Elevated cancer-associated hyaluronan correlates with diagnosis and lymph node metastasis of papillary thyroid cancer.

The glycosaminoglycan hyaluronan (HA) plays an important role in tumor progression. However, its biological and clinical significance in papillary thyroid cancer (PTC) remains unknown. Immunohistochemistry was performed to examine HA expression in tissues from PTC patients. Two PTC cell lines were treated with HA synthesized inhibitor against HA production to assess its function. Serum HA levels from 107 PTC patients, 30 Hashimoto thyroiditis, and 45 normal controls (NC) were measured by chemiluminescence immunoassay. HA levels in FNA washouts obtained from thyroid nodules and lymph nodes (LNs) were measured by chemiluminescence immunoassay. Area under the curve (AUC) were computed to evaluate HA`s clinical value. HA was highly expressed in PTC. Reducing HA production significantly inhibited PTC cell proliferation and invasion. Importantly, serum HA levels in PTC were significantly higher than in NCs and Hashimoto thyroiditis and allowed distinguishing of thyroid cancers from NCs with high accuracy (AUC=0.782). Moreover, elevated serum HA levels in PTC correlate with LN metastasis. HA levels in fine needle aspiration (FNA) washouts from PTC patients were significantly higher than in benign controls, with a high AUC value (0.8644) for distinguishing PTC from benign controls. Furthermore, HA levels in FNA washouts from metastatic LN were significantly higher than in non-metastatic LN, with a high AUC value (0.8007) for distinguishing metastatic LNs from non-metastatic LNs. HA in serum and FNA washout exhibited a potential significance for PTC diagnosis and indicator for LN metastasis in patients with PTC.

Purification of inorganic nitrogen from the mariculture tail water by anaerobic/anoxic/oxic (A2O) process.

This study aims to address the suboptimal performance of conventional denitrifying strains in treating mariculture tail water (MTW) containing inorganic nitrogen (IN). The concentration of inorganic nitrogen in the mariculture tail water is about 5-20 mg·L-1. A biofilm treatment process was developed and evaluated using an anoxic-anoxic-aerobic biofilter composite system inoculated with the denitrifying strain Meyerozyma guilliermondii Y8. The removal effect of total nitrogen (TN), IN, and Chemical Oxygen Demand (CODMn) from MTW was investigated. The results indicate that the A2O composite biological filter has excellent pollutant removal efficiency within 25 days of operation, after the acclimation of the denitrifying microorganisms. The initial concentrations of TN, IN, and CODMn ranged between 10.24 and 12.89 mg·L-1, 7.84-10.49 mg·L-1, and 9.44-11.52 mg·L-1, respectively, and the removal rates of these indexes reached 38-68 %, 45-70 %, and 55-70 %, respectively. The experiments with different hydraulic retention times (HRT = 6 h, 8 h, 10 h) demonstrated that longer HRT was more conducive to the removal of inorganic nitrogen. Moreover, scanning electron microscopy observations revealed that the target strain successfully grew and attached to the filler in large quantities. The findings of this study provide practical guidance for the development of efficient biofilm processes for the treatment of MTW.

Exosomes derived from HUVECs alleviate ischemia-reperfusion induced inflammation in neural cells by upregulating KLF14 expression.

Neuroinflammation plays a key role in the progression of secondary brain injury after ischemic stroke, and exosomes have been increasingly recognized to eliminate inflammatory responses through various mechanisms. This study aimed to explore the effect and possible mechanism of human umbilical vein endothelial cells derived exosomes (H-EXOs) on neuroinflammation. We established a transient middle cerebral artery occlusion/reperfusion (tMCAO/R) in male rats and oxygen-glucose-deprivation/reoxygenation (OGD/R) model in cultured neurons to mimic secondary brain injury after ischemic stroke in vivo. H-EXOs were administered at the same time of reperfusion. Results showed that the production of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6, and the transcription factor Krüppel-like factor 14 (KLF14) were significantly increased both in rat brain tissue and cultured neural cells after ischemic-reperfusion (I/R) injury. H-EXOs treatment significantly improved the cultured cell viability, reduced infarct sizes, mitigated neurobehavioral defects, and alleviated the expression of pro-inflammatory cytokines compared with the control group, indicating that H-EXOs exerted anti-inflammatory effect against I/R injury. Further studies revealed that the anti-inflammatory effect of H-EXOs could be weakened by small-interfering RNA (siKLF4) transfection. KLF14 was a protective factor produced during cerebral ischemia-reperfusion injury. In conclusion, H-EXOs protect neurons from inflammation after I/R injury by enhancing KLF14 expression.

Causal effect of gut microbiota on DNA methylation phenotypic age acceleration: a two-sample Mendelian randomization study.

The causal relationship between gut microbiota and DNA methylation phenotypic age acceleration remains unclear. This study aims to examine the causal effect of gut microbiota on the acceleration of DNA methylation phenotypic age using Mendelian randomization. A total of 212 gut microbiota were included in this study, and their 16S rRNA sequencing data were obtained from the Genome-wide Association Study (GWAS) database. The GWAS data corresponding to DNA methylation phenotypic age acceleration were selected as the outcome variable. Two-sample Mendelian randomization (TSMR) was conducted using R software. During the analysis process, careful consideration was given to address potential biases arising from linkage disequilibrium and weak instrumental variables. The results from inverse-variance weighting (IVW) analysis revealed significant associations (P < 0.05) between single nucleotide polymorphisms (SNPs) corresponding to 16 gut microbiota species and DNA methylation phenotypic age acceleration. Out of the total, 12 gut microbiota species exhibited consistent and robust causal effects. Among them, 7 displayed a significant positive correlation with the outcome while 5 species showed a significant negative correlation with the outcome. This study utilized Mendelian randomization to unravel the intricate causal effects of various gut microbiota species on DNA methylation phenotypic age acceleration.

Auxin contributes to jasmonate-mediated regulation of abscisic acid signaling during seed germination in Arabidopsis.

Abscisic acid (ABA) represses seed germination and postgerminative growth in Arabidopsis thaliana. Auxin and jasmonic acid (JA) stimulate ABA function; however, the possible synergistic effects of auxin and JA on ABA signaling and the underlying molecular mechanisms remain elusive. Here, we show that exogenous auxin works synergistically with JA to enhance the ABA-induced delay of seed germination. Auxin biosynthesis, perception, and signaling are crucial for JA-promoted ABA responses. The auxin-dependent transcription factors AUXIN RESPONSE FACTOR10 (ARF10) and ARF16 interact with JASMONATE ZIM-DOMAIN (JAZ) repressors of JA signaling. ARF10 and ARF16 positively mediate JA-increased ABA responses, and overaccumulation of ARF16 partially restores the hyposensitive phenotype of JAZ-accumulating plants defective in JA signaling in response to combined ABA and JA treatment. Furthermore, ARF10 and ARF16 physically associate with ABSCISIC ACID INSENSITIVE5 (ABI5), a critical regulator of ABA signaling, and the ability of ARF16 to stimulate JA-mediated ABA responses is mainly dependent on ABI5. ARF10 and ARF16 activate the transcriptional function of ABI5, whereas JAZ repressors antagonize their effects. Collectively, our results demonstrate that auxin contributes to the synergetic modulation of JA on ABA signaling, and explain the mechanism by which ARF10/16 coordinate with JAZ and ABI5 to integrate the auxin, JA, and ABA signaling pathways.

CO interacts with JAZ repressors and bHLH subgroup IIId factors to negatively regulate jasmonate signaling in Arabidopsis seedlings.

CONSTANS (CO) is a master flowering-time regulator that integrates photoperiodic and circadian signals in Arabidopsis thaliana. CO is expressed in multiple tissues, including young leaves and seedling roots, but little is known about the roles and underlying mechanisms of CO in mediating physiological responses other than flowering. Here, we show that CO expression is responsive to jasmonate. CO negatively modulated jasmonate-imposed root-growth inhibition and anthocyanin accumulation. Seedlings from co mutants were more sensitive to jasmonate, whereas overexpression of CO resulted in plants with reduced sensitivity to jasmonate. Moreover, CO mediated the diurnal gating of several jasmonate-responsive genes under long-day conditions. We demonstrate that CO interacts with JASMONATE ZIM-DOMAIN (JAZ) repressors of jasmonate signaling. Genetic analyses indicated that CO functions in a CORONATINE INSENSITIVE1 (COI1)-dependent manner to modulate jasmonate responses. Furthermore, CO physically associated with the basic helix-loop-helix (bHLH) subgroup IIId transcription factors bHLH3 and bHLH17. CO acted cooperatively with bHLH17 in suppressing jasmonate signaling, but JAZ proteins interfered with their transcriptional functions and physical interaction. Collectively, our results reveal the crucial regulatory effects of CO on mediating jasmonate responses and explain the mechanism by which CO works together with JAZ and bHLH subgroup IIId factors to fine-tune jasmonate signaling.

Time in range assessed by capillary blood glucose in relation to insulin sensitivity and ß-cell function in patients with type 2 diabetes mellitus: A cross-sectional study in China.

AIMS: This study investigated the association of capillary blood glucose (CBG)-assessed time in range (TIR) (3.9-10.0 mmol/L) with insulin sensitivity and islet ß-cell function. MATERIALS AND METHODS: We recruited 455 patients with type 2 diabetes mellitus. Seven-point glucose-profile data (pre- and 120 min post-main meals, bedtime) were collected over three consecutive days. Plasma glucose and serum insulin concentrations were measured at 0, 60, and 120 min after a 100 g standard steamed bread meal test. The homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda index were computed to evaluate insulin resistance. The HOMA of ß-cell function (HOMA-ß) and the area under the curve between insulin and blood glucose (IAUC0-120 /GAUC0-120 ) were used to estimate ß-cell function. RESULTS: TIR was positively correlated with the 60 and 120 min insulin values, IAUC0-120 , the Matsuda index, HOMA-ß, and IAUC0-120 /GAUC0-120 (rs : 0.154, 0.129, 0.137, 0.194, 0.341, and 0.334, respectively; P < 0.05) but inversely correlated with HOMA-IR (rs : -0.239, P < 0.001). After adjusting for confounders, multinomial multiple logistic regression analysis revealed that the odds ratios (ORs) of achieving the target time in range (>70%) increased by 12% (95% confidence interval [CI]: 3-21%), 7% (95% CI: 1-14%), 10% (95% CI: 5-16%), and 45% (95% CI: 25-68%) for each 10 mIU/L increase in the 60 and 120 min insulin values, 10 unit increase in HOMA-ß, and unit increase in IAUC0-120 /GAUC0-120 , respectively (P < 0.05). Nevertheless, the OR decreased by 10% (95% CI: 1-18%) for each unit increase in HOMA-IR (P < 0.05). CONCLUSIONS: Insulin resistance and islet ß-cell function are related to capillary blood glucose-assessed TIR.

Spot-Adaptive Knowledge Distillation.

Knowledge distillation (KD) has become a well established paradigm for compressing deep neural networks. The typical way of conducting knowledge distillation is to train the student network under the supervision of the teacher network to harness the knowledge at one or multiple spots (i.e., layers) in the teacher network. The distillation spots, once specified, will not change for all the training samples, throughout the whole distillation process. In this work, we argue that distillation spots should be adaptive to training samples and distillation epochs. We thus propose a new distillation strategy, termed spot-adaptive KD (SAKD), to adaptively determine the distillation spots in the teacher network per sample, at every training iteration during the whole distillation period. As SAKD actually focuses on "where to distill" instead of "what to distill" that is widely investigated by most existing works, it can be seamlessly integrated into existing distillation methods to further improve their performance. Extensive experiments with 10 state-of-the-art distillers are conducted to demonstrate the effectiveness of SAKD for improving their distillation performance, under both homogeneous and heterogeneous distillation settings. Code is available at https://github.com/zju-vipa/spot-adaptive-pytorch.

First analyses of lysine succinylation proteome and overlap between succinylation and acetylation in Solenopsis invicta Buren (Hymenoptera: Formicidae).

BACKGROUND: Lysine succinylation (Ksu) exists in both eukaryotes and prokaryotes, and influences a variety of metabolism processes. However, little attention has been paid to Ksu in insects, especially the notorious invasive pest Solenopsis invicta. RESULTS: In this study, the first analyses of Ksu proteome and overlap between Ksu and lysine acetylation (Kac) in S. invicta were presented. 3753 succinylated sites in 893 succinylated proteins were tested. The dihydrolipoyl dehydrogenase, V-type proton ATPase subunit G, and tubulin alpha chain all had evolutionary conservatism among diverse ant or bee species. Immunoblotting validation showed that there were many Ksu protein bands with a wide range of molecular mass. In addition, 1230 sites in 439 proteins were highly overlapped between Ksu and Kac. 54.05% of Ksu proteins in cytoplasm were acetylated. The results demonstrated that Ksu may play a vital part in the allergization, redox metabolism, sugar, fat, and protein metabolism, energy production, immune response, and biosynthesis of various secondary metabolites. CONCLUSIONS: Ksu and Kac were two ubiquitous protein post-translational modifications participated in a variety of biological processes. Our results may supply rich resources and a starting point for the molecular basic research of regulation on metabolic pathways and other biological processes by succinylation and acetylation.

GDF11 protects against glucotoxicity-induced mice retinal microvascular endothelial cell dysfunction and diabetic retinopathy disease.

Growth differentiation factor 11 (GDF11) has been implicated in the regulation of embryonic development and age-related dysfunction, including the regulation of retinal progenitor cells. However, little is known about the functions of GDF11 in diabetic retinopathy. In this study, we demonstrated that GDF11 treatment improved diabetes-induced retinal cell death, capillary degeneration, pericyte loss, inflammation, and blood-retinal barrier breakdown in mice. Treatment of isolated mouse retinal microvascular endothelial cells with recombinant GDF11 in vitro attenuated glucotoxicity-induced retinal endothelial apoptosis and the inflammatory response. The protective mechanisms exerted are associated with TGF-ß/Smad2, PI3k-Akt-FoxO1 activation，and NF-κB pathway inhibition. This study indicated that GDF11 is a novel therapeutic target for diabetic retinopathy.

First proteomic analysis of the role of lysine acetylation in extensive functions in Solenopsis invicta.

Lysine acetylation (Kac) plays a critical role in the regulation of many important cellular processes. However, little is known about Kac in Solenopsis invicta, which is among the 100 most dangerous invasive species in the world. Kac in S. invicta was evaluated for the first time in this study. Altogether, 2387 Kac sites were tested in 992 proteins. The prediction of subcellular localization indicated that most identified proteins were located in the cytoplasm, mitochondria, and nucleus. Venom allergen Sol i 2, Sol i 3, and Sol i 4 were found to be located in the extracellular. The enriched Kac site motifs included Kac H, Kac Y, Kac G, Kac F, Kac T, and Kac W. H, Y, F, and W frequently occurred at the +1 position, whereas G, Y, and T frequently occurred at the -1 position. In the cellular component, acetylated proteins were enriched in the cytoplasmic part, mitochondrial matrix, and cytosolic ribosome. Furthermore, 25 pathways were detected to have significant enrichment. Interestingly, arginine and proline metabolism, as well as phagosome, which are related to immunity, involved several Kac proteins. Sequence alignment analyses demonstrated that V-type proton ATPase subunit G, tubulin alpha chain, and arginine kinase, the acetylated lysine residues, were evolutionarily conserved among different ant species. In the investigation of the interaction network, diverse interactions were adjusted by Kac. The results indicated that Kac may play an important role in the sensitization, cellular energy metabolism, immune response, nerve signal transduction, and response to biotic and abiotic stress of S. invicta. It may be useful to confirm the functions of Kac target proteins for the design of specific and effective drugs to prevent and control this dangerous invasive species.

Neural Style Transfer: A Review.

The seminal work of Gatys et al. demonstrated the power of Convolutional Neural Networks (CNNs) in creating artistic imagery by separating and recombining image content and style. This process of using CNNs to render a content image in different styles is referred to as Neural Style Transfer (NST). Since then, NST has become a trending topic both in academic literature and industrial applications. It is receiving increasing attention and a variety of approaches are proposed to either improve or extend the original NST algorithm. In this paper, we aim to provide a comprehensive overview of the current progress towards NST. We first propose a taxonomy of current algorithms in the field of NST. Then, we present several evaluation methods and compare different NST algorithms both qualitatively and quantitatively. The review concludes with a discussion of various applications of NST and open problems for future research. A list of papers discussed in this review, corresponding codes, pre-trained models and more comparison results are publicly available at: https://osf.io/f8tu4/.

Edge-Sensitive Human Cutout with Hierarchical Granularity and Loopy Matting Guidance.

Human parsing and matting play important roles in various applications, such as dress collocation, clothing recommendation, and image editing. In this paper, we propose a lightweight hybrid model that unifies the fully-supervised hierarchical-granularity parsing task and the unsupervised matting one. Our model comprises two parts, the extensible hierarchical semantic segmentation block using CNN and the matting module composed of guided filters. Given a human image, the segmentation block stage-1 first obtains a primitive segmentation map to separate the human and the background. The primitive segmentation is then fed into stage-2 together with the original image to give a rough segmentation of human body. This procedure is repeated in the stage-3 to acquire a refined segmentation. The matting module takes as input the above estimated segmentation maps and produces the matting map, in a fully unsupervised manner. The obtained matting map is then in turn fed back to the CNN in the first block for refining the semantic segmentation results.

A dual-label time-resolved fluorescence immunoassay for the simultaneous determination of carcinoembryonic antigen and squamous cell carcinoma antigen.

Among women worldwide, cervical cancer is the second-most common cancer, and cervical smears and DNA detection have low sensitivity or are too expensive. The concentrations of carcinoembryonic antigen (CEA) and squamous cell carcinoma (SCC) in the serum were detected using a sandwich immunoassay. The CEA and SCC in the serum were captured by anti-CEA and anti-SCC antibodies. After combining other anti-CEA- and anti-SCC-labeled antibodies with europium (III) (Eu3+ ) and samarium (III) (Sm3+ ) chelates, CEA and SCC were detected with time-resolved fluorometry (TRF). The linear correlation coefficients (R2 ) of the CEA and SCC standard curves were 0.9997 and 0.9997, respectively. The minimum detection level for CEA was 1.15 ng/mL (the linear dynamic range was 3.24-543.67 ng/mL), and the average recovery was 100.83%. The sensitivity for SCC detection was 0.54 ng/mL (the linear dynamic range was 2.47-96.58 ng/mL), and the average recovery was 101.02%. High R2 between the results of commercial assays and this method were obtained (R2  = 0.9983 for CEA, R2   = 0.9878 for SCC). These findings indicated that the dual-label TRFIA invented in this study has high sensitivity, accuracy, and specificity in clinical analysis, which indicates that this method could be used for the early diagnosis and follow-up surveillance of cervical cancer.

Pectin methylesterases contribute the pathogenic differences between races 1 and 4 of Fusarium oxysporum f. sp. cubense.

Plant cell walls, which are mainly composed of pectin, play important roles in plant defence responses to pathogens. Pectin is synthesised in a highly esterified form and then de-esterified by pectin methylesterases (PMEs). Because of this, PMEs are directly involved in plant defence. However, the molecular mechanisms of their interactions with pectins remain unclear. In this study, we compared the expression level and enzyme activities of PMEs in a banana Cavendish cultivar (Musa AAA 'Brazilian') inoculated with Fusarium oxysporum f. sp. cubense pathogenic races 1 (Foc1) and 4 (Foc4). We further examined the spatial distribution of PMEs and five individual homogalacturonans (HGs) with different degree of pectin methylesterification (DM). Results suggested that the banana roots infected with Foc1 showed lower PME activity than those infected with Foc4, which was consisted with observed higher level of pectin DM. The level of HGs crosslinked with Ca2+ was significantly higher in roots infected with Foc1 compared with those infected with Foc4. Therefore, banana exhibited significantly different responses to Foc1 and Foc4 infection, and these results suggest differences in PME activities, DM of pectin and Ca2+-bridged HG production. These differences could have resulted in observed differences in virulence between Foc1 and Foc4.

Rearing of Mallada basalis (Neuroptera: Chrysopidae) on modified artificial diets.

Mallada basalis (Walker) has the potential to be a valuable biological control agent because of its predatory abilities, strong reproductive capacity, and broad prey range. This study aimed to improve on a previously used artificial diet for M. basalis, to achieve a longer oviposition period and greater survival rate and fecundity. We analyzed the development, survival, longevity, and reproduction of M. basalis (F1 and F2 generations) fed two artificial diets (AD1 and AD2). Both diets contained chicken egg yolk, beer yeast powder, honey, trehalose, seawater spirulina, and potassium sorbate. AD1 also contained sucrose and vitamin C. The duration of F1 1st larvae, F1 2nd larvae, F1 pupae, F2 egg, and F2 2nd larvae reared on AD1 were significantly shorter than those reared on AD2. F1 adult longevity and F2 oviposition period for AD1 (45.40 d and 31.00 d) were significantly longer than for AD2 (30.74 d and 20.80 d). All the following were significantly greater for AD1 compared with AD2: F1 female proportion, F1 daily oviposition, F1 female oviposition, F2 daily oviposition, F2 female oviposition, F1 emergence rate, F2 pupation rate, and F3 egg hatching rate. Moreover, for M. basalis fed AD2, the duration of F2 2nd and 3rd larvae (9.00 d and 8.64 d) were significantly longer than for F1 (4.70 d and 4.92 d). The F1 oviposition period (31.57 d) was significantly longer than F2 (20.80 d). The F2 female oviposition (189.20 egg/female) was significantly less than F1 (307.14 egg/female). We found that the oviposition period and female longevity of F1 reared on AD1 was longer than that reared on the artificial diet in a previous study. The daily oviposition and female oviposition of F1 from AD1 was larger, while the F2 egg hatching rate was greater compared with that from the previous diet. However, the offspring of M. basalis fed AD2 were less thrifty. We found diet AD1 supported development and reproduction better than AD2 and the diets in our previous study. These findings may contribute to the mass rearing of this economically important predatory green lacewing.

Evaluation of a New Entomopathogenic Strain of Beauveria bassiana and a New Field Delivery Method against Solenopsis invicta.

Solenopsis invicta Buren is one of the most important pests in China, and control measures are mainly based on the use of synthetic pesticides, which may be inadequate and unsustainable. Hence, there is a growing interest in developing biological control alternatives for managing S. invicta, such as the use of entomopathogenic fungi. To facilitate the commercialization of entomopathogenic fungi against S. invicta, 10 Beauveria bassiana isolates originating from different hosts were tested for virulence in laboratory bioassays, and the most pathogenic strain, ZGNKY-5, was tested in field studies using an improved pathogen delivery system. The cumulative mortality rate reached 93.40% at 1×108 mL-1 conidia after 504 h. The germination and invasion of the spores were observed under a scanning electron microscope, and several conidia adhered to the cuticle of S. invicta after 2 h. Furthermore, the germ tubes of the conidia oriented toward the cuticle after 48 h, and the mycelium colonized the entire body after 96 h. Based on the efficacy observed in the laboratory trials, further experiments were performed with ZGNKY-5 strain to evaluate its utility in an injection control technology against S. invicta in the field. We found that three dosage treatments of ZGNKY-5 strain (500 mL, 750 mL, and 1,000 mL per nest) had significant control effects. Our results show that this strain of Beauveria bassiana and our control method were effective against S. invicta in both laboratory and field settings.