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Abstract Background NUP98 rearrangements (NUP98-r) are rare but overrepresented mutations in pediatric acute myeloid leukemia (AML) patients. NUP98-r is often associated with chemotherapy resistance and a particularly poor prognosis. Therefore, characterizing pediatric AML with NUP98-r to identify aberrations is critically important. Methods Here, we retrospectively analyzed the clinicopathological features, genomic and transcriptomic landscapes, treatments, and outcomes of pediatric patients with AML. Results Nine patients with NUP98-r mutations were identified in our cohort of 142 patients. Ten mutated genes were detected in patients with NUP98-r. The frequency of FLT3-ITD mutations differed significantly between the groups harboring NUP98-r and those without NUP98-r (P = 0.035). Unsupervised hierarchical clustering via RNA sequencing data from 21 AML patients revealed that NUP98-r samples clustered together, strongly suggesting a distinct subtype. Compared with that in the non-NUP98-r fusion and no fusion groups, CMAHP expression was significantly upregulated in the NUP98-r samples (P

Background There is limited evidence suggesting that osteoporosis might exacerbate depressive symptoms, while more studies demonstrate that depression negatively affects bone density and increases fracture risk.Aims To explore the relationship between major depressive disorder (MDD) and fracture risk.Methods We conducted a nested case-control analysis (32 670 patients with fracture and 397 017 individuals without fracture) and a matched cohort analysis (16 496 patients with MDD and 435 492 individuals without MDD) in the same prospective UK Biobank data set. Further, we investigated the shared genetic architecture between MDD and fracture with linkage disequilibrium score regression and the MiXeR statistical tools. We used the conditional/conjunctional false discovery rate approach to identify the specific shared loci. We calculated the weighted genetic risk score for individuals in the UK Biobank and logistic regression was used to confirm the association observed in the prospective study.Results We found that MDD was associated with a 14% increase in fracture risk (hazard ratio (HR) 1.14, 95% CI 1.14 to 1.15, p

Abstract Background Surface polysaccharides (SPs), such as lipopolysaccharide (O antigen) and capsular polysaccharide (K antigen), play a key role in the pathogenicity of Escherichia coli (E. coli). Gene cluster for polysaccharide antigen biosynthesis encodes various glycosyltransferases (GTs), which drive the process of SP synthesis and determine the serotype. Results In this study, a total of 7,741 E. coli genomic sequences were chosen for systemic data mining. The monosaccharides in both O and K antigens were dominated by D-hexopyranose, and the SPs in 70–80% of the strains consisted of only the five most common hexoses (or some of them). The linkages between the two monosaccharides were mostly α-1,3 (23.15%) and β-1,3 (20.49%) bonds. Uridine diphosphate activated more than 50% of monosaccharides for glycosyltransferase reactions. These results suggest that the most common pathways could be integrated into chassis cells to promote glycan biosynthesis. We constructed a database (EcoSP, http://ecosp.dmicrobe.cn/ ) for browse this information, such as monosaccharide synthesis pathways. It can also be used for serotype analysis and GT annotation of known or novel E. coli sequences, thus facilitating the diagnosis and typing. Conclusions Summarizing and analyzing the properties of these polysaccharide antigens and GTs are of great significance for designing glycan-based vaccines and the synthetic glycobiology.

Abstract Background Brucellosis, caused by Brucella spp., is a major zoonotic public health threat. Although several Brucella vaccines have been demonstrated for use in animals, Brucella spp. can cause human infection and to date, there are no human‐use vaccines licensed by any agency. Recently, methods in vaccine informatics have made major breakthroughs in peptide‐based epitopes, opening up a new avenue of vaccine development. Objectives The purpose of this article was to identify potential antigenic peptides in Brucella by proteome and peptidome analyses. Methods Mouse infection models were first established by injection with Brucella and spleen protein profiles were then analysed. Subsequently, the major histocompatibility complex class I or II (major histocompatibility complex [MHC]‐I/II)‐binding peptides in blood samples were collected by immunoprecipitation and peptides derived from Brucella proteins were identified through liquid chromatography–mass spectrometry (LC‐MS/MS). These peptides were then evaluated in a variety of ways, such as in terms of conservation in Brucella and synchronicity in predicted peptides (similarity and coverage), which allowed us to more effectively measure their antigenic potential. Results The expression of the inflammatory cytokines IL1B and IFN‐γ was significantly altered in the spleen of infected mice and some Brucella proteins, such as Muri, AcpP and GroES, were also detected. Meanwhile, in blood, 35 peptides were identified and most showed high conservation, highlighting their potential as antigen epitopes for vaccine development. In particular, we identified four proteins containing both MHC‐I‐ and MHC‐II‐binding peptides including AtpA, AtpD, DnaK and BAbS19_II02030. They were also compared with the predicted peptides to estimate their reliability. Conclusions The peptides we screened could bind to MHC molecules. After being stimulated with antigen T epitopes, Memory T cells can stimulate T cell activation and promote immune responses. Our results indicated that the peptides we identified may be good candidate targets for the design of subunit vaccines and these results pave the way for the study of safer vaccines against Brucella.

BackgroundWhile targeted systemic inflammatory modulators show promise in preventing chronic kidney disease (CKD) progression, the causal link between specific inflammatory factors and CKD remains uncertain.MethodsUsing a genome-wide association study of 41 serum cytokines from 8,293 Finnish individuals, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis. In addition, we genetically predicted causal associations between inflammatory factors and 5 phenotypes, including CKD, estimated glomerular filtration rate (eGFR), dialysis, rapid progression of CKD, and rapid decline in eGFR. Inverse variance weighting (IVW) served as the primary MR method, while MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO) were utilized for sensitivity analysis. Cochrane’s Q test for heterogeneity. Leave-one-out method ensured stability of MR results, and Bonferroni correction assessed causal relationship strength.ResultsSeventeen cytokines were associated with diverse renal outcomes. Among them, after Bonferroni correction test, higher tumor necrosis factor alpha levels were associated with a rapid decrease in eGFR (OR = 1.064, 95% CI 1.028 – 1.103, P = 0.001), higher interleukin-4 levels were associated with an increase in eGFR (β = 0.003, 95% CI 0.001 – 0.005, P = 0.002), and higher growth regulated oncogene alpha (GROα) levels were associated with an increased risk of CKD (OR=1.035, 95% CI 1.012 - 1.058, P = 0.003). In contrast, genetic susceptibility to CKD was associated with an increase in GROa, and a decrease in eGFR may lead to an increase in stem cell factor. We did not find the presence of horizontal pleiotropy during the analysis.ConclusionWe discovered causally related inflammatory factors that contribute to the initiation and progression of CKD at the genetic prediction level.

2- arachidonoylglycerol (2-AG), an abundant endocannabinoid in the brain, regulates diverse neural functions. Here, the authors identified four loss-of-function mutations in dicylglycerol lipase β (DAGLB) from six patients with early onset Parkinsonism. In mice, loss of DAGLB in dopamine neurons reduced neuronal activity and impaired locomotor function and augmentation of 2-AG levels boosted neuronal activity and rescued locomotor deficits.

The COVID-19 vaccines have been developed in a wide range of countries. This study aimed to examine factors that related to vaccination rates and willingness to be vaccinated against COVID-19 among Chinese healthcare workers (HCWs). From 3rd February to 18th February, 2021, an online cross-sectional survey was conducted among HCWs to investigate factors associated with the acceptance and willingness of COVID-19 vaccination. Sociodemographic characteristics and the acceptance of COVID-19 vaccination among Chinese HCWs were evaluated. A total of 2156 HCWs from 21 provinces in China responded to this survey (effective rate: 98.99%)), among whom 1433 (66.5%) were vaccinated with at least one dose. Higher vaccination rates were associated with older age, working as a clinician, having no personal religion, working in a fever clinic or higher hospital grade, and having received vaccine education, family history for influenza vaccination and strong familiarity with the vaccine. Willingness for vaccination was related to working in midwestern China, considerable knowledge of the vaccine, received vaccine education, and strong confidence in the vaccine. Results of this study can provide evidence for the government to improve vaccine coverage by addressing vaccine hesitancy in the COVID-19 pandemic and future public health emergencies.

BackgroundObservational studies have identified a possible link between thyroid function and diabetic microangiopathy, specifically in diabetic kidney disease (DKD) and diabetic retinopathy (DR). However, it is unclear whether this association reflects a causal relationship.ObjectiveTo assess the potential direct effect of thyroid characteristics on DKD and DR based on Mendelian randomization (MR).MethodsWe conducted an MR study using genetic variants as an instrument associated with thyroid function to examine the causal effects on DKD and DR. The study included the analysis of 4 exposure factors associated with thyroid hormone regulation and 5 outcomes. Genomewide significant variants were used as instruments for standardized freethyroxine (FT4) and thyroid-stimulating hormone (TSH) levels within the reference range, standardized free triiodothyronine (FT3):FT4 ratio, and standardized thyroid peroxidase antibody (TPOAB) levels. The primary outcomes were DKD and DR events, and secondary outcomes were estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (ACR) in diabetes, and proliferative diabetic retinopathy (PDR). Satisfying the 3 MR core assumptions, the inverse-variance weighted technique was used as the primary analysis, and sensitivity analysis was performed using MR-Egger, weighted median, and MR pleiotropy residual sum and outlier techniques.ResultsAll outcome and exposure instruments were selected from publicly available GWAS data conducted in European populations. In inverse-variance weighted random-effects MR, gene-based TSH with in the reference range was associated with DKD (OR 1.44; 95%CI 1.04, 2.41; P = 0.033) and eGFR (β: -0.031; 95%CI: -0.063, -0.001; P = 0.047). Gene-based increased FT3:FT4 ratio, decreased FT4 with in the reference range were associated with increased ACR with inverse-variance weighted random-effects β of 0.178 (95%CI: 0.004, 0.353; P = 0.046) and -0.078 (95%CI: -0.142, -0.014; P = 0.017), respectively, and robust to tests of horizontal pleiotropy. However, all thyroid hormone instruments were not associated with DR and PDR at the genetic level.ConclusionIn diabetic patients, an elevated TSH within the reference range was linked to a greater risk of DKD and decreased eGFR. Similarly, decreased FT4 and an increased FT3:FT4 ratio within the reference range were associated with increased ACR in diabetic patients. However, gene-based thyroid hormones were not associated with DR, indicating a possible pathway involving the thyroid-islet-renal axis. However, larger population studies are needed to further validate this conclusion.

In recent years, it has been determined that primitive myxoid mesenchymal tumors of infancy (PMMTI) are solid tumors. To date, very few cases of PMMTI have been reported, and there is no consensus regarding treatment. To provide additional references, it is necessary to collect and report the diagnoses and treatment outcomes of related cases. We report the case of a 38-day-old girl who presented with a 5-cm purple tumor in the right shoulder. Upon hospital admission, the patient received an intratumoral injection of bleomycin after diagnosis of a possible lymphangioma. 10 days after the treatment, the tumor began to develop inflammation and necrosis, resulting in a clear demarcation between the tumor and surrounding tissue. Hence, during the second hospitalization, we performed a successful tumor resection. Postoperatively, the tumor was pathologically diagnosed as PMMTI. 3 months after excision, the patient showed no local recurrence on re-examination. To the best of our knowledge, this is the first report of a PMMTI in which bleomycin, or other similar chemotherapeutic drugs, have been injected into tumors. This result offers novel insights into the treatment of PMMTI. Injection therapy with bleomycin and similar chemotherapeutics may result in specific responses to PMMTI, which may help in developing better surgical conditions or improving outcomes in non-surgical patients.

Copyright of Rare Metals is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The well-known dispatcher training simulator (DTS), as a good tool to train power system dispatchers, has been widely used for over 40 years. However, with the high-speed development of the smart grid, the traditional DTSs have struggled to meet the power industry’s expectations. To enhance the effectiveness of dispatcher training, technical innovations in DTSs are becoming more and more demanding. Meanwhile, the ever-advancing artificial intelligence (AI) technology provides the basis for the design of intelligent DTSs. This paper systematically reviews the traditional DTS in terms of its origin, structure, and functions, as well as limitations in the context of the smart grid. Then, this paper summarizes the AI techniques commonly used in the field of power systems, such as expert systems, artificial neural networks, and the fuzzy set theory, and employs them to develop intelligent DTSs. Regarding a less studied aspect of DTSs, i.e., intelligent training control, we introduce the Adaptive Learning System (ALS) to develop a personalized training program, which will also be an important aspect of future research.

Methane (CH4) is one of the potent greenhouse gases emitted from municipal wastewater treatment plants. The characteristics of methane emission from municipal wastewater treatment plants (WWTPs) have attracted lots of concern from related researchers. The present work investigated the source of methanogens and methane emission properties from two WWTPs in Xi'an, and one is employed in an Orbal oxidation ditch, and the other is anaerobic/anoxic/oxic (A/A/O). The measurement of specific methanogenic activity (SMA) and coenzyme F420 concentration, together with Fluorescence in situ hybridization (FISH), was used to determine the amount and activity of methanogens in two WWTPs. Additionally, a combined activated sludge model was built and predicted the growth of methanogens and other key microorganisms in the sludge. The results showed that the average CH4 emission flux from the Orbal oxidation ditch (22.74 g CH4 /(m2·d)) was much higher than that from A/A/O (9.57 g CH4/(m2·d)). The methane emission factors in the Orbal oxidation ditch and A/A/O processes were 1.18 and 0.21 g CH4 /(m3 INF), respectively. These distinct methane emission characteristics between two WWTPs are mainly attributed to the higher activity and content of methanogens, as well as the discontinuous aeration in the Orbal oxidation ditch. Additionally, dissolved oxygen concentration, water temperature, and the presence of nitrate/nitrite were also important factors that influenced methane emission. The FISH analysis showed that Methanococcus was the dominant methanogen in both WWTPs. In addition, the combined model successfully simulated the growth of methanogens in WWTPs. Methanogens in WWTPs were mainly derived from the sewer system, and the cumulative effect led to an increase in the abundance of methanogens in activated sludge. The outcomes of this study provide new insights in the prediction and management of GHG emission from WWTPs. [ABSTRACT FROM AUTHOR]

Copyright of Rare Metals is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: Our research investigated the relationship between childhood leukemia and breastfeeding in the P. R. of China. Methods: We conducted a retrospective case-control study from March 2008 to April 2017 at the Children’s Hospital of Zhejiang University, Zhejiang province, P. R. of China, which reviewed 958 children who had been diagnosed with leukemia in case group and 785 healthy children in control group. Data were obtained from medical records, and if the medical records were incomplete, we called mothers of children by phone to complete the data. Results: Breastfeeding reduces the risk of childhood leukemia; the effect is greater, if feeding continued for 7–9 months (p = 0.002). In addition, we suggest that some factors such as maternal age, smoking during pregnancy, abortion history, genetic factors, parents use of hair dye, and the history of using birth control pills before pregnancy can increase the risk of childhood leukemia. Conclusions: This study indicates that promoting breastfeeding for 7–9 months may help lower the childhood leukemia incidence. Our study firstly demonstrates that breastfeeding has protective effects against childhood leukemia in the P. R. of China. Abbreviations: ALL: Acute lymphocytic leukemia; AML: Acute myeloid leukemia

Cell-cell communication via gap junctions regulates a wide range of physiological processes by enabling the direct intercellular electrical and chemical coupling. However, the in vivo distribution and function of gap junctions remain poorly understood, partly due to the lack of non-invasive tools with both cell-type specificity and high spatiotemporal resolution. Here, we developed PARIS (pairing actuators and receivers to optically isolate gap junctions), a new fully genetically encoded tool for measuring the cell-specific gap junctional coupling (GJC). PARIS successfully enabled monitoring of GJC in several cultured cell lines under physiologically relevant conditions and in distinct genetically defined neurons in Drosophila brain, with ~10 s temporal resolution and sub-cellular spatial resolution. These results demonstrate that PARIS is a robust, highly sensitive tool for mapping functional gap junctions and study their regulation in both health and disease.

Gap junctions are channels that physically connect adjacent cells, mediating the rapid exchange of small molecules, and playing an essential role in a wide range of physiological processes in nearly every system in the body, including the nervous system. Thus, altered function of gap junctions has been linked with a plethora of diseases and pathological conditions. Being able to measure and characterize the distribution, function, and regulation of gap junctions in intact tissue is therefore essential for understanding the physiological and pathophysiological roles that gap junctions play. In recent decades, several robust in vitro and in vivo methods have been developed for detecting and characterizing gap junctions. Here, we review the currently available methods with respect to invasiveness, signal-to-noise ratio, temporal resolution and others, highlighting the recently developed chemical tracers and hybrid imaging systems that use novel chemical compounds and/or genetically encoded enzymes, transporters, channels, and fluorescent proteins in order to map gap junctions. Finally, we discuss possible avenues for further improving existing techniques in order to achieve highly sensitive, cell type-specific, non-invasive measures of in vivo gap junction function with high throughput and high spatiotemporal resolution.

Multiple sclerosis (MS) and neuromyelitis optica (NMO) are inflammatory demyelinating disorders of the central nervous system (CNS). Various genetic and environmental factors have been identified to contribute to etiology of MS and NMO. Aquaporin 4 (AQP4), is the most abundant water channel in CNS. AQP4 is expressed in astrocytes of the brain, spinal cord, optic nerve and supportive cells in sensory organs. In contrast to MS, immunoreactivity of AQP4 is abolished in NMO lesions. However, conflicting results have been reported regarding the association between AQP4 polymorphisms and demyelinating disorders. Considering the ethnic differences of genetic variations, replications in other cohorts are required. In this study, single nucleotide polymorphisms (SNPs) of AQP4 gene in patients with NMO/neuromyelitis optica spectrum disorders (NMOSD), and MS in the Northern Han Chinese population were examined. Six selected AQP4 SNPs were genotyped by high-resolution melting (HRM) method. Compared with healthy control (HC), there was no significant difference of AQP4 allele and genotype frequency in MS or NMO/NMOSD group. This study showed no significant association of common AQP4 SNPs with MS or NMO/NMOSD, strongly suggesting that polymorphisms of AQP4 gene are unlikely to confer MS or NMO/NMOSD susceptibility, at least in Northern Han Chinese population.

Cerebral venous abnormalities, distinct from traditional arterial diseases, have been linked to brain atrophy in a previous community‐based cohort study, specifically in relation to the reduction of deep medullary veins (r‐DMVs). To better understand the properties and biological functions of serum extracellular vesicles (EVs) in cerebral venous disease‐associated brain atrophy, EVs are extracted from the serum of both participants with r‐DMV and normal controls and analyzed their proteomic profiles using Tandem Mass Tag label quantitation analysis. Phenotypic experiments showed that EVs from individuals with r‐DMVs are able to disrupt the normal functions of neurons, endothelial cells, and smooth muscle cells, and induce A1 reactive astrocytes. Additionally, this study provided a comprehensive characterization of the proteomic profile of DMV EVs and found that the collagen hydroxyproline is upregulated, while complement C3 is downregulated in the r‐DMV group, suggesting that r‐DMV may not be a simple pathological phenomenon and highlighting the potential involvement of EVs in the progression of brain atrophy in r‐DMVs which has implications for the development of future therapeutic strategies. [ABSTRACT FROM AUTHOR]

Bistatic Synthetic Aperture Radar (BSAR) based on the Global Navigation Service System (GNSSBSAR) uses navigation satellites as radar transmitters, which are low in cost. However, GNSS-BSAR images have poor resolution and low Signal-to-Noise Ratios (SNR). In this paper, a multiangle observation and data processing strategy are presented based on BeiDou-2 navigation satellite imagery, from which twenty-six BSAR images in different configurations are obtained. A region-based fusion algorithm using region of interest segmentation is proposed, and a high-quality fusion image is obtained. The results reveal that the multiangle imaging method can extend the applications of GNSS-BSAR.

The thermoelectric performance of the CuSbS2 monolayer is determined using the relaxation times obtained from electron–phonon coupling calculations and the transport properties of phonons and electrons. Based on the fully relaxed structure, the lattice thermal conductivity and the electronic transport coefficients are evaluated by solving the Boltzmann transport equation for phonons and electrons under relaxation time approximation, respectively. The tendencies of the transport coefficients depending on the carrier concentrations and temperatures are studied to understand the thermoelectric performance. Based on the bipolar effect, the transport coefficients and intrinsic carrier concentrations, we determined the dimensionless figure of merit ZT in the 300–800 K range. The results demonstrate that the CuSbS2 monolayer should be an p-type semiconductor, and the maximum ZT of 1.36 is obtained, indicating that the monolayer is a good candidate for high-temperature thermoelectric devices. Substantial bipolar effects are observed, and the ones in the x-direction are stronger in comparison to those in the y-direction, which is responsible for the smaller ZT in the x-direction. [ABSTRACT FROM AUTHOR]

The fast-growing wind power industry faces the challenge of reducing operation and maintenance (O&M) costs for wind power plants. Predictive maintenance is essential to improve wind turbine reliability and prolong operation time, thereby reducing the O&M cost for wind power plants. This study presents a solution for predictive maintenance of wind turbine generators. The proposed solution can: (1) predict the remaining useful life (RUL) of wind turbine generators before a fault occurs and (2) diagnose the state of the wind turbine generator when the fault occurs. Moreover, the proposed solution implies low-deployment costs because it relies solely on the information collected from the widely available supervisory control and data acquisition (SCADA) system. Extra sensing hardware is needless. The proposed solution has been deployed and evaluated in two real-world wind power plants located in China. The experimental study demonstrates that the RUL of the generators can be predicted 18 days ahead with about an 80% prediction accuracy. When faults occur, the specific type of generator fault can be diagnosed with an accuracy of 94%.