Serum ASGR2 level: an efficacy biomarker for balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension.

Background: This study aimed to employ plasma proteomics to investigate the molecular changes, pathway alterations, and potential novel biochemical markers associated with balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Methods: Pre- and post-BPA plasma samples from five CTEPH patients in the PRACTICE study were analyzed to identify differentially expressed proteins. Proteomic and bioinformatics analyses were conducted, and the identified proteins were further validated using ELISA assays in a separate cohort of the same study. Correlation and multivariate regression analyses were performed to investigate the associations between these differentially expressed proteins and clinical parameters. Results: Significantly higher serum levels of asialoglycoprotein receptor 2 (ASGR2) were detected in 5 CTEPH patients compared to those in healthy individuals but decreased significantly after successful BPA procedures. The decrease in serum levels of ASGR2 after the completion of BPA procedures was further validated in a separate cohort of 48 patients with CTEPH [0.70 (0.51, 1.11) ng/mL vs. 0.38 (0.27, 0.59) ng/mL, P < 0.001]. Significant associations were found between the pre-BPA ASGR2 level and clinical parameters, including neutrophil percentage (R = 0.285, P < 0.05), platelet (PLT) count (R = 0.386, P < 0.05), and high-density lipoprotein cholesterol (HDL-C) before BPA (R = -0.285, P < 0.05). Significant associations were detected between post-BPA serum ASGR2 levels and lymphocyte percentage (LYM%) (R = 0.306, P < 0.05), neutrophil-to-lymphocyte ratio (R = -0.294, P < 0.05), and pulmonary vascular resistance after BPA (R = -0.35, P < 0.05). Multivariate stepwise regression analysis revealed that pre-BPA ASGR2 levels were associated with HDL-C and PLT count (both P < 0.001), while post-BPA ASGR2 levels were associated with LYM% (P < 0.05). Conclusion: Serum levels of ASGR2 may be a biomarker for the effectiveness of BPA treatment in CTEPH patients. The pre-BPA serum level of ASGR2 in CTEPH patients was associated with HDL-C and the PLT count. The post-BPA serum level of ASGR2 was correlated with the LYM%, which may reflect aspects of immune and inflammatory status.

Interlayer coupled dual-layer metagratings for broadband and high-efficiency anomalous reflection.

Recent progress in metagratings highlights the promise of high-performance wavefront engineering devices, notably for their exterior capability to steer beams with near-unitary efficiency. However, the narrow operating bandwidth of conventional metagratings remains a significant limitation. Here, we propose and experimentally demonstrate a dual-layer metagrating, incorporating enhanced interlayer couplings to realize high-efficiency and broadband anomalous reflection within the microwave frequency band. The metagrating facilitated by both intralayer and interlayer couplings is designed through the combination of eigenmode expansion (EME) algorithm and particle swarm optimization (PSO) to significantly streamline the computational process. Our metagrating demonstrates the capacity to reroute a normally incident wave to +1 order diffraction direction across a broad spectrum, achieving an average efficiency approximately 90% within the 14.7 to 18 GHz range. This study may pave the way for future applications in sophisticated beam manipulations, including spatial dispersive devices, by harnessing the intricate dynamics of multi-layer metagratings with complex interlayer and intralayer interactions.

Bifunctional transcription factors SlERF.H5 and H7 activate cell wall and repress gibberellin biosynthesis genes in tomato via a conserved motif.

The plant cell wall is a dynamic structure that plays an essential role in development, but the mechanism regulating cell wall formation remains poorly understood. We demonstrate that two transcription factors, SlERF.H5 and SlERF.H7, control cell wall formation and tomato fruit firmness in an additive manner. Knockout of SlERF.H5, SlERF.H7, or both genes decreased cell wall thickness, firmness, and cellulose contents in fruits during early development, especially in double-knockout lines. Overexpressing either gene resulted in thicker cell walls and greater fruit firmness with elevated cellulose levels in fruits but severely dwarf plants with lower gibberellin contents. We further identified that SlERF.H5 and SlERF.H7 activate the cellulose biosynthesis gene SlCESA3 but repress the gibberellin biosynthesis gene GA20ox1. Moreover, we identified a conserved LPL motif in these ERFs responsible for their activities as transcriptional activators and repressors, providing insight into how bifunctional transcription factors modulate distinct developmental processes.

[Corrigendum] MicroRNA­222­3p promotes tumor cell migration and invasion and inhibits apoptosis, and is correlated with an unfavorable prognosis of patients with renal cell carcinoma.

Following the publication of the above article, an interested reader drew to the attention of the Editorial Office that, in Fig. 3A on p. 530, two pairs of data panels were overlapping, such that certain of the panels appeared to have been derived from the same original sources where the results from differently performed experiments were intended to have been portrayed. The authors have examined their original data, and realize that errors associated with data handling/labelling during the preparation of the representative images in Fig. 3A had occurred. The revised version of Fig. 3, showing the correct data for the 'NC/ACHN/Invasion and Migration' data panels, the 'Inhibitor NC/786­O' panel and the 'Inhibitor NC/ACHN/Invasion' panel, is shown on the next page. The authors can confirm that the errors associated with this figure did not have any significant impact on either the results or the conclusions reported in this study, and all the authors agree with the publication of this Corrigendum. The authors are grateful to the Editor of International Journal of Molecular Medicine for giving them the opportunity to publish this Corrigendum; furthermore, they apologize to the readership of the Journal for any inconvenience caused. [International Journal of Molecular Medicine 43: 525­534, 2019; DOI: 10.3892/ijmm.2018.3931].

Erratum: [Corrigendum] miR­216a­5p acts as an oncogene in renal cell carcinoma.

[This corrects the article DOI: 10.3892/etm.2018.5881.].

The TET-Sall4-BMP regulatory axis controls craniofacial cartilage development.

Craniofacial microsomia (CFM) is a congenital defect that usually results from aberrant development of embryonic pharyngeal arches. However, the molecular basis of CFM pathogenesis is largely unknown. Here, we employ the zebrafish model to investigate mechanisms of CFM pathogenesis. In early embryos, tet2 and tet3 are essential for pharyngeal cartilage development. Single-cell RNA sequencing reveals that loss of Tet2/3 impairs chondrocyte differentiation due to insufficient BMP signaling. Moreover, biochemical and genetic evidence reveals that the sequence-specific 5mC/5hmC-binding protein, Sall4, binds the promoter of bmp4 to activate bmp4 expression and control pharyngeal cartilage development. Mechanistically, Sall4 directs co-phase separation of Tet2/3 with Sall4 to form condensates that mediate 5mC oxidation on the bmp4 promoter, thereby promoting bmp4 expression and enabling sufficient BMP signaling. These findings suggest the TET-BMP-Sall4 regulatory axis is critical for pharyngeal cartilage development. Collectively, our study provides insights into understanding craniofacial development and CFM pathogenesis.

A transcriptional cascade mediated by two APETALA2 family members orchestrates carotenoid biosynthesis in tomato.

Carotenoids are important nutrients for human health that must be obtained from plants since they cannot be biosynthesized by the human body. Dissecting the regulatory mechanism of carotenoid metabolism in plants represents the first step toward manipulating carotenoid contents in plants by molecular design breeding. In this study, we determined that SlAP2c, an APETALA2 (AP2) family member, acts as a transcriptional repressor to regulate carotenoid biosynthesis in tomato (Solanum lycopersicum). Knockout of SlAP2c in both the "MicroTom" and "Ailsa Craig" backgrounds resulted in greater lycopene accumulation, whereas overexpression of this gene led to orange-ripe fruit with significantly lower lycopene contents than the wild type. We established that SlAP2c represses the expression of genes involved in lycopene biosynthesis by directly binding to the cis-elements in their promoters. Moreover, SlAP2c relies on its EAR motif to recruit the co-repressors TOPLESS (TPL)2/4 and forms a complex with histone deacetylase (had)1/3, thereby reducing the histone acetylation levels of lycopene biosynthesis genes. Furthermore, SlAP2a, a homolog of SlAP2c, acts upstream of SlAP2c and alleviates the SlAP2c-induced repression of lycopene biosynthesis genes by inhibiting SlAP2c transcription during fruit ripening. Therefore, we identified a transcriptional cascade mediated by AP2 family members that regulates lycopene biosynthesis during fruit ripening in tomato, laying the foundation for the manipulation of carotenoid metabolism in plants.

The transcriptional landscape of Populus pattern/effector-triggered immunity and how PagWRKY18 involved in it.

Plants trigger a robust immune response by activating massive transcriptome reprogramming through crosstalk between PTI and ETI. However, how PTI and ETI contribute to the quantitative or/and qualitative output of immunity and how they work together when both are being activated were unclear. In this study, we performed a comprehensive overview of pathogen-triggered transcriptomic reprogramming by analyzing temporal changes in the transcriptome up to 144 h after Colletotrichum gloeosporioides inoculated in Populus. Moreover, we constructed a hierarchical gene regulatory network of PagWRKY18 and its potential target genes to explore the underlying regulatory mechanisms of PagWRKY18 that are not yet clear. Interestingly, we confirmed that PagWRKY18 protein can directly bind the W-box elements in the promoter of a transmembrane leucine-rich repeat receptor-like kinase, PagSOBIR1 gene, to trigger PTI. At the same time, PagWRKY18 functions in disease tolerance by modulation of ROS homeostasis and induction of cell death via directly targeting PagGSTU7 and PagPR4 respectively. Furthermore, PagPR4 can interact with PagWRKY18 to inhibit the expression of PagPR4 genes, forming a negative feedback loop. Taken together, these results suggest that PagWRKY18 may be involved in regulating crosstalk between PTI and ETI to activate a robust immune response and maintain intracellular homeostasis.

Potential mechanisms underlying inhibition of xenograft lung cancer models by kaempferol: modulation of gut microbiota in activating immune cell function.

Context: As a flavonoid compound, kaempferol has great potential in anti-lung cancer therapy, but the mechanism of its therapeutic effect needs further exploration. Objective: To explore the therapeutic effect of kaempferol on lung cancer, as well as its capability to regulate the gut microbiota and stimulate immune function. Materials & methods: Twenty-four BALB/c mice were divided into four groups. The first two groups, consisting of 12 normal mice, were administered either PBS or Kaempferol (Kaem) via gavage. The remaining 12 mice, which were subcutaneously inoculated with Lewis Lung Carcinoma (LLC) cells, were similarly divided and subjected to the same treatments respectively. The inhibitory effect of kaempferol on xenograft lung cancer models was explored with in vivo experiments, the diversity of gut microbiota was investigated by 16S rDNA sequencing, and the treatment effect on immune cells was quantified using flow cytometry. Results: Kaempferol exerted a significant inhibitory effect on xenograft lung cancer models in vivo. It effectively inhibited the proliferation of LLC cells and significantly activated cytotoxic T cells, natural killer cells, and other immune cells in mice. 16S rRNA sequencing of fecal samples from tumor-bearing mice treated with kaempferol showed a significant increase in the abundances of potentially advantageous microbial species such as c_Bacilli, o_Lactobacillales, f_Lachnospiraceae, s_uncultured_bacterium_g_Lactobacillus, g_Lactobacillus, f_Bacteroidaceae, g_Bacteroides, and s_uncultured_bacterium_g_Bacteroides, s_Bacteroides_acidifaciens. An increase in the proportions of three types of immune cells might associated with the above dominant bacterial species. Conclusion: Kaempferol can inhibit xenograft lung cancer models. Such inhibition effect might come from the activation of T cells, NK cells, and other immune cells which are modulated by the gut microbiota.

Erratum: [Corrigendum] miR­199b­5p serves as a tumor suppressor in renal cell carcinoma.

[This corrects the article DOI: 10.3892/etm.2018.6151.].

Biochar co-pyrolyzed from peanut shells and maize straw improved soil biochemical properties, rice yield, and reduced cadmium mobilization and accumulation by rice: Biogeochemical investigations.

Biochar is an eco-friendly amendment for the remediation of soils contaminated with cadmium (Cd). However, little attention has been paid to the influence and underlying mechanisms of the co-pyrolyzed biochar on the bioavailability and uptake of Cd in paddy soils. The current study explored the effects of biochar co-pyrolyzed from peanut shells (P) and maize straw (M) at different mixing ratios (1:0, 1:1, 1:2, 1:3, 0:1, 2:1 and 3:1, w/w), on the bacterial community and Cd fractionation in paddy soil, and its uptake by rice plant. Biochar addition, particularly P1M3 (P/M 1:3), significantly elevated soil pH and cation exchange capacity, transferred the mobile Cd to the residual fraction, and reduced Cd availability in the rhizosphere soil. P1M3 application decreased the concentration of Cd in different rice tissues (root, stem, leaf, and grain) by 30.0%- 49.4%, compared to the control. Also, P1M3 enhanced the microbial diversity indices and relative abundance of iron-oxidizing bacteria in the rhizosphere soil. Moreover, P1M3 was more effective in promoting the formation of iron plaque, increasing the Cd sequestration by iron plaque than other treatments. Consequently, the highest yield and lowest Cd accumulation in rice were observed following P1M3 application. This study revealed the feasibility of applying P1M3 for facilitating paddy soils contaminated with Cd.

Design of arbitrary energy distribution beam splitters base on multilayer metagratings by a hybrid evolutionary particle swarm optimization.

Multilayer metagratings have strong wavefront manipulation capabilities and find important applications in beam splitters. Traditional methods rely on the phase gradient design of generalized Snell's law, which can achieve highly efficient beam splitters with uniform energy distribution. However, designing arbitrary energy distributions in different channels under two orthogonal polarizations remains a challenge because it requires more complex structures to modulate the energy flow. In this work, we employed a hybrid evolutionary particle swarm optimization (HEPSO) from the combination of particle swarm optimization (PSO) and genetic algorithm (GA) which has a strong ability to find the optimal structures that satisfy the specific energy flow distributions. We used the crossover and mutation operators of GA to improve the global search capabilities, and the velocity updating formula of PSO to replace the selection operator of GA to avoid local optimization. Using this approach, we successfully designed a uniform beam splitter with an efficiency of over 90% and two beam splitters with arbitrary energy distributions, achieving an average error of about 0.5%. The optimal and average efficiencies obtained from running 10 optimizations are 2.2% and 4% higher than those obtained using PSO alone with 30 populations and 75 iterations. We envision that the proposed method can also provide an idea for other photonics design problems.

The Effect of Cuelure on Attracting and Feeding Behavior in Zeugodacus tau (Walker) (Diptera: Tephritidae).

As a vital pest control strategy, trapping plays an important role in the system of monitoring, catching and killing fruit flies. Cuelure (4-(4-acetoxyphenyl)-2-butanone, CL) is a male lure that attracts Zeugodacus tau and also stimulates feeding in this species. In this study, the attraction of Z. tau to CL and its subsequent feeding behavior were investigated. Under the significant influence of age and time of day, the attraction of CL to Z. tau was found to be optimal when flies were 14 days old, and the number of flies trapped increased with trapping duration. It was determined that consumption can improve the mating success and female adult fertility of Z. tau. After the observation period, the mating success rate of flies that ingested CL was significantly higher than that of the control group and was maintained at a higher level. It was found that parental consumption of CL could accelerate the development of eggs and larvae, resulting in increased pupation and emergence rates. The results of this study will further clarify the dynamic relationship between pest and lure, and provide a research basis for navigating the integrated management of Z. tau in the field.

Rhodaelectro-Catalyzed Decarboxylative Cross-Dehydrogenative Coupling of Indole-3-carboxylic Acids and Olefins via Weakly Coordinating Carboxyl Groups.

A rhodaelectro-catalyzed C2-H selectively decarboxylative alkenylation of 3-carboxy-1H-indoles employing electricity as the traceless terminal oxidant has been accomplished. The weakly coordinating carboxyl group serves as the traceless directing groups. External oxidant-free in an undivided cell with constant current in aqueous solution ensures the decarboxylative C-H alkenylation to be viable and sustainable.

Dual-stream EfficientNet with adversarial sample augmentation for COVID-19 computer aided diagnosis.

Though a series of computer aided measures have been taken for the rapid and definite diagnosis of 2019 coronavirus disease (COVID-19), they generally fail to achieve high enough accuracy, including the recently popular deep learning-based methods. The main reasons are that: (a) they generally focus on improving the model structures while ignoring important information contained in the medical image itself; (b) the existing small-scale datasets have difficulty in meeting the training requirements of deep learning. In this paper, a dual-stream network based on the EfficientNet is proposed for the COVID-19 diagnosis based on CT scans. The dual-stream network takes into account the important information in both spatial and frequency domains of CT scans. Besides, Adversarial Propagation (AdvProp) technology is used to address the insufficient training data usually faced by the deep learning-based computer aided diagnosis and also the overfitting issue. Feature Pyramid Network (FPN) is utilized to fuse the dual-stream features. Experimental results on the public dataset COVIDx CT-2A demonstrate that the proposed method outperforms the existing 12 deep learning-based methods for COVID-19 diagnosis, achieving an accuracy of 0.9870 for multi-class classification, and 0.9958 for binary classification. The source code is available at https://github.com/imagecbj/covid-efficientnet.

Accelerated organic matter decomposition in thermokarst lakes upon carbon and phosphorus inputs.

Mineralization of dissolved organic matter (DOM) in thermokarst lakes plays a non-negligible role in the permafrost carbon (C) cycle, but remains poorly understood due to its complex interactions with external C and nutrient inputs (i.e., aquatic priming and nutrient effects). Based on large-scale lake sampling and laboratory incubations, in combination with 13 C-stable-isotope labeling, optical spectroscopy, and high-throughput sequencing, we examined large-scale patterns and dominant drivers of priming and nutrient effects of DOM biodegradation across 30 thermokarst lakes along a 1100-km transect on the Tibetan Plateau. We observed that labile C and phosphorus (P) rather than nitrogen (N) inputs stimulated DOM biodegradation, with the priming and P effects being 172% and 451% over unamended control, respectively. We also detected significant interactive effects of labile C and nutrient supply on DOM biodegradation, with the combined labile C and nutrient additions inducing stronger microbial mineralization than C or nutrient treatment alone, illustrating that microbial activity in alpine thermokarst lakes is co-limited by both C and nutrients. We further found that the aquatic priming was mainly driven by DOM quality, with the priming intensity increasing with DOM recalcitrance, reflecting the limitation of external C as energy sources for microbial activity. Greater priming intensity was also associated with higher community-level ribosomal RNA gene operon (rrn) copy number and bacterial diversity as well as increased background soluble reactive P concentration. In contrast, the P effect decreased with DOM recalcitrance as well as with background soluble reactive P and ammonium concentrations, revealing the declining importance of P availability in mediating DOM biodegradation with enhanced C limitation but reduced nutrient limitation. Overall, the stimulation of external C and P inputs on DOM biodegradation in thermokarst lakes would amplify C-climate feedback in this alpine permafrost region.

Experimental probe of twist angle-dependent band structure of on-chip optical bilayer photonic crystal.

Recently, twisted bilayer photonic materials have been extensively used for creating and studying photonic tunability through interlayer couplings. While twisted bilayer photonic materials have been experimentally demonstrated in microwave regimes, a robust platform for experimentally measuring optical frequencies has been elusive. Here, we demonstrate the first on-chip optical twisted bilayer photonic crystal with twist angle-tunable dispersion and great simulation-experiment agreement. Our results reveal a highly tunable band structure of twisted bilayer photonic crystals due to moiré scattering. This work opens the door to realizing unconventional twisted bilayer properties and novel applications in optical frequency regimes.

Interleukin-6 and pulmonary hypertension: from physiopathology to therapy.

Pulmonary hypertension (PH) is a progressive, pulmonary vascular disease with high morbidity and mortality. Unfortunately, the pathogenesis of PH is complex and remains unclear. Existing studies have suggested that inflammatory factors are key factors in PH. Interleukin-6 (IL-6) is a multifunctional cytokine that plays a crucial role in the regulation of the immune system. Current studies reveal that IL-6 is elevated in the serum of patients with PH and it is negatively correlated with lung function in those patients. Since IL-6 is one of the most important mediators in the pathogenesis of inflammation in PH, signaling mechanisms targeting IL-6 may become therapeutic targets for this disease. In this review, we detailed the potential role of IL-6 in accelerating PH process and the specific mechanisms and signaling pathways. We also summarized the current drugs targeting these inflammatory pathways to treat PH. We hope that this study will provide a more theoretical basis for targeted treatment in patients with PH in the future.

Target and Mechanism of the Xihuang Pill Based on Network Pharmacology for Lung Squamous Cell Carcinoma.

Context: Lung squamous cell carcinoma (LUSC) accounts for 30% of non-small-cell lung cancers (NSCLC), and an effective pharmacological treatment for LUSC isn't yet available. The Xihuang Pill is a potent Chinese medicinal preparation widely prescribed for the management of LUSC. Objective: The study intended to use the network-pharmacology method to ascertain the effective active ingredients, targets of action, and cellular-signal transduction involved in the prevention and treatment of LUSC when using the Xihuang Pill and to identify the mechanism of action of the pills against LUSC, to provide a more adequate scientific basis for subsequent studies. Design: The research team performed a genetic study. Setting: The study took place at Shanghai. Outcome Measures: The research team: (1) created the feature sets, for both the LUSC and normal features, using the Cancer Genome Atlas' (TCGA's) LUSC dataset; (2) performed a weighted correlation network analysis (WGCNA) of the differentially expressed genes (DEGs) using the R package WGCNA; (3) searched for the chemical components of the Xihuang Pill using the Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform (TCMSP) and the Herb Group Identification Platform, and (4) selected the novel the Matthews correlation coefficient (MCC) algorithm to screen the hub genes. Results: The study found 8713 DEGs between the LUSC and normal groups. The top ten, important, downregulated genes included: (1) advanced glycosylation end product (AGER), (2) chitinase, acidic pseudogene 2 (CHIAP2), (3) CD300 molecule like family member G (CD300LG), (4) solute carrier family 6 member 4 (SLC6A4), (5) carboxypeptidase B2 (CPB2), (6) claudin 18 (CLDN18), (7) gamma-glutamyltransferase light chain 1 (GGTLC1), (8) gastrokine 2 (GKN2), (9) progastricsin (PGC), and (10) pulmonary surfactant-associated protein C (SFTPC). The top 10 upregulated genes included: (1) cancer susceptibility 9 (CASC9), (2) homeobox C13 (HOXC13), (3) keratin 6a (KRT6A), (4) desmoglein 3 (DSG3), (5) keratin 16 (KRT16), (6) forkhead box E1 (FOXE1), (7) preferentially expressed antigen in melanoma (PRAME), (8) calmodulin-like protein 3 (CALML3), (9) KRT68, and (10) aldo-keto reductase family 1 member B10 (AKR1B10). The study found 41 active ingredients and 843 targets for the Xihuang Pill. The PPI network included 10 hub genes, including cyclin dependent kinase 1 (CDK1), cyclin B1 (CCNB1), cyclin B2 (CCNB2), polo-like kinase 1 (PLK1), aurora kinase B (AURKB), baculoviral IAP repeat containing 5 (BIRC5), cyclin A2 (CCNA2), aurora kinase A (AURKA), centrosome-associated protein E (CENPE), and threonine tyrosine kinase (TTK), which were the principal target genes at the core of the gene-pathway network for the drug compound to central-target relationship. The enrichment analyses used the overlapping genes and the 10 hub genes and found 390 biological processes (BPs), 25 molecular functions (MFs), 43 cellular components (CCs), and 10 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The main enrichment occurred in the regulation of protein serine-threonine kinase activity, mitotic nuclear division, progesterone-mediated oocyte maturation, and the cell cycle. Conclusions: The study found the targets and relevant pathways of the hub genes of Xihuang Pill using biological analysis and molecular docking and demonstrated the interactions of critical chemical compounds with the hub's targeted genes were. More research is necessary to further determine whether the Xihuang Pill can improve LUSC patients' survival rate by regulation of those genes.