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Abstract Background Microhabitat environmental factors (e.g., temperature, oxygen concentration, nutrients, osmotic stress, and topography) are critical to the survival of intertidal organisms. Understanding how transcription responses are regulated in relation to intertidal microhabitat variation has important implications for studying adaptive evolution in these organisms. The barnacle Chthamalus challengeri, which survives in the intertidal zone and is subjected to periodic tidal changes, serves as an ideal species for detecting adaptive evolution in intertidal organisms. Results In this study, we designed a series of in situ tidal conditions for C. challengeri and sequenced their transcriptome collected from various microhabitats. We aimed to detect the genetic adaptation mechanisms of barnacles responding to the microhabitat changes in the intertidal zone based on comparative transcriptomics. Our results indicated that different intertidal microhabitats significantly affected the gene expression models of C. challengeri, particularly for genes related to physiological and biochemical functions. Specifically, the expression of genes such as CYP450, HSP70, CYTB, and COX1 was significantly increased under low tide (air-exposed conditions), while genes like CNGA3, AK, and CP52 showed significantly increased expression under high tide (seawater-immersed conditions). Conclusion The results suggest that C. challengeri relies on cytochrome p450 enzymes to enhance oxidative capacity, counts on heat shock proteins and cell phagocytosis to resist microhabitat changes in response to different tidal conditions, and produces a hypoxic stress response to regulate energy metabolism and body temperature changes upon entering into seawater. This study provides genetic resources and clues for investigating the adaptation mechanisms of intertidal barnacles and identifies different gene expression models for C. challengeri responding to various microhabitats.

IntroductionThis study systematically reviewed and conducted a network meta-analysis to assess the efficacy and safety of first-line and second-line immunotherapy treatments for recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). The findings aim to provide robust evidence to guide clinical decision-making.MethodsWe conducted an comprehensive literature search in PubMed, Embase, Cochrane Library, and Web of Science. The outcome measures included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade 3 or higher adverse events (AEs ≥3). To compare the efficacy and safety of various first-line and second-line immunotherapy regimens for R/M HNSCC with different PD-L1 expression levels, we conducted a Bayesian network meta-analysis. This study is registered in the Prospective Register of Systematic Reviews (CRD42024551711).ResultsThis analysis included 9 randomized controlled trials (RCTs) involving 5,946 patients and seven immunotherapy regimens. Among patients with R/M HNSCC, pembrolizumab combined with chemotherapy as a first-line treatment was the only immunotherapy regimen to show a PFS benefit compared to SOC (HR = 0.92, 95% CI: 0.77–1.10); however, the difference was not statistically significant. Meanwhile, nivolumab provided the most pronounced OS benefit (HR=0.71,95%CI:0.52-0.98). Additionally, pembrolizumab exhibited the most favorable safety profile relative to SOC (OR=0.12, 95% CI: 0.05-0.29). In second-line therapy, nivolumab outperformed SOC in multiple aspects, including OS (HR=0.68, 95% CI: 0.54-0.86), ORR (OR=0.40, 95% CI: 0.17-0.95), and grade ≥3 adverse events (OR=0.32, 95% CI: 0.19-0.54). Subgroup analysis by PD-L1 expression revealed that nivolumab, compared to SOC, conferred the greatest OS benefit (HR=0.59, 95% CI: 0.34-1.00) as a first-line therapy in patients with PD-L1 expression ≥1%, while pembrolizumab combined with chemotherapy(pem-chemo) showed the most substantial PFS benefit (HR=0.82, 95% CI: 0.67-1.00). For patients with PD-L1 expression ≥20%, pem-chemo delivered the optimal OS (HR=0.60, 95% CI: 0.44-0.81) and PFS (HR=0.73, 95% CI: 0.55-0.97) outcomes compared to SOC. Furthermore, in patients with PD-L1 expression ≥1%, nivolumab as a second-line treatment demonstrated superior OS (HR=0.55, 95% CI: 0.39-0.78) and PFS (HR=0.59, 95% CI: 0.41-0.84) compared to SOC.ConclusionsThese results suggest that immunotherapy may improve survival outcomes compared to SOC for patients with R/M HNSCC, while maintaining a comparable safety profile. For patients, pembrolizumab combined with chemotherapy and nivolumab as first-line treatments may represent the most optimal options, with nivolumab also showing promise as a second-line therapy. In patients with PD-L1 expression ≥1% or ≥20%, pembrolizumab combined with chemotherapy may be the preferred first-line therapy, while nivolumab remains the most favorable second-line treatment.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024551711.

Pro-IL-1β is an important inflammatory factor and is also a biomarker for detecting early pro-inflammatory immune responses. However, commercially available antibodies against chicken inflammatory factors are lacking, which prohibits an in-depth exploration of the mechanism of chicken inflammation. This study cloned and expressed chicken pro-IL-1β, and developed a hybridoma cell line 1E12 capable of stably secreting chicken pro-IL-1β monoclonal antibody (mAb). The secreted mAb 1E12 can recognize exogenous or endogenous chicken pro-IL-1β by Western blot and IFA techniques, and for the first time, a novel antigen epitope 13SSLSEETFY21 of chicken pro-IL-1β recognized by this mAb was identified. This study not only provides an important tool for the detection and research of chicken pro-IL-1β, but also has significant implications for understanding the antigenic structure and biochemical characteristics of chicken pro-IL-1β.

Abstract Background Plant-parasitic nematodes are economically important pests responsible for substantial losses in agriculture. Researchers focusing on plant-parasitic nematodes, especially on finding new ways of their control, often need to assess basic parameters such as their motility, viability, and reproduction. Traditionally, these assays involve visually counting juveniles and eggs under a dissecting microscope, making this investigation time-consuming and laborious. Results In this study, we established a procedure to efficiently determine the motility of two plant-parasitic nematode species, Heterodera schachtii and Ditylenchus destructor, using the WMicrotracker ONE platform. Additionally, we demonstrated that hatching of the cyst nematode H. schachtii can be evaluated using both the WMicrotracker ONE and by assessing the enzymatic activity of chitinase produced during hatching. Conclusions We present fast and straightforward protocols for studying nematode motility and hatching that allow us to draw conclusions about viability and survival. Thus, these methods are useful tools for facilitating fast and efficient evaluation in various fields of research focused on plant-parasitic nematodes.

C-type lectins are a family of calcium-dependent carbohydrate-recognition domain (CRD) containing proteins that play a pivotal role in innate immunity. In this study, we characterized a novel C-type lectin, MsCL-P1, from the largemouth bass (Micropterus salmoides), an economically important fish species in aquaculture. MsCL-P1, a transmembrane protein with a CRD, was identified through liver transcriptome sequencing and further analyzed for its immune functions. The full-length cDNA of MsCL-P1 encodes a polypeptide of 789 amino acids, including one CRD, four coiled coil regions, and two collagen domains. Sequence analysis revealed high similarity among CRD domains from different species, suggesting conserved binding specificity. The recombinant CRD of MsCL-P1 (rCRD) demonstrated binding activity to various pathogen-associated molecular patterns (PAMPs), including lipopolysaccharide (LPS), peptidoglycan (PGN), and glucan (GLU), as determined by ELISA. Furthermore, the rCRD showed significant binding activity towards multiple microbes, including Gram-positive bacteria, Gram-negative bacteria, and fungi. Agglutination assays revealed that rCRD could agglutinate Aeromonas veronii and Saccharomyces cerevisiae, but not Micrococcus luteus. Carbohydrate binding specificity assays indicated that rCRD's agglutination activity could be suppressed by D-mannose and D-galactose. Lastly, antibacterial activity assays showed that rCRD inhibited the growth of M. luteus, E. coli, and A. veronii. These results suggest that MsCL-P1 plays a multifaceted role in the innate immune response of largemouth bass, potentially through recognition of PAMPs, agglutination of microbes, and direct inhibition of microbial growth. This study enhances our understanding of the immune mechanisms in largemouth bass and contributes to the broader knowledge of C-type lectin functions in fish species.

Abstract Human pluripotent stem cells (hPSCs) have been suggested as a potential source for the production of blood cells for clinical application. In two decades, almost all types of blood cells can be successfully generated from hPSCs through various differentiated strategies. Meanwhile, with a deeper understanding of hematopoiesis, higher efficiency of generating progenitors and precursors of blood cells from hPSCs is achieved. However, how to generate large-scale mature functional cells from hPSCs for clinical use is still difficult. In this review, we summarized recent approaches that generated both hematopoietic stem cells and mature lineage cells from hPSCs, and remarked their efficiency and mechanisms in producing mature functional cells. We also discussed the major challenges in hPSC-derived products of blood cells and provided some potential solutions. Our review summarized efficient, simple, and defined methodologies for developing good manufacturing practice standards for hPSC-derived blood cells, which will facilitate the translation of these products into the clinic.

ABSTRACT Viruses have evolved intricate mechanisms to evade host antiviral responses and exploit cellular resources by manipulating the expression profile of host genes. During infection, viruses encode proteins with shutoff activity to globally inhibit host protein synthesis, which is an effective strategy for immune evasion. In this study, compelling evidence shows that infectious bursal disease virus (IBDV) infection triggers the suppression of host protein synthesis. Furthermore, using both in vitro and in vivo viral infection models, we have identified that IBDV specifically impedes the transcription of host genes via the shutoff activity of viral VP5, simultaneously conferring advantages to IBDV infection in these circumstances. The proposed mechanism suggests that VP5 competitively binds to RanBP1, disrupting the RanGDP/GTP gradient. This disruption interferes with cellular nucleocytoplasmic transport, impairing the nuclear import of proteins bearing nuclear localization signals. The nuclear transport of pivotal transcriptional regulatory factors, such as p65 and IFN regulatory factor 7, is also compromised, leading to the inhibition of pro-inflammatory cytokines and interferon expression. This newly discovered strategy employed by IBDV enables them to manipulate host gene expression, providing novel insights into how viruses evade host immune responses and establish infections.IMPORTANCEViruses manipulate host processes at various levels to regulate or evade both innate and adaptive immune responses, promoting self-survival and efficient transmission. The “host shutoff,” a global suppression of host gene expression mediated by various viruses, is considered a critical mechanism for evading immunity. In this study, we have validated the presence of host shutoff during infectious bursal disease virus (IBDV) infection and additionally uncovered that the viral protein VP5 plays a pivotal role in inhibiting the overall synthesis of host proteins, including cytokines, through a transcription-dependent pathway. VP5 competitively binds with RanBP1, leading to disruption of the Ran protein cycle and consequently interfering with nucleocytoplasmic transport, which ultimately results in the suppression of host gene transcription. These findings unveil a novel strategy employed by IBDV to evade host innate immunity and rapidly establish infection. This study also suggests a novel supplement to understanding the pathway through which viruses inhibit host protein synthesis.

Changes to the microbial community during pickled cucumber fermentation were studied using the 16S rDNA technique. The changes of volatile organic compounds (VOCs) during pickled cucumber fermentation were studied by gas chromatograph–ion mobility spectrometry. At the phylum level, Cyanophyta and Proteobacteria were the dominant flora in the natural fermentation group, and Firmicutes were the dominant flora in the added-bacteria fermentation group. At the generic level, the addition of Lactobacillus led to changes in the community of the bacteria in the added-bacterial fermentation group and decreased the species abundance of other bacteria. In total, 75 volatile organic compounds were identified from naturally fermented pickled cucumber, and 60 volatile organic compounds were identified from fermented pickled cucumber with bacterial addition. The main metabolites were esters, aldehydes, acids, alcohols, ketones, alkanes, nitriles, and alkenes. These metabolites will bring their unique aroma components to the pickled cucumber. Metabolomic analysis of the O2PLS model showed that Weissella and Lactobacillus were closely and positively correlated with nine alcohols, six esters, five aldehydes, four acids, three ketones, and one pyrazine. Pseudomonas and norank_f_Mitochondria show a close positive correlation with four kinds of alcohols, two kinds of esters, one kind of aldehyde, and one kind of nitrile.

Sonodynamic therapy (SDT) is one of the promising strategies for tumor therapy, but its application is usually hindered by fast clearance in blood-circulation, abnormal tumor microenvironment, and inefficient generation of reactive oxygen species. To solve these problems, we proposed an on-demand assembly-disassembly strategy, where the assembly is favorable for longer-blood-circulation and then the disassembly in tumor is favorable for boosting SDT. Hematoporphyrin monomethyl ether (HMME) as the model of organic sonosensitizers were conjugated with hyaluronic acid (HA). Then HA-HMME was mixed with catalase (CAT) and assembled into polymeric nanoparticles (CAT@HA-HMME NPs) with size of ∼80 nm. CAT@HA-HMME NPs exhibit good biocompatibility and a longer blood half-time (t1/2 = 4.17 h) which is obviously longer than that (∼0.82 h) of HMME molecules. After HA receptor-mediated endocytosis of cancer cells, CAT@HA-HMME NPs can be cleaved by endogenous hyaluronidase, resulting in the on-demand disassembly in tumor to release HA-HMME molecules and CAT. The CAT catalyzes the endogenous H2O2 into O2 to relieve the hypoxic microenvironment, and the released HA-HMME exhibits a higher ROS generation ability, greatly boosting SDT for the inhibition of tumor growth. Therefore, the on-demand assembly-disassembly strategy may provide some insight in the design and development of nanoagents for tumor therapy.

The developmental mechanisms responsible for the structural defects observed in hypoplastic left heart syndrome remain controversial. Using rbfox-deficient zebrafish, the authors implicate impaired cardiac function as a primary driver of disease.

Abstract Background and Aims Differentiated thyroid carcinoma (DTC) patients are associated with excellent prognosis but impaired health‐related quality of life (HRQOL) by initial and subsequent therapy. Health literacy plays a pivotal role in public health and medical settings, but data on its relationship with DTC patients' HRQOL are insufficient and equivocal. This study was designed to explore the relationship between health literacy and HRQOL in patients with DTC from West China areas. Methods A cross‐sectional study with a descriptive correlational design was conducted. 126 patients with DTC were recruited between 2020 and 2021. Levels of health literacy and HRQOL (including fatigue level, anxiety/depression status, and somatoform symptoms) were assessed by questionnaires. Pearson product–moment correlation and Stepwise multiple regression were used to examined the adjusted association of health literacy with HRQOL. Results Health literacy and receiving DTC‐related education together explained 16.2% of the variance in fatigue level. Patients who had higher health literacy, received more DTC‐related education were currently employed and less fatigue. Health literacy, fatigue level and DTC‐related education together explained 31.0% of the variance in anxiety and depression of DTC patients. Patients who had higher health literacy, received more DTC‐related education and less fatigue level were less anxious and depressive. Age explained 8.3% of the variance in DTC patients' somatoform symptoms. Older patients complained more somatoform symptoms. Conclusion Health literacy was positively associated with HRQOL in DTC patients regarding to fatigue level and anxiety/depression status across the entire sample. Interventions to improve HRQOL should take the patients' health literacy into account.

Abstract Plant-parasitic nematodes wreak havoc on crops by root parasitism worldwide. An approach to combat nematode root parasitism is the application of antagonistic microbes like the rhizobacterium Bacillus firmus I-1582 which is promoted as biological control agent. Although B. firmus is a known nematode antagonist in general, the underlying mechanisms about its interaction with nematodes and plants have not yet been elucidated. Therefore, we explored the influence of B. firmus I-1582 as well as its extracellular and secreted molecules on plant–nematode interaction utilizing the plant–pathogen system Arabidopsis thaliana–Heterodera schachtii. We demonstrated that B. firmus I-1582 is attracted by A. thaliana root exudates, particularly by those of young plants. The bacterium colonized the root and showed a strictly pH-dependent development and plant growth promotion effect. Our results revealed that root colonization by B. firmus I-1582 significantly protected A. thaliana from infestation by the beet cyst nematode whereas dead bacterial cells or the culture supernatant were not effective. The bacterium also negatively affected nematode reproduction as well as pathogenicity and development of next generation nematodes. The obtained results highlight B. firmus I-1582 as a promising biocontrol agent that is well suited as an element of integrated control management strategies in sustainable agriculture.

C-type lectins are pattern recognition receptors (PRRs) involved in innate immunity. They possess one or more carbohydrate recognition domains (CRDs) belonging to Ca2+-dependent carbohydrate binding proteins. Herein, two C-type lectins were identified from the mud crab Scylla paramamosain. The open reading frame (ORF) of SpCTL-E encodes 160 amino acids including a CRD and a signal peptide, while the SpCTL-F ORF encodes a 244 amino acid polypeptide with a signal peptide and a CRD, and the key motifs for carbohydrate binding specificity are Asp-Pro-Asn (DPN) and Gln-Pro-Asp (QPD), respectively. DPN is a newly discovered motif, while QPD is typical of C-type lectins. The binding specificity toward different pathogen-associated molecular patterns (PAMPs) was analysed, and both bound three PAMPs: lipopolysaccharide (LPS), glucan (GLU) and peptidoglycan (PGN). SpCTL-F bound more strongly than SpCTL-E. SpCTL-E and SpCTL-F bound to five and seven microbial species, respectively, both agglutinated Gram-negative bacteria and fungi, and both promoted the phagocytosis activity of hemocytes toward Escherichia coli, and both enhanced the encapsulation activity of hemocytes towards Ni-NTA beads. SpCTL-E inhibited the growth of Micrococcus luteus and E. coli, while SpCTL-F also inhibited Vibrio parahaemolyticus. Thus, SpCTL-E and SpCTL-F are important PRRs with a broad nonself-recognition spectrum and play a key role in pathogen elimination.

Recently, atypical infectious bursal disease (IBD) caused by a novel variant infectious bursal disease virus (varIBDV) suddenly appeared in immunized chicken flocks in East Asia and led to serious economic losses. The epizootic varIBDV can partly circumvent the immune protection of the existing vaccines against the persistently circulating very virulent IBDV (vvIBDV), but its mechanism is still unknown. This study proved that the neutralizing titer of vvIBDV antiserum to the epizootic varIBDV reduced by 7.0 log2, and the neutralizing titer of the epizootic varIBDV antiserum to vvIBDV reduced by 3.2 log2. In addition, one monoclonal antibody (MAb) 2-5C-6F had good neutralizing activity against vvIBDV but could not well recognize the epizootic varIBDV. The epitope of the MAb 2-5C-6F was identified, and two mutations of G318D and D323Q of capsid protein VP2 occurred in the epizootic varIBDV compared to vvIBDV. Subsequently, the indirect immunofluorescence assay based on serial mutants of VP2 protein verified that residue mutations 318 and 323 influenced the recognition of the epizootic varIBDV and vvIBDV by the MAb 2-5C-6F, which was further confirmed by the serial rescued mutated virus. The following cross-neutralizing assay directed by MAb showed residue mutations 318 and 323 also affected the neutralization of the virus. Further data also showed that the mutations of residues 318 and 323 of VP2 significantly affected the neutralization of the IBDV by antiserum, which might be deeply involved in the immune circumvention of the epizootic varIBDV in the vaccinated flock. This study is significant for the comprehensive prevention and control of the emerging varIBDV.

Infectious bursal disease (IBD) is an acute, highly contagious, immunosuppressive, and fatal infectious disease of young chickens caused by infectious bursal disease virus (IBDV). Since 2017, a new trend has been discovered in the IBDV epidemic, with very virulent IBDV (vvIBDV) and novel variant IBDV (nVarIBDV) becoming the two current dominant strains in East Asia including China. In this study, we compared the biological characteristics of the vvIBDV (HLJ0504 strain), nVarIBDV (SHG19 strain), and attenuated IBDV (attIBDV, Gt strain) using specific-pathogen-free (SPF) chicken infection model. The results showed that vvIBDV distributed in multiple tissues, replicated the fastest in lymphoid organs such as bursa of Fabricius, induced significant viremia and virus excretion, and is the most pathogenic virus with a mortality of more than 80%. The nVarIBDV had a weaker replication capability and did not kill the chickens but caused severe damage to the central immune organ bursa of Fabricius and B lymphocytes and induced significant viremia and virus excretion. The attIBDV strain was found not to be pathogenic. Further studies preliminarily suggested that the expression level of inflammatory factors triggered by HLJ0504 was the highest, followed by the SHG19 group. This study is the first to systematically compare the pathogenic characteristics of three IBDVs closely related to poultry industry from the perspectives of clinical signs, micro-pathology, virus replication, and distribution. It is of great importance to obtain an extensive knowledge of epidemiology, pathogenicity, and comprehensive prevention, and control of various IBDV strains.

Aortic root aneurysm is a common cause of morbidity and mortality in Loeys-Dietz and Marfan syndromes, where perturbations in transforming growth factor beta (TGFβ) signaling play a causal or contributory role, respectively. Despite the advantages of cross-species disease modeling, animal models of aortic root aneurysm are largely restricted to genetically engineered mice. Here, we report that zebrafish devoid of the genes encoding latent-transforming growth factor beta-binding protein 1 and 3 (ltbp1 and ltbp3, respectively) develop rapid and severe aneurysm of the outflow tract (OFT), the aortic root equivalent. Similar to syndromic aneurysm tissue, the distended OFTs display evidence for paradoxical hyperactivated TGFβ signaling. RNA-sequencing revealed significant overlap between the molecular signatures of disease tissue from mutant zebrafish and a mouse model of Marfan syndrome. Moreover, chemical inhibition of TGFβ signaling in wild-type animals phenocopied mutants but chemical activation did not, demonstrating that TGFβ signaling is protective against aneurysm. Human relevance is supported by recent studies implicating genetic lesions in LTBP3 and, potentially, LTBP1 as heritable causes of aortic root aneurysm. Ultimately, our data demonstrate that zebrafish can now be leveraged to interrogate thoracic aneurysmal disease and identify novel lead compounds through small-molecule suppressor screens. This article has an associated First Person interview with the first author of the paper.

A 28 day feeding trial was conducted to investigate the growth performance, immune response and intestinal microbiota of laminarin (LAM) supplemented diets in juvenile largemouth bass (Micropterus salmoides). Four hundred and eighty fish (initial average weight: 0.72 ± 0.04 g) were randomly divided into four groups (40 fish per tank with three replicates in each group) Four diets were prepared with LAM supplementation at the doses of 0 (control), 5 g Kg−1 (LL), 10 g Kg−1 (ML) and 15 g Kg−1 (HL), respectively. No significant difference in the specific growth rate (SGR) and hepatosomatic index (HSI) was observed in fish among the four groups, or in the lipid and ash content of fish flesh. In addition, fish in the LL group exhibited much higher antioxidant capacity (p < 0.05), while the diets with the inclusion of 5 and 10 g Kg−1 LAM remarkably decreased the antioxidant capacity of fish (p > 0.05). Dietary LAM at the dose of 5 g Kg−1 inhibited the transcription of interleukin-1β (il-1β) and tumor necrosis factor-α (tnf-α), while promoting the expression of transforming growth factor-β (tgf-β) in fish intestine. Moreover, the beneficial intestinal bacteria Bacteroide, Comamonas and Mycoplasma abundance significantly increased in fish from the LL group, while the content of opportunistic pathogens Plesiomonas, Aeromonas and Brevinema in fish of the HL group was substantially higher than the control group. Overall, the appropriate dose of supplemented LAM in the diet was 5 g Kg−1, while an excessive supplementation of LAM in the diet led to microbial community instability in largemouth bass.

Infectious bursal disease (IBD) is an acute and highly contagious immunosuppressive disease caused by the infectious bursal disease virus (IBDV), which seriously threatens the healthy development of the poultry industry. Since its spread to China in the early 1990s, the very virulent IBDV (vvIBDV) characterized by high lethality, has been the focus of prevention and control. However, the novel variant IBDV (nVarIBDV), which has been widely prevalent in China since 2017, has brought a new threat to the poultry industry. In this study, the prevalence of IBDV in the important poultry-raising areas of China from 2019 to 2020 was detected. Of these, 45.1% (101/224) of the samples and 61.9% (26/42) of the chicken flocks were shown to be positive for IBDV. For 50 IBDVs, the sequences of the hypervariable region of the VP2 gene in segment A and of the B-marker of the VP1 gene in segment B were analyzed. The results revealed the coexistence of a number of different IBDV genotypes, including A2dB1 (nVar, 26/50, 52.0%), A3B3 (HLJ0504-like, 15/50, 30.0%), A1B1 (classical, 1/50, 2.0%), and A8B1 (attenuated, 1/50, 2.0%). This indicated that the newly emerging nVarIBDV of A2dB1 and the persistently circulating HLJ0504-like vvIBDV of A3B3 are the two important epidemic strains. Furthermore, we established that segment reassortment has occurred among these circulating strains. This study is the first to reveal the novel epidemic characteristics of IBDV since the report of the emerging nVarIBDV of A2dB1 in China.

Synthetic Aperture Radar (SAR), as one of the important and significant methods for obtaining target characteristics in the field of remote sensing, has been applied to many fields including intelligence search, topographic surveying, mapping, and geological survey. In SAR field, the SAR automatic target recognition (SAR ATR) is a significant issue. However, on the other hand, it also has high application value. The development of deep learning has enabled it to be applied to SAR ATR. Some researchers point out that existing convolutional neural network (CNN) paid more attention to texture information, which is often not as good as shape information. Wherefore, this study designs the enhanced-shape CNN, which enhances the target shape at the input. Further, it uses an improved attention module, so that the network can highlight target shape in SAR images. Aiming at the problem of the small scale of the existing SAR data set, a small sample experiment is conducted. Enhanced-shape CNN achieved a recognition rate of 99.29% when trained on the full training set, while it is 89.93% on the one-eighth training data set.

Abstract Background Dexmedetomidine (DEX), a highly sensitive α2-adrenoceptor agonist that possesses anxiolytic, sedative, and analgesic effects, has been documented as a preventative and treatment for emergence agitation (EA). The therapeutic should be given as a loading dose that is infused during a 10 min period, but if a rapid bolus injection is deemed to be hemodynamically appropriate, it would be a more opportune route of administration. So we studied the efficacy of different doses of DEX as a rapid bolus for children to prevent and treat EA. Methods One hundred patients were enrolled and randomly divided into five groups: the control group (group D1), the 0.25 μg/kg DEX group (group D2), the 0.5 μg/kg DEX group (group D3), the 0.75 μg/kg DEX group (group D4), and the 1 μg/kg DEX group (group D5). Heart rate (HR), mean blood pressure (MBP) and blood oxygen saturation (SaO2) were recorded immediately before the study drug injection (baseline) and every minute for 5 min thereafter and at the time points of the skin cut and hernial sac pull. EA and pain were assessed in the post -anesthesia care unit, and any complementary medicine and adverse events were recorded too. Results The incidence of EA was significantly decreased in group D4 and group D5 compared with D1.All groups exhibited similar baseline HR and MBP. After administered, HR and MBP were significantly decreased in all DEX group compared with group D1.In groups D3, D4 and D5, the minimal HR was decreased significantly compared with the groups D1 and duration time of minimal HR significantly prolonged in group D5, but no patient needed treatment. As the dosage increased, the recovery time was significantly prolonged. There were no significant differences in occurrence time of minimal HR, the incidence of complementary medicine and adverse events among groups. Conclusion Rapid intravenous injection (IV) bolus administration of 0.75 and 1.0 μg/kg of DEX could improve the recovery profile by reducing the incidence of EA in children. Although its use resulted in a transient decreases in HR and MBP, DEX was clinically well-tolerated in children. Trial registration No. ChiCTR-IPR-17010658. Registered 17 February 2017.

The aim of this study is to explore the influence of Ganoderma lucidum-derived polysaccharides (GLP) to coix oil-based microemulsion on pharmaceutical performance and anti-lung cancer treatment. GLP-integrated coix oil-based microemulsion (MEs(PS-GLP)) exhibited a clear spherical shape, small particle size, and good hydrodynamics similar to the coix oil-based microemulsion, but showed a lower zeta potential and a better stability. Fluorescence resonance energy transfer analysis presented that GLP was integrated with microemulsion as a single system. Notably, the average molecular distance between polysaccharide and microemulsion was approximately 1.7 nm. The half-maximal inhibitory concentration of MEs(PS-GLP) against A549 cells was about 119 μg/mL. In vivo imaging studies showed that introduction of GLP promoted the tumor-specific accumulation of microemulsion in comparison with controls. In vivo, antitumor results showed that MEs(PS-GLP) markedly inhibited the tumor growth of A549-bearing xenograft nude mice and obviously improve the serum immune index. Collectively, this study demonstrates the potential mechanism of spatial relation between polysaccharides and microemulsion and validates the significances of GLP on tumoral accumulation and antitumor efficacy.

A preferable approach of a combination of a multiwavelength fusion HPLC fingerprint and chemometrics for the quality control of Xiaoer Chiqiao Qingre granules (XCQG) was established in this study. A single-wavelength HPLC fingerprint was performed to identify 18 peaks as common peaks in the beginning, and 12 of them were recognized by HPLC-Q/TOF-MS. To overcome the limitation of the single-wavelength HPLC fingerprint, a three-wavelength (230 nm, 250 nm, and 330 nm) fusion fingerprint was established for a more thorough quality assessment. Six main active ingredients (geniposide, paeoniflorin, forsythin, forsythoside A, baicalin, and wogonoside) were selected as chemical markers for simultaneous quantitative analysis, while the results indicated that the content of other five ingredients except forsythoside A presented comparatively stable. Chemometrics including hierarchical cluster analysis (HCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were performed to evaluate the homogeneity and heterogeneity of sixteen batches of XCQG. The results of the multiwavelength fingerprint were clearly classified into two clusters by HCA, whereas the single-wavelength fingerprint showed no distinct difference between them. OPLS-DA was further employed to prove that the above six main active ingredients made great contributions to clustering. In summary, this integrated analysis provided a better promoted and more comprehensive method to control the quality of XCQG.

Background: Perchlorate, nitrate, and thiocyanate are well-known thyroid disrupters and may contribute to changes in body weight. However, the associations between environmental exposure to these chemicals and obesity-related outcomes remain unclear. Objectives: We aim to examine the urinary levels of perchlorate, nitrate, and thiocyanate and their associations with obesity and abdominal obesity in the U.S. population. Methods: Here, we investigated the data of 16,265 adults aged 20–85 years from the National Health and Nutritional Examination Survey (NHANES) in 2001–2014. Urinary levels of perchlorate, nitrate, and thiocyanate were measured by ion chromatography combined with electrospray tandem mass spectrometry. Obesity and abdominal obesity were defined by the body mass index and waist circumference, respectively. Logistic regression models were used to estimate the associations. Results: Overall, 5794 (35.6%) cases of obesity and 9090 cases (55.9%) of abdominal obesity were observed among the participants. In multivariable-adjusted logistic regression models, urinary nitrate was inversely associated with obesity (p = 0.0022 for trend), while urinary thiocyanate was positively related to obesity (p

Infectious bursal disease virus (IBDV) is a non-enveloped, bi-segmented double-stranded RNA virus and the causative agent of a poultry immunosuppressive disease known as infectious bursal disease (IBD). The novel variant IBDV (nVarIBDV) recently posed a great threat to the development of the poultry industry. In this study, we identified a novel segment-reassortant IBDV strain, IBDV-JS19-14701 (Genotype A2dB3). Phylogenic analysis showed that Segments A and B of IBDV-JS19-14701 were derived from emerging nVarIBDV (Genotype A2dB1) and long-prevalent HLJ0504-like strains (Genotype A3B3) in China, respectively. The pathogenicity of IBDV-JS19-14701 was further evaluated via animal experiments. IBDV-JS19-14701 exhibited a similar virulence to chickens with the nVarIBDV. The identification of this reassortment event is beneficial for understanding the epidemiology of nVarIBDV and will contribute to the efficient prevention and control of IBD.

DM9 domain was first identified in Drosophila melanogaster, and it was subsequently found to integrate with or without other protein domains across a wide range of invertebrates and vertebrates. In the present study, a member of DM9 domain containing protein (DM9CP) family from marine invertebrate Crassostrea gigas (designated CgDM9CP-1), which was only composed of two DM9 domains, was taken as a protein model to study the biological functions of DM9 domain and its molecular determinants. CgDM9CP-1 was found to exhibit high binding specificity and avidity toward d-mannose residue. It served as a pattern recognition receptor (PRR) with a broad range of recognition spectrum to various pathogen-associated molecular patterns, including lipopolysaccharide, peptidylglycan, mannan, and β-1, 3-glucan in a d-mannose-dependent manner, as well as bacteria and fungi. In order to reveal the molecular mechanism underlying its pattern recognition activity, the crystal structures of wild-type and loss-of-function mutants were solved, and Asp22 and Lys43 were found to be the critical residues for ligand recognition. Moreover, CgDM9CP-1 protein was found to mainly distribute on the surface of C. gigas hemocytes, and it could be translocated into cytoplasm and colocalized with the engulfed microbes during hemocyte phagocytosis. The present result clearly indicated that CgDM9CP-1 was a PRR, and it provided an important clue for the better understanding of DM9CP function.

BACKGROUND: MicroRNAs (miRNAs) represent a class of small ncRNAs that repress gene expression on the post-transcriptional level by the degradation or translation inhibition of target mRNA. METHODOLOGY: Three small RNA libraries from oyster haemocytes were sequenced on the Illumina platform to investigate the latent immunomodulation of miRNAs after bacteria challenge and heat stress. Totally, 10,498,663, 8,588,606 and 9,679,663 high-quality reads were obtained in the control, bacteria and bacteria+heat library, respectively, from which 199 oyster miRNAs including 71 known and 128 novel ones were identified. Among these miRNAs, 6 known and 23 novel ones were predicted to possess more than one precursor-coding region, and cgi-miR-10a, cgi-miR-184b, cgi-miR-100, cgi-miR-1984 and cgi-miR-67a were observed to be the most abundant miRNAs in the control library. The expression levels of 22 miRNAs in the bacteria library were significantly higher than those in the control library, while there were another 33 miRNAs whose expression levels were significantly lower than that in the control library. Meanwhile, the expression levels of 65 miRNAs in the bacteria+heat library changed significantly compared to those in the bacteria library. The target genes of these differentially expressed miRNAs were annotated, and they fell in immune and stress-related GO terms including antioxidant, cell killing, death, immune system process, and response to stimulus. Furthermore, there were 42 differentially expressed miRNAs detected in both control/bacteria and bacteria/bacteria+heat comparisons, among which 9 miRNAs displayed the identical pattern in the two comparisons, and the expression alterations of 8 miRNAs were confirmed using quantitative RT-PCR. CONCLUSIONS: These results indicated collectively that immune challenge could induce the expression of immune-related miRNAs, which might modulate the immune response such as redox reaction, phagocytosis and apoptosis, and the expression of some immune-related miRNAs could be also regulated by heat stress to improve the environmental adaption of oyster.

Treatment of wastewater from natural-pigment-manufacturing process is a challenge due to its complex composition and recalcitrance. This study investigated the use of biological method to degrade high-concentration gardenia-yellow-manufacturing wastewater (GYMW) in a laboratory and then applied the anaerobic-aerobic (A/O) process in pilot- and full-scale plants. The maximum anaerobic volume load reached 6 kg chemical oxygen demand (COD) m-3 d in laboratory and 5.5 kg COD m-3 d in full-scale reactor, while the COD removal efficiency was consistently above 90%. Singlefactor control experiments were conducted in sequencing batch reactors to examine the factors that have an influence on the anaerobic treatment, which is responsible for the majority of COD removal. After adjusting the operating temperature, pH, and influent COD, the effluent COD further decreased by 300 mg L-1. In addition, high-performance liquid chromatography, which was used to analyze the main contaminants in GYMW, confirmed that the toxic geniposide was considerably reduced. The high-throughput sequencing analysis illustrated that, under the selective pressure from GYMW, the microbial community structure can degrade biorefractory pollutants enriched in the A/O reactors and contributed to the satisfactory performance of GYMW treatment. [ABSTRACT FROM AUTHOR]

Background: As one of the most popular expression systems, recombinant protein expression in Pichia pastoris relies on the AOX1 promoter (PAOX1) which is strongly induced by methanol. However, the toxic and inflammatory nature of methanol restricts its application, especially in edible and medical products. Therefore, constructing a novel methanol-free system becomes necessary. The kinases involved in PAOX1 activation or repression by different carbon sources may be promising targets. Results: We identified two kinase mutants: Δgut1 and Δdak, both of which showed strong alcohol oxidase activity under non-methanol carbon sources. Based on these two kinases, we constructed two methanol-free expression systems: Δgut1-HpGCY1-glycerol (PAOX1 induced by glycerol) and Δdak-DHA (PAOX1 induced by DHA). By comparing their GFP expression efficiencies, the latter one showed better potential. To further test the Δdak-DHA system, three more recombinant proteins were expressed as examples. We found that the expression ability of our novel methanol-free Δdak-DHA system was generally better than the constitutive GAP promoter, and reached 50-60 % of the traditional methanol induced system. Conclusions: We successfully constructed a novel methanol-free expression system Δdak-DHA. This modified expression platform preserved the favorable regulatable nature of PAOX1, providing a potential alternative to the traditional system. [ABSTRACT FROM AUTHOR]

With high regioselectivity, a series of benzoheterocyclic compounds were synthesized via palladiium-catalyzed phosphine-free C–H arylation of benzothiophenes/benzofurans with aryl MIDA boronates at 30-50 °C in moderate to excellent yields. MIDA boronates were used in C–H arylation of heterocycles for the first time. Under the optimal conditions, the benzothiophenes could be transformed into the β-arylbenzothiophenes, and the benzofurans gave only α-aryl-substituted products. [ABSTRACT FROM AUTHOR]

Designer transcription-activator like effectors (TALEs) is a promising technology and made it possible to edit genomes with higher specificity. Such specific engineering and gene regulation technologies are also being developed using RNA-binding proteins like PUFs and PPRs. The main feature of TALEs, PUFs and PPRs is their repetitive DNA/RNA-binding domains which have single nucleotide binding specificity. Available kits today allow researchers to assemble these repetitive domains in any combination they desire when generating TALEs for gene targeting and editing. However, PCR amplifications of such repetitive DNAs are highly problematic as these mostly fail, generating undesired artifact products or deletions. Here we describe the molecular mechanisms leading to these artifacts. We tested our models also in plasmid templates containing one copy versus two copies of GFP-coding sequence arranged as either direct or inverted repeats. Some limited solutions in amplifying repetitive DNA regions are described. [ABSTRACT FROM AUTHOR]

A new palladium(II) complex based on N,N-dimethylethanolamine, (SP-4-1')-bis[N,N-dimethylaminoethoxy-kN,O]palladium( II) which coordinates with two moles of AcOH, has been synthesized. The structure of the complex has been established by X-ray diffraction analysis. Using this complex as a catalyst, a series of conjugated enynes were successfully synthesized by Sonogashira cross-coupling reaction in the absence of co-catalyst CuX and any ligand at room temperature during 20 hours affording the corresponding products in moderate to excellent yields. The optimized catalytic systems are tolerant in the presence of a broad variety of functional groups in the substrates. The catalytic system was found to be ineffective for vinyl chloride. Moreover, it was found that (Z)- β-bromostyrene reacts with terminal alkynes with retention of the steric configuration and the transformation of most of the Z-isomer did not occur in this reaction. [ABSTRACT FROM AUTHOR]

Infections by many bacterial pathogens rely on their ability to degrade host glycans by producing glycoside hydrolases (GHs). Here, we discovered a conserved multifunctional GH, SsGal-NagA, containing a unique combination of two family 32 carbohydrate-binding modules (CBM), a GH16 domain and a GH20 domain, in the zoonotic pathogen Streptococcus suis 05ZYH33. Enzymatic assays revealed that the SsCBM-GH16 domain displays endo-(β1,4)-galactosidase activity specifically toward the host-derived aGal epitope Gal(a1,3)Gal(b1,4)Glc(NAc)-R, whereas the SsGH20 domain has a wide spectrum of exo-β-Nacetylhexosaminidase activities, including exo-(β1,3)-N-acetylglucosaminidase activity, and employs this activity to act in tandem with SsCBM-GH16 on the αGal-epitope glycan. Further, we found that the CBM32 domain adjacent to the SsGH16 domain is indispensable for SsGH16 catalytic activity. Surface plasmon resonance experiments uncovered that both CBM32 domains specifically bind to αGal-epitope glycan, and together they had a KD of 3.5mM toward a pentasaccharide αGal-epitope glycan. Cell-binding and αGal epitope removal assays revealed that SsGalNagA efficiently binds to both swine erythrocytes and tracheal epithelial cells and removes the aGal epitope from these cells, suggesting that SsGalNagA functions in nutrient acquisition or alters host signaling in S. suis. Both binding and removal activities were blocked by an αGal-epitope glycan. SsGalNagA is the first enzyme reported to sequentially act on a glycan containing the αGal epitope. These findings shed detailed light on the evolution of GHs and an important hostpathogen interaction. [ABSTRACT FROM AUTHOR]

The immune signaling pathway mediated by Dectin-1 is important in mammals to modulate the production of IL-17 and TNF-α. Recently, IL-17 and TNF have also been characterized in invertebrates to play crucial roles in antibacterial immune responses, although the immune recognition and regulation mechanisms to produce IL-17 and TNF are still not well investigated. In the current study, a novel C-type lectin receptor (named CgCLec-HTM) with a signal peptide, a carbohydrate recognition domain, a transmembrane domain, and a nonclassical ITAM (hemITAM) in the cytoplasmic tail was identified from oyster Crassostrea gigas. CgCLec-HTM could bind LPS and various bacteria. After binding to its ligands, CgCLec-HTM was associated with the Src homology 2 (SH2) domain of spleen tyrosine kinase (CgSyk) by the hemITAM in its cytoplasmic tail to promote ERK (CgERK) phosphorylation. The activated CgERK could interact with CgRel to induce CgRel nuclear translocation. The CgRel in the nucleus eventually induced the transcription of CgIL-17s and CgTNF. The results demonstrated that CgCLec-HTM with a broad binding spectrum of bacteria could be associated with CgSyk to transfer immune signals into the intracellular ERK-Rel pathway to induce CgIL-17 and CgTNF production. [ABSTRACT FROM AUTHOR]