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Cerebral cavernous malformation (CCM) is a polygenic disease with intricate genetic interactions contributing to quantitative pathogenesis across multiple factors. The principal pathogenic genes of CCM, specifically KRIT1, CCM2, and PDCD10, have been reported, accompanied by a growing wealth of genetic data related to mutations. Furthermore, numerous other molecules associated with CCM have been unearthed. However, tackling such massive volumes of unstructured data remains challenging until the advent of advanced large language models. In this study, we developed an automated analytical pipeline specialized in single nucleotide variants (SNVs) related biomedical text analysis called BRLM. To facilitate this, BioBERT was employed to vectorize the rich information of SNVs, while a deep residue network was used to discriminate the classes of the SNVs. BRLM was initially constructed on mutations from 12 different types of TCGA cancers, achieving an accuracy exceeding 99%. It was further examined for CCM mutations in familial sequencing data analysis, highlighting an upstream master regulator gene fibroblast growth factor 1 (FGF1). With multi-omics characterization and validation in biological function, FGF1 demonstrated to play a significant role in the development of CCMs, which proved the effectiveness of our model. The BRLM web server is available at http://1.117.230.196.

The successful launch of Landsat-9 in 2020 ensures the continuity of Landsat Earth observation data. However, before Landsat-9 data can be effectively used in conjunction with Landsat-8, it is necessary to consider the differences between data from different sensors. This study utilized the Reduced Major Axis (RMA) regression to compare simulated reflectance data derived from the spectral response functions and spectral library data, showing minor spectral response differences between the two sensors (RMA slope close to 1, RMSD ≤ 0.0005); The consistency of more than 100 million pairs of top-of-atmosphere (TOA) and surface reflectance (SR) data from two sensors extracted based on Google Earth Engine was then evaluated using RMA and ordinary least squares (OLS) regression, and a transfer function developed using OLS regression was provided (R2 > 0.84); The results showed that the atmospheric state has a significant effect on the continuity of the sensors, especially in the shorter wavelength bands; there are differences in the TOA and SR data, with the absolute mean difference |MD| ≤ 0. 0011, root mean square difference |RMSD| ≤ 0.0278 and mean relative difference |MRD| ≤ 0.47%; In addition, the influence of seasonal factors on the consistency of the two sensors was investigated, and the corresponding transformation functions were provided; The OLS transformation functions developed in this paper were validated on over 10 million samples in Africa, with R2 > 0.86 for TOA, R2 > 0.93 for SR, and R2 > 0.91 for the SR seasonal transformations.

Abstract TIMM9 has been identified as a mediator of essential functions in mitochondria, but its association with pan-cancer is poorly understood. We herein employed bioinformatics, computational chemistry techniques and experiments to investigate the role of TIMM9 in pan-cancer. Our analysis revealed that overexpression of TIMM9 was significantly associated with tumorigenesis, pathological stage progression, and metastasis. Missense mutations (particularly the S49L variant), copy number variations (CNV) and methylation alterations in TIMM9 were found to be associated with poor cancer prognosis. Moreover, TIMM9 was positively related with cell cycle progression, mitochondrial and ribosomal function, oxidative phosphorylation, TCA cycle activity, innate and adaptive immunity. Additionally, we discovered that TIMM9 could be regulated by cancer-associated signaling pathways, such as the mTOR pathway. Using molecular simulations, we identified ITFG1 as the protein that has the strongest physical association with TIMM9, which show a promising structural complement.

Abstract Temozolomide (TMZ) resistance is a major challenge in the treatment of glioblastoma (GBM). Tumour reproductive cells (TRCs) have been implicated in the development of chemotherapy resistance. By culturing DBTRG cells in three-dimensional soft fibrin gels to enrich GBM TRCs and performing RNA-seq analysis, the expression of stanniocalcin-1 (STC), a gene encoding a secreted glycoprotein, was found to be upregulated in TRCs. Meanwhile, the viability of TMZ-treated TRC cells was significantly higher than that of TMZ-treated 2D cells. Analysis of clinical data from CGGA (Chinese Glioma Genome Atlas) database showed that high expression of STC1 was closely associated with poor prognosis, glioma grade and resistance to TMZ treatment, suggesting that STC1 may be involved in TMZ drug resistance. The expression of STC1 in tissues and cells was examined, as well as the effect of STC1 on GBM cell proliferation and TMZ-induced DNA damage. The results showed that overexpression of STC1 promoted and knockdown of STC1 inhibited TMZ-induced DNA damage. These results were validated in an intracranial tumour model. These data revealed that STC1 exerts regulatory functions on MGMT expression in GBM, and provides a rationale for targeting STC1 to overcome TMZ resistance.

ABSTRACTLand cover is an important variable for climate, hydrology, and ecology studies. With the availability of various high-resolution global land cover (GLC) products, conducting a comprehensive assessment on their accuracy and consistency is important. In this study, we compared the performance of three latest 10-m-resolution GLC products, which include FROMGLC10 in 2017, ESA’s Worldcover10 in 2020, and ESRIGLC10 in 2020, and three latest 30-m-resolution GLC products, which include FROMGLC30 in 2017, GLC_FCS30 in 2020, and Globeland30 in 2020, in China. The consistency of these products was investigated in terms of spatial consistency and area consistency. Though the six GLC products demonstrate similar overall distribution patterns, their detailed spatial distributions are quite different, especially for the three 10-m-resolution products. Evidently, the cropland, forest, grassland, and bareland exhibited high inconsistencies than the other types. The classification accuracy of the six GLC products was also quantitatively assessed based on a visual-interpretation-based reference dataset. FROMGLC10 exhibits the highest overall accuracy of 65.57%, followed by FROMGLC30 (64.96%) and Worldcover10 (62.74%). ESRIGLC10 (49.79%) exhibits the lowest accuracy. The accuracies of shrubland, wetland, and tundra were relatively low. This study provides a valuable reference for selecting appropriate GLC products for potential users.

Abstract Background As the most common subtype of adult muscular dystrophy worldwide, large cohort reports on myotonic dystrophy type I (DM1) in China are still lacking. This study aims to analyze the genetic and clinical characteristics of Chinese Han DM1 patients. Methods Based on the multicenter collaborating effort of the Pan-Yangtze River Delta Alliance for Neuromuscular Disorders, patients with suspected clinical diagnoses of DM1 were genetically confirmed from January 2020 to April 2023. Peak CTG repeats in the DMPK gene were analyzed using triplet repeat-primed PCR (TP-PCR) and flanking PCR. Time-to-event analysis of onset age in females and males was performed. Additionally, detailed clinical features and longitudinal changes from the disease onset in 64 DM1 patients were retrospectively collected and analyzed. The Epworth Sleepiness Scale and Fatigue Severity Scale were used to quantify the severity of daytime sleepiness and fatigue. Results Among the 211 genetically confirmed DM1 patients, the mean age at diagnosis was 40.9 ± 12.2 (range: 12–74) with a male-to-female ratio of 124:87. The average size of CTG repeats was 511.3 (range: 92–1945). Among the DM1 patients with comprehensive clinical data (n = 64, mean age 41.0 ± 12.0), the age at onset was significantly earlier in males than in females (4.8 years earlier, p = 0.026). Muscle weakness (92.2%), myotonia (85.9%), and fatigue (73.4%) were the most prevalent clinical features. The predominant involved muscles at onset are hands (weakness or myotonia) (52.6%) and legs (walking disability) (42.1%). Of them, 70.3% of patients had daytime sleepiness, 14.1% had cataract surgery, 7.8% used wheelchairs, 4.7% required ventilatory support, and 1.6% required gastric tubes. Regarding the comorbidities, 4.7% of patients had tumors, 17.2% had diabetes, 23.4% had dyspnea, 28.1% had intermittent insomnia, 43.8% experienced dysphagia, and 25% exhibited cognitive impairment. Chinese patients exhibited smaller size of CTG repeats (468 ± 139) than those reported in Italy (613 ± 623), the US (629 ± 386), and Japan (625 [302, 1047]), and milder phenotypes with less multisystem involvement. Conclusion The Chinese Han DM1 patients presented milder phenotypes compared to their Caucasian and Japanese counterparts. A male predominance and an early age of onset were identified in male Chinese Han DM1 patients.

Urban parks provide essential ecosystem services (ESs) that enhance human wellbeing. However, discrepancies often arise between objective assessments of these services and stakeholders’ subjective perceptions. This study addresses a research gap concerning the synergies and tradeoffs between objective evaluations and subjective perceptions of key ecosystem services across various spatial scales. We investigated six key ecosystem services in Century Park, Shanghai, across seven buffer radii (8–100 m). Objective data were obtained from park view images (PVIs) and spatial analysis, while subjective perceptions were gathered through a scoring survey of 33 stakeholders. The key finding is that a buffer radius of 35 m offers optimal synergy between objective and subjective assessments for most ESs, particularly in pollution mediation, temperature regulation, and cultural services. Professionals showed stronger alignment in regulatory services like pollution mediation and temperature regulation, while residents exhibited higher synergy in net primary production (NPP) beyond a 75 m radius. Notably, cultural services displayed nuanced differences, with professionals preferring simpler landscapes and residents demonstrating varied aesthetic preferences. These findings emphasize the importance of integrating objective data and human perceptions in urban green space planning and governance. By incorporating diverse stakeholders and identifying optimal buffer zones, planners and designers can effectively balance ESs with human experiences. This approach ultimately fosters more sustainable and wellbeing-centered urban environments.

As urbanization accelerates globally, urban areas have become major sources of greenhouse gas emissions. In this context, urban parks are crucial as significant components of carbon sinks. Using Shanghai Century Park as a case study, this study aims to develop an applicable and reliable workflow to accurately assess the carbon sequestration capacity of urban parks from a spatial–temporal perspective. Firstly, the random forest model is employed for biotope classification and mapping in the park based on multi-source data, including raw spectral bands, vegetation indices, and texture features. Subsequently, the Net Primary Productivity and biomass of different biotope types are calculated, enabling dynamic monitoring of the park’s carbon sequestration capacity from 2018 to 2023. Moreover, the study explores the main factors influencing changes in carbon sequestration capacity from the management perspective. The findings reveal: (1) The application of multi-source imagery data enhances the accuracy of biotope mapping, with winter imagery proving more precise in classification. (2) From 2018 to 2023, Century Park’s carbon sequestration capacity showed a fluctuating upward trend, with significant variations in the carbon sequestration abilities of different biotope types within the park. (3) Renovation and construction work related to biotope types significantly impacted the park’s carbon sequestration capacity. Finally, the study proposes optimization strategies focused on species selection and layout, planting density, and park management.

Emerging pollutants (EPs) are receiving increasing attention due to the threats they pose to the environment and human health. As EPs continue to emerge, risk assessment requires many model animals. Caenorhabditis elegans (C. elegans) has been an outstanding toxicological model organism due to its growth and development characteristics. Particularly, in studying the transgenerational influences of EPs, C. elegans has advantages in saving time and cost due to its short generation cycle. As infertility has become a major problem in human reproductive health, reproductive toxicities of EPs on contemporary nematodes and across generations of C. elegans were introduced in this review. Moreover, the underlying mechanisms involved in germ cell apoptosis, spermatogenesis, and epigenetic alteration were discussed. Future research opportunities and challenges are also discussed to expand our understanding of the reproductive influences of EPs.

Several types of non-coding RNAs such as circRNAs, lncRNAs, and miRNAs have been identified to regulate mRNAs through the mechanism known as the competitive endogenous RNA (ceRNA) network. To explore the role of the ceRNA regulatory network in the immune microenvironment of bladder cancer, whole-transcriptome sequencing of bladder tumor and its peritumoral tissues from 38 bladder cancer patients, with a total of 63 samples, was performed to screen differentially expressed circ-, lnc-, mi-, and mRNAs to construct a circ/lnc-mi-mRNA regulatory network with pruning algorithms. We excavated a key immune-related gene BDNF to build the final ceRNA network as hsa-miR-107 sponged by hsa-circ-000211, AC108488.1, and LINC00163. Finally, a meta-analysis of 7 public datasets demonstrated that low expression of BDNF and high expression of hsa-miR-107 were associated with longer survival. Our study identified a ceRNA regulatory network as a potentially new prognostic marker and molecular therapeutic target of bladder cancer.

Abstract Background Mastitis is an inflammatory disease of the mammary gland that has serious economic impacts on the dairy industry and endangers food safety. Our previous study found that the body has a gut/rumen-mammary gland axis and that disturbance of the gut/rumen microbiota could result in ‘gastroenterogenic mastitis’. However, the mechanism has not been fully clarified. Recently, we found that long-term feeding of a high-concentrate diet induced mastitis in dairy cows, and the abundance of Stenotrophomonas maltophilia (S. maltophilia) was significantly increased in both the rumen and milk microbiota. Accordingly, we hypothesized that ‘gastroenterogenic mastitis’ can be induced by the migration of endogenous gut bacteria to the mammary gland. Therefore, this study investigated the mechanism by which enterogenic S. maltophilia induces mastitis. Results First, S. maltophilia was labelled with superfolder GFP and administered to mice via gavage. The results showed that treatment with S. maltophilia promoted the occurrence of mastitis and increased the permeability of the blood-milk barrier, leading to intestinal inflammation and intestinal leakage. Furthermore, tracking of ingested S. maltophilia revealed that S. maltophilia could migrate from the gut to the mammary gland and induce mastitis. Subsequently, mammary gland transcriptome analysis showed that the calcium and AMPK signalling pathways were significantly upregulated in mice treated with S. maltophilia. Then, using mouse mammary epithelial cells (MMECs), we verified that S. maltophilia induces mastitis through activation of the calcium-ROS-AMPK-mTOR-autophagy pathway. Conclusions In conclusion, the results showed that enterogenic S. maltophilia could migrate from the gut to the mammary gland via the gut-mammary axis and activate the calcium-ROS-AMPK-mTOR-autophagy pathway to induce mastitis. Targeting the gut-mammary gland axis may also be an effective method to treat mastitis.

This paper investigates a global fixed-time control strategy for a search and rescue unmanned surface vehicle (SRUSV) targeting water rescue missions. Firstly, an improved time allocation trajectory generation (ITATG) method is proposed to generate a smooth and continuous desired trajectory, incorporating position, velocity, and acceleration information. Secondly, a fixed-time sideslip angle observer-based adaptive line-of-sight (FTSOALOS) guidance law is designed. This law integrates time-varying look-ahead distances with a fixed-time sideslip angle observer (FTSO) to ensure rapid convergence of positional errors within a fixed timeframe. Additionally, this paper employs a first-order fixed-time disturbance observer (FOFTDO) to accurately estimate external disturbances. To alleviate network pressure and reduce actuator failure rates, a fixed-time event-triggered sliding mode control (FTETSMC) mechanism is developed, ensuring the convergence of tracking errors within a fixed timeframe. Finally, using Lyapunov theory, this paper proves that the entire control system designed possesses consistent global fixed-time stability. Comparative simulation experiments validate the effectiveness and superiority of the FTSOALOS guidance law and the FTETSMC controller.

Long non-coding RNAs (lncRNAs) are well known for their oncogenic or anti-oncogenic roles in cancer development. AGAP2-AS1, a new lncRNA, has been extensively demonstrated as an oncogenic lncRNA in various cancers. Abundant experimental results have proved the aberrantly high level of AGAP2-AS1 in a great number of malignancies, such as glioma, colorectal, lung, ovarian, prostate, breast, cholangiocarcinoma, bladder, colon and pancreatic cancers. Importantly, the biological functions of AGAP2-AS1 have been extensively demonstrated. It could promote the proliferation, migration and invasion of cancer cells. Simultaneously, the clinical significances of AGAP2-AS1 were also illustrated. AGAP2-AS1 was exceptionally overexpressed in various cancer tissues. Clinical studies disclosed that the abnormal overexpression of AGAP2-AS1 was tightly connected with overall survival (OS), lymph nodes metastasis (LNM), clinical stage, tumor infiltration, high histological grade (HG), serous subtype and PFI times. However, to date, the biological actions and clinical significances of AGAP2-AS1 have not been systematically reviewed in human cancers. In the present review, the authors overviewed the biological actions, potential mechanisms and clinical features of AGAP2-AS1 according to the previous studies. In summary, AGAP2-AS1, as a vital oncogenic gene, is a promising biomarker and potential target for carcinoma prognosis and therapy.

Abstract Blue copper proteins are models for illustrating how proteins tune metal properties. Nevertheless, the mechanisms by which the protein controls the metal site remain to be fully elucidated. A hindrance is that the closed shell Cu(I) site is inaccessible to most spectroscopic analyses. Carbon deuterium (C-D) bonds used as vibrational probes afford nonperturbative, selective characterization of the key cysteine and methionine copper ligands in both redox states. The structural integrity of Nostoc plastocyanin was perturbed by disrupting potential hydrogen bonds between loops of the cupredoxin fold via mutagenesis (S9A, N33A, N34A), variably raising the midpoint potential. The C-D vibrations show little change to suggest substantial alteration to the Cu(II) coordination in the oxidized state or in the Cu(I) interaction with the cysteine ligand. They rather indicate, along with visible and NMR spectroscopy, that the methionine ligand distinctly interacts more strongly with the Cu(I) ion, in line with the increases in midpoint potential. Here we show that the protein structure determines the redox properties by restricting the interaction between the methionine ligand and Cu(I) in the reduced state.

Abstract Vertebrate embryogenesis is a remarkable process, during which numerous cell types of different lineages arise within a short time frame. An overwhelming challenge to understand this process is the lack of dynamic chromatin accessibility information to correlate cis-regulatory elements (CREs) and gene expression within the hierarchy of cell fate decisions. Here, we employed single-nucleus ATAC-seq to generate a chromatin accessibility dataset on the first day of zebrafish embryogenesis, including 3.3 hpf, 5.25 hpf, 6 hpf, 10 hpf, 12 hpf, 18 hpf and 24 hpf, obtained 51,620 high-quality nuclei and 23 clusters. Furthermore, by integrating snATAC-seq data with single-cell RNA-seq data, we described the dynamics of chromatin accessibility and gene expression across developmental time points, which validates the accuracy of the chromatin landscape data. Together, our data could serve as a fundamental resource for revealing the epigenetic regulatory mechanisms of zebrafish embryogenesis.

Abstract Background To compare the preventive effects of levetiracetam and valproate on late-onset post-traumatic seizures in patients with traumatic brain injury (TBI). Methods A total of 95 patients with TBI were recruited from 2017 to 2020. They were randomized into three groups: levetiracetam (LEV) group (n = 30) receiving LEV treatment (500 mg, bid, po); valproate group (n = 32) receiving sodium valproate (500 mg/d, once daily, po); and control group (n = 33) receiving no anti-seizure medication. LEV and valproate were given to corresponding groups within seven days after TBI, and the administration lasted for one month. The incidence of epilepsy and adverse events were evaluated at 7 days and 12 months post-TBI. Results The cumulative incidences of late post-traumatic seizures at the 12-month follow-up in the LEV, valproate, and control groups were 3.33%, 12.50% and 15.63%, respectively. The cumulative incidence of late post-traumatic seizures in the LEV group was significantly lower than those in the valproate and control groups (P 0.05). Conclusions LEV can reduce the cumulative incidence of late post-traumatic seizures, whereas valproate can not.

Background: Depression is the third leading cause of worldwide disease burden among youth, and nutrition- and diet-related behaviors have been considered as an effective strategy for reducing the risk of depressive symptoms. This systematic review aims to examine associations between dietary intake and diet quality with depressive symptoms among youth. Methods: In this systematic review, a search of scientific articles published between 2000 and 2021 was performed in four databases (CINAHL, Embase, PsycInfo, and PubMed) according to the PRISMA checklist. After applying inclusion and exclusion criteria, observational studies that focused on associations between micronutrient, macronutrient, food group intake, and diet quality and depressive symptoms among youth, ages 3 to 18, were selected for review. Results: Thirty-two articles met the review criteria. Dietary intake of magnesium, vitamin B12, fiber, fruits, vegetables, and fish were consistently inversely related to depressive symptoms. However, the evidence of associations between intake of vitamins B6, C, D, and E, iron, copper, zinc, omega-3 fatty acids, carbohydrate, and dietary fat and depressive symptoms was mixed. Dietary effects on decreased depressive symptoms were more pronounced in children than adolescents. Additionally, most studies failed to adjust for potential confounding variables. Conclusion: This review provides preliminary and comprehensive evidence for a relationship between dietary intake, diet quality, and depressive symptoms in youth. Although the results are heterogeneous and more research is needed, our findings indicate the importance of nutrition interventions for youth for decreasing depressive symptoms or for preventing further symptom exacerbation.

Electrochemical hydrogen-participating processes are commonly relevant in multiple clean energy technologies. Here, authors achieve in situ quantification of H sorption kinetics during Pd-catalyzed CO2 reduction, unravelling its key role within the interfacial network of local pH, proton donors and CO2 molecules.

Objectives Mitofusion-2 (Mfn2) may have a role in mitochondrial oxidative stress and insulin resistance that can promote the development of metabolic dysfunction associated fatty liver disease (MAFLD). This retrospective and case control study aimed to explore the relationships between common Mfn2 single nucleotide polymorphisms (SNPs) and MAFLD in a northern Han Chinese population. Methods Six Mfn2 SNPs (rs2336384, rs873458, rs873457, rs4846085, rs2878677, and rs2236057) were genotyped using the ligase detection reaction in 466 MAFLD patients and 423 healthy controls. Genotype and allele frequencies were calculated, along with haplotype analysis and pairwise linkage disequilibrium. Results The genotype distribution of rs2336384, rs2878677, and rs2236057 among the MAFLD patients showed a significantly different pattern from that of healthy controls. The data showed that an increased risk of MAFLD was significantly correlated with patients carrying the GG genotype of rs2336384, CC genotype of rs873457, TT genotype of rs4846085, TT genotype of rs2878677, and the AA genotype of rs2236057. Moreover, The GGCTTA haplotype was found to be adversely linked with MAFLD by haplotype analysis. Conclusion The current findings suggest a strong link between certain Mfn2 gene polymorphisms and MAFLD.

Understanding the spatiotemporal characteristics of merging behavior is crucial for the advancement of autonomous driving technology. This study aims to analyze on-ramp vehicle merging patterns, and investigate how various factors, such as merging scenarios and vehicle types, influence driving behavior. Initially, a framework based on a high-definition (HD) map is developed to extract trajectory information in a meticulous manner. Subsequently, eight distinct merging patterns are identified, with a thorough examination of their behavioral characteristics from both temporal and spatial perspectives. Merging behaviors are examined temporally, encompassing the sequence of events from approaching the on-ramp to completing the merge. This study specifically analyzes the target lane’s spatial characteristics, evaluates the merging distance (ratio), investigates merging speed distributions, compares merging patterns and identifies high-risk situations. Utilizing the latest aerial dataset, exiD, which provides HD map data, the study presents novel findings. Specifically, it uncovers patterns where the following vehicle in the target lane chooses to accelerate and overtake rather than cutting in front of the merging vehicle, resulting in Time-to-Collision (TTC) values of less than 2.5 s, indicating a significantly higher risk. Moreover, the study finds that differences in merging speed, distance, and duration can be disregarded in patterns where vehicles are present both ahead and behind, or solely ahead, suggesting these patterns could be integrated for simulation to streamline analysis and model development. Additionally, the practice of truck platooning has a significant impact on vehicle merging behavior. Overall, this study enhances the understanding of merging behavior, facilitating autonomous vehicles’ ability to comprehend and adapt to merging scenarios. Furthermore, this research is significant in improving driving safety, optimizing traffic management, and enabling the effective integration of autonomous driving systems with human drivers.

There is still a huge gap between the emissions pathways of megacities and the pathways to meeting the targets set by the Paris agreement. Compared with technological emission reductions, structural emission reduction can provide cities with more stable and sustainable carbon-peaking solutions. This study constructs a scenario-based input–output optimization model, adopting a novel carbon emission accounting method for purchased electricity that considers shared responsibility, and systematically evaluates the decarbonization paths of megacities and their impacts on economic growth, energy consumption, and carbon emissions. The results show that (a) through industry substitution and manufacturing restructuring, Shenzhen is projected to peak at 57.68 MtCO _2 emissions in 2026, with a 10.57% energy and a 19.55% carbon reduction by 2030. (b) Shenzhen can achieve its carbon emission peak target through the energy transition while accepting a loss of 0.97%–3.23% of GDP, requiring the maximum economic concession of 16.45% from the transportation sector (S10) in the early stage of transformation, while 12.24% from the extractive industry (S2) in the later stage. (c) The comprehensive structure adjustment proved to be more effective than other mitigation approaches, capable of achieving high-quality economic growth of 6.4% during the study period while reaching a peak target of 53.55 million tons of CO _2 by 2026. (d) The emission reduction effect of the power sector was the most significant among all the scenarios, with emission reduction rates between 6.26% and 35.63%, and the cumulative emission reduction potential reached 38.1–110.6 MtCO _2 . The priority for emission reduction in the power sector is the coal phase-out plan, which is essential for achieving these significant reductions. This study provides an important reference for megacities facing similar challenges, especially those in developing countries, to achieve a stable and sustainable carbon peak pathway through structural adjustment.

In order to more accurately analyze the problem of time delay simulation and calculation in the time-sensitive network (TSN) of vehicular Ethernet, a TSN reservation class data delay analysis model improved based on the State–Action–Reward–State–Action (SARSA) reinforcement learning algorithm is proposed. Firstly, the TSN data queue forwarding delay model and reservation class data delay analysis intelligent body model are established, then the TSN traffic scheduling mechanism is improved by the SARSA reinforcement learning algorithm, and the improved TSN network reservation class data analysis model is established for the uncertainty of traffic scheduling in the network; finally, the fitting performance of the proposed method is verified by simulation and experimental validation. The results show that the deviation between the two is less than 5% under different BE loads, i.e., the established reservation class data delay analysis model is able to correctly fit the scheduling mechanism of the vehicle-mounted TSN network, which proves the reasonableness of the model simulation.

Transplantation of neural stem cells (NSCs) has been proved to promote functional rehabilitation of brain lesions including ischemic stroke. However, the therapeutic effects of NSC transplantation are limited by the low survival and differentiation rates of NSCs due to the harsh environment in the brain after ischemic stroke. Here, we employed NSCs derived from human induced pluripotent stem cells together with exosomes extracted from NSCs to treat cerebral ischemia induced by middle cerebral artery occlusion/reperfusion in mice. The results showed that NSC-derived exosomes significantly reduced the inflammatory response, alleviated oxidative stress after NSC transplantation, and facilitated NSCs differentiation in vivo. The combination of NSCs with exosomes ameliorated the injury of brain tissue including cerebral infarction, neuronal death, and glial scarring, and promoted the recovery of motor function. To explore the underlying mechanisms, we analyzed the miRNA profiles of NSC-derived exosomes and the potential downstream genes. Our study provided the rationale for the clinical application of NSC-derived exosomes as a supportive adjuvant for NSC transplantation after stroke.

“Intelligence” and “networking” have become the inevitable trends in the global automobile industry; the intelligent connected vehicle industry has developed rapidly. Existing studies on innovative technology policies of the automobile industry mainly focus on new energy vehicles and seldom analyze or evaluate the industrial policies of intelligent connected vehicles. In this paper, we compared the intelligent connected vehicle policies of the U.S., the EU, Japan and China and sorted out, classified and explored the local industrial policies of intelligent connected vehicles issued by major cities in China since 2016. We then evaluate the innovation performance of local industrial policies for intelligent connected vehicles using the multiperiod difference-in-differences (DID) method. The results show that local intelligent connected vehicle policies in cities such as Beijing, Shanghai and Guangzhou can significantly promote industrial innovation. Moreover, these cities choose more environment-oriented industrial policies represented by target planning and legal regulation, making the industrial layout more comprehensive and industrial development more systematic. We further provide a reference and policy suggestions for other cities to formulate local industrial policies in the initial stage of the intelligent connected vehicle industry.

By combining the analytic hierarchy process (AHP) and system dynamics (SD) models, a compound index system is established for simulating and evaluating the water environment carrying capacity (WECC) of the Weihe River Basin. The development tendencies of the population, economy, water resource demand and supply, water environment, water pollution, and water management were obtained from 2005 to 2040 by applying the five scenarios designed in this study. The results indicate that the comprehensive solution scenario was the optimal scenario, and the WECC would upgrade from a ‘general’ status to a ‘good’ status. Moreover, the blind pursuit of rapid economic growth is inadvisable, and it will compromise the sustainability of the river basin area. The river basin area should divert local development modes toward increased sustainability, emphasizing the coordinated development of society, the economy, and the environment. HIGHLIGHTS By using an integrated application of the AHP and SD models, the WECC evaluation index and simulation scenarios were established.; Obtaining the development tendencies of the WECC under different scenarios.; The comprehensive solution scenario was the optimal scenario.; The water resources would reach a balance between supply and demand in 2030.; Strengthening the WECC requires the coordinated development.;

Affected by the movement of drones, missiles, and other aircraft platforms and the limitation of the accuracy of image sensors, the obtained images have low-resolution and serious loss of image details. Aiming at these problems, this paper studies the image super-resolution reconstruction technology. Firstly, a natural image degradation model based on a generative adversarial network is designed to learn the degradation relationship between image blocks within the image; then, an unsupervised learning residual network is designed based on the idea of image self-similarity to complete image super-resolution reconstruction. The experimental results show that the unsupervised super-resolution reconstruction algorithm is equivalent to the mainstream supervised learning algorithm under ideal conditions. Compared to mainstream algorithms, this algorithm has significantly improved its various indicators in real-world environments under nonideal conditions.

Abstract Aims With advancements in cancer treatments, the survival rates of patients with their first primary cancer (FPC) have increased, resulting in a rise in the number of patients with second primary cancer (SPC). However, there has been no assessment on the incidence of suicide among patients with SPC. This study assessed the occurrence of suicide among patients with SPC and compared them with that in patients with FPC. Methods This was a retrospective, population-based cohort study that followed patients with FPC and SPC diagnosed from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) 17 registries database between 1 January 2000 and 31 December 2019. Results For patients with SPC, an age of 85+ years at diagnosis was associated with a higher incidence of suicide death (HR, 1.727; 95% CI, 1.075–2.774), while the suicide death was not considerably different in the chemotherapy group (P > 0.05). Female genital system cancers (HR, 3.042; 95% CI, 1.819–6.361) accounted for the highest suicide death among patients with SPC. The suicide death distribution of patients with SPC over time indicated that suicide events mainly occurred within 5 to 15 years of diagnosis. Compared with patients with FPC, patients with SPC in general had a lower risk of suicide, but increased year by year. Conclusion The risk of suicide was reduced in patients with SPC compared with patients with FPC, but increased year by year. Therefore, oncologists and related health professionals need to provide continuous psychological support to reduce the incidence of suicide. The highest suicide death was found among patients with female genital system cancer.

PurposeModerately hypofractionated radiotherapy (MHRT) holds an important position in prostate cancer management. Existing hydrogel spacers can protect the rectum from radiation damage, but need improvement. We explored the application of a novel hydrogel in MHRT with adaptive degradation and durable imaging functions.Methods and materialsThe hydrogels were irradiated with 6MV x-ray to detect the radio-resistance property. Male SD rats (n=45) underwent hydrogel injection between the prostate and rectum. CT was used for investigating the novel spacer’s degradation and imaging functions over three months. The hydrogel’s radiation-attenuation properties and biocompatibility were further assessed.ResultsHydrogel weight and volume remained stable for six weeks post-injection. After MHRT ended, the hydrogel showed accelerated degradation characteristics and remained in the body for at most three months. CT values of hydrogels exceeded 300 Hounsfield units (HU) throughout treatment, significantly higher than in surrounding normal tissues. A significant dose drop behind the hydrogel was observed post-implantation. Biocompatibility tests of hydrogel found it safe enough for living organisms.ConclusionsThe novel hydrogel application was fully adaptable to prostate cancer MHRT modalities, largely stable during treatment, rapidly degraded after radiotherapy ended, and consistently maintained superior imaging performance and biocompatibility. This novel spacer will be an effective tool in the era of hypofractionated radiotherapy.

Antibiotic resistance genes (ARGs) are a new environmental contaminant that poses a major hazard to humans and the environment. This research discusses the methods and drawbacks of two ARG removal approaches, constructed wetlands (CWs) and photocatalysis. CWs primarily rely on the synergistic effects of substrate adsorption, plant uptake, and microbial processes to remove ARGs. The removal of ARGs can be influenced by wetland plants, substrate type, wetland type, and hydraulic conditions. The absolute abundance of ARGs in effluent decreased, but their relative abundance increased. Photocatalysis deactivates ARGs predominantly through reactive oxygen species, with removal effectiveness determined by catalyst type, radiation type, and radiation intensity. The drawback is that it exposes intracellular resistance genes, perhaps increasing the risk of ARG spread. To address the current shortcomings, this paper proposes the feasibility of combining a constructed wetland with photocatalysis technology, which provides a novel strategy for ARG removal.

Abstract Carbon fiber-reinforced polymer (CFRP) easily realizes the integrated manufacturing of components with high specific strength and stiffness, and it has become the preferred material in the aerospace field. Grinding is the key approach to realize precision parts and matching the positioning surface for assembly and precision. Hygroscopicity limits the application of flood lubrication in CFRP grinding, and dry grinding leads to large force, surface deterioration, and wheel clogging. To solve the above technical bottleneck, this study explored the grindability and frictional behavior of CNT biological lubricant MQL through grinding experiments and friction-wear tests. Results showed that the CNT biological lubricant reduced the friction coefficient by 53.47% compared with dry condition, showing optimal and durable antifriction characteristics. The new lubrication was beneficial to suppressing the removal of multifiber block debris, tensile fracture, and tensile-shear fracture, with the advantages of tribological properties and material removal behavior, the tangential and normal grinding force, and the specific grinding energy were reduced by 40.41%, 31.46%, and 55.78%, respectively, compared with dry grinding. The proposed method reduced surface roughness and obtained the optimal surface morphology by preventing burrs, fiber pull-out, and resin smearing, and wheel clogging was prevented by temperature reduction and lubricating oil film formation. S a and S q of the CNT biological lubricant were reduced by 8.4% and 7.9%, respectively, compared with dry grinding. This study provides a practical basis for further application of CNT biological lubricant in CFRP grinding.

In this work, the removal efficiency and mechanism of various constructed wetlands microcosm systems on antibiotic wastewater, as well as the biological community response of microalgae and microorganisms were explored. Overall, the algal-bacteria symbiosis in conjunction with the gravel matrix had the most comprehensive treatment efficiency for antibiotic wastewater. However, pollutants such as high-concentration antibiotics impaired the biological community and functions. In the systems fed with microorganisms, both abundance and diversity of them were significantly reduced comparing with the initial value. According to the correlation analysis revealed that the pollutants removal rate increased with the addition of the relative abundance of some bacterial genera, while decreased with the addition of relative abundance of other bacterial genera. The presence of gravel matrix could lessen the stressful effect of antibiotics and other pollutants on the growth of microalgae and microorganisms, as well as improved treatment efficiency of antibiotic wastewater. Based on the findings of the study, the combination of gravel matrix and algal-bacteria symbiosis can considerably increase the capacity of constructed wetlands to treat antibiotic wastewater and protect biological community, which is an environmentally friendly way.

Cadmium (Cd) is a type of high-risk heavy metal that can damage organs such as the liver, but its mechanism is not yet clear. Ferroptosis is a newly discovered mode of regulatory cell death. We explored whether ferroptosis is involved in Cd-induced liver damage and the underlying mechanism. Our research showed that Cd induced liver damage by inducing ferroptosis, and the use of ferroptosis inhibitors reduced the degree of liver damage. Moreover, the occurrence of ferroptosis was accompanied by the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway, and inhibiting endoplasmic reticulum (ER) stress reduced ferroptosis demonstrating that ferroptosis induced by Cd is dependent on ER stress. In addition, chloroquine, a common autophagy inhibitor, mitigated ferroptosis caused by Cd exposure. Then, the iron chelator deferoxamine reduced Cd-induced lipid peroxidation and cell death, demonstrating that the iron regulation disorder caused by ferritin phagocytosis contributes to the Cd-induced ferroptosis. In conclusion, our results show that Cd-induced liver toxicity is accompanied by ferroptosis, which contributes to Cd inducing oxidative stress to trigger autophagy and ER stress to promote the process of ferroptosis.

BackgroundVogt-Koyanagi-Harada (VKH) disease is an autoimmune inflammatory disorder characterized by bilateral granulomatous uveitis. The objective of this study was to identify immune hub genes involved in the pathogenesis and progression of VKH disease.MethodsHigh throughput sequencing data were downloaded from the Gene Expression Omnibus (GEO) and an immune dataset was downloaded from ImmPort. Immune differentially expressed genes (DEGs) were obtained from their intersection in the GEO and ImmPort datasets. Immune hub genes for VKH disease were selected through differential expression analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Disease Ontology (DO), protein-protein interaction (PPI) network, and clustering analyses. Confidence in the immune hub genes was subsequently validated using box plots and receiver operating characteristic (ROC) curves.ResultsA total of 254 DEGs were screened and after the intersection with ImmPort, 20 genes were obtained as immune DEGs. Functional enrichment analysis indicated that the key genes were mainly involved in several types of immune pathways (such as the lymphocyte mediated and leukocyte mediated immune responses, natural killer cell mediated cytotoxicity, and antigen binding) and immunodeficiency diseases. Following PPI network analysis, the top seven genes in cluster 1 were selected as potential immune hub genes in VKH. After evaluating the accuracy of the hub genes, one gene (GNLY) was excluded because its expression level was statistically similar in VKH patients and healthy controls. Finally, six immune hub genes, namely KLRC2, KLRC3 SH2D1B, GZMB, KIR2DL3, and KIR3DL2 were identified as playing important roles in the occurrence and development of VKH disease.ConclusionSix immune hub genes (KLRC2, KLRC3 SH2D1B, GZMB, KIR2DL3, and KIR3DL2) identified by our bioinformatics analyses may provide new diagnostic and therapeutic targets for VKH disease.

Autoimmune diseases are a series of diseases involving multiple tissues and organs, characterized by the over production of abnormal multiple antibodies. Although most studies support that the impaired immune balance participates in the development of autoimmune diseases, the specific pathogenesis of it is not fully understood. Intestinal immunity, especially the intestinal mucosal barrier has become a research hotspot, which is considered to be an upstream mechanism leading to the impaired immune balance. As an important defense barrier, the intestinal mucosal barrier regulates and maintains the homeostasis of internal environment. Once the intestinal barrier function is impaired under the effect of multiple factors, it will destroy the immune homeostasis, trigger inflammatory response, and participate in the development of autoimmune diseases in the final. However, the mechanism of the intestinal mucosal barrier how to regulate the homeostasis and inflammation is not clear. Some studies suggest that it maintains the balance of immune homeostasis through the zonulin pathway, intestinal microbiome, and Toll-like receptor signaling pathway. Our review focused on the composition and the function of the intestinal mucosal barrier to describe the research progress of it in regulating the immune homeostasis and inflammation, and also pointed that the intestinal mucosal barrier was the potential targets in the treatment of autoimmune diseases.

A reliable system simulation combining socio-economic development with water environment and comprehensively reflect a watershed's dynamic features is crucial. In this study, a complex system dynamics model is constructed to evaluate dynamic changes of socio-economic development and ecological environment of Weihe River Basin (WHR). Development trends of the population, economy, land resources, water demand and supply, water environment and water pollution and management are obtained from 2005 to 2030 through scenarios analysis representing different regional development orientations, namely, population growth (S1), economic leading (S2), resources saving (S3), environment leading (S4), collaborative development (S5). Compared with other scenarios, the total population and GDP will, respectively, reach 3,716.55 × 104 person and 40,077.30 × 108 yuan, and the gap between demand and supply and the amount of water pollution will, respectively, narrow to 0.56 × 108 and 12.26 × 108 cubic meters in collaborative development scenario (S5). The results reveal the collaborative development scenario (S5) can achieve not only steady population and economy growth, as well as narrow down the gap between water supply and demand, but also optimize watershed environment management of the WHR. Thus, the system dynamics model used in our research provides a powerful tool for assisting decision-making on issues of coordinative socio-economic development, environmental health protection, water resources conservation, etc., in a river basin area. Highlights Discussing interrelations among socio-economy, resources and environment in watershed.; Evaluating the joint effects of socio-economic development and watershed environment management.; Water resource demand causes the water resource imbalance in the Weihe River Basin.; Strengthening environmental protection requires coordinative development.; Identifying optimal and practical strategy for coordinative development mode.;

Cloud manufacturing is characterized by large uncertainties and disturbances due to its networked, distributed, and loosely coupled features. To target the problem of frequent cloud resource node failure, this paper proposes (1) three resource substitution strategies based on node redundancy and (2) a new robustness analysis method for cloud manufacturing systems based on a combination of the complex network and multi-agent simulation. First, a multi-agent simulation model is constructed, and simulation evaluation indexes are designed to study the robustness of the dynamic cloud manufacturing process (CMP). Second, a complex network model of cloud manufacturing resources is established to analyze the static topological robustness of the cloud manufacturing network. Four types of node failure modes are defined, based on the initial and recomputed topologies. Further, three resource substitution strategies are proposed (i.e., internal replacement, external replacement, and internal–external integration replacement) to enable the normal operation of the system after resource node failure. Third, a case study is conducted for a cloud manufacturing project of a new energy vehicle. The results show that (1) the proposed robustness of service index is effective at describing the variations in CMP robustness, (2) the two node failure modes based on the recalculated topology are more destructive to the robustness of the CMP than the two based on the initial topology, and (3) under all four failure modes, all three resource substitution strategies can improve the robustness of the dynamic CMP to some extent, with the internal–external integration replacement strategy being most effective, followed by the external replacement strategy, and then the internal replacement strategy.

Thermoelectric materials have gained wide attention to realize multilevel efficient energy management to alleviate the increasingly severe energy crisis. Oxide ceramics were well-explored as potential thermoelectric candidates because of their outstanding merits, including abundance, eco-friendliness, high-temperature stability, and chemical stability. In this work, we aim to provide a comprehensive summary of the diversified state-of-the-art oxide ceramics and establish the links between composition designing, preparation process, structural characteristics, and properties to summarize the underlying chemistry and physics mechanism of band engineering, doping, composited with the second phase, defects engineering, and entropy engineering. Furthermore, advanced device design and applications such as thermoelectric modules, miniature generators, sensors, and coolers were reviewed. Ultimately, the challenges and future perspective of oxides ceramics for the device design and thermoelectric applications in the development of energy harvesting technology have been prospected.

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults, which is fast growing and tends to invade surrounding normal brain tissues. Uncovering the molecular and cellular mechanisms of GBM high invasion potential is of great importance for the treatment and prognostic prediction. However, the commonly used two-dimensional (2D) cell culture and analysis system suffers from lack of the heterogeneity and in vivo property of brain tissues. Here, we established a three-dimensional (3D) cell culture-based analysis system that could better recapitulate the heterogeneity of GBM and mimic the in vivo conditions in the brain. The GBM cell lines, DBTRG and U251, were cultured by hanging drop culture into the GBM multicellular spheroids, which were embedded in the optimized 3D brain-stiffness-mimicking matrix gel (0.5 mg/ml Collagen Ⅰ + 3 mg/ml Matrigel+ 3.3 mg/ml Hyaluronic Acid (HA)). The biochemical composition of the optimized matrix gel is similar to that of the brain microenvironment, and the elastic modulus is close to that of the brain tissue. The dynamics of the GBM spheroids was examined using high-content imaging for 60 h, and four metrics including invasion distance, invasion area, single-cell invasion velocity, and directionality were employed to quantify the invasion capacity. The result showed that DBTRG cells possess higher invasion capacity than U251 cells, which was consistent with the results of the classic transwell test. Transcriptome analysis of both cell lines was performed to explore the underlying molecular mechanisms. Our novel brain-stiffness-mimicking matrix gel enables comprehensive invasion analysis of the 3D cultured GBM cells and provides a model basis for in-depth exploration of the mechanisms regulating GBM invasion including the interaction between GBM cells and brain stroma.

Retinal progenitor cells (RPCs) transplantation has become a promising therapy for retinal degeneration, which is a major kind of ocular diseases causing blindness. Since RPCs have limited proliferation and differentiation abilities toward retinal neurons, it is urgent to resolve these problems. MicroRNAs have been reported to have vital effects on stem cell fate. In our study, the data showed that overexpression of miR-381-3p repressed Hes1 expression, which promoted RPCs differentiation, especially toward neuronal cells, and inhibited RPCs proliferation. Knockdown of endogenous miR-381-3p increased Hes1 expression to inhibit RPCs differentiation and promote proliferation. In addition, a luciferase assay demonstrated that miR-381-3p directly targeted the Hes1 3’ untranslated region (UTR). Taken together, our study demonstrated that miR-381-3p regulated RPCs proliferation and differentiation by targeting Hes1, which provides an experimental basis of RPCs transplantation therapy for retinal degeneration.

The electronic structure and thermoelectric properties of Bi3+-doped (Sr0.889-xLa0.111Bix)TiO2.963 were studied by the first principles method. Doping Bi3+ can increase the cell parameters, cell asymmetry and band gap. With increasing Bi3+ content, the asymmetry of DOS relative to the Fermi level increases, which results in an enhanced Seebeck coefficient, increasing carrier mobility and decreasing carrier concentration. An appropriate Bi3+-doping concentration (7.4–14.8%) can increase the lattice distortion and reduce the lattice thermal conductivity of the material. An appropriate Bi3+-doping concentration (7.4%) can effectively optimize the electrical transport performance and improve the thermoelectric properties of strontium titanate. The optimal Bi3+-doping concentration is 7.4%, and Sr0.815La0.111Bi0.074TiO2.963 obtains a maximum ZT of 0.48. This work shows the mechanism of Bi3+ doping in enhancing the thermoelectric properties of strontium titanate.

Acrylamide (ACR) is a widely used chemical compound that has neurotoxicity in human, but whether ACR could impair the cerebellum and the related mechanism were still unknown. This study aimed to observe the changes in behavioral performance and cerebellar morphology caused by chronic ACR exposure, and to evaluate its influence on apoptosis, endoplasmic reticulum stress (ERS) and autophagy. Rats were treated with 0, 0.5 and 5 mg/kg ACR by drinking water for 12 months. Results showed that 5 mg/kg ACR treatment damaged the gait, balance ability, hindlimb muscle strength and motor coordination ability of rats. The results of hematoxylin and eosin and Nissl staining indicated that ACR impaired the structures of all three layers of the cerebellum, especially the Purkinje cell layer, showing abnormal morphology with nucleus condensation and pyknosis. Accumulation of autophagosomes, dilated endoplasmic reticulum and swollen mitochondria were observed in neurons under transmission electron microscopy. The enhanced apoptotic rates and the increased Bax expression indicated the elevated level of apoptosis. The results of Western blot showed that ACR treatment elevated protein levels of Beclin1, LC3-II/LC3-I, p-PERK/t-PERK, ATF4 and CHOP, indicating the initiation of autophagy, the activation of PERK pathway in ERS. This work helps to demonstrate the ACR neurotoxicity on cerebellum under chronic treatment and its underlying mechanism.

Momordica grosvenorii saponin (MGS), as a promising dietary supplement with remarkable biological properties, has poor stability under acidic conditions and thus hinders its application in functional foods. In this study, capsules of chitosan and sodium alginate were successfully prepared to enhance the stability of MGS. The optimized parameters for preparing MGS capsules were established. Sodium alginate of 20.8 mg/mL and triplication of MGS powder were added to chitosan of 4 mg/mL and calcium chloride of 10 mg/mL at a volume ratio of 3:1, stirring at 1000 r/min for 30 min to form the capsules. In this case, the fresh particles averaged 1687 μm with an encapsulation efficiency (EE) of 80.25% MGS. The capsule tolerated acidic environments better, and in vitro MGS could be controlled to release in a stimulated gastrointestinal tract system. The antioxidant activity and delayed release of MGS could be achieved by microencapsulation of chitosan/sodium alginate. Moreover, one drink containing 19 mg/mL MGS was successfully developed for the fruit.

Abstract Background The development of Systemic lupus erythematosus (SLE) has been associated with the balance of Th17 and Treg cells. IL-2 and rapamycin can influence the populations of both Th17 and Treg cells. However, it is unclear whether low dose of IL-2 and rapamycin can relieve the symptoms of SLE patients and what is the mechanisms. In this study, we aim to analyze the effect of low dose of IL-2 plus rapamycin on the number of Tregs, Th17 cells and the ratio of Th17/Treg cells, as well as to evaluate its therapeutic efficacy in refractory SLE patients. Result Fifty refractory SLE patients and 70 healthy controls were enrolled and followed up for 24 weeks. We found that compared with HC, the refractory SLE patients had a lower number of Tregs, a similar number of Th17 cells, but an increased ratio of Th17/Treg. After the treatment, the number of Tregs of the patients at 12th and 24th week was significantly increased. While the number of Th17 cells was unchanged, the ratio of Th17/Treg was significantly decreased at both 6 weeks and 24 weeks. After 6, 12 and 24 weeks of treatment, the SLEDAI score was significantly reduced. The prednison dosage at 6th,12th and 24th week post treatment was significantly decreased. Conclusion Our results support that the reduction of Tregs and the imbalance of Th17/Treg cells were correlated with the occurrence and development of refractory SLE. Low dose of IL-2 combined with rapamycin was able to restore the number of Tregs and the balance of Th17/Treg cells. As a result, this approach was able to induce immune tolerance and promote disease remission, allowing for the reduction in prednisone dosage. Trial registration ChiCTR-IPR-16009451 Registration date: 2016/10/16

A sudden large-scale bloom event of the haptophyte Phaeocystis globosa that lasted over one month in the winter of 2021 was observed offshore Qingdao, China. This P. globosa bloom event was unusual as it was the first P. globosa bloom recorded in Qingdao offshore. Furthermore, the temperature at which this event occurred was much lower than that of previous P. globosa blooms in China. We hypothesize that the P. globosa strains that drove the development of this bloom offshore Qingdao were genetically unique and have a competitive advantage in the environmental conditions. To test this hypothesis, we analyzed P. globosa genetic diversity and the temporal dynamics of the bloom, using the high-resolution molecular markers pgcp1 and cox1 that we developed recently. The analysis revealed that the genetic compositions of P. globosa offshore Qingdao were rather limited, containing two dominant genotypes and other rare genotypes with low abundance, representing a small portion of the genetic diversities identified in coastal waters in China, and were rather different from the P. globosa genotypes outside of the Jiaozhou Bay before the P. globosa bloom in the winter of 2021. This suggested only certain strains contribute to the development of blooms under certain environmental conditions. The genetic composition may indicate the unusual timing and scale of this P. globosa event.

Background: Toll-like receptor 4 (TLR4) initiates both innate and adaptive immune responses, which plays an important protective role in self-defense mechanisms. Excessive or inappropriate TLR4 activation causes the development of many autoimmune diseases. Dihydropyrimidinone derivatives are medicinally important molecules with diverse pharmacological activities, including anti-inflammatory activity. The present study focused on novel synthesized 3,4-dihydropyrimidinone derivatives and evaluated their inhibitory effects on TLR4.Methods: A series of 3,4-dihydropyrimidinone derivatives were recently synthesized and evaluated for their TLR4 inhibition activities and cytotoxic on HEK-BlueTM hTLR4 cells with the help of QUANTI-Blue assay and MTS assay. Selected compound 3 was analyzed for its molecular docking with TLR4 by using Autodock vina 1.1.2. Its effect on the TLR4 pathway related cytokines was also evaluated in THP-1 cells and human peripheral blood mononuclear cells by using real-time PCR, ELISA and western blot.Results: Five compounds were synthesized and characterized for effectiveness based on 3,4-dihydropyrimidinone. Compound 3 was found to be the potent hybrid among the synthesized compounds, with high TLR4 inhibition activities and low cytotoxic activities against HEK-BlueTM hTLR4 cells. Molecular docking analysis showed that two hydrogen bonds between compound 3 and residues Asp209(TLR4) and Asp99(MD-2) mainly contribute to the TLR4 inhibition. In addition, compound 3 suppressed LPS-induced of the mRNA expression of TLR4, IP-10, TNF-α, IL-6, IL-12A, and IL-12B, the protein expression of pIRF3 and pNFκB and the secretion of IP-10, TNF-α in THP-1 cell line. Compound 3 also inhibited LPS-induced expression of TNF-α, IL-6, and IL-1β but increased IP-10 at mRNA levels in human peripheral blood mononuclear cells.Conclusion: Our study reveals compound 3, a novel 3,4-dihydropyrimidinone derivative, is a potential TLR4 antagonist, which opens up new research avenues for the development of promising therapeutic agents for inflammatory and autoimmune diseases.

In this paper, an improved simultaneous fault diagnostic algorithm with cohesion-based feature selection and improved backpropagation multilabel learning (BP-MLL) classification is proposed to localize and diagnose different simultaneous faults on gearbox and bearings in rotating machinery. Cohesion evaluation algorithm selects high sensitivity feature parameters from time and frequency domain in high-dimensional vectors to construct low-dimensional feature vectors. The BP-MLL neural network is utilized for fault diagnosis by classifying the feature vectors. An effective global error function is proposed in BP-MLL neural network by modifying distance function to improve both generalization ability and fault diagnostic ability of full-labeled and nonlabeled situations. To demonstrate the effectiveness of the proposed method, simultaneous fault diagnosis experiments are conducted via wind turbine drivetrain diagnostics simulator (WTDDS). The experiment results show that the proposed method has better overall performance compared with conventional BP-MLL algorithm and some other learning algorithms.

Eupatorium lindleyanum DC. (EL) has a long history of traditional use in China to cure coughs, chronic bronchitis, lobar pneumonia, and hypertension. Because of this extensive use of EL in traditional medicine, this present review gives a systematic overview of the conventional applications, phytochemistry, and pharmacological effects of the herb. Literature was systematically searched using the scientific databases ScienceDirect, SciFinder, CNKI, Wiley, Baidu Scholar, SpringerLink, PubMed, Web of Science, and other professional websites. Information was also gathered from books on traditional Chinese herbal medicine, the Chinese Pharmacopoeia and Chinese Materia Medica. To date, many preparations of EL have been widely used clinically to treat various diseases of the respiratory system. More than 100 compounds have been isolated from the herb, including triterpenes, sesquiterpenes, sesquiterpene lactones, flavonoids, acyclic diterpenoids, sterols, and so on. Among them, terpenoids are considered to be the most important bioactive substances in EL. The pharmacological functions of EL, including anti-asthmatic, anti-tussive, anti-inflammatory, anti-hyperlipidemic, anti-hypertensive, anti-virus, and anti-tumor activities, have been widely investigated. However, most of the studies are preclinical research. Further studies are required to examine the underlying mechanisms of action. Traditionally, EL is used for treating many diseases, especially respiratory diseases. Unfortunately, up to now, modern studies have not yet well elucidated the conventional usage of EL. Most importantly, its biological activities and the corresponding constituents are still unclear. Moreover, studies on the pharmacokinetics and toxicity of EL are few, so data on the clinical safety of EL are lacking. Taken together, research work on EL is quite preliminary. More in-depth studies of phytochemistry, pharmacological activities, pharmacokinetics, and toxicity of the herb are needed. This review aims to provide valuable information on EL to guide future investigations and applications.

Abstract Background NGS data contains many machine-induced errors. The most advanced methods for the error correction heavily depend on the selection of solid k-mers. A solid k-mer is a k-mer frequently occurring in NGS reads. The other k-mers are called weak k-mers. A solid k-mer does not likely contain errors, while a weak k-mer most likely contains errors. An intensively investigated problem is to find a good frequency cutoff f 0 to balance the numbers of solid and weak k-mers. Once the cutoff is determined, a more challenging but less-studied problem is to: (i) remove a small subset of solid k-mers that are likely to contain errors, and (ii) add a small subset of weak k-mers, that are likely to contain no errors, into the remaining set of solid k-mers. Identification of these two subsets of k-mers can improve the correction performance. Results We propose to use a Gamma distribution to model the frequencies of erroneous k-mers and a mixture of Gaussian distributions to model correct k-mers, and combine them to determine f 0. To identify the two special subsets of k-mers, we use the z-score of k-mers which measures the number of standard deviations a k-mer’s frequency is from the mean. Then these statistically-solid k-mers are used to construct a Bloom filter for error correction. Our method is markedly superior to the state-of-art methods, tested on both real and synthetic NGS data sets. Conclusion The z-score is adequate to distinguish solid k-mers from weak k-mers, particularly useful for pinpointing out solid k-mers having very low frequency. Applying z-score on k-mer can markedly improve the error correction accuracy.

Abstract Background Whole-genome sequencing (WGS) plays an increasingly important role in clinical practice and public health. Due to the big data size, WGS data analysis is usually compute-intensive and IO-intensive. Currently it usually takes 30 to 40 h to finish a 50× WGS analysis task, which is far from the ideal speed required by the industry. Furthermore, the high-end infrastructure required by WGS computing is costly in terms of time and money. In this paper, we aim to improve the time efficiency of WGS analysis and minimize the cost by elastic cloud computing. Results We developed a distributed system, GT-WGS, for large-scale WGS analyses utilizing the Amazon Web Services (AWS). Our system won the first prize on the Wind and Cloud challenge held by Genomics and Cloud Technology Alliance conference (GCTA) committee. The system makes full use of the dynamic pricing mechanism of AWS. We evaluate the performance of GT-WGS with a 55× WGS dataset (400GB fastq) provided by the GCTA 2017 competition. In the best case, it only took 18.4 min to finish the analysis and the AWS cost of the whole process is only 16.5 US dollars. The accuracy of GT-WGS is 99.9% consistent with that of the Genome Analysis Toolkit (GATK) best practice. We also evaluated the performance of GT-WGS performance on a real-world dataset provided by the XiangYa hospital, which consists of 5× whole-genome dataset with 500 samples, and on average GT-WGS managed to finish one 5× WGS analysis task in 2.4 min at a cost of $3.6. Conclusions WGS is already playing an important role in guiding therapeutic intervention. However, its application is limited by the time cost and computing cost. GT-WGS excelled as an efficient and affordable WGS analyses tool to address this problem. The demo video and supplementary materials of GT-WGS can be accessed at https://github.com/Genetalks/wgs_analysis_demo .

Fibrous membranes with a nonwoven random structure and a quasi-parallel fibrous structure can be fabricated by the electrospinning technique. The membranes with different structures exhibited different behaviors to a hydraulic flow passing through the membranes. This work presents the effects of the fiber arrangement, fiber diameter, and deformations of the fibers on the hydraulic permeability. The results showed that the hydraulic flow can generate an extrusion pressure which affects the porosity and pore structure of the fibrous membranes. The quasi-parallel fibrous membranes and nonwoven membranes exhibited similar variation tendencies to the change of the experimental variables. However, the quasi-parallel fibrous membranes exhibited a higher sensibility to the change of the hydraulic flow rate. The hydraulic permeability of the quasi-parallel fibrous membranes was further analyzed with packing state models in this work.