Comprehensive analysis of PLATZ family genes and their responses to abiotic stresses in Barley.

BACKGROUND: Plant A/T-rich protein and zinc-binding protein (PLATZ) transcription factors are pivotal regulators in various aspects of plant biology, including growth, development, and responses to environmental stresses. While PLATZ genes have been extensively studied and functionally characterized in various plants, limited information is available for these genes in barley. RESULTS: Here, we discovered a total of 11 PLATZ genes distributed across seven chromosomes in barley. Based on phylogenetic and conserved motif analysis, we classified PLATZ into five subfamilies, comprising 3, 1, 2, 1 and 4 genes, respectively. Analysis of gene structure demonstrated that these 11 HvPLATZ genes typically possessed two to four exons. Most HvPLATZ genes were found to possess at least one ABRE cis-element in their promoter regions, and a few of them also contained LTR, CAT-box, MRE, and DRE cis-elements. Then, we conducted an exploration of the expression patterns of HvPLATZs, which displayed notable differences across various tissues and in response to abiotic stresses. Functional analysis of HvPLATZ6 and HvPLATZ8 in yeast cells showed that they may be involved in drought tolerance. Additionally, we constructed a regulatory network including miRNA-targeted gene predictions and identified two miRNAs targeting two HvPLATZs, such as hvu-miR5053 and hvu-miR6184 targeting HvPLATZ2, hvu-miR6184 targeting HvPLATZ10. CONCLUSION: In summary, these findings provide valuable insights for future functional verification of HvPLATZs and contribute to a deeper understanding of the role of HvPLATZs in response to stress conditions in barley.

Redox Activity of Co Species in the Active Sites of CoNx/CoOx Facilitates Oxygen Electrocatalysis for Zn-Air Batteries.

Developing efficient bifunctional oxygen electrocatalysts is crucial for enhancing the performance of rechargeable Zn-air batteries (ZABs). In this study, cobalt/cobalt oxides embedded in N-doped carbon nanofibers (Co/CoOx/NCNFs) were synthesized through a combination of electrospinning and annealing processes. The resulting Co/CoOx/NCNFs catalysts feature abundant CoNx and CoOx active species, leveraging the large specific surface area of nanofibers to facilitate oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). The optimized Co/CoOx/NCNFs-0.1 achieved a half-wave potential (vs. RHE) of 0.82 V and required only 429 mV to reach 10 mA cm-2 in a typical three-electrode system with 0.1 M KOH using an electrochemical workstation equipped with a pine instruments rotator, outperforming the Pt/C+RuO2. The assembled ZABs exhibited high specific capacity (771 mAh gZn -1), substantial power density (981.6 mWh gZn -1), and long-term stability (>325 h). In situ Raman spectroscopy confirmed that the electrocatalytic processes involve the redox activity of Co (II and III) species derived from abundant CoNx and CoOx, elaborating the origin of the catalysts' exceptional oxygen electrocatalysis performance. This work not only presents a straightforward and effective approach for producing bifunctional oxygen electrocatalysts in ZABs but also sheds light on the catalytic mechanisms underlying ORR and OER for CoNx/CoOx-based oxygen electrocatalysts.

Repurposing crizotinib to target RIPK1-dependent cell death.

Receptor-interacting protein kinase 1 (RIPK1) has emerged as a key regulator of cell death and inflammation, which are implicated in the pathogenesis of many inflammatory and degenerative diseases. RIPK1 is therefore a putative therapeutic target in many of these diseases. However, no pharmacological inhibitor of RIPK1-mediated cell death is currently in clinical use. Recognizing that a repurposed drug has an expedited clinical development pipeline, here we performed a high-throughput drug screen of Food and Drug Administration (FDA)-approved compounds and identified a novel use for crizotinib as an inhibitor of RIPK1-dependent cell death. Furthermore, crizotinib rescued TNF-α-induced death in mice with systemic inflammatory response syndrome. RIPK1 kinase activity was directly inhibited by crizotinib. These findings identify a new use for an established compound and are expected to accelerate drug development for RIPK1-spectrum disorders.

Quizartinib inhibits necroptosis by targeting receptor-interacting serine/threonine protein kinase 1.

Systemic inflammatory response syndrome (SIRS), at least in part driven by necroptosis, is characterized by life-threatening multiple organ failure. Blocking the progression of SIRS and consequent multiple organ dysfunction is challenging. Receptor-interacting serine/threonine protein kinase 1 (RIPK1) is an important cell death and inflammatory mediator, making it a potential treatment target in several diseases. Here, using a drug repurposing approach, we show that inhibiting RIPK1 is also an effective treatment for SIRS. We performed cell-based high-throughput drug screening of an US Food and Drug Administration (FDA)-approved drug library that contains 1953 drugs to identify effective inhibitors of necroptotic cell death by SYTOX green staining. Dose-response validation of the top candidate, quizartinib, was conducted in two cell lines of HT-22 and MEFs. The effect of quizartinib on necroptosis-related proteins was evaluated using western blotting, immunoprecipitation, and an in vitro RIPK1 kinase assay. The in vivo effects of quizartinib were assessed in a murine tumor necrosis factor α (TNFα)-induced SIRS model. High-throughput screening identified quizartinib as the top "hit" in the compound library that rescued cells from necroptosis in vitro. Quizartinib inhibited necroptosis by directly inhibiting RIPK1 kinase activity and blocking downstream complex IIb formation. Furthermore, quizartinib protected mice against TNFα-induced SIRS. Quizartinib, as an FDA-approved drug with proven safety and efficacy, was repurposed for targeted inhibition of RIPK1. This work provides essential preclinical data for transferring quizartinib to the treatment of RIPK1-dependent necroptosis-induced inflammatory diseases, including SIRS.

Heteroatom Doping Promoting CoP for Driving Water Splitting.

CoP nanomaterials have been extensively regarded as one of the most promising electrocatalysts for overall water splitting due to their unique bifunctionality. Although the great promise for future applications, some important issues should also be addressed. Heteroatom doping has been widely acknowledged as a potential strategy for improving the electrocatalytic performance of CoP and narrowing the gap between experimental study and industrial applications. Recent years have witnessed the rapid development of heteroatom-doped CoP electrocatalysts for water splitting. Aiming to provide guidance for the future development of more effective CoP-based electrocatalysts, we herein organize a comprehensive review of this interesting field, with the special focus on the effects of heteroatom doping on the catalytic performance of CoP. Additionally, many heteroatom-doped CoP electrocatalysts for water splitting are also discussed, and the structure-activity relationship is also manifested. Finally, a systematic conclusion and outlook is well organized to provide direction for the future development of this interesting field.

Survival Analysis and Immune Differences of HIV Long-Term Non-progressors in Xinjiang China: A 12-Year Prospective Cohort Observation.

This 12-year cohort study of 80 long-term non-progressors (LTNPs) observed a cumulative follow-up duration of 628.5 person-years. Among them, 60 received antiretroviral therapy (ART) for a total of 418.6 person-years. Twenty-four deaths occurred during the follow-up period, with an average age of 42.36 years and a lowest 8-year survival rate of 0.90. Cox model analysis revealed that the risk of AIDS-related death was 1.47 times higher for non-marital, non-commercial heterosexual transmission than for injection drug use. Treatment initiation at ages 31-40 was correlated with an elevated risk of mortality, while treatment for 3-10 years reduced mortality risks in untreated LTNPs. Flow cytometry observed significant differences in the proportion of NK cells. Long-term ART (> 2 years) before LTNPs developed AIDS symptoms could lower mortality risk and potentially extend lifespan, especially when it was initiated at a younger age without affecting NK cell balance. Epidemiological and immunological studies on ART-treated LTNPs are vital for advancing HIV treatment and achieving functional cures for AIDS individuals.

RESUMEN: Este estudio de cohorte de 12 años con 80 no progresores a largo plazo (LTNPs) observó un total acumulado de 628.5 personas-año. De ellos, 60 recibieron terapia antirretroviral (TAR) durante un total de 418.6 personas-año. Se produjeron veinticuatro muertes durante el período del estudio, con una edad promedio de 42.36 años y una tasa de supervivencia más baja de 0.90 a los 8 años. El análisis del modelo de Cox identificó que la transmisión heterosexual no marital ni comercial presentaba un riesgo 1.47 veces mayor de muerte relacionada con el SIDA en comparación con el uso de drogas inyectables. Comenzar el tratamiento entre los 31-40 años mostró incrementos en los riesgos de mortalidad, mientras que 3-10 años de tratamiento redujeron los riesgos de mortalidad en LTNPs no tratados. Se observaron diferencias significativas en las proporciones de células NK desde el punto de vista inmunológico. La TAR a largo plazo (> 2 años) antes de la aparición de síntomas del SIDA en LTNPs podría disminuir el riesgo de mortalidad y potencialmente prolongar la vida, especialmente si se inicia a una edad más temprana sin afectar el equilibrio de las células NK. Los estudios epidemiológicos e inmunológicos sobre LTNPs tratados con TAR son fundamentales para el progreso del tratamiento del VIH y la cura funcional del SIDA.

Liver injury and prolonged hospitalization as indicators of severity in patients with adenovirus infections.

BACKGROUND: Adenovirus (ADV) is a prevalent infective virus in children, accounting for around 5-10% of all cases of acute respiratory illnesses and 4-15% of pneumonia cases in children younger than five years old. Without treatment, severe ADV pneumonia could result in fatality rates of over 50% in cases of emerging strains or disseminated disease. This study aims to uncover the relationship of clinical indicators with primary ADV infection severity, regarding duration of hospitalization and liver injury. METHODS: In this retrospective study, we collected and analyzed the medical records of 1151 in-patients who met the inclusion and exclusion criteria. According to duration of hospitalization, all patients were divided into three groups. Then the difference and correlation of clinical indicators with ADV infection were analyzed, and the relationship among liver injury, immune cells and cytokines was evaluated. RESULTS: The study revealed that patients with a duration of hospitalization exceeding 14 days had the highest percentage of abnormalities across most indicators. This was in contrast to the patients with a hospitalization duration of either less than or equal to 7 days or between 7 and 14 days. Furthermore, correlation analysis indicated that a longer duration of body temperature of ≥ 39°C, bilateral lung lobes infiltration detected by X ray, abnormal levels of AST, PaO2, and SPO2, and a lower age were all predictive of longer hospital stays. Furthermore, an elevated AST level and reduced liver synthesis capacity were related with a longer hospital stay and higher ADV copy number. Additionally, AST/ALT was correlated positively with IFN-γ level and IFN-γ level was only correlated positively with CD4+ T cells. CONCLUSIONS: The study provided a set of predicting indicators for longer duration of hospitalization, which responded for primary severe ADV infection, and elucidated the possible reason for prolonged duration of hospitalization attributing to liver injury via higher ADV copy number, IFN-γ and CD4+ T cells, which suggested the importance of IFN-γ level and liver function monitoring for the patients with primary severe ADV infection.

Results of a Pilot External Quality Assessment Scheme for Genetic Testing of Newborns with Spinal Muscular Atrophy.

BACKGROUND: This study aims to evaluate the ability of laboratories to perform spinal muscular atrophy (SMA) genetic testing in newborns based on dried blood spot (DBS) samples, and to provide reference data and advance preparation for establishing the pilot external quality assessment (EQA) scheme for SMA genetic testing of newborns in China. METHODS: The pilot EQA scheme contents and evaluation principles of this project were designed by National Center for Clinical Laboratories (NCCL), National Health Commission. Two surveys were carried out in 2022, and 5 batches of blood spots were submitted to the participating laboratory each time. All participating laboratories conducted testing upon receiving samples, and test results were submitted to NCCL within the specified date. RESULTS: The return rates were 75.0% (21/28) and 95.2% (20/21) in the first and second surveys, respectively. The total return rate of the two examinations was 83.7% (41/49). Nineteen laboratories (19/21, 90.5%) had a full score passing on the first survey, while in the second survey twenty laboratories (20/20, 100%) scored full. CONCLUSIONS: This pilot EQA survey provides a preliminary understanding of the capability of SMA genetic testing for newborns across laboratories in China. A few laboratories had technical or operational problems in testing. It is, therefore, of importance to strengthen laboratory management and to improve testing capacity for the establishment of a national EQA scheme for newborn SMA genetic testing.

Au/PANI@PtCu-based electrochemical immunosensor for ultrasensitive determination of pro-gastrin-releasing peptide.

An ultrasensitive sandwich-type electrochemical immunosensor for pro-gastrin-releasing peptide (ProGRP) detection was constructed based on PtCu nanodendrites functionalized Au/polyaniline nanospheres (Au/PANI@PtCu). The prepared Au/PANI@PtCu nanocomposites not only possessed excellent electro-catalytic activity of H2O2 reduction due to the synergistic effect between the Au/PANI and PtCu NDs but also provided large specific surface area for detection of antibodies (Ab2) immobilization. In addition, Au nanoparticles encapsulated multi-wall carbon nanotubes (AuNPs@MWCNTs) were also applied to modify the glassy carbon electrode interface for loading numerous capture antibodies (Ab1). In the presence of target ProGRP, a sandwich-type electrochemical immunosensor showed a strong current response from the electro-catalysis of Au/PANI@PtCu toward H2O2 reduction. Benefiting from the exceptional electro-catalytic performance of Au/PANI@PtCu and the high conductivity of AuNPs@MWCNTs, the sandwich-type immunoassay exhibited remarkable sensitivity in detection. The linear range extended from 100 fg/mL to 10 ng/mL, while achieving an impressively low limit of detection of 77.62 fg/mL.

A Multiple Targeting Nanoprobe for Identifying Cancer Metastatic Sites Based on Detection of Various mRNAs in Circulating Tumor Cells.

Identification of cancer metastatic sites is of importance for adjusting therapeutic interventions and treatment choice. However, identifying the location of metastatic lesions with easy accessibility and high safety is challenging. Here we demonstrate that cancer metastatic sites can be accurately detected by a triple targeting nanoprobe. Through coencapsulating molecular beacons probing a cancer biomarker (CXCR4 mRNA), a lung metastatic biomarker (CTSC mRNA), and a bone metastatic biomarker (JAG1 mRNA), the nanoprobe decorated by SYL3C conjugated hyaluronic acid and ICAM-1 specific aptamer conjugated hyaluronic acid can target diverse phenotyped circulating tumor cells (CTCs) during epithelial-mesenchymal and mesenchymal-epithelial transitions in whole blood for sensitive probing. The detection of CTCs from cancer patients shows that the nanoprobe can provide accurate information to distinguish different cancer metastasis statuses including nonmetastasis, lung metastasis, and bone metastasis. This study proposes an efficient screening tool for identifying the location of distant metastatic lesions via facile blood biopsy.

Comparative Long Non-Coding Transcriptome Analysis of Three Contrasting Barley Varieties in Response to Aluminum Stress.

Aluminum toxicity is a major abiotic stress on acidic soils, leading to restricted root growth and reduced plant yield. Long non-coding RNAs are crucial signaling molecules regulating the expression of downstream genes, particularly under abiotic stress conditions. However, the extent to which lncRNAs participate in the response to aluminum (Al) stress in barley remains largely unknown. Here, we conducted RNA sequencing of root samples under aluminum stress and compared the lncRNA transcriptomes of two Tibetan wild barley genotypes, XZ16 (Al-tolerant) and XZ61 (Al-sensitive), as well as the aluminum-tolerant cultivar Dayton. In total, 268 lncRNAs were identified as aluminum-responsive genes on the basis of their differential expression profiles under aluminum treatment. Through target gene prediction analysis, we identified 938 candidate lncRNA-messenger RNA (mRNA) pairs that function in a cis-acting manner. Subsequently, enrichment analysis showed that the genes targeted by aluminum-responsive lncRNAs were involved in diterpenoid biosynthesis, peroxisome function, and starch/sucrose metabolism. Further analysis of genotype differences in the transcriptome led to the identification of 15 aluminum-responsive lncRNAs specifically altered by aluminum stress in XZ16. The RNA sequencing data were further validated by RT-qPCR. The functional roles of lncRNA-mRNA interactions demonstrated that these lncRNAs are involved in the signal transduction of secondary messengers, and a disease resistance protein, such as RPP13-like protein 4, is probably involved in aluminum tolerance in XZ16. The current findings significantly contribute to our understanding of the regulatory roles of lncRNAs in aluminum tolerance and extend our knowledge of their importance in plant responses to aluminum stress.

Comparative Transcriptome Analysis Reveals the Genes and Pathways Related to Wheat Root Hair Length.

Tube-like outgrowths from root epidermal cells, known as root hairs, enhance water and nutrient absorption, facilitate microbial interactions, and contribute to plant anchorage by expanding the root surface area. Genetically regulated and strongly influenced by environmental conditions, longer root hairs generally enhance water and nutrient absorption, correlating with increased stress resistance. Wheat, a globally predominant crop pivotal for human nutrition, necessitates the identification of long root hair genotypes and their regulatory genes to enhance nutrient capture and yield potential. This study focused on 261 wheat samples of diverse genotypes during germination, revealing noticeable disparities in the length of the root hair among the genotypes. Notably, two long root hair genotypes (W106 and W136) and two short root hair genotypes (W90 and W100) were identified. Transcriptome sequencing resulted in the development of 12 root cDNA libraries, unveiling 1180 shared differentially expressed genes (DEGs). Further analyses, including GO function annotation, KEGG enrichment, MapMan metabolic pathway analysis, and protein-protein interaction (PPI) network prediction, underscored the upregulation of root hair length regulatory genes in the long root hair genotypes. These included genes are associated with GA and BA hormone signaling pathways, FRS/FRF and bHLH transcription factors, phenylpropanoid, lignin, lignan secondary metabolic pathways, the peroxidase gene for maintaining ROS steady state, and the ankyrin gene with diverse biological functions. This study contributes valuable insights into modulating the length of wheat root hair and identifies candidate genes for the genetic improvement of wheat root traits.

Genome-Wide Identification and Expression Profiling of the ABF Transcription Factor Family in Wheat (Triticum aestivum L.).

Members of the abscisic acid (ABA)-responsive element (ABRE) binding factor (ABF) and ABA-responsive element binding protein (AREB) families play essential roles in the regulation of ABA signaling pathway activity and shape the ability of plants to adapt to a range of stressful environmental conditions. To date, however, systematic genome-wide analyses focused on the ABF/AREB gene family in wheat are lacking. Here, we identified 35 ABF/AREB genes in the wheat genome, designated TaABF1-TaABF35 according to their chromosomal distribution. These genes were further classified, based on their phylogenetic relationships, into three groups (A-C), with the TaABF genes in a given group exhibiting similar motifs and similar numbers of introns/exons. Cis-element analyses of the promoter regions upstream of these TaABFs revealed large numbers of ABREs, with the other predominant elements that were identified differing across these three groups. Patterns of TaABF gene expansion were primarily characterized by allopolyploidization and fragment duplication, with purifying selection having played a significant role in the evolution of this gene family. Further expression profiling indicated that the majority of the TaABF genes from groups A and B were highly expressed in various tissues and upregulated following abiotic stress exposure such as drought, low temperature, low nitrogen, etc., while some of the TaABF genes in group C were specifically expressed in grain tissues. Regulatory network analyses revealed that four of the group A TaABFs (TaABF2, TaABF7, TaABF13, and TaABF19) were centrally located in protein-protein interaction networks, with 13 of these TaABF genes being regulated by 11 known miRNAs, which play important roles in abiotic stress resistance such as drought and salt stress. The two primary upstream transcription factor types found to regulate TaABF gene expression were BBR/BPC and ERF, which have previously been reported to be important in the context of plant abiotic stress responses. Together, these results offer insight into the role that the ABF/AREB genes play in the responses of wheat to abiotic stressors, providing a robust foundation for future functional studies of these genes.

Iron oxyhydroxide catalyzes production of artificial humic substances from waste biomass.

Production of artificial humic substances (AHS) from waste biomass will contribute to environmental protection and agricultural productivity. However, there is still a lack of a faster, more efficient and eco-friendly way for sustainable production. In this study, we proposed a method to accelerate the production of AHS from cotton stalks by mild pyrolysis and H2O2 oxidation in only 4 hours, and investigated the formation of AHS during biomass transformation. We found that the process increased the aromatic matrix and facilitated biomass transformation by enhancing the depolymerization of lignin into micromolecular phenolics (e.g., guaiacol, p-ethyl guaiacol, etc.). The optimum conditions of pyrolysis at 250 °C and oxidation with 6 mL H2O2 (5 wt%) yielded up to 19.28 ± 1.30 wt% artificial humic acid (AHA) from cotton stalks. In addition, we used iron oxyhydroxide (FeOOH) to catalyze biomass transformation and investigated the effect of FeOOH on the composition and properties of AHS. 1.5 wt% FeOOH promoted the increased content of artificial fulvic acid (AFA) in AHS from 10.1% to 26.5%, eventually improving the activity of AHS. FeOOH raised the content of oxygen-containing groups, such as carboxylic acids and aldehyde, and significantly increased polysaccharide (10.94%-18.95%) and protein (1.95%-2.18%) derivatives. Polymerization of amino acid analogs and many small-molecule carbohydrates (e.g., furans, aldehydes, ketones, and their derivatives) promoted AFA formation. Finally, carbon flow analysis and maize incubation tests confirmed that AHS were expected to achieve carbon emission reductions and reduce environmental pollution from fertilizers. This study provides a sustainable strategy for the accelerated production of AHS, which has important application value for waste biomass resource utilization.

Meta-analysis of the influence of tracheal intubation with cuff and without cuff on the incidence of total wound complications in ICU intubation patients.

At present, it is still controversial whether patients in intensive care unit (ICU) use tracheal intubation with or without cuff. This paper evaluates the effect of tracheal intubation with and without cuff on overall complication rate of patients with intubation in ICU. The database of PubMed, Embase, Conchrane Library and Web of Science was searched by computer, and the clinical research on intubation with and without cuff in ICU was collected. The time range was from the database establishment to November 2023. Literature was independently screened, information was extracted, and quality was assessed by two researchers. Finally, there were nine studies included, with 11 068 patients (7391 in cuff group and 3677 in non-cuff group). The results showed that the overall complication rate of cuff group was significantly lower than that of non-cuff group, and that of cuff group (RR = 0.53, p < 0.01). In addition, compared with the non-cuff group, the cuff group had a lower number of tracheal intubation changes [RR = 0.05, p < 0.01] and a lower incidence of aspiration pneumonia (RR = 0.45, p = 0.01). Compared with the non-cuff group, the cuff group had a higher incidence of oral mucosal ulcers and pharyngitis (RR = 1.99, p = 0.04), while the cuff group had a lower incidence of laryngeal edema (RR = 0.39, p < 0.01). In ICU intubation patients, the use of cuffs reduces overall complication rate in comparison to patients without cuffs. Therefore, patients with intubation in ICU can recommend tracheal intubation with cuff.

Carrier-Free H2 O2 Self-Supplier for Amplified Synergistic Tumor Therapy.

Chemodynamic therapy (CDT) utilizes Fenton or Fenton-like reactions to convert hydrogen peroxide (H2 O2 ) into cytotoxic hydroxyl radicals (•OH) and draws extensive interest in tumor therapy. Nevertheless, high concentrations of glutathione (GSH) and insufficient endogenous H2 O2 often cause unsatisfactory therapeutic efficacy. Herein, a GSH-depleting and H2 O2 self-providing carrier-free nanomedicine that can efficiently load indocyanine green (ICG), ß-lapachone (LAP), and copper ion (Cu2+ ) (ICG-Cu2+ -LAP, LICN) to mediate synergetic photothermal and chemotherapy in enhanced chemodynamic therapy is designed. The results show that  LICNs successfully enter tumors owing to the enhanced permeability and retention effect. Through the reductive intracellular environment, Cu2+ in LICN can react with intracellular GSH, alleviate the antioxidant capacity of tumor tissues, and trigger the release of drugs. When LICN is subjected to near-infrared (NIR) irradiation, enhanced photothermal effect and upregulated expression of NAD(P)H quinone oxidoreductase-1 (NQO1) are observed. Meanwhile, the released LAP not only supports chemotherapy but also catalyzes NQO1 and produces sufficient endogenous H2 O2 , thereby increasing the efficiency of Cu+ -based Fenton-like reaction. Notably, GSH depletion and H2 O2 self-sufficiency generate sufficient •OH and kill tumor cells with high specificity. Overall, the study provides an innovative strategy to self-regulate GSH and H2 O2 levels for effective anticancer therapy.

LncRNA AC142119.1 facilitates the progression of neuroblastoma by epigenetically initiating the transcription of MYCN.

BACKGROUND: Oncogene MYCN is closely related with malignant progression and poor prognosis of neuroblastoma (NB). Recently, long non-coding RNAs (lncRNAs) have been recognized as crucial regulators in various cancers. However, whether lncRNAs contribute to the overexpression of MYCN in NB is unclear. METHODS: Microarray analysis were applied to analyze the differentially expressed lncRNAs between MYCN-amplified and MYCN-non-amplified NB cell lines. Bioinformatic analyses were utilized to identify lncRNAs nearby MYCN locus. qRT-PCR was used to detect the expression level of lncRNA AC142119.1 in NB cell lines and tissues. Gain- and loss-of-function assays were conducted to investigate the biological effect of AC142119.1 in NB. Fluorescence in situ hybridization, RNA pull-down, RNA immunoprecipitation, mass spectrometry, RNA electrophoretic mobility shift, chromatin immunoprecipitation and chromatin isolation by RNA purification assays were performed to validate the interaction between AC142119.1 and WDR5 protein as well as MYCN promoter. RESULTS: AC142119.1 was significantly elevated in NB tissues with MYCN amplification, advanced INSS stage and high risk, and associated with poor survival of NB patients. Moreover, enforced expression of AC142119.1 reinforced the proliferation of NB cells in vitro and in vivo. Additionally, AC142119.1 specifically recruited WDR5 protein to interact with MYCN promoter, further initiating the transcription of MYCN and accelerating NB progression. CONCLUSIONS: We identified a novel lncRNA AC142119.1, which promoted the progression of NB through epigenetically initiating the transcription of MYCN via interacting with both WDR5 protein and the promoter of MYCN, indicating that AC142119.1 might be a potential diagnostic biomarker and therapeutic target for NB.

Systems biological assessment of altered cytokine responses to bacteria and fungi reveals impaired immune functionality in schizophrenia.

Evidence suggests that complex interactions between the immune system and brain have important etiological and therapeutic implications in schizophrenia. However, the detailed cellular and molecular basis of immune dysfunction in schizophrenia remains poorly characterized. To better understand the immune changes and molecular pathways, we systemically compared the cytokine responses of peripheral blood mononuclear cells (PBMCs) derived from patients with schizophrenia and controls against bacterial, fungal, and purified microbial ligands, and identified aberrant cytokine response patterns to various pathogens, as well as reduced cytokine production after stimulation with muramyl dipeptide (MDP) in schizophrenia. Subsequently, we performed single-cell RNA sequencing on unstimulated and stimulated PBMCs from patients and controls and revealed widespread suppression of antiviral and inflammatory programs as well as impaired chemokine/cytokine-receptor interaction networks in various immune cell subpopulations of schizophrenic patients after MDP stimulation. Moreover, serum MDP levels were elevated in these patients and correlated with the course of the disease, suggesting increased bacterial translocation along with disease progression. In vitro assays revealed that MDP pretreatment altered the functional response of normal PBMCs to its re-stimulation, which partially recapitulated the impaired immune function in schizophrenia. In conclusion, we delineated the molecular and cellular landscape of impaired immune function in schizophrenia, and proposed a mutual interplay between innate immune impairment, reduced pathogen clearance, increased MDP translocation along schizophrenia development, and blunted innate immune response. These findings provide new insights into the pathogenic mechanisms that drive systemic immune activation, neuroinflammation, and brain abnormalities in schizophrenia.

Adenoma Detection Rate in Average-Risk Population: An Observational Consecutive Retrospective Study.

BACKGROUND: Although colonoscopy is considered the most effective tool for reducing colorectal cancer-related morbidity, the age at which average-risk individuals begin colonoscopic screening is undetermined. This study aimed to compare the adenoma and advanced adenoma detection rates according to age and sex in a large average-risk population in the rural areas of Eastern China. METHODS: This observational, single-center, retrospective study included patients with average colorectal cancer risk and examined the adenoma and advanced adenoma detection rates using age intervals of 5 years. We also compared the size and age of patients with and without advanced adenoma. RESULTS: We included 18 928 patients with a median age of 54 years (range 15-90 years), including 10 143 men and 8785 women. The adenoma and advanced adenoma detection rates were 17.08% and 5.24%, respectively, and increased with age in the whole population. The adenoma detection rates increased from 8.97% (aged 40-44) to 14.98% (aged 45-49) and 6.24% (aged 45-49) to 11.00% (aged 50-54) in men and women (both P < .001), respectively. The advanced adenoma detection rates increased from 2.19% (aged 40-44) to 4.76% (aged 45-49) and 1.89% (aged 45-49) to 3.13% (aged 50-54) in men (P = .002) and women (P = .056), respectively. Patients with advanced adenomas were significantly older than those with non-advanced adenomas (P < .001). The tumors in the advanced adenoma group were significantly larger than those in the non-advanced adenoma group (P < .001). CONCLUSION: The adenoma and advanced adenoma detection rates increased significantly in average-risk population aged 45 years and older, especially in men.

Spartinivicinus marinus sp. nov., isolated from intertidal sediment.

A Gram-stain-negative, aerobic, flagellated, and long rod-shaped bacterium, designated strain SM1973T, was isolated from an intertidal sediment sample collected from the coast of Qingdao, PR China. Strain SM1973T grew at 15-37 °C and with 0-5.5 % NaCl. It reduced nitrate to nitrite and hydrolysed aesculin but did not hydrolyse casein and gelatin. The strain showed the highest 16S rRNA gene sequence similarity (98.2 %) to the type strain of Spartinivicinus ruber. The phylogenetic trees based on the 16S rRNA genes and single-copy orthologous clusters showed that strain SM1973T clustered with S. ruber, forming a separate lineage within the family Zooshikellaceae. The major cellular fatty acids were summed feature 3 (C16 : 1 ω7с and/or C16 : 1 ω6с) and C16 : 0. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The main respiratory quinone was ubiquinone-9. The genomic DNA G+C content of strain SM1973T was 40.4 mol%. Based on the polyphasic evidence presented in this paper, strain SM1973T is considered to represent a novel species within the genus Spartinivicinus, for which the name Spartinivicinus marinus sp. nov. is proposed. The type strain is SM1973T (=MCCC 1K04833T=KCTC 72846T).