Relationship between clinical features and droplet digital PCR copy number in non-HIV patients with pneumocystis pneumonia.

OBJECTIVE: Droplet digital PCR (ddPCR) is a novel assay to detect pneumocystis jjrovecii (Pj) which has been defined to be more sensitive than qPCR in recent studies. We aimed to explore whether clinical features of pneumocystis pneumonia (PCP) were associated with ddPCR copy numbers of Pj. METHODS: A total of 48 PCP patients were retrospectively included. Pj detection was implemented by ddPCR assay within 4 h. Bronchoalveolar fluid (BALF) samples were collected from 48 patients with molecular diagnosis as PCP via metagenomic next generation sequencing (mNGS) or quantitative PCR detection. Univariate and multivariate logistic regression were performed to screen out possible indicators for the severity of PCP. The patients were divided into two groups according to ddPCR copy numbers, and their clinical features were further analyzed. RESULTS: Pj loading was a pro rata increase with serum (1,3)-beta-D glucan, D-dimmer, neutrophil percentage, procalcitonin and BALF polymorphonuclear leucocyte percentage, while negative correlation with albumin, PaO2/FiO2, BALF cell count, and BALF lymphocyte percentage. D-dimmer and ddPCR copy number of Pj were independent indicators for moderate/severe PCP patients with PaO2/FiO2 lower than 300. We made a ROC analysis of ddPCR copy number of Pj for PaO2/FiO2 index and grouped the patients according to the cut-off value (2.75). The high copy numbers group was characterized by higher level of inflammatory markers. Compared to low copy number group, there was lower level of the total cell count while higher level of polymorphonuclear leucocyte percentage in BALF in the high copy numbers group. Different from patients with high copy numbers, those with high copy numbers had a tendency to develop more severe complications and required advanced respiratory support. CONCLUSION: The scenarios of patients infected with high ddPCR copy numbers of Pj showed more adverse clinical conditions. Pj loading could reflect the severity of PCP to some extent.

Long non-coding RNA HOXC-AS1 exerts its oncogenic effects in esophageal squamous cell carcinoma by interaction with IGF2BP2 to stabilize SIRT1 expression.

BACKGROUND: Long non-coding RNA HOXC cluster antisense RNA 1 (HOXC-AS1) is a novel lncRNA whose cancer-promoting effect in gastric cancer and nasopharyngeal carcinoma has already been demonstrated. However, its functions in esophageal squamous cell carcinoma (ESCC) remains unknown. LncRNAs can interact with RNA-binding proteins (RBPs) and affect gene expression levels through post-transcriptional regulation. Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is a widely studied RBP, and sirtuin 1 also known as SIRT1 has been reported to be involved in cancer progression. METHODS: Establishment of in vivo models, HE and immunohistochemistry staining verified the oncogenic effect of HOXC-AS1. The interaction relationship between HOXC-AS1, IGF2BP2 and SIRT1 was verified by RNA pulldown and RNA immunoprecipitation (RIP) assay. Relative expression and stability changes of genes were detected by qPCR and actinomycin D experiments. Finally, the effect of HOXC-AS1-IGF2BP2-SIRT1 axis on ESCC was verified by rescue experiments. RESULTS: HOXC-AS1 is highly expressed in ESCC cells and plays oncogenic effects in vivo. qPCR showed the positive relationship between HOXC-AS1 and SIRT1 following HOXC-AS1 knockdown or overexpression. RNA-pulldown, mass spectrometry and RIP assay demonstrated that IGF2BP2 is an RBP downstream of HOXC-AS1. Then, RIP and qPCR showed that IGF2BP2 could bind to SIRT1 mRNA and knockdown IGF2BP2 resulted in decreased SIRT1 mRNA level. Finally, a series of rescue assay showed that the HOXC-AS1-IGF2BP2-SIRT1 axis can affect the function of ESCC. CONCLUSION: LncRNA HOXC-AS1 acts as an oncogenic role in ESCC, which impacts ESCC progression by interaction with IGF2BP2 to stabilize SIRT1 expression.

Electrospinning micro-nanofibers immobilized aerobic denitrifying bacteria for efficient nitrogen removal in wastewater.

Electrospinning micro-nanofibers with exceptional physicochemical properties and biocompatibility are becoming popular in the medical field. These features indicate its potential application as microbial immobilized carriers in wastewater treatment. Here, aerobic denitrifying bacteria were immobilized on micro-nanofibers, which were prepared using different concentrations of polyacrylonitrile (PAN) solution (8%, 12% and 15%). The results of diameter distribution, specific surface area and average pore diameter indicated that 15% PAN micro-nanofibers with tighter surface structure were not suitable as microbial carriers. The bacterial load results showed that the cell density (OD600) and total protein of 12% PAN micro-nanofibers were 107.14% and 106.28% higher than those of 8% PAN micro-nanofibers. Subsequently, the 12% PAN micro-nanofibers were selected for aerobic denitrification under the different C/N ratios (1.5-10), and stable performance was obtained. Bacterial community analysis further manifested that the micro-nanofibers effectively immobilized bacteria and enriched bacterial structure under the high C/N ratios. Therefore, the feasibility of micro-nanofibers as microbial carriers was confirmed. This work was of great significance for promoting the application of electrospinning for microbial immobilization in wastewater treatment.

Uncovering the global task-modulated brain network in chunk decomposition with Chinese characters.

Chunk decomposition, which requires the mental representation transformation in accordance with behavioral goals, is of vital importance to problem solving and creative thinking. Previous studies have identified that the frontal, parietal, and occipital cortex in the cognitive control network selectively activated in response to chunk tightness, however, functional localization strategy may overlook the interaction brain regions. Based on the notion of a global brain network, we proposed that multiple specialized regions have to be interconnected to maintain goal representation during the course of chunk decomposition. Therefore, the present study applied a beta-series correlation method to investigate interregional functional connectivity in the event-related design of chunk decomposition tasks using Chinese characters, which would highlight critical nodes irrespective to chunk tightness. The results reveal a network of functional hubs with highly within or between module connections, including the orbitofrontal cortex, superior/inferior parietal lobule, hippocampus, and thalamus. We speculate that the thalamus integrates information across modular as an integrative hub while the orbitofrontal cortex tracks the mental states of chunk decomposition on a moment-to-moment basis. The superior and inferior parietal lobule collaborate to manipulate the mental representation of chunk decomposition and the hippocampus associates the relationship between elements in the question and solution phase. Furthermore, the tightness of chunks is not only associated with different processors in visual systems but also leads to increased intermodular connections in right superior frontal gyrus and left precentral gyrus. To summary up, the present study first reveals the task-modulated brain network of chunk decomposition in addition to the tightness-related nodes in the frontal and occipital cortex.

Expression and prognostic significance of m6A-related genes in TP53-mutant non-small-cell lung cancer.

BACKGROUND: TP53 is an important tumor suppressor gene on human 17th chromosome with its mutations more than 60% in tumor cells. Lung cancer is the highest incidence malignancy in men around the world. N-6 methylase (m6A) is an enzyme that plays an important role in mRNA splicing, translation, and stabilization. However, its role in TP53-mutant non-small-cell lung cancer (NSCLC) remains unknown. METHOD: First, we investigated 17 common m6A regulators' prognostic values in NSCLC. Then, after the establishment of risk signature, we explored the diagnostic value of m6A in TP53-mutant NSCLC. Finally, gene set enrichment analysis (GSEA), gene ontology (GO) enrichment analysis, and differential expression analysis were used to reveal the possible mechanism of m6A regulators affecting TP53-mutant NSCLC patients. RESULTS: Study showed that nine m6A regulators (YTHDC2, METTL14, FTO, METTL16, YTHDF1, HNRNPA2B1, RBM15, KIAA1429, and WTAP) were expressed differently between TP53-mutant and wild-type NSCLC (p < 0.05); and ALKBH5 and HNRNPA2B1 were associated with the prognostic of TP53-mutant patients. After construction of the risk signature combined ALKBH5 and HNRNPA2B1, we divided patients with TP53 mutations into high- and low-risk groups, and there was a significant survival difference between two groups. Finally, 338 differentially expression genes (DEGs) were found between high- and low-risk groups. GO enrichment analysis, PPI network, and GSEA enrichment analysis showed that m6A may affect the immune environment in extracellular and change the stability of mRNA. CONCLUSION: In conclusion, m6A regulators can be used as prognostic predictors in TP53-mutant patients.

Long non-coding RNA LINC01559 exerts oncogenic role via enhancing autophagy in lung adenocarcinoma.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been verified to play fatal role in regulating the progression of lung adenocarcinoma (LUAD). Although lncRNAs play important role in regulating the autophagy of tumor cells, the function and molecular mechanism of LINC01559 in regulating lung cancer development remain to be elucidated. METHOD AND MATERIALS: In this study, we used bioinformatics to screen out autophagy-related lncRNAs from TCGA-LUAD repository. Then the least absolute shrinkage and selection operator (LASSO) regression was applied to establish the signature of autophagy-related lncRNAs so that clinical characteristics and survival in LUAD patients be evaluated. Finally, we selected the most significant differences lncRNA, LINC01559, to verify its function in regulating LUAD progression in vitro. RESULTS: We found high expression of LINC01559 indicates lymph node metastasis and poor prognosis. Besides, LINC01559 promotes lung cancer cell proliferation and migration in vitro, by enhancing autophagy signal pathway via sponging hsa-miR-1343-3p. CONCLUSION: We revealed a novel prognostic model based on autophagy-related lncRNAs, and provide a new therapeutic target and for patients with lung adenocarcinoma named LINC01559.

N-6 methylation-related lncRNA is potential signature in lung adenocarcinoma and influences tumor microenvironment.

BACKGROUND: N-6 methylation (m6A) pushes forward an immense influence on the occurrence and development of lung adenocarcinoma (LUAD). However, the methylation on non-coding RNA in LUAD, especially long non-coding RNA (lncRNA), has not been received sufficient attention. METHODS: Spearman correlation analysis was used to screen lncRNA correlated with m6A regulators expression from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) repositories, respectively. Then, the least absolute shrinkage and selection operator (LASSO) was applied to build a risk signature consisting m6A-related lncRNA. Univariate and multivariate independent prognostic analysis were applied to evaluate the performance of signature in predicting patients' survival. Next, we applied Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) to conduct pathway enrichment analysis of 3344 different expression genes (DEGs). Finally, we set up a competing endogenous RNAs (ceRNA) network to this lncRNA. RESULTS: A total of 85 common lncRNAs were selected to acquire the components related to prognosis. The final risk signature established by LASSO regression contained 11 lncRNAs: ARHGEF26-AS1, COLCA1, CRNDE, DLGAP1-AS2, FENDRR, LINC00968, TMPO-AS1, TRG-AS1, MGC32805, RPARP-AS1, and TBX5-AS1. M6A-related lncRNA risk score could predict the prognostic of LUAD and was significantly associated with clinical pathological. And in the evaluation of lung adenocarcinoma tumor microenvironment (TME) by using ESTIMATE algorithm, we found a statistically significant correlation between risk score and stromal/immune cells. CONCLUSION: M6A-related lncRNA was a potential prognostic and therapy target for lung adenocarcinoma.

Efficient tandem electroreduction of nitrate into ammonia through coupling Cu single atoms with adjacent Co3O4.

The nitrate (NO3-) electroreduction into ammonia (NH3) represents a promising approach for sustainable NH3 synthesis. However, the variation of adsorption configurations renders great difficulties in the simultaneous optimization of binding energy for the intermediates. Though the extensively reported Cu-based electrocatalysts benefit NO3- adsorption, one of the key issues lies in the accumulation of nitrite (NO2-) due to its weak adsorption, resulting in the rapid deactivation of catalysts and sluggish kinetics of subsequent hydrogenation steps. Here we report a tandem electrocatalyst by combining Cu single atoms catalysts with adjacent Co3O4 nanosheets to boost the electroreduction of NO3- to NH3. The obtained tandem catalyst exhibits a yield rate for NH3 of 114.0 mg NH 3 h-1 cm-2, which exceeds the previous values for the reported Cu-based catalysts. Mechanism investigations unveil that the combination of Co3O4 regulates the adsorption configuration of NO2- and strengthens the binding with NO2-, thus accelerating the electroreduction of NO3- to NH3.

Ferroptosis-associated circular RNAs: Opportunities and challenges in the diagnosis and treatment of cancer.

Ferroptosis is an emerging form of non-apoptotic regulated cell death which is different from cell death mechanisms such as autophagy, apoptosis and necrosis. It is characterized by iron-dependent lipid peroxide accumulation. Circular RNA (circRNA) is a newly studied evolutionarily conserved type of non-coding RNA with a covalent closed-loop structure. It exhibits universality, conservatism, stability and particularity. At present, the functions that have been studied and found include microRNA sponge, protein scaffold, transcription regulation, translation and production of peptides, etc. CircRNA can be used as a biomarker of tumors and is a hotspot in RNA biology research. Studies have shown that ferroptosis can participate in tumor regulation through the circRNA molecular pathway and then affect cancer progression, which may become a direction of cancer diagnosis and treatment in the future. This paper reviews the molecular biological mechanism of ferroptosis and the role of circular RNA in tumors and summarizes the circRNA related to ferroptosis in tumors, which may inspire research prospects for the precise prevention and treatment of cancer in the future.

TMEM44-AS1 promotes esophageal squamous cell carcinoma progression by regulating the IGF2BP2-GPX4 axis in modulating ferroptosis.

The long non-coding RNA (lncRNA) TMEM44-AS1 is a novel lncRNA whose pro-carcinogenic role in gastric cancer and glioma has been demonstrated. However, its function in esophageal squamous cell carcinoma (ESCC) is unknown. In this study, we identified that TMEM44-AS1 was highly expressed in ESCC tissues and cells. Functionally, TMEM44-AS1 promoted ESCC cell proliferation, invasion and metastasis in vitro and in vivo. TMEM44-AS1 inhibited ferroptosis in ESCC cells, and ferroptosis levels were significantly increased after knockdown of TMEM44-AS1. Mechanistically, TMEM44-AS1 was positively correlated with GPX4 expression, and TMEM44-AS1 could bind to the RNA-binding protein IGF2BP2 to enhance the stability of GPX4 mRNA, thereby affecting ferroptosis and regulating the malignant progression of ESCC. In summary, this study reveals the TMEM44-AS1-IGF2BP2-GPX4 axis could influence cancer progression in ESCC. TMEM44-AS1 can be used as a potential treatment target against ESCC.

Electrosynthesis of polymer-grade ethylene via acetylene semihydrogenation over undercoordinated Cu nanodots.

The removal of acetylene impurities remains important yet challenging to the ethylene downstream industry. Current thermocatalytic semihydrogenation processes require high temperature and excess hydrogen to guarantee complete acetylene conversion. For this reason, renewable electricity-based electrocatalytic semihydrogenation of acetylene over Cu-based catalysts is an attractive route compared to the energy-intensive thermocatalytic processes. However, active Cu electrocatalysts still face competition from side reactions and often require high overpotentials. Here, we present an undercoordinated Cu nanodots catalyst with an onset potential of -0.15 V versus reversible hydrogen electrode that can exclusively convert C2H2 to C2H4 with a maximum Faradaic efficiency of ~95.9% and high intrinsic activity in excess of -450 mA cm-2 under pure C2H2 flow. Subsequently, we successfully demonstrate simulated crude ethylene purification, continuously producing polymer-grade C2H4 with <1 ppm C2H2 for 130 h at a space velocity of 1.35 × 105 ml gcat-1 h-1. Theoretical calculations and in situ spectroscopies reveal a lower energy barrier for acetylene semihydrogenation over undercoordinated Cu sites than nondefective Cu surface, resulting in the excellent C2H2-to-C2H4 catalytic activity of Cu nanodots.

Shared increased entropy of brain signals across patients with different mental illnesses: A coordinate-based activation likelihood estimation meta-analysis.

Entropy is a measurement of brain signal complexity. Studies have found increased/decreased entropy of brain signals in psychiatric patients. There is no consistent conclusion regarding the relationship between the entropy of brain signals and mental illness. Therefore, this meta-analysis aimed to identify consistent abnormalities in the brain signal entropy in patients with different mental illnesses. We conducted a systematic search to collect resting-state functional magnetic resonance imaging (rs-fMRI) studies in patients with psychiatric disorders. This work identified 9 eligible rs-fMRI studies, which included a total of 14 experiments, 67 activation foci, and 1383 subjects. We tested the convergence across their findings by using the activation likelihood estimation method. P-value maps were corrected by using cluster-level family-wise error p < 0.05 and permuting 2000 times. Results showed that patients with different psychiatric disorders shared commonly increased entropy of brain signals in the left inferior and middle frontal gyri, and the right fusiform gyrus, cuneus, precuneus. No shared alterations were found in the subcortical regions and cerebellum in the patient group. Our findings suggested that the increased entropy of brain signals in the cortex, not subcortical regions and cerebellum, might have associations with the pathophysiology across mental illnesses. This meta-analysis study provided the first comprehensive understanding of the abnormality in brain signal complexity across patients with different psychiatric disorders.

A multi-modal open dataset for mental-disorder analysis.

According to the WHO, the number of mental disorder patients, especially depression patients, has overgrown and become a leading contributor to the global burden of disease. With the rising of tools such as artificial intelligence, using physiological data to explore new possible physiological indicators of mental disorder and creating new applications for mental disorder diagnosis has become a new research hot topic. We present a multi-modal open dataset for mental-disorder analysis. The dataset includes EEG and recordings of spoken language data from clinically depressed patients and matching normal controls, who were carefully diagnosed and selected by professional psychiatrists in hospitals. The EEG dataset includes data collected using a traditional 128-electrodes mounted elastic cap and a wearable 3-electrode EEG collector for pervasive computing applications. The 128-electrodes EEG signals of 53 participants were recorded as both in resting state and while doing the Dot probe tasks; the 3-electrode EEG signals of 55 participants were recorded in resting-state; the audio data of 52 participants were recorded during interviewing, reading, and picture description.

Synergistic Effects of APOE and CLU May Increase the Risk of Alzheimer's Disease: Acceleration of Atrophy in the Volumes and Shapes of the Hippocampus and Amygdala.

BACKGROUND: The volume loss of the hippocampus and amygdala in non-demented individuals has been reported to increase the risk of developing Alzheimer's disease (AD). Many neuroimaging genetics studies mainly focused on the individual effects of APOE and CLU on neuroimaging to understand their neural mechanisms, whereas their synergistic effects have been rarely studied. OBJECTIVE: To assess whether APOE and CLU have synergetic effects, we investigated the epistatic interaction and combined effects of the two genetic variants on morphological degeneration of hippocampus and amygdala in the non-demented elderly at baseline and 2-year follow-up. METHODS: Besides the widely-used volume indicator, the surface-based morphometry method was also adopted in this study to evaluate shape alterations. RESULTS: Our results showed a synergistic effect of homozygosity for the CLU risk allele C in rs11136000 and APOEɛ4 on the hippocampal and amygdalar volumes during a 2-year follow-up. Moreover, the combined effects of APOEɛ4 and CLU C were stronger than either of the individual effects in the atrophy progress of the amygdala. CONCLUSION: These findings indicate that brain morphological changes are caused by more than one gene variant, which may help us to better understand the complex endogenous mechanism of AD.