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Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and is characterized by multiple biological and clinical features. N6-methyladenosine (m6A) modification is the most common type of RNA modifications in eukaryotes and plays an important regulatory role in various biological processes. Recently, m6A modification has been found to be involved in the regulation of immune responses in sepsis. In addition, several studies have shown that m6A modification is involved in sepsis-induced multiple organ dysfunctions, including cardiovascular dysfunction, acute lung injury (ALI), acute kidney injury (AKI) and etc. Considering the complex pathogenesis of sepsis and the lack of specific therapeutic drugs, m6A modification may be the important bond in the pathophysiological process of sepsis and even therapeutic targets. This review systematically highlights the recent advances regarding the roles of m6A modification in sepsis and sheds light on their use as treatment targets for sepsis. [Display omitted] • M6A modification can regulate immune function of immune cells in sepsis. • Homeostasis of immune cells is regulated by m6A regulators. • M6A regulators participate in sepsis by acting on the metabolism of specific RNAs. • Targeting m6A regulators serves as a potential strategy for the treatment of sepsis. [ABSTRACT FROM AUTHOR]

• miR-141-3p was down-regulated in the brain tissues of BM rats and SP-treated astrocytes. • miR-141-3p suppressed astrocytes activation and the release of TNF-α, IL-1β, IL-6 in BM by down-regulating HMGB1. • Low miR-141-3p expression in BM was due to the methylation of miR-141 promoter. Bacterial meningitis (BM) is a serious infectious disease of the central nervous system that often occurs in children and adolescents. Many studies have suggested that microRNAs (miRNAs) are involved in BM. This study aimed to address the effects of miR-141-3p on astrocyte activation and inflammatory response in BM through HMGB1. The 3-week-old rats were injected with Streptococcus pneumoniae (SP) into the lateral ventricle to establish a BM model. Loeffler scoring method was used to evaluate the recovery of neurological function. Brain pathological damage was observed by hematoxylin and eosin (H&E) staining. Primary astrocytes were isolated from brain tissues of BM or non-infected SD rats. The levels of TNF-α, IL-1β, and IL-6 in brain tissues and astrocyte culture supernatant were measured by enzyme-linked immunosorbent assay (ELISA). The targeting relationship between miR-141-3p and HMGB1 was tested using dual-luciferase reporter assay. The expression of miR-141-3p, HMGB1, and the astrocytic marker glial fibrillary acidic protein (GFAP) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blotting. Methylation-specific PCR (MSP) analysis was performed to measure the methylation status of miR-141 promoter. The results showed that lower Loeffler scores were exhibited in rats with BM. The subarachnoid space of brain tissues of BM rats was widened, and obvious inflammatory cells were observed. miR-141-3p expression was reduced in BM rats and SP-treated astrocytes. Additionally, we found that overexpression of miR-141-3p led to the downregulation of HMGB1, GFAP, and inflammatory cytokines (TNF-α, IL-1β, and IL-6) in astrocytes. Furthermore, the results of dual-luciferase reporter assay confirmed that miR-141-3p directly targeted HMGB1. Overexpression of miR-141-3p inhibited the levels of GFAP, TNF-α, IL-1β, and IL-6 in astrocytes, which was eliminated by the up-regulation of HMGB1. The results of MSP analysis indicated that miR-141 promoter was highly methylated in brain tissues and astrocytes. DNMT1 was involved in the methylation of miR-141 promoter in BM. The present study verified that miR-141-3p affected inflammatory response by suppressing HMGB1 in SP-induced astrocytes and BM rat model. [ABSTRACT FROM AUTHOR]

Epilepsy in Sturge-Weber syndrome (SWS) is common, but drug-refractory epilepsy (DRE) in SWS has rarely been studied in children. We investigated the characteristics of epilepsy and risk factors for DRE in children with SWS. A retrospective study was conducted to analyze the clinical characteristics of children with SWS with epilepsy in our hospital from January 2013 to October 2022. Univariate and multivariate logistic analyses were performed to investigate the factors influencing DRE in children with SWS. A total of 35 SWS children with epilepsy were included (51% male; mean age of presentation 3.6 ± 0.5 years), 71% of children with SWS had their first seizure within the first year of life, and the most common type of seizure was focal seizure (77%). Eleven (31%) patients developed DRE. The median age of onset for the first seizure was 1.0 years and all these cases were of SWS type I. Multivariate logistic analysis revealed that stroke-like episodes and seizure clusters were risk factors for DRE in SWS children. A poor neurological function group was observed in twenty-five children with SWS. Status epilepticus was a risk factor that affected the neurological function of SWS children with epilepsy. Conclusion: The study explored the epileptic features of children with SWS. The results revealed that stroke-like episodes and seizure clusters are risk factors for DRE in children with SWS. The occurrence of status epilepticus impacts the neurological function of SWS children with epilepsy. Thus, long-term follow-up is necessary to monitor outcomes. What is Known: • Sturge-Weber syndrome (SWS) is a rare neurocutaneous disorder, over 75% of children with SWS experience seizures, and 30–57% develop drug-refractory epilepsy (DRE), which leads to a poor outcome. • Drug-refractory epilepsy in SWS has been rarely studied in children, and the risk factors associated with DRE are unclear. What is New: • Clinical features of SWS children with drug-refractory epilepsy. • In SWS, stroke-like episodes and seizure clusters are risk factors of DRE, the occurrence of status epilepticus impacts the neurological function. [ABSTRACT FROM AUTHOR]

The pathophysiology of septic acute kidney injury (AKI) is very complex and the fatality is high. Nrf2 is crucial for septic AKI, and dihydromyricetin (DMY) has a protective effect on LPS-induced AKI. We aimed to explore whether DMY could affect Nrf2 pathway by regulating miR-199b-3p and played a protective role in septic AKI. The mouse model was induced by cecal ligation and puncture (CLP) and the cell model was stimulated by LPS. Enzyme-linked immunosorbent assay was conducted to examine MDA, SOD, LDH, GSH, TNF-α, kidney injury molecule 1 (KIM-1), and IL-6 levels. The pathological changes were observed by hematoxylin–eosin staining. The targeted relationship between miR-199b-3p and Nrf2 was verified by a dual-luciferase reporter assay. Levels of SOD, GSH, NQO-1, Nrf2, and HO-1 were decreased, MDA, LDH, TNF-α, IL-6, and KIM-1, and miR-199b-3p were increased in the CLP group and LPS-induced HK-2 cells, while the effect was reversed after DMY treatment. There existed renal tubule cell edema and necrosis, inflammatory cell infiltration in the CLP group, the situation was partially improved by DMY. MiR-199b-3p bound to Nrf2. Nrf2 levels were increased, TNF-α, IL-6, and KIM-1 were decreased after transfected with miR-199b-3p inhibitor, these effects were reversed when co-transfected with si-Nrf2. TNF-α, IL-6, KIM-1, and miR-199b-3p levels were increased; Nrf2, NQO-1, and HO-1 levels were decreased in the LPS + DMY + mimics-miR group. MiR-199b-3p was increased in septic AKI models, DMY might alleviate septic AKI by regulating miR-199b-3p to affect the Nrf2 pathway. [ABSTRACT FROM AUTHOR]

Objective: Herpes simplex encephalitis (HSE) is a common form of sporadic encephalitis and is prone to neurological sequelae such as epilepsy in young children, which can have a significant impact on young children at the time of neurological development. This study aimed to analyze the clinical features of HSE in children and to explore its risk factors for post-encephalitic epilepsy (PE). Methods: The case data of children who met the HSE diagnostic criteria between January 2013 and June 2021 at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. Results: The incidence of PE in children with HSE was 42.2% (19/45cases). The initial symptoms were fever with headache or convulsions. In the acute phase, there were 13 cases (28.9%) with psychiatric behavior disorders, 16 cases (35.6%) with neurological deficit symptoms, and 24 cases (53.3%) with altered consciousness. Univariate analysis of fever duration, fever peak, psychiatric behavior disorders, neurological deficit symptoms, acute phase seizures and seizure frequency, ICU length of stay, admission GCS, and cranial imaging in children with HSE indicated statistically significant mixed involvement (all P < 0.05), and multivariate logistic regression analysis suggested that repetitive seizures (more than 5 seizures) (OR = 1.551;95% CI 1.229–1.958, P < 0.001) in the acute phase was an independent risk factor for the occurrence of PE. Conclusion: The main symptoms in children with HSE in the acute phase include seizures, altered consciousness, neurological deficit symptoms, and psychiatric behavioral abnormalities. Children with HSE has a high incidence of PE, especially if they have repetitive seizures (more than 5 seizures) in the acute phase. [ABSTRACT FROM AUTHOR]

Background: Childhood moyamoya disease (MMD) can lead to progressive and irreversible neurological impairment. Early age at onset is likely associated with a worst prognosis of the disease. The study aims to summarize the clinical characteristics of childhood MMD for supporting the diagnosis and treatment of early MMD.Methods: A retrospective study was conducted on children aged zero to 16 years who were diagnosed with MMD in the Department of Neurology and neurosurgery of our hospital from October 2016 to April 2020. The clinical characteristics of children with MMD were summarized for analysis, and the distribution of sex and initial attack type among different age groups was determined by data comparison.Results: The study surveyed 114 children (male to female sex ratio of 1:1.07) with MMD, and 6.1% of them had family history. The mean age of onset was 7.15 ± 3.30 years, and the peak age of onset was five to eight years. The most common initial attack type was transient ischemic attack (TIA) (62 cases, 54.4%) with limb weakness. The incidence of the initial attack type in the three age groups was varied (P < 0.05). The result of overall prognosis was good in 86 cases (89.6%).Conclusions: In this study, MMD cases were mainly ischemic type and TIA was the most common initial attack type. Infant group was more prone to have cerebral infarction, whereas preschool and school-age groups tended to have TIA. The treatments and prognosis of the studied MMD cases were achieved with good outcomes. [ABSTRACT FROM AUTHOR]

Background: Chronic granulomatous disease (CGD) is a rare inherited primary immunodeficiency syndrome, manifested as recurrent infections and inflammatory complications. Although prophylactic treatment with antibiotics and antifungals improved the outcome of CGD patients, infections remain the major cause of mortality.Case Presentation: A boy aged 3 years and 8 months was admitted to hospital complaining of lip swelling with fever for half a month and neck abscess for 11 days. After a thorough examination, severe pneumonia, respiratory failure, oral and maxillofacial space infection, and perianal abscess were confirmed. However, his condition didn't improve after initial comprehensive therapy. Subsequently, overlapping infections of Nocardia farcinica and Aspergillus fumigatus were identified by metagenomic next-generation sequencing. He was treated with imipenem, linezolid, and voriconazole intravenously, plus taking oral compound sulfamethoxazole. Later, his condition improved. Through whole-exome sequencing, the child was ultimately diagnosed as X-linked chronic granulomatous disease (X-CGD) caused by CYBB gene mutation. Allogeneic hematopoietic stem cell transplantation was the potential sanative approach but there were no available human leukocyte antigen compatible donors for the child. The family requested to transfer to a superior hospital for further treatment. Two months later, we followed up the child's family. Unfortunately, the child had expired due to severe infection.Conclusion: To our knowledge, this is the first case of overlapping infection of Nocardia farcinica and Aspergillus fumigatus identified by metagenomic next-generation sequencing in a child with X-CGD from China. For infectious pathogens that are hard to diagnosis by traditional detection methods, metagenomic next-generation sequencing is recommended as an adminicle or indispensable approach for microbial identification. Patients with X-CGD have poor prognosis, early diagnosis and intervention of X-CGD may reduce the mortality. [ABSTRACT FROM AUTHOR]

Emerging evidence has demonstrated the crucial roles of long noncoding RNAs in human cancers, including neuroblastoma (NB). DLX6 antisense RNA 1 (DLX6‐AS1) has been identified as an oncogenic driver in NB. However, the mechanisms of DLX6‐AS1 in NB progression are not fully understood. Our data showed that DLX6‐AS1 was significantly overexpressed in NB tissues and cells. Moreover, DLX6‐AS1 silencing repressed NB cell viability, colony formation, migration, and invasion, and promoted cell cycle arrest and apoptosis in vitro, as well as decreased tumor growth in vivo. Mechanistically, DLX6‐AS1 operated as a miR‐513c‐5p sponge. MiR‐513c‐5p mediated the regulation of DLX6‐AS1 on NB cell malignant progression in vitro. PLK4 was a target of miR‐513c‐5p‐ and DLX6‐AS1‐controlled PLK4 expression via sponging miR‐513c‐5p. Furthermore, the suppressive effect of miR‐513c‐5p overexpression on NB cell malignant progression in vitro was reversed by PLK4 upregulation. Our findings identified a novel regulatory mechanism, the DLX6‐AS1/miR‐513c‐5p/PLK4 axis, in NB progression, highlighting a strong rationale for developing DLX6‐AS1 as a new target for NB management. [ABSTRACT FROM AUTHOR]

The production cost of controlled-release fertilizers is an important factoring limiting their applications. To reduce the coating cost of diammonium phosphate (DAP) and improve its nutrition release characteristics, the fertilizer cores were modified by water polishing with three dosages at 1, 2, and 3%. The effects of modification were evaluated in terms of particle hardness, size distribution, angle of repose and specific surface area. Castor oil-based polyurethane was used as coating material for fertilizer performance evaluation. A pot experiment was conducted to verify the fertilizer efficiency of coated diammonium phosphate (CDAP) with maize. The results showed that polishing with 2% water reduced the angle of repose by 2.48–10.57% and specific surface area by 5.70–48.76%, making it more suitable for coating. The nutrient release period of CDAP was significantly prolonged by 5.36 times. Soil available phosphorous, enzyme activities, maize grain yield, and phosphorous use efficiency were all improved through the blending application of coated and normal phosphate fertilizer. This study demonstrated that water-based surface modification is a low-cost and effective method for improvement and promotion of controlled release P fertilizers. [ABSTRACT FROM AUTHOR]

A rapid expansion of HFMD with enterovirus 71 infection outbreaks has occurred and caused deaths in recent years in China, but no vaccine or antiviral drug is currently available for EV71 infection. This study aims to provide treatment programs for HFMD patients. We conducted a randomized, double-blind, controlled trial and evaluated clinical efficacy of therapy with rHuIFN-α1b in HFMD patients with EV71 infection. There were statistical differences in outcomes including the fever clearance time, healing time of typical skin or oral mucosa lesions, and EV71 viral load of the HFMD patients among ultrasonic aerosol inhalation group, intramuscular injection group and control group. rHuIFN-α1b therapy reduced the fever clearance time, healing time of typical skin or oral mucosa lesions, and EV71 viral load in children with HFMD. Trial Registration: Chinese Clinical Trial Registry [ABSTRACT FROM AUTHOR]

[Display omitted] • An integrative framework was proposed from view of strong sustainability. • The framework can coordinate socio-economic and environmental dimensions well. • Large differences were found among socio-economic and environmental dimensions. Sustainability is related to the coordination of a complex system that constitutes by society, economy, and environment. In particular, environmental factor is frequently considered irreplaceable among them. This paper proposed a framework for regional sustainability assessment by coupling environmental factor and an improved Human Development Index (HDI). The performance of the framework was then analyzed using the 66 counties in the Yangtze River Delta (YRD) in China as a case study. On this basis, spatio-temporal assessment on the regional sustainability was assessed from the dimensions of society, economy, and environment. Results showed that the proposed framework could capture both socio-economic and environmental dimensions well to reflect the regional sustainability in the YRD. Specifically, it showed that sustainability was continuously improved in the YRD from 2000 to 2015. However, the sustainability revealed large differences among distinct dimensions. For instances, socio-economic sustainability was improved in 78.79% of the counties in the YRD from 2000 to 2015, but their environmental sustainability was declining in the same period. Spatially, the overall sustainability of the YRD showed autocorrelations and diverse aggregation characteristics among counties from 2000 to 2015. It is therefore essential to coordinate environment protection and economic development according to each city's characteristic to realize sustainable development in future decades. [ABSTRACT FROM AUTHOR]

[Display omitted] • Applying of BBF (blending CRK and soluble potassium chloride) improved root architect. • Optimal rates of BBF increased wheat leaf area index and photosynthetic capacity. • The auxin and abscisic acid content in the root of BBF regulated the growth of wheat. The crop yields and potassium use efficiency (KUE) could be enhanced by controlled-release potassium chloride (CRK), yet the effects of blending 50 % CRK and 50 % soluble potassium chloride (BBF), on crop physiological-biochemical characteristics were not reported. We carried out a five-year field experiment during 2014–2019 with five K fertilization treatments in a completely randomized block design using wheat (Triticum aestivum. L.) as a testing crop. The results showed that: compared with K1 (full-dose of soluble potassium chloride (KCl)) treatment, the SPAD value and photosynthetic rate of BBF1 (full-dose of BBF) treatment were increased by 7.3–12.2 % and 36.5–59.0 %, respectively, at jointing and grain-filling stages; the auxin and abscisic acid in leaves and roots of BBF1 treatment proliferated by 14.0 %, 27.2 % and 19.5 %, 25.0 %, respectively, at jointing stage; the root total volume and surface area of BBF1 treatment were sharply risen by 80.2 % and 38.8 %, respectively, at jointing stage. The yield and net profit of BBF1 treatment increased by 5.0–19.7 % and 7.2–28.7 %, respectively. With K fertilization rate reduced by 30 %, BBF2 treatment produced almost the same yield as with the 100 % rate of monotypic soluble KCl treatment. This study demonstrated that combining CRK and soluble KCl improved the root physiological characteristics and endogenous hormones of wheat and consequently increased wheat yield. [ABSTRACT FROM AUTHOR]

We report a novel mutation in the electron transfer flavoprotein dehydrogenase (EFTDH) gene in an adolescent Chinese patient with late-onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (MADD) characterized by muscle weakness as early symptom. At the age of 9 years, the patient experienced progressive muscle weakness. Blood creatine kinase level and aminotransferase were higher than normal. The muscle biopsy revealed lipid storage myopathy. Serum acylcarnitine and urine organic acid analyses were consistent with MADD. Genetic mutation analysis revealed a compound heterozygous mutation in EFTDH gene. The patients showed good response to riboflavin and l -carnitine treatment. [ABSTRACT FROM AUTHOR]

• The bio-based polymer film was prepared using starch-based polyol and castor oil. • The starch-based polyol generated micropores in the film, regulated early N release. • Mutual modification regulated nutrient release more accurately. • The bio-based coating material was degradable and has no toxic effect to seeds. Due to the poor controlled release ability, bio-based materials are difficult for large scale application on controlled release fertilizers (CRFs). Starch-based polyol (SP) and castor oil (CO) were mutually modified, and a cross-linked polymer film was formed on the surface of urea by in-situ reaction, which improved the slow release ability of the bio-based material. The results showed that increasing the CO ratio reduced porosity of coating and prolonged the nitrogen (N) release period, while the SP changed the high-temperature wrinkle characteristics and regulated the early N release rate. The mutual modification achieved an ultra-long release period of bio-based CRUs for 7 months. The degradation rate during nine months of bio-based coatings (5.05 %) was significantly higher than that of petroleum-based (3.74 %), and the coating was non-toxic to rice seeds. Mutual modification provided a safe and effective solution for the preparation of bio-based CRFs with long-term controlled release capability. [ABSTRACT FROM AUTHOR]