Energy demand forecasting using convolutional neural network and modified war strategy optimization algorithm.

Predicting the electricity demand is a key responsibility for the energy industry and governments in order to provide an effective and dependable energy supply. Traditional projection techniques frequently rely on mathematical models, which are limited in their ability to recognize complex patterns and correlations in data. Machine learning has emerged as a viable tool for estimating electricity in the last decade. In this study, the Modified War Strategy Optimization-Based Convolutional Neural Network (MWSO-CNN) has been provided for electricity demand prediction. To increase the precision of electricity demand prediction, the MWSO-CNN approach integrates the benefits of the modified war strategy optimization technique and the convolutional neural network. To improve efficiency, the modified war strategy optimization technique is employed to adjust the hyperparameters of the CNN algorithm. The suggested MWSO-CNN approach is tested on a real-world electricity demand dataset, and the findings show that it outperforms many state-of-the-art machine learning techniques for predicting electricity demand. In general, the suggested MWSO-CNN approach could offer a successful and cost-effective strategy for predicting energy consumption, which will benefit both the energy business and society as a whole.

Knockdown of NR4A1 alleviates doxorubicin-induced cardiotoxicity through inhibiting the activation of the NLRP3 inflammasome.

Doxorubicin (DOX) is a widely used antitumor drug, but its clinical applicability is hampered by the unfortunate side effect of DOX-induced cardiotoxicity (DIC). In our current study, we retrieved three high-throughput sequencing datasets related to DIC from the Gene Expression Omnibus (GEO) datasets. We conducted differential analysis using R (DESeq2) to pinpoint differentially expressed genes (DEGs, and identified 11 genes that were consistently altered in both the control and DOX-treated groups. Notably, our Random Forest analysis of these three GEO datasets highlighted the significance of nuclear receptor subfamily 4 group A member 1 (NR4A1) in the context of DIC. The DOX-induced mouse model and cell model were used for the in vivo and in vitro studies to reveal the role of NR4A1 in DIC. We found that silencing NR4A1 by adeno-associated virus serotype 9 (AAV9) contained shRNA in vivo alleviated the DOX-induced cardiac dysfunction, cardiomyocyte injury and fibrosis. Mechanistically, we found NR4A1 silencing was able to inhibit DOX-induced the cleavage of NLRP3, IL-1ß and GSDMD in vivo. Further in vitro studies have shown that inhibition of NR4A1 suppressed DOX-induced cytotoxicity and oxidative stress through the same molecular mechanism. We prove that NR4A1 plays a critical role in DOX-induced cardiotoxicity by inducing pyroptosis via activation of the NLRP3 inflammasome, and it might be a promising therapeutic target for DIC.

Single-cell RNA-seq reveals MIF-(CD74 + CXCR4) dependent inhibition of macrophages in metastatic papillary thyroid carcinoma.

BACKGROUND: The mechanism promoting papillary thyroid carcinoma (PTC) metastasis remains unclear. We aimed to investigate the potential metastatic mechanisms at a single-cell resolution. METHODS: We performed single-cell RNA-seq (scRNA-seq) profiling of thyroid tumour (TT), adjacent normal thyroid (NT) and lymph node metastasized tumour (LN) from a young female with PTC. Validation of our results was conducted in 31 tumours with metastasis and 30 without metastasis. RESULTS: ScRNA-seq analysis generated data on 38,215 genes and 0.14 billion transcripts from 28,839 cells, classified into 18 clusters, each annotated to represent 10 cell types. PTC cells were found to originate from epithelial cells. Epithelial cells and macrophages emerged as the strongest signal emitters and receivers, respectively. After reclustering epithelial cells and macrophages, our analysis, incorporating gene set variation analysis (GSVA), SCENIC analysis, and pseudotime trajectory analysis, indicated that subcluster 0 of epithelial cells (EP_0) showed a more malignant phenotype, and subclusters 3 and 4 of macrophages (M_3 and M_4) demonstrated heightened activity. Further analysis suggested that EP_0 may suppress the activity of M_3 and M_4 via MIF - (CD74 + CXCR4) in the MIF pathway. After analysing the expression of the 4 genes in the MIF pathway in both the TCGA cohort and our cohort (n = 61), CD74 was identified as significantly overexpressed in PTC tumours particularly those with lymph node metastasis. CONCLUSION: Our study revealed that PTC may facilitate lymph node metastasis by inhibiting macrophages via MIF signalling. It is suggested that malignant PTC cells may suppress the immune activity of macrophages by consistently releasing signals to them via MIF-(CD74 + CXCR4).

Emerging roles of ferroptosis in male reproductive diseases.

Ferroptosis is a type of programmed cell death mediated by iron-dependent lipid peroxidation that leads to excessive lipid peroxidation in different cells. Ferroptosis is distinct from other forms of cell death and is associated with various diseases. Iron is essential for spermatogenesis and male reproductive function. Therefore, it is not surprising that new evidence supports the role of ferroptosis in testicular injury. Although the molecular mechanism by which ferroptosis induces disease is unknown, several genes and pathways associated with ferroptosis have been linked to testicular dysfunction. In this review, we discuss iron metabolism, ferroptosis, and related regulatory pathways. In addition, we analyze the endogenous and exogenous factors of ferroptosis in terms of iron metabolism and testicular dysfunction, as well as summarize the relationship between ferroptosis and male reproductive dysfunction. Finally, we discuss potential strategies to target ferroptosis for treating male reproductive diseases and provide new directions for preventing male reproductive diseases.

Nitrate removal in iron sulfide-driven autotrophic denitrification biofilter: Biochemical and chemical transformation pathways and its underlying microbial mechanism.

Iron sulfides-based autotrophic denitrification (IAD) is effective for treating nitrate-contaminated wastewater. However, the complex nitrate transformation pathways coupled with sulfur and iron cycles in IADs are still unclear. In this study, two columns (abiotic vs biotic) with iron sulfides (FeS) as the packing materials were constructed and operated continuously. In the abiotic column, FeS chemically reduced nitrate to ammonium under the ambient condition; this chemical reduction reaction pathway was spontaneous and has been overlooked in IAD reactors. In the biotic column (IAD biofilter), the complex nitrogen-transformation network was composed of chemical reduction, autotrophic denitrification, dissimilatory nitrate reduction to ammonium (DNRA) and sulfate reducing ammonium oxidation (Sulfammox). Metagenomic analysis and XPS characterization of the IAD biofilter further validated the roles of functional microbial communities (e.g., Acidovorax, Diaphorobacter, Desulfuromonas) in nitrate reduction process coupled with iron and sulfur cycles. This study gives an in-depth insight into the nitrogen transformations in IAD system and provides fundamental evidence about the underlying microbial mechanism for its further application in biological nitrogen removal.

Structural basis of human PRPS2 filaments.

BACKGROUND: PRPP synthase (PRPS) transfers the pyrophosphate groups from ATP to ribose-5-phosphate to produce 5-phosphate ribose-1-pyrophosphate (PRPP), a key intermediate in the biosynthesis of several metabolites including nucleotides, dinucleotides and some amino acids. There are three PRPS isoforms encoded in human genome. While human PRPS1 (hPRPS1) and human PRPS2 (hPRPS2) are expressed in most tissues, human PRPS3 (hPRPS3) is exclusively expressed in testis. Although hPRPS1 and hPRPS2 share 95% sequence identity, hPRPS2 has been shown to be less sensitive to allosteric inhibition and specifically upregulated in certain cancers in the translational level. Recent studies demonstrate that PRPS can form a subcellular compartment termed the cytoophidium in multiple organisms across prokaryotes and eukaryotes. Forming filaments and cytoophidia is considered as a distinctive mechanism involving the polymerization of the protein. Previously we solved the filament structures of Escherichia coli PRPS (ecPRPS) using cryo-electron microscopy (cryo-EM) 1. RESULTS: Order to investigate the function and molecular mechanism of hPRPS2 polymerization, here we solve the polymer structure of hPRPS2 at 3.08 Å resolution. hPRPS2 hexamers stack into polymers in the conditions with the allosteric/competitive inhibitor ADP. The binding modes of ADP at the canonical allosteric site and at the catalytic active site are clearly determined. A point mutation disrupting the inter-hexamer interaction prevents hPRPS2 polymerization and results in significantly reduced catalytic activity. CONCLUSION: Findings suggest that the regulation of hPRPS2 polymer is distinct from ecPRPS polymer and provide new insights to the regulation of hPRPS2 with structural basis.

Coordinated Patient Care via Mobile Phone-Based Telemedicine in Secondary Stroke Prevention: A Propensity Score-Matched Cohort Study.

BACKGROUND: To prevent recurrent stroke, patients need to follow evidence-based practices following discharge; however, adherence to these practices is suboptimal. PURPOSE: To evaluate whether a smartphone mobile application can improve medication adherence and stroke awareness in secondary stroke prevention. METHODS: A retrospective study design was used. Patients with ischemic stroke registered in a database between August 2018 and January 2019 were enrolled. Propensity score matching was used to match patients managed with the mobile application compared with regular practice in a 1:2 ratio. RESULTS: Sixty-five patients were paired with 123 controls. Three-month medication adherence was 93.8% in the application group versus 82.9% in the control group ( P = .036). Patients in the application group were more likely to know stroke warning signs ( P = .003) and when to call an ambulance for stroke symptoms (87.7% vs 72.4%, P = .016). CONCLUSIONS: Using a mobile application may increase medication adherence and stroke awareness in secondary stroke prevention.

Oncogenic KRAS signaling drives evasion of innate immune surveillance in lung adenocarcinoma by activating CD47.

KRAS is one of the most frequently activated oncogenes in human cancers. Although the role of KRAS mutation in tumorigenesis and tumor maintenance has been extensively studied, the relationship between KRAS and the tumor immune microenvironment is not fully understood. Here, we identified a role of KRAS in driving tumor evasion from innate immune surveillance. In samples of lung adenocarcinoma from patients and Kras-driven genetic mouse models of lung cancer, mutant KRAS activated the expression of cluster of differentiation 47 (CD47), an antiphagocytic signal in cancer cells, leading to decreased phagocytosis of cancer cells by macrophages. Mechanistically, mutant KRAS activated PI3K/STAT3 signaling, which restrained miR-34a expression and relieved the posttranscriptional repression of miR-34a on CD47. In 3 independent cohorts of patients with lung cancer, the KRAS mutation status positively correlated with CD47 expression. Therapeutically, disruption of the KRAS/CD47 signaling axis with KRAS siRNA, the KRASG12C inhibitor AMG 510, or a miR-34a mimic suppressed CD47 expression, enhanced the phagocytic capacity of macrophages, and restored innate immune surveillance. Our results reveal a direct mechanistic link between active KRAS and innate immune evasion and identify CD47 as a major effector underlying the KRAS-mediated immunosuppressive tumor microenvironment.

BMP4 is insufficient to differentiate umbilical cord mesenchymal stem cells into germ cell-like cells in vitro.

OBJECTIVES: Mesenchymal stem cell (MSC)-based therapies are expected to restore the fertility of infertile patients. In addition to MSC-derived paracrine effects to improve reproductive function, the differentiation of MSCs into germ cell (GC)-like cells is still a promising method to repair the injured reproductive system. The aim of this study was to examine the effect and potential mechanism of BMP4 in inducing umbilical cord MSC (UcMSC) transdifferentiation into GC-like cells. MATERIAL AND METHODS: UcMSCs were isolated, cultured and identified by flow cytometry and multilineage differentiation assays. After induction with 12.5 ng/mL BMP4 for 21 days, UcMSCs were collected for further examination. Immunofluorescence was used to detect the expression of Prdm1 and Prdm14; RT-PCR and RNA sequencing were used to detect differential gene expression (DEGs). RESULTS: The morphology of UcMSCs became large and flat after treatment with BMP4; the expression of GC-related genes (OCT4, Prdm1, Ifitm3 and Stella) was significantly downregulated, and further immunofluorescence results also confirmed the significant downregulation of Prdm1 in UcMSCs with BMP4 induction, while the expression of Prdm14 was significantly upregulated. The results of RNA sequencing and further analysis revealed no explicit correlation between BMP4 induction and the differentiation of UcMSCs into GC-like cells based on the 662 screened DEGs in UcMSCs with or without BMP4 induction. CONCLUSIONS: The differentiation of MSCs into GC-like cells is rather complex, and BMP4 alone is insufficient to induce UcMSCs to differentiate into GC-like cells, regardless of protein level or gene expression level.

Filamentation modulates allosteric regulation of PRPS.

Phosphoribosyl pyrophosphate (PRPP) is a key intermediate in the biosynthesis of purine and pyrimidine nucleotides, histidine, tryptophan, and cofactors NAD and NADP. Abnormal regulation of PRPP synthase (PRPS) is associated with human disorders, including Arts syndrome, retinal dystrophy, and gouty arthritis. Recent studies have demonstrated that PRPS can form filamentous cytoophidia in eukaryotes. Here, we show that PRPS forms cytoophidia in prokaryotes both in vitro and in vivo. Moreover, we solve two distinct filament structures of E. coli PRPS at near-atomic resolution using Cryo-EM. The formation of the two types of filaments is controlled by the binding of different ligands. One filament type is resistant to allosteric inhibition. The structural comparison reveals conformational changes of a regulatory flexible loop, which may regulate the binding of the allosteric inhibitor and the substrate ATP. A noncanonical allosteric AMP/ADP binding site is identified to stabilize the conformation of the regulatory flexible loop. Our findings not only explore a new mechanism of PRPS regulation with structural basis, but also propose an additional layer of cell metabolism through PRPS filamentation.

Evaluation of Left Ventricular Systolic Function in Patients with Coronary Microvascular Dysfunction by Three-Dimensional Speckle-Tracking Imaging

Abstract Introduction: The objective of this study is to evaluate the left ventricular systolic function of patients with coronary microvascular dysfunction (CMD) using the three-dimensional speckle-tracking imaging (3D-STI) technique. Methods: From June 2018 to June 2019,72 subjects from Huzhou Central Hospital were enrolled, including 42 CMD in-patients with typical chest pain or chest tightness and positive treadmill exercise stress test, but without coronary stenosis on coronary angiography, (the CMD group) and another 30 healthy individuals who were undergoing physical examinations in an outpatient clinic (the control group). Using 3D-STI technique, the global longitudinal strain (GLS), global radial strain (GRS), global circumferential strain (GCS), global area strain (GAS), and left ventricle were measured. Results: Compared with the control group, GLS and GAS were significantly reduced in the CMD group (P<0.05), while GRS and GCS were similar in both groups (P>0.05). Univariate logistic regression analysis showed that GLS and GAS were the influencing factors of CMD. For the diagnosis of CMD, the area under the receiver operating characteristic (ROC) curve of GLS was 0.883, and the area under the ROC curve of GAS was 0.875. GAS of -29.3% (log-rank test chi-square=34.245, P<0.001) was a strong predictor of major adverse cardiac events. Conclusion: 3D-STI technique has obvious advantages in the evaluation of the left ventricular systolic function for CMD patients. Moreover, 3D-STI parameters, especially GLS and GAS, can detect the early abnormal changes in the ischaemic myocardium. Being timelier and more sensitive than echocardiography, 3D-STI should be recommended for clinical application.

Accurate quantification of 3'-terminal 2'-O-methylated small RNAs by utilizing oxidative deep sequencing and stem-loop RT-qPCR.

The continuing discoveries of novel classes of RNA modifications in various organisms have raised the need for improving sensitive, convenient, and reliable methods for quantifying RNA modifications. In particular, a subset of small RNAs, including microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), are modified at their 3'-terminal nucleotides via 2'-O-methylation. However, quantifying the levels of these small RNAs is difficult because 2'-O-methylation at the RNA 3'-terminus inhibits the activity of polyadenylate polymerase and T4 RNA ligase. These two enzymes are indispensable for RNA labeling or ligation in conventional miRNA quantification assays. In this study, we profiled 3'-terminal 2'-O-methyl plant miRNAs in the livers of rice-fed mice by oxidative deep sequencing and detected increasing amounts of plant miRNAs with prolonged oxidation treatment. We further compared the efficiency of stem-loop and poly(A)-tailed RT-qPCR in quantifying plant miRNAs in animal tissues and identified stem-loop RT-qPCR as the only suitable approach. Likewise, stem-loop RT-qPCR was superior to poly(A)-tailed RT-qPCR in quantifying 3'-terminal 2'-O-methyl piRNAs in human seminal plasma. In summary, this study established a standard procedure for quantifying the levels of 3'-terminal 2'-O-methyl miRNAs in plants and piRNAs. Accurate measurement of the 3'-terminal 2'-O-methylation of small RNAs has profound implications for understanding their pathophysiologic roles in biological systems.

Structural basis of dynamic P5CS filaments.

The bifunctional enzyme Δ1-pyrroline-5-carboxylate synthase (P5CS) is vital to the synthesis of proline and ornithine, playing an essential role in human health and agriculture. Pathogenic mutations in the P5CS gene (ALDH18A1) lead to neurocutaneous syndrome and skin relaxation connective tissue disease in humans, and P5CS deficiency seriously damages the ability to resist adversity in plants. We have recently found that P5CS forms cytoophidia in vivo and filaments in vitro. However, it is difficult to appreciate the function of P5CS filamentation without precise structures. Using cryo-electron microscopy, here we solve the structures of Drosophila full-length P5CS in three states at resolution from 3.1 to 4.3 Å. We observe distinct ligand-binding states and conformational changes for the GK and GPR domains, respectively. Divergent helical filaments are assembled by P5CS tetramers and stabilized by multiple interfaces. Point mutations disturbing those interfaces prevent P5CS filamentation and greatly reduce the enzymatic activity. Our findings reveal that filamentation is crucial for the coordination between the GK and GPR domains, providing a structural basis for the catalytic function of P5CS filaments.

Paternal environmental exposure-induced spermatozoal small noncoding RNA alteration meditates the intergenerational epigenetic inheritance of multiple diseases.

Studies of human and mammalian have revealed that environmental exposure can affect paternal health conditions as well as those of the offspring. However, studies that explore the mechanisms that meditate this transmission are rare. Recently, small noncoding RNAs (sncRNAs) in sperm have seemed crucial to this transmission due to their alteration in sperm in response to environmental exposure, and the methodology of microinjection of isolated total RNA or sncRNAs or synthetically identified sncRNAs gradually lifted the veil of sncRNA regulation during intergenerational inheritance along the male line. Hence, by reviewing relevant literature, this study intends to answer the following research concepts: (1) paternal environmental factors that can be passed on to offspring and are attributed to spermatozoal sncRNAs, (2) potential role of paternal spermatozoal sncRNAs during the intergenerational inheritance process, and (3) the potential mechanism by which spermatozoal sncRNAs meditate intergenerational inheritance. In summary, increased attention highlights the hidden wonder of spermatozoal sncRNAs during intergenerational inheritance. Therefore, in the future, more studies should focus on the origin of RNA alteration, the target of RNA regulation, and how sncRNA regulation during embryonic development can be sustained even in adult offspring.

Nonprecious bimetallic Fe, Mo-embedded N-enriched porous biochar for efficient oxidation of aqueous organic contaminants.

Bimetallic Fe- and Mo-embedded N-enriched porous biochar (Fe-Mo@N-BC) is developed and serves as a cost-effective and highly efficient catalyst for mineralization of non-biodegradation organic contaminants. Fe-Mo@N-BC was prepared by pyrolysis of complex Fe/Mo -containing precursors. Transmission electron microscopy and elemental mapping suggested that Fe and Mo are uniformly dispersed in nitrogen-doped biochar with hierarchical mesopores. In comparison to Fe@N-BC and Mo@N-BC, Fe-Mo@N-BC exhibited a superior activity for activating peroxymonosulfate (PMS). The stable activity was ascribed to N-doping and synergistic effect of Fe and Mo species, where both Fe-Nx and Mo-Nx can simultaneously serve as the active sites and N-BC can act as a carrier and an activator as well as an electron mediator. Electron paramagnetic resonance and quenching experiments indicated that HO•, O2•- and 1O2 were responsible for organic degradation. The effects of PMS dosage, initial Orange II concentration, temperature, solution pH, coexisting anions and humic acids on organic degradation were also investigated. With the assistance of an external magnet, Fe-Mo@N-BC can be easily separated after reaction and remains stable in the reusability tests. This work demonstrates a feasible strategy towards the fabrication of Fe, Mo-embedded N-enriched porous biochar catalysts for the detoxification of organic contaminants.

Evaluation of Left Ventricular Systolic Function in Patients with Coronary Microvascular Dysfunction by Three-Dimensional Speckle-Tracking Imaging.

INTRODUCTION: The objective of this study is to evaluate the left ventricular systolic function of patients with coronary microvascular dysfunction (CMD) using the three-dimensional speckle-tracking imaging (3D-STI) technique. METHODS: From June 2018 to June 2019,72 subjects from Huzhou Central Hospital were enrolled, including 42 CMD in-patients with typical chest pain or chest tightness and positive treadmill exercise stress test, but without coronary stenosis on coronary angiography, (the CMD group) and another 30 healthy individuals who were undergoing physical examinations in an outpatient clinic (the control group). Using 3D-STI technique, the global longitudinal strain (GLS), global radial strain (GRS), global circumferential strain (GCS), global area strain (GAS), and left ventricle were measured. RESULTS: Compared with the control group, GLS and GAS were significantly reduced in the CMD group (P<0.05), while GRS and GCS were similar in both groups (P>0.05). Univariate logistic regression analysis showed that GLS and GAS were the influencing factors of CMD. For the diagnosis of CMD, the area under the receiver operating characteristic (ROC) curve of GLS was 0.883, and the area under the ROC curve of GAS was 0.875. GAS of -29.3% (log-rank test chi-square=34.245, P<0.001) was a strong predictor of major adverse cardiac events. CONCLUSION: 3D-STI technique has obvious advantages in the evaluation of the left ventricular systolic function for CMD patients. Moreover, 3D-STI parameters, especially GLS and GAS, can detect the early abnormal changes in the ischaemic myocardium. Being timelier and more sensitive than echocardiography, 3D-STI should be recommended for clinical application.

Extracellular vesicles: Their functions in plant-pathogen interactions.

Extracellular vesicles (EVs) are rounded vesicles enclosed by a lipid bilayer membrane, released by eukaryotic cells and by bacteria. They carry various types of bioactive substances, including nucleic acids, proteins, and lipids. Depending on their cargo, EVs have a variety of well-studied functions in mammalian systems, including cell-to-cell communication, cancer progression, and pathogenesis. In contrast, EVs in plant cells (which have rigid walls) have received very little research attention for many decades. Increasing evidence during the past decade indicates that both plant cells and plant pathogens are able to produce and secrete EVs, and that such EVs play key roles in plant-pathogen interactions. Plant EVs contains small RNAs (sRNAs) and defence-related proteins, and may be taken up by pathogenic fungi, resulting in reduced virulence. On the other hand, EVs released by gram-negative bacteria contain a wide variety of effectors and small molecules capable of activating plant immune responses via pattern-recognition receptor- and BRI1-ASSOCIATED RECEPTOR KINASE- and SUPPRESSOR OF BIR1-mediated signalling pathways, and salicylic acid-dependent and -independent processes. The roles of EVs in plant-pathogen interactions are summarized in this review, with emphasis on important molecules (sRNAs, proteins) present in plant EVs.

Synthesis and characterization of iron-nitrogen-doped biochar catalysts for organic pollutant removal and hexavalent chromium reduction.

Fe, N atoms deposited on porous biochar (Fe-N@BC) composites were synthesized and employed as an efficient catalyst for organic pollutant removal and CrVI reduction. Naturally abundant, renewable and N-rich pomelo peel as a carbon and nitrogen source and unsubstituted phthalocyanine/iron phthalocyanine complexes as a Fe and nitrogen resource were used to develop the Fe-N@BC via a carbonization process. It is found that Fe-N@BC hybrids have homogeneous dispersion of Fe and N atoms on 3D hierarchically porous biochar, which significantly improves the performance toward the detoxification of organic pollutants using peroxymonosulfate as an oxidant, as well as the reduction of hexavalent chromium by formic acid as a reductant. Furthermore, the effects of Fe loading and pyrolytic temperature on catalysis were comprehensively analyzed and optimized. The excellent activity of Fe-N@BC in acid media can be attributed to the high dispersion of Fe species, high content of doped nitrogen as well as hierarchical micro-mesopores, which induce to expose more active sites for catalysis. Owing to the structure-enabled acidic stability, Fe-N@BC efficiently retains its activity as well as its structural stability after several cycles of reactions. This work provides a new approach to construct Fe, N-doped biochar as an effective catalyst for the detoxification of organic and inorganic pollutants.