetic characteristics of the previously published patients were briefly reviewed for highlighting the potential link between mutations and phenotypes. Our research further confirms that NR4A2 is a disease-causing gene of neurodevelopmental disorders and suggests alterations in different domains of NR4A2 cause various severity of symptoms.

Abstract FUN14 domain-containing protein 1 (FUNDC1) is an integral mitochondrial outer-membrane protein, and mediates the formation of mitochondria-associated endoplasmic reticulum membranes (MAMs). This study aims to determine the contributions of FUNDC1-mediated MAMs to angiogenesis in vitro and in vivo. In cultured endothelial cells, VEGF significantly increases the formation of MAMs and MAM-related proteins, including FUNDC1. Endothelial cell-specific deletion of FUNDC1, which disrupts MAM formation in endothelial cells, lowers VEGFR2 expression and reduces tube formation, spheroid-sprouting, and functional blood vessel formation in vitro and in vivo. Conversely, increased MAM formation using MAM linkers mimics the effects of VEGF and promotes endothelial angiogenesis. Mechanistically, increased MAMs formation led to increased levels of Ca2+ in cytosol, promoted the phosphorylation of serum response factor (SRF) and enhanced the binding of SRF to VEGFR2 promoter, resulting in increased VEGFR2 production, with consequent angiogenesis. Moreover, blocking FUNDC1-related MAM formation with a cell-penetrating inhibitory peptide significantly suppresses the expressions of downstream angiogenic genes and inhibits tumor angiogenesis. We conclude that decreased MAMs formation by silencing FUNDC1 can inhibit angiogenesis by decreasing VEGFR2 expression, and targeting FUNDC1-dependent MAMs might be a promising approach for treating human disorders characterized by defective angiogenesis.

Focusing on the dynamic improvement of the underlying service network configuration, this paper aims to address a specific challenge of redesigning a multi-echelon city logistics distribution network. By considering the intra-echelon connection of facilities within the same layer of echelon, we propose a new distribution network design model by reformulating the classical quadratic assignment problem (QAP). To minimize the overall transportation costs, the proposed model jointly optimizes two types of decisions to enable agile distribution with dynamic “shortcuts”: (i) the allocation of warehouses to supply the corresponding distribution centers (DCs), and (ii) the demand coverage decision from distribution centers to delivery stations. Furthermore, a customized branch-and-bound algorithm is developed, where the lower bound is obtained by adopting Gilmore and Lawler lower Bound (GLB) for QAP. We conduct extensive computational experiments, highlighting the significant contribution of GLB-oriented lower bound, to obtain practical solutions; this type of efficient mathematical lower bounds offers a powerful tool for balancing theoretical research ideas with practical and industrial applicability.

Abstract. Endothelial dysfunction characterized by impaired endothelium-dependent vaso-relaxation is one of the earliest detectable pathological events in smoking, diabetes, and many cardiovascular diseases including hypertension, atherosclerosis. Overwhelming data from human and animals demonstrate that the endothelial dysfunction associated with diabetes is due to the local formation of oxidants and free radicals. However, the mechanisms by which diabetes instigates oxidative stress, and those by which oxidative stress perpetuates endothelial dysfunction are the subjects of intensive research in the last 3 decades. The studies from us and others have demonstrated that adenosine monophosphate-activated protein kinase (AMPK), a well-characterized energy sensor and modulator, serves as a highly efficient sensor as AMPK can be activated by very low levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) generated by physiological, pharmacological, and pathologic stimuli (redox sensor). Interestingly, oxidants-activated AMPK feedback lowers the levels of ROS by either suppressing ROS/RNS from reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and mitochondria or by increasing the levels of antioxidant enzymes (redox modulator). Further, our studies demonstrate that AMPK's functions as a redox sensor and modulator are vital to maintain endothelial cell function under physiological conditions. Finally, we discover that under chronic oxidative stress or large influx of ROS, AMPK is particularly susceptible to inhibition by ROS. We conclude that oxidative inactivation of AMPK in diabetes perpetuates oxidative stress and accelerates atherosclerosis in diabetes.

Abstract Background Methylmalonic acidemia is an inherited organic acid metabolic disease. It involves multiple physiological systems and has variable manifestations. The primary causative gene MMUT carries wide range of mutations, and one of them, c.1663G > A (p.A555T), is considered to be a rare type, which is seen more frequently in Asian than other populations. So far, little is known about the clinical features of patients carrying this mutation. In the present study, we aimed to define the clinical and biochemical features of the patients with this genotype. Methods Among 328 mut type methylmalonic acidemia patients from multiple hospitals in China, we collected 30 compound heterozygous patients sharing the mutation c.1663G > A (p.A555T) in the MMUT gene. Their clinical characteristics and biochemical index were described in detail and compared with methylmalonic acidemia patients without this variant. Results Most of these patients were diagnosed via newborn screening (26/30), treated in a timely manner, and kept healthy (24/30). Disease onset occurred in 7 patients. Developmental delay or intellectual impairment occurred in 4 patients. 100% of these patients (29/29) were responsive to Vitamin B12 administration. The blood propionylcarnitine, blood propionylcarnitine/acetylcarnitine ratio, urinary methylmalonic acid, urinary methylcitric acid before and after treatment in c.1663G > A (p.A555T) carrying patients were much lower than those in non-c.1663G > A (p.A555T) carrying patients. Conclusion Compared to patients with other mutations in the MMUT gene, patients with the c.1663G > A (p.A555T) mutation showed later onset, milder clinical phenotype, lighter biochemical abnormalities, better vitamin B12 responsiveness, lower morbidity, easier metabolic control, and thereby better prognosis. Newborn screening project plays an important role in early diagnosis, treatment, and prognosis of these patients.

The complex and severe problem of energy poverty seriously affects the health and quality of life of residents and poses a significant challenge to the country’s macroeconomic development. The purpose of this paper is to analyze the spatial distribution of energy poverty and the characteristics of regional differences in 30 provinces in mainland China from 2008 to 2019 by constructing an energy poverty evaluation index system and explore the main reasons for the gap between energy poverty regions in China from the perspective of “relational data.” The results show that the spatial distribution of energy poverty in China is “high in the west and central area and low in the east,” and the spatial pattern is relatively stable. From the perspective of the time dimension, the problem of energy poverty in China has been alleviated during the sample period, and the overall gap in energy poverty has shown a decreasing trend. The difference in energy poverty between regions is the primary source of the overall gap, but its contribution is gradually decreasing. The empirical results suggest that reducing the imbalance of industrial structure, energy price, and energy investment among regions can effectively narrow the inter-regional energy poverty gap. Moreover, there are differences in the dominant factors that determine the difference in energy poverty within the eastern, central, and western regions. In this regard, it is recommended to further improve the relevant policies in developing new energy sources according to local conditions, reasonably increasing energy construction investment, strengthening technological innovation, establishing financial guarantee mechanisms, and guiding residents to consume modern, clean energy.

Earthquakes occur frequently in fragile alpine grassland areas on the Qinghai-Tibet Plateau (QTP), but few studies have evaluated the impacts of seismo-fault of earthquake on alpine grassland vegetation diversity. In this study, we conducted a field survey of plant communities of alpine grassland along the fault zone in the 7.4 Maduo earthquake occurred on 22 May 2021. Surrounding grassland habitat far from the seismo-fault of earthquake was selected as the control. Plant community metrics around and far from seismic rupture were studied. The results showed that plant community metrics were negatively affected by seismo-fault of earthquake. Species composition around seismo-fault was being shifted from sedges-dominant into forbs-dominant. In addition, the diversity and aboveground biomass were significantly decreased around seismo-fault compared with the control. Our findings highlighted that earthquakes can cause species loss and plant community shift and finally lead to productivity reduction of alpine grassland. Additionally, forbs may be more competitive than other functional groups after the earthquake.

Heat stress jeopardised animal health by inducing oxidative stress and inflammation. This study was done to investigate the effects of chitosan oligosaccharides (COS) on oxidative stress and inflammation response in liver and spleen of yellow-feather broilers under high ambient temperature. A total of 144 35-day-old female Chinese indigenous yellow-feather broilers (body weight 450.21 ± 10.05 g) were randomly allocated into 3 dietary treatments with 6 replication pens, each pen had 8 broilers. The treatments were: Control, basal diet; COS100, basal diet with 100 mg/kg COS; COS200, basal diet with 200 mg/kg COS. During day 22 to 42 (57 to 77 days of age), broilers in the COS200 group had higher (p

Hydrate formed in the wellbore during deepwater shallow drilling will affect the operation safety, so it is necessary to predict and analyze the hydrate formation range and degree in the wellbore annulus. One development well in Lingshui Gas Field in South China Sea was taken as the research object, and the numerical simulation method for hydrate formation in deepwater drilling was built based on CSMHyK hydrate dynamics model and OLGA multiphase flow equation. The temperature-pressure field of the wellbore under various working conditions was calculated, the subcooling density was introduced to present the possibility of hydrate formation, the range and degree of hydrate formation in the wellbore annulus were predicted, and the parameter sensitivity of drilling fluid displacement, inlet temperature, density and shallow gas storage pressure was analyzed. The results show that under the assumed working conditions, the riser annulus near the mudline has the risk of hydrate formation, with the largest amount of hydrate formation in the annulus with a water depth of 800-1 000 m. The smaller the displacement of drilling fluid is, the lower the inlet temperature is, the greater the risk of hydrate formation will be, and the amount of hydrate formed in hazardous pipe section may exceed 40 kg/m3. The subcooling density, length of interval where hydrate is formed, total amount of hydrate formed and peak rate were selected as the characteristic values for assessing hydrate formation, and the quantitative analysis method for wellbore hydrate risk level was built. The research results are expected to provide theoretical guidance for hydrate control and optimization design of drilling schemes during deep water shallow drilling.

Background: Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency (HMGCS2D) is a rare autosomal recessive metabolic disorder caused by mutations of the HMGCS2 gene. To date, no more than 60 patients have been reported throughout the world.Purpose: To analyze the clinical, biochemical, molecular, and outcome features of HMGCS2D in a case series of 10 new Chinese patients.Methods: This retrospective study includes 10 Chinese patients diagnosed with HMGCS2D. We collected and analyzed clinical data for all patients. We also reviewed clinical data for 39 cases that had been reported previously.Results: All of our patients had experienced their first metabolic crisis before 12 months old. The most common clinical manifestations were anorexia, dyspnea, and disturbance of consciousness (10/10), followed by vomiting (8/10), fever (7/10), cough (4/10), diarrhea, and seizures (3/10). Each patient (10/10) had a different degree of hepatomegaly and increased aminotransferase, severe metabolic acidosis, and hypofibrinogenemia. 9 patients presented with severe hypoglycemia and weak positives on qualitative tests of urinary ketone body. Patient 3 was the only one without hypoglycemia. Five patients had hypocalcemia, five patients had hyperammonemia, four patients had hyperuricemia, and three had hypertriglyceridemia. During the metabolic acidosis episode, we observed high dicarboxylic acid values in urine, and the elevated ratio of blood acetylcarnitine to free carnitine may have been an additional biochemical signature. However, all returned to normal during the interictal interval. Molecular analysis identified 15 variants in the HMGCS2 gene, of which 10 were novel (c.220G>A/p.E74K, c.407A>G/p.D136G, c.422T>A/p.V141D, c.719A>C/p.D240A, c.821G>A/p.R274H, c.39dupA/p.L14Tfs*59, c.1394delA/p.N465Tfs*10, c.788delT/p.L263Cfs*36, c.717T>G/p.Y239*, and c.1017-2A>G). Combining these with previous cases, the known mutation c.1201G>T/p.E401* has been found in 6/40 (15.0%) of mutated alleles in 21 Chinese patients from 20 families, while none have been found in other populations. We found that patients with biallelic truncation mutation appeared to show a more severe clinical condition through a literature review.Conclusion: This study analyzed the phenotypic and genetic features of HMGCS2D in a Chinese case series. We also expanded the HMGCS2 mutational spectrum with 10 novel variants. The c.1201G>T/p.E401* mutation was the most frequent, representing 15.0% of the mutated alleles in reported unrelated Chinese patients, and thus, it may be a hot spot mutation.

Background: The chromodomain helicase DNA-binding protein 2 (CHD2) gene, is an ATPase and part of the CHD family of chromatin remodelers. Mutations in the CHD2 gene are inherited in an autosomal-dominant manner and can lead to intellectual disability, epilepsy, and autism. We investigated the clinical characteristics of CHD2-related conditions and their possible pathogenesis.Methods: We collected and analysed the clinical data of patients that were identified as having CHD2 mutations. Genetic testing was performed using targeted sequencing or whole-exome sequencing. We analysed the expression of CHD2 and repressor element 1-silencing transcription factor (REST) in blood samples using quantitative PCR and the conservation of the mutations. The CHD2 mutations we identified were compared with the known mutations reported in the CHD2-related literature.Results: Eight patients with CHD2 gene mutations were analysed. Six mutations were identified; four were unreported previously (c.670C>T; c.4012A>C; c.2416dup; c.1727–1728insAT), and two were known mutations: c.5035C>T (two cases) and c.4173dup (two cases). Among these mutations, seven were de novo mutations, and one could not be determined because the parents refused genetic testing. The clinical manifestations included mild or severe intellectual disability, epilepsy, and behavioural abnormalities. Quantitative PCR showed that the CHD2 gene expression levels among the patients, parents, and the controls were not significantly different. The levels of REST gene expression in the patients were significantly higher than those of the controls; thus, mutation of the CHD2 gene led to an increase in the expression level of the REST gene. The mutations reported were all located in conserved positions in different species. Among the various medications administered for treatment, valproate showed the best results for the treatment of epilepsy caused by CHD2 gene mutation.Conclusion: Mutation in CHD2 did not lead to a significant decrease in its expression level, indicating that the clinical phenotype was unrelated to its expression level, and the mutant protein may retain some function. Most of the mutations relatively stable. In addition, the clinical manifestations from the same mutation in the CHD2 gene were different among the known cases; this may be related to the regulation of REST or other regulatory factors.

Grassland cultivation is the key measure for restoring “Black Beach,” the extremely degraded alpine meadow in the Three River Headwater Area of the Qinghai–Tibetan Plateau. In this study, we examined the inter-specific relationship in the vegetation community of cultivated grasslands with different restoration times through the network analysis method. The results showed that with the extension of restoration time, the development of cultivated grassland would lead to increasing neutral interactions among the plant species. The proportion of species with positive and negative associations in the community decreased, while the number of species-independent pairs increased significantly. The complexity of plant interspecific association (species network density) had more influence on community stability with the extension of recovery time, which can be used to quantify the characteristics of community structure.

Ecological conservation and restoration projects in Three-river Headwater Region (TRHR) have been implemented to respond to the serious degradation of alpine meadow ecosystem. Compared with the substantial amount of studies on the recovery of plant communities, soil quality and ecosystem services, few studies have focused on the restoration performance of target species. Therefore, we conducted this study to analyze the dynamics and underlying mechanisms of species richness and aboveground biomass of plant communities and target species. The results showed that restoration actions (grassland cultivation and fencing) did not significantly improve the community aboveground biomass of the degraded alpine meadows, while the actions did significantly promote community species richness, target species richness and target species aboveground biomass. Community species richness (20%-45%) was significantly impacted by the restoration strategies, and community aboveground biomass (31%-53%) was impacted by the mean annual precipitation and mean annual temperature. The species richness (57%) and aboveground biomass (63%) of the target species were directly and indirectly impacted by restoration actions, climatic factors, biotic factors and soil factors. The implications of this study stress that target species should be highlighted in assessing the restoration success of degraded alpine meadows. Integrating climatic factors, target species and other biotic and abiotic indicators could help us better understand and evaluate restoration actions for degraded alpine meadows in the TRHR or other similar regions worldwide.

Disaster risk management (DRM) is the application of disaster risk reduction policies and strategies to reduce existing disaster risk and manage residual risk. However, due to dynamic human factors, it is challenging to depict and assess the effectiveness of DRM measures, and their implementation usually lacks a sufficient evidence-based evaluation process. Therefore, this study developed an agent-based model to integrate dynamic human behaviors into the DRM measures and evaluated their effectiveness in casualty reduction. The model was calibrated to simulate the debris flow event at Longchi town, China in 13 August 2010. The early warning system (EWS) and related DRM measures were taken as examples. The effectiveness of different DRM measures was quantitated by comparing the number of potential casualties. The main findings were: 1) EWS was very effective for community-based DRM as it could significantly decrease the average casualties by 30%. 2) Credibility of EWS was critical to its effectiveness. Less credible EWS might reduce its effectiveness by 9%. 3) EWS could be supplemented by other measures to further reduce casualties by 6%. 4) The downside effects of other DRM measures to EWS might exist and reduce its effectiveness by up to 5%. This study put forward an evidence-based approach to help policymakers select more cost-effective DRM measure, especially in the less developed countries where the available resources for DRM are limited.

Nitrogen deposition is recognized as one of the major threats to the ecosystem function of alpine grasslands on the Qinghai-Tibetan Plateau (QTP). However, few studies have documented the gradient responses of plant species, functional groups, and communities in alpine grassland ecosystems to various levels of N deposition on the QTP. We applied eight linear mixed-effect models combing acidification, eutrophication, and phosphorus availability to explore if the responses of functional traits (particularly plant height and specific leaf area) of plants from dominant species to functional groups and whole communities in different types of grassland to nitrogen deposition were consistent with the same or different models. We found that the specific leaf area of Stipa capillata, non-forb, and community-weighted mean value in the alpine steppe were synchronous and related to acidification with nitrogen addition; the height of Stipa capillata, non-forb, and community-weighted mean value in the alpine steppe was synchronous and related to acidification, eutrophication, and phosphorus availability with nitrogen addition; the height and specific leaf area of Elymus breviaristatus to functional groups and community-weighted mean value in cultivated grasslands (CGs) were synchronous and related to acidification, eutrophication, and phosphorus availability with nitrogen addition. Most of the responses of functional traits of plants to acidification, eutrophication, and phosphorus availability associated with nitrogen deposition in the alpine steppe and the CG were synchronous, while only the response of the specific leaf area of forb functional groups to eutrophication associated with N deposition in the alpine steppe was asynchronous.

Objective: The cblC type of combined methylmalonic acidemia and homocystinuria, an inherited disorder with variable phenotypes, is included in newborn screening (NBS) programs at multiple newborn screening centers in China. The present study aimed to investigate the long-term clinical benefits of screening individual.Methods: A national, retrospective multi-center study of infants with confirmed cblC defect identified by NBS between 2004 and 2020 was conducted. We collected a large cohort of 538 patients and investigated their clinical data in detail, including disease onset, biochemical metabolites, and gene variation, and explored different factors on the prognosis.Results: The long-term outcomes of all patients were evaluated, representing 44.6% for poor outcomes. In our comparison of patients with already occurring clinical signs before treatment to asymptomatic ones, the incidence of intellectual impairment, movement disorders, ocular complications, hydrocephalus, and death were significantly different (p < 0.01). The presence of disease onset [Odd ratio (OR) 12.39, 95% CI 5.15–29.81; p = 0.000], variants of c.609G>A (OR 2.55, 95% CI 1.49–4.35; p = 0.001), and c.567dupT (OR 2.28, 95% CI 1.03–5.05; p = 0.042) were independently associated with poor outcomes, especially for neurodevelopmental deterioration.Conclusion: NBS, avoiding major disease-related events and allowing an earlier treatment initiation, appeared to have protective effects on the prognosis of infants with cblC defect.

In recent years, with the increase of emerging pick-up requests during service, logistics companies have been driven to integrate delivery and pick-up service in a dynamic environment. To provide a balanced and robust approach to cope with delivery requests and emerging pick-up requests, this article aims at considering and modeling a practically useful service principle as preemptive services. To our knowledge, most existing studies assume that the dynamically arriving requests are handled in a non-preemptive processing sequence; that is, once the delivery person is allocated to a task, the process is noninterruptible till it gets completed. In the preemptive service, a service suspension of the delivery process (with low service utility) is allowed to satisfy the pick-up requests (with high service utility) first. To provide a systematic assessment on the value of preemptive service for evolving urban logistics systems, a dynamic vehicle routing problem with preemptive pick-up service (VRPPS) is proposed to systematically describe the problem with potentially complex dynamic priorities among different tasks. Based on a dynamically constructed space-time network, this study formulates a multicommodity flow model that aims at optimizing the generalized service utility and the operating cost simultaneously. To provide a fast value approximation, we present a solution framework deploying the augmented Lagrangian relaxation approach with embedded dynamic programming algorithms. This framework jointly integrates the processes of updating request information and obtaining optimal routes. Finally, the validity and effectiveness of the proposed methods are evaluated on an illustrative network and a real-world last-mile delivery network operated by a logistics company.

Floods are one of the most frequent and costly natural hazards worldwide, causing significant damage to infrastructure, agriculture, and livelihoods. The Lancang-Mekong River is a major river in Southeast Asia, but the basin is prone to flood disasters that may be exacerbated by climate change. Therefore, to better understand disaster risk and tailor disaster risk reduction measures, this study conducted multiscale flood disaster risk assessments at the watershed and community levels using indicator-based and hydrodynamic model-based methods. Both methods adopted open data with the supplement of local survey data. The results of the study showed that the flood risk is generally higher in the lower reach of the river due to high levels of both hazard and vulnerability. However, the community-scale risk assessment revealed that high flood-risk communities exist in low-risk zones, and vice versa, when the flood risk was assessed at the watershed scale. Such phenomena can lead to inadequate community preparedness for flooding or unnecessary allocation of resources for flood mitigation measures. These findings provide valuable insights for the development of disaster risk reduction strategies, policies, and plans based on an understanding of the risks. Furthermore, they offer a basis for prioritizing and targeting resources, particularly in areas with high population density or vulnerable communities.