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Abstract Background Autism spectrum disorder (ASD) poses a significant challenge due to its diverse impact on individuals, emphasizing the need for personalized treatment plans. The financial burden of ASD-related healthcare is substantial, necessitating a comprehensive understanding of its prevalence and evolving trends. Methods This study aims to analyze the prevalence and trends of ASD, treatment patterns, gender differences, and racial-ethnic disparities in the United States from 2017 to 2020, utilizing nationally representative data from the National Survey of Children's Health (NSCH). The NSCH, a leading annual national survey, provided rich data on child health. A total of 108,142 participants aged 3–17 years were included, with ASD prevalence assessed based on self-reported diagnoses. Results Between 2017 and 2020, ASD prevalence in children aged 3–17 was 2.94% (95% confidence interval: 2.68–3.18). Significant disparities were observed: older age and male gender correlated with higher prevalence, while family income-to-poverty ratio and insurance coverage influenced prevalence. Racial/ethnic disparities existed, with Hispanics showing the highest prevalence. Treatment trends showed stability overall, but age influenced behavioral and medication interventions. The prevalence remained stable from 2017 to 2020, with variations in age groups and a significant increase among non-Hispanic Whites. Conclusions This study highlights a higher but stable overall ASD prevalence, with nuanced disparities among different demographic groups. Gender differences persist, emphasizing the need for tailored interventions. Racial-ethnic disparities call for targeted healthcare strategies. The stability in treatment trends underscores the persistent challenge of addressing core ASD symptoms.

Abstract Background Respiratory syncytial virus (RSV) is a prominent etiological agent of lower respiratory tract infections in children, responsible for approximately 80% of cases of pediatric bronchiolitis and 50% of cases of infant pneumonia. Despite notable progress in the diagnosis and management of pediatric RSV infection, the current biomarkers for early-stage detection remain insufficient to meet clinical needs. Therefore, the development of more effective biomarkers for early-stage pediatric respiratory syncytial virus infection (EPR) is imperative. Methods The datasets used in this study were derived from the Gene Expression Omnibus (GEO) database. We used GSE188427 dataset as the training set to screen for biomarkers. Biomarkers of EPR were screened by Weighted Gene Co-expression Network Analysis (WGCNA), three machine-learning algorithms (LASSO regression, Random Forest, XGBoost), and other comprehensive bioinformatics analysis techniques. To evaluate the diagnostic value of these biomarkers, multiple external and internal datasets were employed as validation sets. Next, an examination was performed to investigate the relationship between the screened biomarkers and the infiltration of immune cells. Furthermore, an investigation was carried out to identify potential small molecule compounds that interact with selected diagnostic markers. Finally, we confirmed that the expression levels of the selected biomarkers exhibited a significant increase following RSV infection, and they were further identified as having antiviral properties. Results The study found that lymphocyte antigen 6E (LY6E) and Transcobalamin-2 (TCN2) are two biomarkers with diagnostic significance in EPR. Analysis of immune cell infiltration showed that they were associated with activation of multiple immune cells. Furthermore, our analysis demonstrated that small molecules, 3ʹ-azido-3ʹ-deoxythymine, methotrexate, and theophylline, have the potential to bind to TCN2 and exhibit antiviral properties. These compounds may serve as promising therapeutic agents for the management of pediatric RSV infections. Additionally, our data revealed an upregulation of LY6E and TCN2 expression in PBMCs from patients with RSV infection. ROC analysis indicated that LY6E and TCN2 possessed diagnostic value for RSV infection. Finally, we confirmed that LY6E and TCN2 expression increased after RSV infection and further inhibited RSV infection in A549 and BEAS-2B cell lines. Importantly, based on TCN2, our findings revealed the antiviral properties of a potentially efficacious compound, vitamin B12. Conclusion LY6E and TCN2 are potential peripheral blood diagnostic biomarkers for pediatric RSV infection. LY6E and TCN2 inhibit RSV infection, indicating that LY6E and TCN2 are potential therapeutic target for RSV infection.

Abstract Objective Employing whole‐exome sequencing (WES) technology to investigate the etiology of infantile epileptic spasm syndrome (IESS), and determining whether different etiologies exhibit phenotypic variations, while elucidating the potential associated factors, might improve short‐term responses to first‐line treatment. Methods We retrospectively evaluated patients with IESS admitted for treatment between January 2018 and June 2023. Clinical phenotypic differences among etiological classifications and clinical manifestations were analyzed. Variable selection using the best subset method was performed, followed by logistic regression analysis to identify the factors influencing treatment response. Results A total of 577 patients were included; 412 completed trio‐WES. Magnetic resonance imaging abnormalities were detected in 387 patients (67.1%). Patients with etiology as structural abnormalities were likelier to have non‐spasms at the initial seizure onset. A total of 532 patients completed the first‐line treatment; 273 patients received it for the first time at our hospital (initial response rates: 30.1% and 42.1%, respectively). The response group had a lower proportion of early‐onset seizures (≤3 months) than the no‐response group (11.3% vs. 23.7%, p

To solve the problem of quality deterioration caused by easy browning in drying of yuba stick, yuba stick made from Jiusan yellow soybean, a specialty of northeast Heilongjiang, was used as the research object. Vacuum freeze drying (VFD) and hot air drying (HAD) were used for dry processing of yuba stick, to obtain the effects of the two drying methods on the quality characteristics, microstructure, and other parameters of yuba stick. The goal was to provide theoretical support for selecting appropriate factory drying methods. The results showed that the effect of the two drying processes on the protein content of yuba stick reached the level of significant difference (P

Traditional positron emission tomography (PET) systems apply analog circuits for signal processing and achieve coincidence event detection through coincident circuitry. However, these systems suffer from a significant loss of information during projection and image data processing, leading to poor algorithm scalability. In contrast, All-Digital PET systems leverage precise sampling and comprehensive digital processing to simplify hardware design while maximizing software capabilities. These advanced systems rely on software algorithms to handle more operations, thereby providing complete process data, abundant algorithms, and convenient optimization for replacement. By treating detectors and algorithms as fundamental “building blocks,” the plug and imaging (PnI) platform constructs imaging protocols, algorithms, and equipment layers to define the imaging process, extend algorithmic capabilities, and support the construction of diverse animal or clinical PET system types. Moreover, integrating PnI into All-Digital PET systems allows for early information mining from scintillation pulse data levels rather than at the image level, facilitating flexible additional algorithm integration. Based on the aforementioned background, in this study, we critically investigated PnI software-related research advancements, precisely elucidating the comprehensive structure of All-Digital PET systems, architectural flowcharting of the imaging process, and exemplary application cases. Our primary objective was to enhance flexibility for scientists involved in constructing All-Digital PET research instruments while providing valuable references for the expeditious and efficient development of diverse PET systems alongside software algorithmic enhancements.

ABSTRACT Background Rearrangements of the histone‐lysine‐N‐methyltransferase (KMT2A), previously referred to as mixed‐lineage leukemia (MLL), are among the most common chromosomal abnormalities in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), involving numerous different fusion partners. KMT2A‐rearranged (KMT2A‐r) leukemia is characterized by a rapid onset, aggressive progression, and significantly worse prognosis compared to non‐KMT2A‐r leukemias. Even with contemporary chemotherapeutic treatments and hematopoietic stem cell transplantations (HSCT), patients with KMT2A‐r leukemia typically experience poor outcomes and limited responses to these therapies. Objectives This review aims to consolidate recent studies on the general gene characteristics and associated mechanisms of KMT2A‐r acute leukemia, as well as the cytogenetics, immunophenotype, clinical presentation, and risk stratification of both KMT2A‐r‐AML and KMT2A‐r‐ALL. Particularly, the treatment targets in KMT2A‐r acute leukemia are examined. Methods A comprehensive review was carried out by systematically synthesizing existing literature on PubMed, using the combination of the keywords ‘KMT2A‐rearranged acute leukemia’, ‘lymphoblastic leukemia’, ‘myeloid leukemia’, and ‘therapy’. The available studies were screened for selection based on quality and relevance. Conclusions Studies indicate that KMT2A rearrangements are present in over 70% of infant leukemia cases, approximately 10% of adult AML cases, and numerous instances of secondary acute leukemias, making it a disease of critical concern to clinicians and researchers alike. The future of KMT2A‐r acute leukemia research is characterized by an expanding knowledge of the disease's biology, with an emphasis on personalized therapies, immunotherapies, genomic advancements, and innovative therapeutic combinations. The overarching aim is to enhance patient outcomes, lessen the disease burden, and elevate the quality of life for those affected. Ongoing research and clinical trials in this area continue to offer promising opportunities for refining treatment strategies and improving patient prognosis.

The patterns of material accumulation in buildings and infrastructure accompanied by rapid urbanization offer an important, yet hitherto largely missing stock perspective for facilitating urban system engineering and informing urban resources, waste, and climate strategies. However, our existing knowledge on the patterns of built environment stocks across and particularly within cities is limited, largely owing to the lack of sufficient high spatial resolution data. This study leveraged multi-source big geodata, machine learning, and bottom-up stock accounting to characterize the built environment stocks of 50 cities in China at 500 m fine-grained levels. The per capita built environment stock of many cities (261 tonnes per capita on average) is close to that in western cities, despite considerable disparities across cities owing to their varying socioeconomic, geomorphology, and urban form characteristics. This is mainly owing to the construction boom and the building and infrastructure-driven economy of China in the past decades. China’s urban expansion tends to be more “vertical” (with high-rise buildings) than “horizontal” (with expanded road networks). It trades skylines for space, and reflects a concentration–dispersion–concentration pathway for spatialized built environment stocks development within cities in China. These results shed light on future urbanization in developing cities, inform spatial planning, and support circular and low-carbon transitions in cities.

Objective: To investigate the source of infection in a patient with recurrent severe neck infections caused by Klebsiella pneumoniae and to analyze the virulence of isolates obtained from different sites of the patient. Methods: We collected preoperative neck abscess puncture fluid, intraoperative neck drainage fluid, sputum, intestinal fecal specimens, and blood samples from a patient who visited Wuxi Second People's Hospital twice between 2017 and 2018. We conducted isolation, identification, drug sensitivity tests, and string tests on the isolates. Capsule serotyping and virulence gene analysis were performed using PCR. The genetic relationship of different isolates was assessed by Multilocus Sequence Typing and virulence was evaluated using the Galleria mellonella infection model. Additionally, whole-genome sequencing was used to analyze the chromosomal and plasmid genes of one isolate. Results: Klebsiella pneumoniae was detected in the sputum and fecal specimens from both hospitalizations, as well as the preoperative ultrasound-guided puncture fluid and intraoperative drainage fluid from the first hospitalization, resulting in six isolates. These isolates were all K16 serotype, positive in the string test, and identified as ST660 by Multilocus Sequence Typing, indicating they belonged to the same clone. Virulence gene analysis showed that wcaG, iucB, iroNB, rmpA, rmpA2, Aer, kfuBC, ureA, fimH, mrkD, uge, and peg344 were positive, while allS, cf29a, and Wzy_K1 were negative. In the Galleria mellonella virulence assay, the lethality of different isolates was dose-dependent. The K16 group showed significantly higher larval mortality compared to other control groups (including K1, K2, K5, K20, and K57 groups). Genome sequencing revealed that plasmid p17388 carried numerous virulence genes and insertion sequences, particularly ISKPN74, and showed high homology with other Klebsiella plasmids. Conclusion: This study is the first to report severe cervical necrotizing fasciitis caused by the K16-ST660 Klebsiella pneumoniae Isolate. The high virulence of these isolates was confirmed by the Galleria mellonella virulence assay and the detection of numerous virulence genes. In-depth analysis of plasmid p17388 suggests that ISKPN74 may enhance stable integration of the plasmid into the bacterial chromosome through recombinases and transposases, thereby reducing the likelihood of plasmid loss and increasing bacterial virulence. Additionally, IS5 family insertion sequences may carry extra promoters or enhancers that, when inserted upstream of mucoviscosity-associated genes such as rmpA, may increase the transcription levels of downstream genes. This ISKPN74-mediated integration or insertion reveals a complex genetic mechanism that may contribute to the severity of infections caused by ST660 isolates. Our findings offer new insights into the virulence and structure of ST660-K16 Klebsiella pneumoniae, suggesting that further investigation into the specific mechanisms by which these insertion sequences enhance virulence could aid in developing novel infection management strategies.

Abstract With the increasing incidence of kidney diseases, there is an urgent need to develop therapeutic strategies to combat post‐injury fibrosis. Immune cells, including platelets, play a pivotal role in this repair process, primarily through their released cytokines. However, the specific role of platelets in kidney injury and subsequent repair remains underexplored. Here, the detrimental role of platelets in renal recovery following ischemia/reperfusion injury and its contribution to acute kidney injury to chronic kidney disease transition is aimed to investigated. In this study, it is shown that depleting platelets accelerates injury resolution and significantly reduces fibrosis. Employing advanced single‐cell and spatial transcriptomic techniques, macrophages as the primary mediators modulated by platelet signals is identified. A novel subset of macrophages, termed “cycling M2”, which exhibit an M2 phenotype combined with enhanced proliferative activity is uncovered. This subset emerges in the injured kidney during the resolution phase and is modulated by platelet‐derived thrombospondin 1 (THBS1) signaling, acquiring profibrotic characteristics. Conversely, targeted inhibition of THBS1 markedly downregulates the cycling M2 macrophage, thereby mitigating fibrotic progression. Overall, this findings highlight the adverse role of platelet THBS1‐boosted cycling M2 macrophages in renal injury repair and suggest platelet THBS1 as a promising therapeutic target for alleviating inflammation and kidney fibrosis.

Abstract Objective The doctor-patient relationship (DPR) plays a crucial role in the Chinese healthcare system, functioning to improve medical quality and reduce medical costs. This study examined the psychometric properties of the Chinese version of the Difficult Doctor-Patient Relationship Questionnaire (DDPRQ-10) among general hospital inpatients in China. Methods The research recruited 38 resident doctors responsible for 120 participants, and factor analyses were used to assess the construct validity of the scale. Convergent validity was evaluated by examining the correlation between DDPRQ-10 and depressive symptoms, burnout, and self-efficacy, using the Patient Health Questionnaire Depression Scale-9 item (PHQ-9), and the Maslach Burnout Inventory (MBI). Both multidimensional item response theory (MIRT) and unidimensional item response theory (IRT) frameworks were used to estimate the parameters of each item. Results The Chinese version of DDPRQ-10 showed satisfactory internal consistency (Cronbach's alpha = 0.931), and fitted in a modified two-factor model of positive feelings and negative feelings (χ2/df = 1.494, GFI = 0.925, RMSEA = 0.071, SRMR = 0.008, CFI = 0.985, NFI = 0.958, NNFI = 0.980, TLI = 0.980, IFI = 0.986). Significant correlations with PHQ-9 with DDPRQ-10 and both subscales were revealed (r = 0.293 ~ 0.333, p

Abstract Ferroptosis is an iron-dependent programmed cell death associated with severe kidney diseases, linked to decreased glutathione peroxidase 4 (GPX4). However, the spatial distribution of renal GPX4-mediated ferroptosis and the molecular events causing GPX4 reduction during ischemia-reperfusion (I/R) remain largely unknown. Using spatial transcriptomics, we identify that GPX4 is situated at the interface of the inner cortex and outer medulla, a hyperactive ferroptosis site post-I/R injury. We further discover OTU deubiquitinase 5 (OTUD5) as a GPX4-binding protein that confers ferroptosis resistance by stabilizing GPX4. During I/R, ferroptosis is induced by mTORC1-mediated autophagy, causing OTUD5 degradation and subsequent GPX4 decay. Functionally, OTUD5 deletion intensifies renal tubular cell ferroptosis and exacerbates acute kidney injury, while AAV-mediated OTUD5 delivery mitigates ferroptosis and promotes renal function recovery from I/R injury. Overall, this study highlights a new autophagy-dependent ferroptosis module: hypoxia/ischemia-induced OTUD5 autophagy triggers GPX4 degradation, offering a potential therapeutic avenue for I/R-related kidney diseases.

Abstract Background Several biallelic truncating and missense variants of the gem nuclear organelle–associated protein 5 (GEMIN5) gene have been reported to cause neurodevelopmental disorders characterized by cerebellar atrophy, intellectual disability, and motor dysfunction. However, the association between biallelic GEMIN5 variants and early‐infantile developmental and epileptic encephalopathies (EIDEEs) has not been reported. Purpose This study aimed to expand the phenotypic spectrum of GEMIN5 and explore the correlations between epilepsy and molecular sub‐regional locations. Methods We performed whole‐exome sequencing in two patients with EIDEE with unexplained etiologies. The damaging effects of variants were predicted using multiple in silico tools and modeling. All reported patients with GEMIN5 pathogenic variants and detailed neurological phenotypes were analyzed to evaluate the genotype–phenotype relationship. Results Novel biallelic GEMIN5 variants were identified in two unrelated female patients with EIDEE, including a frameshift variant (Hg19, chr5:154284147‐154284148delCT: NM_015465: c.2551_c.2552delCT: p.(Leu851fs*30)), a nonsense mutation (Hg19, chr5:154299603‐154299603delTinsAGA: NM_015465: c.1523delTinsAGA: p.(Leu508*)), and two missense variants (Hg19, chr5:154282663T > A: NM_015465: c.2705T > A: p.(Leu902Gln) and Hg19, chr5:154281002C > G: NM_015465: c.2911C > G: p.(Gln971Glu)), which were inherited from asymptomatic parents and predicted to be damaging or probably damaging using in silico tools. Except p.Leu508*, all these mutations are located in tetratricopeptide repeat (TPR) domain. Our two female patients presented with seizures less than 1 month after birth, followed by clusters of spasms. Brain magnetic resonance imaging suggests dysgenesis of the corpus callosum and cerebellar hypoplasia. Video electroencephalogram showed suppression‐bursts. Through a literature review, we found 5 published papers reporting 48 patients with biallelic variants in GEMIN5. Eight of 48 patients have epilepsy, and 5 patients started before 1 year old, which reminds us of the relevance between GEMIN5 variants and EIDEE. Further analysis of the 49 GEMIN5 variants in those 50 patients demonstrated that variants in TPR‐like domain or RBS domain were more likely to be associated with epilepsy. Conclusions We found novel biallelic variants of GEMIN5 in two individuals with EIDEE and expanded the clinical phenotypes of GEMIN5 variants. It is suggested that the GEMIN5 gene should be added to the EIDEE gene panel to aid in the clinical diagnosis of EIDEE and to help determine patient prognosis.

Klebsiella pneumoniae is an opportunistic pathogen causing severe infections. The circadian rhythm is the internal rhythm mechanism of an organism and plays an important role in coping with changes in the 24-h circadian rhythm. Disruption of the circadian rhythm can lead to immune, behavioral, mental, and other related disorders. Whether K. pneumoniae can disrupt the circadian rhythm after infection remains unclear. Here, we examined the effects of K. pneumoniae NTUH-K2044 infection on biological rhythm and inflammation in zebrafish using behavioral assays, quantitative real-time reverse transcription PCR, neutrophil and macrophage transgenic fish, and drug treatment. The results showed that K. pneumoniae infection decreased the motor activity of zebrafish and reduced the circadian rhythm amplitude, phase, and period. The expression of core circadian rhythm-associated genes increased under light-dark conditions, whereas they were downregulated under continuous darkness. Analysis of Klebsiella pneumoniae-mediated inflammation using Tg(mpx:EGFP) and Tg(mpeg:EGFP) transgenic zebrafish, expressing fluorescent neutrophils and macrophages, respectively, showed increased induction of inflammatory cells, upregulated expression of inflammatory factor genes, and stronger inflammatory responses under light-dark conditions. These effects were reversed by the anti-inflammatory drug G6PDi-1, and the expression of clock genes following K. pneumoniae treatment was disrupted. We determined the relationship among K. pneumoniae, inflammation, and the circadian rhythm, providing a theoretical reference for studying circadian rhythm disorders caused by inflammation.

Abstract Objective Biallelic variants of RARS1, a gene that encodes the cytoplasmic tRNA synthetase for arginine (ArgRS), are associated with central nervous system (CNS) manifestations, such as hypomyelinating leukodystrophy‐9 and developmental and epileptic encephalopathy (DEE). This study aimed to better understand the RARS1 biallelic mutations and the associated phenotypes, particularly in patients with DEE. Methods We identified two patients with RARS1 biallelic mutations and functionally validated these mutations in vitro. Furthermore, we performed a review of the literature. Results Two patients with hypomyelinating leukodystrophy were found to have RARS1 biallelic variants (Patient 1: c.1535G>A (p.Arg512Gln) and c.1382G>A (p.Arg461His); Patient 2: homozygous variants c.5A>T (p.Asp2Val)). Patient 2 had a severe clinical manifestation of DEE. A review of the literature identified 27 patients from five studies. Among the 29 patients, intellectual disability, developmental delay, and hypomyelination were the common symptoms, while 13 of them exhibited DEE and malformations of cortical development. Of the 25 variants identified, c.5A>G (p.Asp2Gly) was identified in 10 patients. ArgRS protein expression and stability were substantially reduced in the two newly identified patients. Significance Patients with RARS1 biallelic mutations frequently exhibit DEE, a severe phenotype, along with hypomyelinating leukodystrophy. Besides its effects on the white matter, this mutation also influences cortical development. Moreover, the variants c.5A>T (p.Asp2Val), c.1382G>A (p.Arg461His), and c.1535G>A (p.Arg512Gln) are pathogenic and affect the expression of ArgRS by reducing the protein stability.

Background:. Pediatric pancreatoblastoma is an extremely rare malignant tumor, posing diagnostic and treatment difficulties for pediatric surgeons. Using the Surveillance, Epidemiology, and End Results (SEER) database, we present an up-to-date report of the epidemiology, clinicopathological features, survival rates, and prognosis of pancreatoblastoma in pediatric patients. Methods:. All pediatric patients diagnosed with pancreatoblastoma between 1975 and 2018 were identified in the SEER registries (SEER 8 registries and SEER 17 registries). We conducted a survival analysis to assess overall survival and 1- and 5-year late mortality rates. Descriptive statistics and log-rank test were performed. Results:. A total of 22 children and adolescents with pancreatoblastoma were identified. In this cohort, 12 of 22 were male (54.55%), 14 were White (63.64%), and 11 were diagnosed between the ages of 1 and 4 years (50.0%). Among the 22 patients, 11 (50.0%) had distant metastases, whereas 7 (31.82%) had localized, and 4 (18.18%) had a regional disease. A total of 5 children and adolescents died during the study period, with cumulative survival rates of 14 of 17 (82.35%) and 10 of 11 (90.95%) among 1- and 5-year survivors, respectively. Cancer-directed surgery was significantly associated with an increased life expectancy (log-rank test, P = .018). Conclusion:. Pediatric pancreatoblastoma is a rare entity. Cases that underwent surgery had a greater likelihood of overall survival and reduced late mortality.

Abstract Objective Performing long‐term video‐electroencephalographic monitoring (LTVEM) to obtain the ictal electroencephalogram (EEG) is important for presurgical evaluation. This study aimed at investigating the safety and efficacy of our protocol developed at Peking University First Hospital (PUFH) for rapid withdrawal of antiseizure medications (ASMs) during LTVEM to induce seizures in children with drug‐resistant epilepsy (DRE) exhibiting nondaily seizures. Methods Children with DRE who followed the PUFH protocol for rapid withdrawal of ASMs during LTVEM between 2018 and 2021 were enrolled. The occurrence of seizures, number of ASMs withdrawn, seizure onset time after ASM tapering initiation, changes in interictal epileptiform discharge (IED), and adverse events were evaluated during LTVEM. Results Among 80 children evaluated in this study, seizures were induced successfully in 72 (90%) children. Furthermore, no change in IED sites was observed in these 72 children following the initiation of ASM tapering while 2 children exhibited secondary bilateral tonic‐clonic seizures. The median time from ASM tapering initiation to the onset of the first seizure was found to be 3 days (2–4), while the median number of ASMs withdrawn was 2 (1–2). Finally, 66 children (91.7%) had habitual seizures while 6 children had nonhabitual seizure semiology. Significance The PUFH protocol can be used for the rapid withdrawal of ASMs during LTVEM in children with DRE. Using this protocol, ictal EEG patterns can be obtained in a relatively short time for most patients with fewer adverse effects during LTVEM, which may provide meaningful electro‐clinical information for presurgical evaluation.

Neurological medical devices have revolutionized the management of neurological disorders, providing diagnostic, therapeutic, and monitoring solutions. High-risk neurological devices, such as deep brain stimulation and neurostimulators, offer groundbreaking treatments, emphasizing patient benefits while considering risks. To gain FDA approval, high-risk Class III devices necessitate premarket approval (PMA) applications with pivotal clinical trials, often assessing patient-reported outcomes (PROs). This article analyzes FDA-approved high-risk neurological devices from 2001 to 2022 via the PMA pathway. It explores device characteristics and pivotal clinical trials, and PRO incorporation. Of the 23 identified devices, pain neurology devices (30.4 %) predominated. All devices were therapeutic, with varying study designs. Pain neurology devices notably emphasized PRO endpoints as expected. This study underscores the significance of PROs in assessing device efficacy and safety, offering insights into regulatory processes and patient-centered care in neurological disorder management.

ObjectiveTo the literature, variants in the ATP6AP2 gene may cause abnormal nervous system development and associated neurological symptoms.MethodsWe report a patient with developmental and epileptic encephalopathy (DEE) carrying an ATP6AP2 c.858G > A (p.Ala286=) synonymous variant. In addition, an overview of reported patients with the same variant were collected and summarized to compare our findings.ResultsThe patient started experiencing tonic seizures at 3.5 months of age, and magnetic resonance imaging (MRI) indicated impaired brain white matter development and reduced left hippocampal volume. Furthermore, electroencephalography showed multifocal interictal epileptiform discharges. Treatment with various anti-seizure medications yielded unsatisfactory results, and the disorder eventually developed into epileptic spasms. An in vitro splicing assay for the ATP6AP2 gene mRNA revealed that the variant caused a deletion in exon 8 and a corresponding protein truncation. A review of previously reported ATP6AP2-related DEE patients found that synonymous variants in the ATP6AP2 gene can cause early DEE onset, progressive changes in early-life MRI, and exon skipping in all ATP6AP2-related DEE patients.SignificanceWe found that synonymous variants in ATP6AP2 may have significant pathogenicity and are highly correlated with DEE. Due to increased isoform production, ATP6AP2 synonymous variants may cause nervous system developmental disorders by competitively reducing the generation of full-length transcripts, resulting in defects in ATP6AP2-related physiological processes.

Abstract Introduction Sotos syndrome (SS) is an overgrowth disease characterized by distinctive facial features, advanced bone age, macrocephaly, and developmental delay is associated with alterations in the NSD1 gene. Here, we report a case of a 4‐year‐old female child with SS caused by NSD1 gene nonsense mutation. Methods Whole‐exome sequencing (WES) was applied for probands and her parents. Sanger sequencing was used to confirm the mutation. We performed the literature review using PubMed and found 12 articles and 14 patients who presented with SS. Results The patient showed typical facial features of SS, hand deformities, and seizure. WES revealed de novo heterozygous variant: NSD1 (NM_022455.5), c.6095G > A, p.TRP2032*. We also reviewed the phenotype spectrum of 14 patients with SS, who exhibited a variety of clinical phenotypes, including developmental delay, seizures, scoliosis, hearing loss, cardiac and urinary system abnormalities, and so on. Discussion The lack of correlation between mutation sites or types and phenotypes was summarized by literature reviewing. The NSD1 protein contains 14 functional domains and this nonsense mutation was located in SET domain. Early appearance of the termination codon leads to protein truncation. Haploinsufficiency of the NSD1 gene causes the overgrowth disorders.

Perforin is essentially involved in the granule-dependent killing activities of cytotoxic T lymphocytes and NK cells. Monoallelic PRF1 mutation increases the risk of autoimmune diseases, and biallelic PRF1 mutation causes familial hemophagocytic lymphohistiocytosis-2. Here, we report a case of a 12-year-old girl with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), followed by a rapidly progressive onset of hemophagocytic lymphohistiocytosis (HLH) 9 months later, alongside manifestations of demyelinating encephalopathy. Genetic sequencing revealed a heterozygous nonsense mutation in the PRF1 gene (c.984G>A; p.W328*) and a heterozygous missense mutation in the PRF1 gene (c.1349C>T; p.T450M). Eventually, she died because of no suitable allogeneic hematopoietic stem cell available in time. Our observations suggest that CIPD might represent the initial phenotype of biallelic PRF1 mutation and could serve as an early sign of subsequent HLH. A comprehensive understanding of this condition is paramount for timely diagnosis, treatment, and ultimately improved patient outcomes.

The rising prosperity of Location-based Social Networks (LBSNs) witnessed an explosion in the availability of geo-tagged social media data, which enables tremendous location-aware online services, especially next point of interest (POI) recommendation. However, previous next POI recommendation studies usually adopt fix-length time windows for user check-in sequence modeling, leading to a limited capacity in capturing fine-grained user temporal preferences that easily change over time. Besides, existing methods often directly leverage multi-modal contexts as auxiliary to alleviate the data sparsity issue, which fails to fully exploit the sequential patterns of contextual information for inferring user interest drift. To address the above challenges, we propose a novel framework named iTourSPOT which extends traditional collaborative filtering methods with a context-aware POI embedding architecture. For enhancing temporal interests modeling capacity, we associate the context feature extraction with varying-length sessions and incorporate check-in frequencies of POIs as prior knowledge to instruct the session representation learning of our model. Moreover, a collaborative sequence transduction model is designed for joint context sequence modeling and session-based POI recommendation. Experimental results on a real-world geo-tagged photo dataset clearly demonstrate the effectiveness of the proposed framework when compared with state-of-the-art baseline methods, especially in both sparse and cold-start scenarios.

Integrating heterogeneous single-cell multi-omics as well as spatially resolved transcriptomic data remains a major challenge. Here the authors report a unified single-cell data integration framework using an unbalanced optimal transport-based deep network.

Background Hemorrhagic cystitis (HC) is a severe complication of allo-HSCT, characterized by irritative symptoms of the urinary tract and a higher morbidity rate. The risk factors and prognosis of HC are still unclear.Objective The objective of this study is to identify risk factors and outcomes to improve treatment in pediatric SAA patients undergoing HSCTs in the Children's Hospital of Soochow University.Methods A total of 97 SAA patients as a cohort were enrolled from 2010 to 2019 in the Children's Hospital of Soochow University and a number of factors related to HC and outcomes were analysed. In all transplants (except UCBT), patients received a combination of G-CSF stimulated bone marrow (BM) and peripheral blood stem cell (PBSC). The minimum number of CD34 + cells is 5 × 106 cells/kg.Results Mononuclear cells dose (MNC, cut off: 8.53 × 108/kg) and grade II–IV acute graft versus host disease (aGVHD) were identified as independent risk factors for HC. Patients without HC had better overall survival (OS) than with HC (No HC: 98.6%±1.4% vs HC: 87.4% ± 6.8%, p = 0.03).Conclusion We concluded that aGVHD and MNC dose in graft might play an important role in the development of HC in pediatric SAA patients undergoing allo-HSCT. HC is also a key complication affecting the prognosis of children with SAA after allo-HSCT.

Abstract The Pacific decadal oscillation (PDO) is a decadal variability phenomenon occurring in the North Pacific Ocean. It has substantial impacts on marine ecosystems and the global climate. Due to the high complexity and unclear evolution mechanism, the accurate long‐term prediction of PDO remains a challenge. In this paper, a deep spatiotemporal embedding network (DSEN) is proposed to extract the spatiotemporal features from historical climate data and achieve end‐to‐end forecasting of the PDO index. The spatiotemporal features are recursive in the continuous forecasting of the PDO index on seasonal time scales, thus the cumulative error is largely reduced. During the test period of 39 years (1982–2020), our model can skillfully predict the PDO index up to 1 year, outperforming six methods used as benchmark. By contrast with physically‐based methods, DSEN can accurately predict the PDO index from a data‐driven perspective.

Abstract Previous studies have demonstrated dysregulated mitochondrial dynamics in fibrotic livers and hepatocytes. Little is currently known about how mitochondrial dynamics are involved, nor is it clear how mitochondrial dynamics participate in hepatic stellate cell (HSC) activation. In the present study, we investigated the role of mitochondrial dynamics in HSC activation and the underlying mechanisms. We verified that mitochondrial fission was enhanced in human and mouse fibrotic livers and active HSCs. Moreover, increased mitochondrial fission driven by fis1 overexpression could promote HSC activation. Inhibiting mitochondrial fission using mitochondrial fission inhibitor-1 (Mdivi-1) could inhibit activation and induce apoptosis of active HSCs, indicating that increased mitochondrial fission is essential for HSC activation. Mdivi-1 treatment also induced apoptosis in active HSCs in vivo and thus ameliorated CCl4-induced liver fibrosis. We also found that oxidative phosphorylation (OxPhos) was increased in active HSCs, and OxPhos inhibitors inhibited activation and induced apoptosis in active HSCs. Moreover, increasing mitochondrial fission upregulated OxPhos, while inhibiting mitochondrial fission downregulated OxPhos, suggesting that mitochondrial fission stimulates OxPhos during HSC activation. Next, we found that inhibition of oxidative stress using mitoquinone mesylate (mitoQ) and Tempol inhibited mitochondrial fission and OxPhos and induced apoptosis in active HSCs, suggesting that oxidative stress contributes to excessive mitochondrial fission during HSC activation. In conclusion, our study revealed that oxidative stress contributes to enhanced mitochondrial fission, which triggers OxPhos during HSC activation. Importantly, inhibiting mitochondrial fission has huge prospects for alleviating liver fibrosis by eliminating active HSCs.

Robust Principal Component Analysis (RPCA) offers a powerful tool for recovering a low-rank matrix from highly corrupted data, with growing applications in computational biology. Biological processes commonly form intrinsic hierarchical structures, such as tree structures of cell development trajectories and tumor evolutionary history. The rapid development of single-cell sequencing (SCS) technology calls for the recovery of embedded tree structures from noisy and heterogeneous SCS data. In this study, we propose RobustTree, a unified framework to reconstruct the inherent topological structure underlying high-dimensional data with noise. By extending RPCA to handle tree structure optimization, RobustTree leverages data denoising, clustering, and tree structure reconstruction. It solves the tree optimization problem with an adaptive parameter selection scheme that we proposed. In addition to recovering real datasets, RobustTree can reconstruct continuous topological structure and discrete-state topological structure of underlying SCS data. We apply RobustTree on multiple synthetic and real datasets and demonstrate its high accuracy and robustness when analyzing high-noise SCS data with embedded complex structures. The code is available at https://github.com/ucasdp/RobustTree.

BackgroundFecal microbiota transplantation (FMT) may be helpful in the treatment of autism spectrum disorder (ASD) as rebalancing the gut microbiome has been shown to potentially improve behavioral symptoms in children with ASD.MethodsThis systematic review was conducted to assess the effect of FMT for children with ASD. The Embase, PubMed, Web of Science, and Cochrane Library databases were searched for articles published from inception to October 6, 2022. Two reviewers independently screened the identified records and undertook data extraction.ResultsThe search identified a total of five studies: two prospective open-label studies, two retrospective observational studies, and a case report; however, no randomized controlled trial was identified. All five studies reported a significant post-FMT-treatment improvement in neuropsychological assessment of ASD. The two prospective open-label studies suggested that the Autism Behavior Checklist (ABC) score, and the Social Responsiveness Scale (SRS) score at the posttreatment assessment decreased from the baseline (Wilcoxon signed-rank test; all p < 0.01]). The two retrospective observational studies suggested that FMT helped to improve the ASD symptoms. One observational study reported that the Childhood Autism Rating Scale (CARS) score and ABC score of the constipation group decreased from the baseline after the second course assessment (CARS [baseline: mean 35.25 ± standard deviation 4.36, second course: 32.5 ± 3.1, p = 0.015]; ABC [baseline: 56.21 ± 16.08, second course: 46.54 ± 16.54, p = 0.046]). Another observational study found that both ABC and CARS scores decreased as the number of FMT courses increased, and significant differences were found at the end of each course as compared with the baseline.ConclusionCompared with the baseline, FMT significantly improved symptoms of autism in children with ASD in observational studies. However, rigorously designed randomized controlled clinical trials are needed to establish the safety and efficacy of FMT as a treatment for ASD.

ObjectiveThe patient-doctor relationship has been considered as a crucial concept in primary healthcare, while the medical reform launched by the Chinese government in 2009 has brought significant changes to the healthcare system, which made it urgent to introduce reliable measurement instruments for assessing today’s doctor-patient relationship in China. This study examined the psychometric properties of the Chinese version of the Patient-Doctor-Relationship Questionnaire-9 item (PDRQ-9) scale among general hospital inpatients in China.Materials and methodsA total of 203 participants responded to the survey, of which 39 completed retest after 7 days. Factor analyses were used to test the construct validity of the scale. Convergent validity was evaluated by the correlation between PDRQ-9 and depressive symptoms measured using PHQ-9 (Patient Health Questionnaire Depression Scale-9 item). Both multidimensional item response theory (MIRT) and unidimensional item response theory (IRT) framework were used to estimate the parameters of each item.ResultsThe two-factor model of relationship quality and treatment quality was supported (χ2/df = 1.494, GFI = 0.925, RMSEA = 0.071, RMR = 0.008, CFI = 0.985, NFI = 0.958, NNFI = 0.980, TLI = 0.980, IFI = 0.986). The PDRQ-9 and both subscales showed significant correlation with PHQ-9 (r = −0.196∼−0.309) and good internal consistency (Cronbach’s alpha = 0.865∼0.933). ANCOVA analysis adjusted with age revealed significant difference in PDRQ-9 ratings between patients with or without significant depressive symptoms (P = 0.019). The 7-day test-retest reliability of the scale was 0.730. The MIRT model of full scale and IRT models of both subscales showed high discrimination of all items (a = 2.46∼38.46), and the test information within the range of low-quality relationship was relatively high.ConclusionThe Chinese version of PDRQ-9 is a valid and reliable rating scale, which can measure the doctor-patient relationship among Chinese patients.

Neuromyelitis optica spectrum disorder (NMOSD), a severe demyelinating disease, is rare among children. Plasma exchange (PE) is widely used as a salvage therapy for severe and corticosteroid-unresponsive patients with NMOSD. Presently, there are limited studies on the safety and efficacy of PE in children with NMOSD. Herein, we report the case of six children with NMOSD who received PE along with the outcomes and adverse events. All six children (female, age at onset 4 years 9 months–13 years 2 months) were AQP4-IgG positive and received standard PE using the COM.TEC Cell Separator. The interval between NMOSD onset and PE was 29 days (range 10–98). Only one patient (P3) who received PE 10 days after acute exacerbations exhibited clinical improvement. Her left visual acuity increased from 0.06 to 0.6 (spectacle-corrected visual acuity was 1.0) and her EDSS score decreased from 4 to 3 points. The other five patients had no clinical improvement and no EDSS scores changes after PE. Adverse events included rashes (P1, P3), acute non-occlusive thrombosis of the internal jugular vein (P1), and thrombocytopenia (P2). In conclusion, the timing of PE initiation as a rescue therapy for severe and corticosteroid-unresponsive pediatric AQP4-IgG positive NMOSD may be crucial to treatment efficacy, and early initiation of PE may be associated with a better outcome. Furthermore, PE has the potential risk for clinically significant adverse effects that should be considered before initiating the therapy and should be weighed against potential benefits.

Background: Vigabatrin (VGB) is currently the most widely prescribed first-line medication for individuals with infantile spasms (IS) and especially for those with tuberous sclerosis complex (TSC), with demonstrated efficacy. Meanwhile, its adverse events, such as vigabatrin-associated brain abnormalities on magnetic resonance imaging (MRI; VABAM), have also been widely reported. Objectives: The objectives of this study were to observe the occurrences of VABAM in patients with IS caused by TSC (IST) and further explore the associated risk factors. Methods: Children with IS receiving VGB were recruited from our institution; clinical, imaging, and medication data were collected. Cerebral MRI was reviewed to determine the occurrence of VABAM. Group comparisons (IS caused by TSC and other etiologies) were performed; subgroup analyses on IST were also performed. Next, a retrospective cohort study of children taking VGB was conducted to explore risk/protective factors associated with VABAM. Results: The study enrolled 172 children with IS who received VGB. VABAM was observed in 38 patients (22.1%) with a peak dosage of 103.5 ± 26.7 mg/kg/day. Subsequent analysis found the incidence of VABAM was significantly lower in the 80 patients with IST than in the 92 patients with IS caused by other etiologies (10% versus 32.6%, p -value

The isoleucine–glutamine (IQ) motif and Sec7 domain-containing protein 2 (IQSEC2) gene, located at Xp11. 2, are associated with nervous system diseases, such as epilepsy, autism, and intellectual disabilities. Gender-related differences in the severity of phenotype severity have been described previously. Here, we report the details of seven male children with IQSEC2 mutations from different families. During this investigation, we explored the relationship between the genotype and phenotype of IQSEC2 mutations; to do so, we recruited seven children with pathogenic/likely pathogenic IQSEC2 mutations who were diagnosed with global developmental delay and/or epilepsy. Their clinical features were assessed, and Trio-based whole-exome sequencing (trio WES) was conducted in seven pedigrees. A variety of algorithms and computational tools were used to calculate the pathogenicity, protein stability, conservation, side chain properties, and protein-protein interactions of mutated proteins. The seven patients ranged in age from 18 months to 5 years. Among them, six children were found to have both developmental delay and epilepsy, and one child only exhibited developmental delay. Four novel mutations (c.316C > T, c.443_4 44dup, c.3235T > C, and c.1417G > T) were newly reported. Two patients did not have truncated aberrant proteins caused by missense mutations. Still, they did have severe phenotypes, such as early-onset epilepsy in infancy, because the mutations were located in domains like the pleckstrin homology and IQ calmodulin-binding motif domains. The bioinformatics analysis also proved that missense mutations may be located in the functional region, which affects protein stability and is harmful. In summary, severe phenotypes, such as early-onset epilepsy in infancy, occur in male patients with a missense mutation in specific domains (e.g., pleckstrin homology and IQ calmodulin-binding motif domains). Some female individuals with IQSEC2 mutations may be asymptomatic because of the skewed inactivation of the X chromosome.

Colorectal cancer (CRC) is a common gastrointestinal tumor with a high degree of malignancy, and most clinical cases are diagnosed at an advanced stage, which has unfortunately missed an opportunity for surgery; therefore, elucidation of the crucial pathways of CRC development and discovery of targeted therapeutic strategies should be anticipated. Autophagy, which is an evolutionarily highly conserved catabolic process, may promote tumorigenesis and development of CRC. On the contrary, autophagy can trigger programmed cell death to inhibit CRC progression. Correspondingly, several targeted therapeutic strategies have been reported in CRC, including small-molecule compounds, polypeptides, non-coding RNAs, photodynamic, and adjuvant therapies. Thus, in this review, we focus on summarizing the crucial pathways of autophagy in CRC, and further discuss the current therapeutic strategies targeting autophagy. Together, these findings may shed light on the key regulatory mechanisms of autophagy and provide more promising therapeutic approaches for the future CRC therapies.

To solve the problems of poor stability and low monitoring precision in the online detection of rice moisture in the drying tower, we designed an online detection device for rice moisture at the outlet of the drying tower. The structure of a tri-plate capacitor was adopted, and the electrostatic field of the tri-plate capacitor was simulated using COMSOL software. A central composite design of three factors and five levels was carried out with the thickness, spacing, and area of the plates as the influencing factors and the capacitance-specific sensitivity as the test index. This device was composed of a dynamic acquisition device and a detection system. The dynamic sampling device was found to achieve dynamic continuous sampling and static intermittent measurements of rice using a ten-shaped leaf plate structure. The hardware circuit of the inspection system with STM32F407ZGT6 as the main control chip was designed to realize stable communication between the master and slave computers. Additionally, an optimized BP neural network prediction model based on the genetic algorithm was established using the MATLAB software. Indoor static and dynamic verification tests were also carried out. The results showed that the optimal plate structure parameter combination includes a plate thickness of 1 mm, plate spacing of 100 mm, and relative area of 18,000.069 mm2 while satisfying the mechanical design and practical application needs of the device. The structure of the BP neural network was 2-90-1, the length of individual code in the genetic algorithm was 361, and the prediction model was trained 765 times to obtain a minimum MSE value of 1.9683 × 10−5, which was lower than that of the unoptimized BP neural network with an MSE of 7.1215 × 10−4. The mean relative error of the device was 1.44% under the static test and 2.103% under the dynamic test, which met the accuracy requirements for the design of the device.

Abstract Background Long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) plays a positive role in the progression of human malignant tumors. However, the molecular mechanism of SNHG1 remains elusive in breast cancer. Results LncRNA SNHG1 was upregulated and had a positive relationship with poor prognosis according to bioinformatics analysis in pan-cancer including breast cancer. Silencing SNHG1 inhibited tumorigenesis in breast cancer both in vitro and in vivo. Mechanistically, SNHG1 functioned as a competing endogenous RNA (ceRNA) to promote TERT expression by sponging miR-18b-5p in breast cancer. miR-18b-5p acted as a tumor repressor in breast cancer. Moreover, the combination of SNHG1 knockdown and TERT inhibitor administration showed a synergistic inhibitory effect on breast cancer growth in vivo. Finally, E2F1 as a transcription factor, binding to SNHG1 promoter and enhanced SNHG1 transcription in breast cancer. Conclusions Our results provide a comprehensive understanding of the oncogenic mechanism of lncRNA SNHG1 in breast cancer. Importantly, we identified a novel E2F1–SNHG1–miR-18b-5p–TERT axis, which may be a potential therapeutic target for breast cancer. Our results also provided a potential treatment for breast cancer when knockdown SNHG1 and TERT inhibitor administration simultaneously.

Abstract Background When Alzheimer’s disease (AD) is occurring at an early onset before 65 years old, its clinical course is generally more aggressive than in the case of a late onset. We aim at identifying [ $$^{18}$$ 18 F]florbetaben PET biomarkers sensitive to differences between early-onset Alzheimer’s disease (EOAD) and late-onset Alzheimer’s disease (LOAD). We conducted [ $$^{18}$$ 18 F]florbetaben PET/CT scans of 43 newly diagnosed AD subjects. We calculated 93 textural parameters for each of the 83 Hammers areas. We identified 41 independent principal components for each brain region, and we studied their Spearman correlation with the age of AD onset, by taking into account multiple comparison corrections. Finally, we calculated the probability that EOAD and LOAD patients have different amyloid- $$\beta$$ β ( $$A\beta$$ A β ) deposition by comparing the mean and the variance of the significant principal components obtained in the two groups with a 2-tailed Student’s t-test. Results We found that four principal components exhibit a significant correlation at a 95% confidence level with the age of onset in the left lateral part of the anterior temporal lobe, the right anterior orbital gyrus of the frontal lobe, the right lateral orbital gyrus of the frontal lobe and the left anterior part of the superior temporal gyrus. The data are consistent with the hypothesis that EOAD patients have a significantly different [ $$^{18}$$ 18 F]florbetaben uptake than LOAD patients in those four brain regions. Conclusions Early-onset AD implies a very irregular pattern of $$A\beta$$ A β deposition. The authors suggest that the identified textural features can be used as quantitative biomarkers for the diagnosis and characterization of EOAD patients.

Identifying urban functional zones is of great significance for understanding urban structure and urban planning. The rapid growth and open accessibility of multisource big data, including remote sensing imagery and social sensing data, lead to a new way for dynamic identification of urban functional zones. In this article, we propose an SOE (scene–object–economy) based learning framework which integrates scene features from remote sensing imagery, object features from building footprints, and economy features from POIs (points of interest). From these three perspectives, rich information hidden in urban zone is excavated for function identification. Convolutional neural networks are used to extract high-level scene information from remote sensing images with different resolutions. Object features comprising a series of building indicators are constructed by measuring the area, perimeter, floor number, and year of the building. Moreover, we extract socioeconomic characteristics from POIs, which reflect different types of human activities in the urban zone. Last, random forest is used to identify functional zones based on SOE features. We apply the SOE-based framework to Shenzhen datasets and achieve 90.8% in accuracy with remote sensing images of 0.3-m spatial resolution. The experimental results show that the predicting performance of SOE-based framework is significantly better than other traditional methods, and the quantitative contribution of SOE factors is also revealed in determining functionality of urban zones.

Abstract Background We investigated the image quality of 11C, 68Ga, 18F and 89Zr, which have different positron fractions, physical half-lifes and positron ranges. Three small animal positron emission tomography/computed tomography (PET/CT) systems were used in the evaluation, including the Siemens Inveon, RAYCAN X5 and Molecubes β-cube. The evaluation was performed on a single scanner level using the national electrical manufacturers association (NEMA) image quality phantom and analysis protocol. Acquisitions were performed with the standard NEMA protocol for 18F and using a radionuclide-specific acquisition time for 11C, 68Ga and 89Zr. Images were assessed using percent recovery coefficient (%RC), percentage standard deviation (%STD), image uniformity (%SD), spill-over ratio (SOR) and evaluation of image quantification. Results 68Ga had the lowest %RC ( 85%) and lowest %STD for the 5 mm rod across all systems. For 11C and 89Zr, the maximum %RC was close (> 76%) to the %RC with 18F. A larger SOR were measured in water with 11C and 68Ga compared to 18F on all systems. SOR in air reflected image reconstruction and data correction performance. Large variation in image quantification was observed, with maximal errors of 22.73% (89Zr, Inveon), 17.54% (89Zr, RAYCAN) and − 14.87% (68Ga, Molecubes). Conclusions The systems performed most optimal in terms of NEMA image quality parameters when using 18F, where 11C and 89Zr performed slightly worse than 18F. The performance was least optimal when using 68Ga, due to large positron range. The large quantification differences prompt optimization not only by terms of image quality but also quantification. Further investigation should be performed to find an appropriate calibration and harmonization protocol and the evaluation should be conducted on a multi-scanner and multi-center level.

ObjectiveA systematic review of the role of stem cell-derived exosomes in repairing spinal cord injury (SCI) and the existing problems in animal experiments to provide a reference for better animal experiments and clinical studies in the future.MethodThree electronic databases, namely PubMed, Web of Science, and Ovid-Embase were searched. The studies were retrieved from inception to October 2021. Two researchers independently screened the literature, extracted data, and evaluated the methodological quality based on the inclusion criteria.Results and DiscussionThirty-two studies were incorporated into the final analyses. Exosomes derived from stem cells could not only significantly improve the motor function of animals with SCI, but also significantly increase the expression of anti-inflammatory factors IL-4 and IL-10 and anti-apoptotic protein Bcl-2, while significantly lowering the pro-inflammatory factor IL-1β and TNF-α and the expression of the apoptotic protein BAX. However, the mechanism of exosome-mediated SCI repair, as well as the best source and dosage remain unknown. In addition, there are still some issues with the design, implementation, and reporting of animal experiments in the included studies. Therefore, future research should further standardize the implementation and reporting of animal studies and fully explore the best strategies for exosomes to repair SCI so as to promote the translation of preclinical research results to clinical research better and faster.

Abstract Background An enzyme activity is influenced by the external environment. It is important to have an enzyme remain high activity in a specific condition. A usual way is to first determine the optimal condition of an enzyme by either the gradient test or by tertiary structure, and then to use protein engineering to mutate a wild type enzyme for a higher activity in an expected condition. Results In this paper, we investigate the optimal condition of an enzyme by directly analyzing the sequence. We propose an embedding method to represent the amino acids and the structural information as vectors in the latent space. These vectors contain information about the correlations between amino acids and sites in the aligned amino acid sequences, as well as the correlation with the optimal condition. We crawled and processed the amino acid sequences in the glycoside hydrolase GH11 family, and got 125 amino acid sequences with optimal pH condition. We used probabilistic approximation method to implement the embedding learning method on these samples. Based on these embedding vectors, we design a computational score to determine which one has a better optimal condition for two given amino acid sequences and achieves the accuracy 80% on the test proteins in the same family. We also give the mutation suggestion such that it has a higher activity in an expected environment, which is consistent with the previously professional wet experiments and analysis. Conclusion A new computational method is proposed for the sequence based on the enzyme optimal condition analysis. Compared with the traditional process that involves a lot of wet experiments and requires multiple mutations, this method can give recommendations on the direction and location of amino acid substitution with reference significance for an expected condition in an efficient and effective way.

An amendment to this paper has been published and can be accessed via the original article.

Strigolactones (SLs) are newly discovered plant hormones which regulate the normal development of different plant organs, especially root architecture. Lateral root formation of rapeseed seedlings before winter has great effects on the plant growth and seed yield. Here, we treated the seedlings of Zhongshuang 11 (ZS11), an elite conventional rapeseed cultivar, with different concentrations of GR24 (a synthetic analogue of strigolactones), and found that a low concentration (0.18 μmol L−1) of GR24 could significantly increase the lateral root growth, shoot growth, and root/shoot ratio of seedlings. RNA-Seq analysis of lateral roots at 12 h, 1 d, 4 d, and 7 d after GR24 treatment showed that 2 301, 4 626, 1 595, and 783 genes were significantly differentially expressed, respectively. Function enrichment analysis revealed that the plant hormone transduction pathway, tryptophan metabolism, and the phenylpropanoid biosynthesis pathway were over-represented. Moreover, transcription factors, including AP2/ERF, AUX/IAA, NAC, MYB, and WRKY, were up-regulated at 1 d after GR24 treatment. Metabolomics profiling further demonstrated that the amounts of various metabolites, such as indole-3-acetic acid (IAA) and cis-zeatin were drastically altered. In particular, the concentrations of endogenous IAA significantly decreased by 52.4 and 75.8% at 12 h and 1 d after GR24 treatment, respectively. Our study indicated that low concentrations of exogenous SLs could promote the lateral root growth of rapeseed through interaction with other phytohormones, which provides useful clues for the effects of SLs on root architecture and crop productivity.

Background. Klebsiella pneumoniae (K. pneu) is a leading cause of gram-negative pneumonia, which requires effective treatment. Adipose-derived mesenchymal stem cell- (ADSC-) derived exosomal microRNAs (miRNAs) have presented the inhibitory effect of multiple diseases. However, the function of ADSC-derived exosomal miRNAs in K. pneu remains unclear. Aim. In this study, we aimed to explore the effect of ADSC-derived exosomal miR-181-5p on K. pneu infection-induced lung injury. Methods. C57BL/6 mouse model was established by infection of K. pneu. ADSCs and exosomes were extracted and characterized in vitro. The translocation of ADSC-derived exosomes to bone marrow-derived macrophages (BMDMs) was detected. The level of miR-181a-5p was detected by real-time PCR. The secretion of inflammatory factors was determined by ELISA. The interaction between miR-181a-5p with STAT3 was identified. Results. We successfully isolated the ADSCs that express positive markers CD90 and CD105 rather than CD31 and CD45. The exosomal miR-181a-5p secreted by ADSCs were internalized by BMDM and K. pneu infection stimulated the miR-181a-5p level in bronchoalveolar lavage fluid (BALF) and BMDM. ADSC-derived exosomal miR-181a-5p repressed pulmonary outgrowth and dissemination of K. pneu infection in mice, repressed cellular infiltration in lung tissue, and attenuated the inflammasome activity and the levels of IL-1β and IL-18 in the lung. Mechanically, miR-181a-5p was able to inhibit STAT3 expression at posttranscriptional levels and repressed Nlrp3 and Asc expression in BMDM. Conclusion. Consequently, we concluded that ADSC-derived exosomal miR-181a-5p alleviated Klebsiella pneumonia infection-induced lung injury by targeting STAT3 signaling. ADSC-derived exosomal miR-181a-5p may serve as a potential candidate for the treatment of Klebsiella pneumonia infection-induced lung injury.

In order to improve the accuracy of medium and long-term load forecasting in the new normal economy, this paper combines the PSO-optimized twin support vector machine to build a medium and long-term load forecasting model under the background of the new normal economy. Moreover, this paper uses the algorithm to debug the filter and studies the accurate prediction of the fine model by the progressive spatial mapping algorithm and the processing of the data by the vector fitting algorithm. In addition, this paper combines the PSO algorithm to optimize the twin support vector machine, constructs the optimized algorithm according to the flow chart, and applies it to the medium and long-term load forecasting under the background of a new normal economy. The experimental results verify that the PSO-optimized twin support vector machine has a very good application effect in medium and long-term load forecasting under the background of the new normal economy.

Time series single-cell RNA sequencing (scRNA-seq) data are emerging. However, dynamic inference of an evolving cell population from time series scRNA-seq data is challenging owing to the stochasticity and nonlinearity of the underlying biological processes. This calls for the development of mathematical models and methods capable of reconstructing cellular dynamic transition processes and uncovering the nonlinear cell-cell interactions. In this study, we present GraphFP, a nonlinear Fokker-Planck equation on graph based model and dynamic inference framework, with the aim of reconstructing the cell state-transition complex potential energy landscape from time series single-cell transcriptomic data. The free energy of our model explicitly takes into account of the cell-cell interactions in a nonlinear quadratic term. We then recast the model inference problem in the form of a dynamic optimal transport framework and solve it efficiently with the adjoint method of optimal control. We evaluated GraphFP on the time series scRNA-seq data set of embryonic murine cerebral cortex development. We illustrated that it 1) reconstructs cell state potential energy, which is a measure of cellular differentiation potency, 2) faithfully charts the probability flows between paired cell states over the dynamic processes of cell differentiation, and 3) accurately quantifies the stochastic dynamics of cell type frequencies on probability simplex in continuous time. We also illustrated that GraphFP is robust in terms of cluster labelling with different resolutions, as well as parameter choices. Meanwhile, GraphFP provides a model-based approach to delineate the cell-cell interactions that drive cell differentiation. GraphFP software is available at https://github.com/QiJiang-QJ/GraphFP.

In order to improve the content of GABA in japonica rice, so as to improve the nutritional composition and enhance the added value of rice, this study explored a combined process of low-pressure steam enrichment of γ-aminobutyric acid (GABA) content in japonica rice and low-pressure superheated steam (LPSS) drying of japonica rice. The low-pressure energy and the energy stored in rice grains were used to promote water absorption and activation of rice germs in a steam environment. Under the action of glutamate decarboxylase, the germ glutamate underwent an enzymatic reaction to generate GABA, which was transferred to and stored in the rice endosperm due to the concentration gradient and water gradient. After germination, LPSS was successively applied to dry the rice grains. The response surface method was used to optimize the parameters of low-pressure wet steam enrichment and LPSS drying of the rice grains. The experimental results showed that when the pressure was 0.026 MPa, the temperature was 60.66°C, the time was 5.01 h, and the flow rate was 0.31 L/h; the GABA content produced by low-pressure wet steam germination of japonica rice peaked at 94.1751 mg/100 g. When the germinated and enriched japonica rice was put through LPSS drying with a pressure of 0.021 MPa, a temperature of 66.55°C, a time of 1.57 h, and a flow rate of 0.28 L/h, the GABA content peaked at 104.161 mg/100 g. The results show that the combined process of low-pressure steam enrichment and drying continuously produced GABA in the soaking enrichment and drying stages, and the content of GABA in the drying stage accounted for 10% of the total content, which effectively increased the content of GABA in japonica rice and shortened the enrichment time. This study provides a technical reference for industrialized production of GABA-rich brown rice, embryonic rice, and polished rice.