bluuebunny/crossref_metadata_2025 huggingface dataset:
Essential Oils Improve the Survival of Gnotobiotic Brine Shrimp (Artemia franciscana) Challenged With Vibrio campbellii
Authors: Zheng Xiaoting , Han Biao , Kumar Vikash , Feyaerts Adam F. , Van Dijck Patrick , Bossier Peter
Published: October 2021

The halophilic aquatic bacterium Vibrio campbellii is an important aquatic pathogen, capable of causing vibriosis in shrimp and fish resulting in significant economic losses. In a previous work, essential oils (EOs) extracts from Melaleuca alternifolia, Litsea citrata, and Eucalyptus citriodora were found to inhibit the growth of V. campbellii in vitro. This study aimed to determine in vivo EOs’ potential protective effect towards gnotobiotic brine shrimp Artemia franciscana, challenged with V. campbellii. The study showed that brine shrimp larvae supplemented with EOs of M. alternifolia (0.0008%) and L. citrata (0.002%) displayed significantly increased survival against V. campbellii. The results indicated that supplementation of these EOs increased the expression of immune-related genes (either in the presence or absence of the pathogen), probably contributing to enhanced protection. Furthermore, in vitro studies indicated that some EOs modulated the expression of virulence factors including swimming motility, biofilm formation, and gelatinase and lipase activity, while flow cytometry data and regrowth assay indicated that these EOs do not exhibit antimicrobial activity as V. campbellii grew at the tested concentrations [M. alternifolia (0.0008%) and L. citrata (0.002%)]. Our findings suggest that EOs extracted from M. alternifolia and L. citrata, can modulate virulence factor production and immunological responses and might hence become part of an intervention strategy to control vibriosis in a fish or shrimp aquaculture setting, a hypothesis that needs to be validated in the future.
New Artificial Intelligence Score and Immune Infiltrates as Prognostic Factors in Colorectal Cancer With Brain Metastases
Authors: Randrian Violaine , Desette Amandine , Emambux Sheik , Derangere Valentin , Roussille Pauline , Frouin Eric , Godet Julie , Karayan-Tapon Lucie , Ghiringhelli François , Tougeron David
Published: October 2021

Incidence of brain metastases has increased in patients with colorectal cancer (CRC) as their survival has improved. CD3 T-cells and, lately, DGMate (DiGital tuMor pArameTErs) score, have been identified as prognostic factors in locally advanced CRC. Until now, there is no data concerning the prognostic value of these markers in patients with CRC-derived brain metastases. All consecutive patients with CRC-derived brain metastases diagnosed between 2000 and 2017 were retrospectively included. Staining for CD3, CD8, PD-1, PD-L1 and DGMate analyses were performed using tissue micro-array from primary tumors and, if available, brain metastases. All in all, 83 patients were included with 80 primary tumor samples and 37 brain metastases samples available. CD3 and CD8 T-cell infiltration was higher in primary tumors compared to brain metastases. We observed a significant higher DGMate score in rectal tumors compared to colon tumors (p=0.03). We also noted a trend of higher CD3 T-cell infiltration in primary tumors when brain metastases were both supra and subtentorial compared to brain metastases that were only subtentorial or supratentorial (p=0.36 and p=0.03, respectively). No correlation was found between CD3 or CD8 infiltration or DGMate score in primary tumors or brain metastases and overall survival (OS) in the overall population. In patients with rectal tumors, a high DGMate score in brain metastases was associated with longer OS (13.4 ± 6.1 months versus 6.1 ± 1.4 months, p=0.02). High CD3 T-cell infiltration in brain metastases was associated with lower OS in patients with supratentorial brain metastases (9.8 ± 3.3 months versus 16.7 ± 5.9 months, p=0.03). PD-L1 overexpression was rare, both in primary tumors and brain metastases, but PD-L1 positive primary tumors were associated with worse OS (p=0.01). In contrast to breast and lung cancer derived brain metastases, CD3 and CD8 infiltration and DGMate score are not major prognostic factors in patients with CRC-derived brain metastases.
Inclusion of the Inducible Caspase 9 Suicide Gene in CAR Construct Increases Safety of CAR.CD19 T Cell Therapy in B-Cell Malignancies
Authors: Guercio Marika , Manni Simona , Boffa Iolanda , Caruso Simona , Di Cecca Stefano , Sinibaldi Matilde , Abbaszadeh Zeinab , Camera Antonio , Ciccone Roselia , Polito Vinicia Assunta , Ferrandino Francesca , Reddel Sofia , Catanoso Maria Luigia , Bocceri Emilia , Del Bufalo Francesca , Algeri Mattia , De Angelis Biagio , Quintarelli Concetta , Locatelli Franco
Published: October 2021

T cells engineered with chimeric antigen receptor (CAR-T cells) are an effective treatment in patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia or B-cell non-Hodgkin lymphoma. Despite the reported exciting clinical results, the CAR-T cell approach needs efforts to improve the safety profile, limiting the occurrence of adverse events in patients given this treatment. Besides the most common side effects, such as cytokine release syndrome and CAR-T cell–related encephalopathy syndrome, another potential issue involves the inadvertent transduction of leukemia B cells with the CAR construct during the manufacturing process, thus leading to the possibility of a peculiar mechanism of antigen masking and treatment resistance. In this study, we investigated whether the inclusion of the inducible caspase 9 (iC9) suicide gene in the CAR construct design could be an effective safety switch to control malignant CAR+ B cells, ultimately counteracting this serious adverse event. iC9 is a suicide gene able to be activated through binding with an otherwise inert small biomolecule, known as AP1903. The exposure of iC9.CAR.CD19-DAUDI lymphoma and iC9.CAR.CD19-NALM-6 leukemia cells in vitro to 20 nM of AP1903 resulted into the prompt elimination of CAR+ B-leukemia/lymphoma cell lines. The results obtained in the animal model corroborate in vitro data, since iC9.CAR.CD19+ tumor cells were controlled in vivo by the activation of the suicide gene through administration of AP1903. Altogether, our data indicate that the inclusion of the iC9 suicide gene may result in a safe CAR-T cell product, even when manufacturing starts from biological materials characterized by heavy leukemia blast contamination.
Single-Cell Analysis Revealed the Role of CD8+ Effector T Cells in Preventing Cardioprotective Macrophage Differentiation in the Early Phase of Heart Failure
Authors: Komai Kyoko , Ito Minako , Nomura Seitaro , Shichino Shigeyuki , Katoh Manami , Yamada Shintaro , Ko Toshiyuki , Iizuka-Koga Mana , Nakatsukasa Hiroko , Yoshimura Akihiko
Published: October 2021

Heart failure is a complex clinical syndrome characterized by insufficient cardiac function. Heart-resident and infiltrated macrophages have been shown to play important roles in the cardiac remodeling that occurs in response to cardiac pressure overload. However, the possible roles of T cells in this process, have not been well characterized. Here we show that T cell depletion conferred late-stage heart protection but induced cardioprotective hypertrophy at an early stage of heart failure caused by cardiac pressure overload. Single-cell RNA sequencing analysis revealed that CD8+T cell depletion induced cardioprotective hypertrophy characterized with the expression of mitochondrial genes and growth factor receptor genes. CD8+T cells regulated the conversion of both cardiac-resident macrophages and infiltrated macrophages into cardioprotective macrophages expressing growth factor genes such as Areg, Osm, and Igf1, which have been shown to be essential for the myocardial adaptive response after cardiac pressure overload. Our results demonstrate a dynamic interplay between cardiac CD8+T cells and macrophages that is necessary for adaptation to cardiac stress, highlighting the homeostatic functions of resident and infiltrated macrophages in the heart.
The Honey Bee Gene Bee Antiviral Protein-1 Is a Taxonomically Restricted Antiviral Immune Gene
Authors: McMenamin Alexander J. , Brutscher Laura M. , Daughenbaugh Katie F. , Flenniken Michelle L.
Published: October 2021

Insects have evolved a wide range of strategies to combat invading pathogens, including viruses. Genes that encode proteins involved in immune responses often evolve under positive selection due to their co-evolution with pathogens. Insect antiviral defense includes the RNA interference (RNAi) mechanism, which is triggered by recognition of non-self, virally produced, double-stranded RNAs. Indeed, insect RNAi genes (e.g., dicer and argonaute-2) are under high selective pressure. Honey bees (Apis mellifera) are eusocial insects that respond to viral infections via both sequence specific RNAi and a non-sequence specific dsRNA triggered pathway, which is less well-characterized. A transcriptome-level study of virus-infected and/or dsRNA-treated honey bees revealed increased expression of a novel antiviral gene, GenBank: MF116383, and in vivo experiments confirmed its antiviral function. Due to in silico annotation and sequence similarity, MF116383 was originally annotated as a probable cyclin-dependent serine/threonine-protein kinase. In this study, we confirmed that MF116383 limits virus infection, and carried out further bioinformatic and phylogenetic analyses to better characterize this important gene—which we renamed bee antiviral protein-1 (bap1). Phylogenetic analysis revealed that bap1 is taxonomically restricted to Hymenoptera and Blatella germanica (the German cockroach) and that the majority of bap1 amino acids are evolving under neutral selection. This is in-line with the results from structural prediction tools that indicate Bap1 is a highly disordered protein, which likely has relaxed structural constraints. Assessment of honey bee gene expression using a weighted gene correlation network analysis revealed that bap1 expression was highly correlated with several immune genes—most notably argonaute-2. The coexpression of bap1 and argonaute-2 was confirmed in an independent dataset that accounted for the effect of virus abundance. Together, these data demonstrate that bap1 is a taxonomically restricted, rapidly evolving antiviral immune gene. Future work will determine the role of bap1 in limiting replication of other viruses and examine the signal cascade responsible for regulating the expression of bap1 and other honey bee antiviral defense genes, including coexpressed ago-2, and determine whether the virus limiting function of bap1 acts in parallel or in tandem with RNAi.
Industry Partnership: Lab on Chip Chemical Sensor Technology for Ocean Observing
Authors: Mowlem Matt , Beaton Alexander , Pascal Robin , Schaap Allison , Loucaides Socratis , Monk Sam , Morris Andrew , Cardwell Christopher L. , Fowell Sara E. , Patey Matthew D. , López-García Patricia
Published: October 2021

We introduce for the first time a new product line able to make high accuracy measurements of a number of water chemistry parameters in situ: i.e., submerged in the environment including in the deep sea (to 6,000 m). This product is based on the developments of in situ lab on chip technology at the National Oceanography Centre (NOC), and the University of Southampton and is produced under license by Clearwater Sensors Ltd., a start-up and industrial partner in bringing this technology to global availability and further developing its potential. The technology has already been deployed by the NOC, and with their partners worldwide over 200 times including to depths of ∼4,800 m, in turbid estuaries and rivers, and for up to a year in seasonally ice-covered regions of the arctic. The technology is capable of making accurate determinations of chemical and biological parameters that require reagents and which produce an electrical, absorbance, fluorescence, or luminescence signal. As such it is suitable for a wide range of environmental measurements. Whilst further parameters are in development across this partnership, Nitrate, Nitrite, Phosphate, Silicate, Iron, and pH sensors are currently available commercially. Theses sensors use microfluidics and optics combined in an optofluidic chip with electromechanical valves and pumps mounted upon it to mix water samples with reagents and measure the optical response. An overview of the sensors and the underlying components and technologies is given together with examples of deployments and integrations with observing platforms such as gliders, autonomous underwater vehicles and moorings.
Similarities and Differences Between Two Deadly Caribbean Coral Diseases: White Plague and Stony Coral Tissue Loss Disease
Authors: Cróquer Aldo , Weil Ernesto , Rogers Caroline S.
Published: October 2021

For several decades, white plagues (WPDs: WPD-I, II and III) and more recently, stony coral tissue loss disease (SCTLD) have significantly impacted Caribbean corals. These diseases are often difficult to separate in the field as they produce similar gross signs. Here we aimed to compare what we know about WPD and SCTLD in terms of: (1) pathology, (2) etiology, and (3) epizootiology. We reviewed over 114 peer-reviewed publications from 1973 to 2021. Overall, WPD and SCTLD resemble each other macroscopically, mainly due to the rapid tissue loss they produce in their hosts, however, SCTLD has a more concise case definition. Multiple-coalescent lesions are often observed in colonies with SCTLD and rarely in WPD. A unique diagnostic sign of SCTLD is the presence of bleached circular areas when SCTLD lesions are first appearing in the colony. The paucity of histopathologic archives for WPDs for multiple species across geographies makes it impossible to tell if WPD is the same as SCTLD. Both diseases alter the coral microbiome. WPD is controversially regarded as a bacterial infection and more recently a viral infection, whereas for SCTLD the etiology has not been identified, but the putative pathogen, likely to be a virus, has not been confirmed yet. Most striking differences between WPD and SCTLD have been related to duration and phases of epizootic events and mortality rates. While both diseases may become highly prevalent on reefs, SCTLD seems to be more persistent even throughout years. Both transmit directly (contact) and horizontally (waterborne), but organism-mediated transmission is only proven for WPD-II. Given the differences and similarities between these diseases, more detailed information is needed for a better comparison. Specifically, it is important to focus on: (1) tagging colonies to look at disease progression and tissue mortality rates, (2) tracking the fate of the epizootic event by looking at initial coral species affected, the features of lesions and how they spread over colonies and to a wider range of hosts, (3) persistence across years, and (4) repetitive sampling to look at changes in the microbiome as the disease progresses. Our review shows that WPDs and SCTLD are the major causes of coral tissue loss recorded in the Caribbean.
Saltmarsh Resilience to Periodic Shifts in Tidal Channels
Authors: Ladd Cai John Tomos , Duggan-Edwards Mollie Frances , Pagès Jordi F. , Skov Martin Wiggers
Published: October 2021

Resilience of coastal ecosystems to climate change is largely determined by the interaction between plants and the surrounding tidal environment. Research has tended to focus on processes operating at the local scale to explain resilience mechanisms, overlooking potentially important landscape-scale processes and patterns. We show from aerial images spanning 67 years across 3 estuaries that saltmarsh loss was compensated by expansion elsewhere in the estuary when tidal channels shifted position. Compensatory expansion rates were as high as 6 m/yr. This phenomenon of “geomorphic compensation” represents a hitherto overlooked large-scale self-organizing pattern that facilitates the long-term persistence of marshes in estuaries. The geomorphic compensation pattern likely also occurs in other hydrological systems including mangrove forests, and seagrass meadows, and river islands. Compensatory erosion-expansion patterns occurred at the same time as net marsh extent increased by between 120 and 235% across all three estuaries. Marsh expansion mostly occurred in the lower parts of each estuary, where channel migration and compensatory expansion was less evident. Patterns of geomorphic compensation therefore appear to operate at discrete spatio-temporal scales, nested within a hierarchy of coastal morphodynamic processes that govern longer-term patterns of either net marsh gain or loss. Coastal ecosystem resilience can therefore only be fully appreciated when examining erosion and expansion patterns at both local and landscape scales. The intrinsic dynamics of marshes described here have important implications for the long-term delivery of ecosystem services.
Imperfect Estimation of Lepeophtheirus salmonis Abundance and Its Impact on Salmon Lice Treatment on Atlantic Salmon Farms
Authors: Jeong Jaewoon , Stormoen Marit , Thakur Krishna K. , Revie Crawford W.
Published: October 2021

Accurate monitoring of sea lice levels on salmon farms is critical to the efficient management of louse infestation, as decisions around whether and when to apply treatment depend on an estimation of abundance. However, as with all sampling, the estimated abundance of salmon lice through sampling salmon cannot perfectly represent the abundance on a given farm. While suggestions to improve the accuracy of lice abundance estimates have previously been made, the significance of the accuracy of such estimation has been poorly understood. Understanding the extent of error or bias in sample estimates can facilitate an assessment as to how influential this “imperfect” information will likely be on management decisions, and support methods to mitigate negative outcomes associated with such imperfect estimates. Here, we built a model of a hypothetical Atlantic salmon farm using ordinary differential equations and simulated salmon lice (Lepeophtheirus salmonis) abundance over an entire production cycle, during which salmon were periodically sampled using Monte Carlo approaches that adopted a variety of sample sizes, treatment thresholds, and sampling intervals. The model could thus track two instances of salmon lice abundance: true abundance (based on the underlying model) and monitored abundance (based on the values that could be estimated under different simulated sampling protocols). Treatments, which depend on monitored abundance, could be characterized as early, timely, or late, as a result of over-estimation, appropriate estimation, and under-estimation, respectively. To achieve timely treatment, it is important to delay treatments until true abundance equals some treatment threshold and to execute treatment as soon as this threshold is reached. Adopting larger sample sizes increased the frequency of timely treatments, largely by reducing the incidence of early treatments due to less variance in the monitored abundance. Changes in sampling interval and treatment threshold also influenced the accuracy of abundance estimates and thus the frequency of timely treatments. This study has implications for the manner in which fish should be sampled on salmon farms to ensure accurate salmon lice abundance estimates and consequently the effective application treatment.
Progress on Polymer Composites With Low Dielectric Constant and Low Dielectric Loss for High-Frequency Signal Transmission
Authors: Wang Lu , Yang Jing , Cheng Wenhua , Zou Jiajia , Zhao Dan
Published: October 2021

The development of information transmission technology towards high-frequency microwaves and highly integrated and multi-functional electronic devices has been the mainstream direction of the current communication technology. During signal transmission, resistance-capacitance time delay, crosstalk, energy consumption increase and impedance mismatch restrict the high density and miniaturization of Printed circuit board (PCB). In order to achieve high fidelity and low delay characteristics of high-frequency signal transmission, the development of interlayer dielectric materials with low dielectric constant (Dk) and low dielectric loss factor (Df) has become the focus of researchers. This review introduces the dielectric loss mechanism of polymer composites and the resin matrix commonly used in several high-frequency copper-clad laminates, and mainly describes how to reduce the dielectric constant and dielectric loss of materials from the level of molecular structure design, as well as the effect of fillers on the dielectric properties of polymer substrates. As a kind of potential functional fillers for dielectric polymeric composites, the carbon nanofillers are used to tailor the dielectric properties of their composites via different dimensions and loadings, as well as their proper preparation methods. This review finally summarizes the interface bonding failure mechanism and a feasible idea to optimize the dielectric properties of polymer matrix composites is also proposed.
Gene Signatures Detect Damaged Liver Sinusoidal Endothelial Cells in Chronic Liver Diseases
Authors: Verhulst Stefaan , van Os Elise Anne , De Smet Vincent , Eysackers Nathalie , Mannaerts Inge , van Grunsven Leo A.
Published: October 2021

Liver sinusoidal endothelial cells have a gatekeeper function in liver homeostasis by permitting substrates from the bloodstream into the space of Disse and regulating hepatic stellate cell activation status. Maintenance of LSEC's highly specialized phenotype is crucial for liver homeostasis. During liver fibrosis and cirrhosis, LSEC phenotype and functions are lost by processes known as capillarization and LSEC dysfunction. LSEC capillarization can be demonstrated by the loss of fenestrae (cytoplasmic pores) and the manifestation of a basement membrane. Currently, no protein or genetic markers can clearly distinguish healthy from damaged LSECs in acute or chronic liver disease. Single cell (sc)RNA sequencing efforts have identified several LSEC populations in mouse models for liver disease and in human cirrhotic livers. Still, there are no clearly defined genesets that can identify LSECs or dysfunctional LSEC populations in transcriptome data. Here, we developed genesets that are enriched in healthy and damaged LSECs which correlated very strongly with healthy and early stage- vs. advanced human liver diseases. A damaged LSEC signature comprised of Fabp4/5 and Vwf/a1 was established which could efficiently identify damaged endothelial cells in single cell RNAseq data sets. In LSECs from an acute CCl4 liver injury mouse model, Fabp4/5 and Vwf/a1 expression is induced within 1–3 days while in cirrhotic human livers these 4 genes are highly enriched in damaged LSECs. In conclusion, our newly developed gene signature of damaged LSECs can be applicable to a wide range of liver disease etiologies, implicating a common transcriptional alteration mechanism in LSEC damage.
Inducible Resistance to β-Lactams in Oxacillin-Susceptible mecA1-Positive Staphylococcus sciuri Isolated From Retail Pork
Authors: Cai Yifei , Zheng Liangjun , Lu Yao , Zhao Xu , Sun Yanting , Tang Xingyuan , Xiao Jinhe , Wang Chen , Tong Chao , Zhao Lili , Xiao Yingping , Zhao Xin , Xue Huping
Published: October 2021

Most isolated strains of Staphylococcus sciuri contain mecA1, the evolutionary origin of mecA, but are sensitive to β-lactams (OS-MRSS, oxacillin-susceptible mecA1-positive S. sciuri). In order to improve the efficacy of antibiotic treatment, it is important to clarify whether the resistance of OS-MRSS to β-lactams is an inducible phenotype. In this study, three OS-MRSS strains with oxacillin MIC = 1 μg/ml were isolated from 29 retail pork samples. The resistance of OS-MRSS to β-lactams (MIC > 256 μg/ml) was found to be induced by oxacillin, and the induced resistance was observed to remain stable within a certain period of time. Interestingly, the induced β-lactam resistance was not caused by mecA1, heterogeneous resistance, or any genetic mutation, but mainly due to increased wall teichoic acid (WTA) synthesis that thickened the cell wall. The induced strains also showed slower growth rate, as well as decreased adhesion ability and biofilm thickness. These phenotypes were found to be achieved through altered gene expression in associated pathways, such as the citrate cycle and pentose phosphate pathway. The results challenge the traditional antibiotic sensitivity test. In the presence of β-lactam antibiotics, OS-MRSS that was initially sensitive to β-lactams was observed to gradually develop β-lactam resistance in several days. This often-neglected phenomenon in antibiotic sensitivity tests requires further research attention.
The Pneumococcal Divisome: Dynamic Control of Streptococcus pneumoniae Cell Division
Authors: Briggs Nicholas S. , Bruce Kevin E. , Naskar Souvik , Winkler Malcolm E. , Roper David I.
Published: October 2021

Cell division inStreptococcus pneumoniae(pneumococcus) is performed and regulated by a protein complex consisting of at least 14 different protein elements; known as the divisome. Recent findings have advanced our understanding of the molecular events surrounding this process and have provided new understanding of the mechanisms that occur during the division of pneumococcus. This review will provide an overview of the key protein complexes and how they are involved in cell division. We will discuss the interaction of proteins in the divisome complex that underpin the control mechanisms for cell division and cell wall synthesis and remodelling that are required inS. pneumoniae, including the involvement of virulence factors and capsular polysaccharides.
Inter-Genera Colonization of Ocimum tenuiflorum Endophytes in Tomato and Their Complementary Effects on Na+/K+ Balance, Oxidative Stress Regulation, and Root Architecture Under Elevated Soil Salinity
Authors: Sahu Pramod K. , Singh Shailendra , Singh Udai B. , Chakdar Hillol , Sharma Pawan K. , Sarma Birinchi K. , Teli Basavaraj , Bajpai Raina , Bhowmik Arpan , Singh Harsh V. , Saxena Anil K.
Published: October 2021

Endophytic bacilli of ethano-botanical plant Ocimum tenuiflorum were screened for salt stress-alleviating traits in tomato. Four promising O. tenuiflorum endophytes (Bacillus safensis BTL5, Bacillus haynesii GTR8, Bacillus paralicheniformis GTR11, and Bacillus altitudinis GTS16) were used in this study. Confocal scanning laser microscopic studies revealed the inter-genera colonization of O. tenuiflorum endophytes in tomato plants, giving insights for widening the applicability of potential endophytes to other crops. Furthermore, in a pot trial under 150 mM NaCl concentration, the inoculated endophytes contributed in reducing salt toxicity and improving recovery from salt-induced oxidative stress by different mechanisms. Reduction in reactive oxygen species (ROS) (sub-cellular H2O2 and superoxide) accumulation was observed besides lowering programmed cell death and increasing chlorophyll content. Endophyte inoculation supplemented the plant antioxidant enzyme system via the modulation of enzymatic antioxidants, viz., peroxidase, ascorbate peroxidase, superoxide dismutase, and catalase, apart from increasing proline and total phenolics. Antioxidants like proline have dual roles of antioxidants and osmoregulation, which might also have contributed to improved water relation under elevated salinity. Root architecture, viz., root length, projection area, surface area, average diameter, tips, forks, crossings, and the number of links, was improved upon inoculation, indicating healthy root growth and enhanced nutrient flow and water homeostasis. Regulation of Na+/K+ balance and water homeostasis in the plants were also evident from the modulation in the expression of abiotic stress-responsive genes, viz., LKT1, NHX1, SOS1, LePIP2, SlERF16, and SlWRKY39. Shoot tissues staining with light-excitable Na+ indicator Sodium GreenTM Tetra (tetramethylammonium) salt showed low sodium transport and accumulation in endophyte-inoculated plants. All four endophytes exhibited different mechanisms for stress alleviation and indicated complementary effects on plant growth. Furthermore, this could be harnessed in the form of a consortium for salt stress alleviation. The present study established inter-genera colonization of O. tenuiflorum endophytes in tomato and revealed its potential in maintaining Na+/K+ balance, reducing ROS, and improving root architecture under elevated salinity.
Nitrogeniibacter aestuarii sp. nov., a Novel Nitrogen-Fixing Bacterium Affiliated to the Family Zoogloeaceae and Phylogeny of the Family Zoogloeaceae Revisited
Authors: Huang Zhaobin , Liu Renju , Chen Fenghua , Lai Qiliang , Oren Aharon , Shao Zongze
Published: October 2021

Members of the family Zoogloeaceae within the order Rhodocyclales are found to play vital roles in terrestrial and aquatic ecosystems by participating in biofloc formation in activated sludge, polycyclic aromatic hydrocarbon degradation, and nitrogen metabolism, such as denitrification and nitrogen fixation. Here, two bacterial strains designated H1-1-2AT and ZN11-R3-1 affiliated to the family Zoogloeaceae were isolated from coastal wetland habitats. The 16S rRNA gene sequences of the two strains were 100% identical and had maximum similarity with Nitrogeniibacter mangrovi M9-3-2T of 98.4% and ≤94.5% with other species. Phylogenetic analysis suggested that the two strains belonged to a single species and formed a novel monophyletic branch affiliated to the genus Nitrogeniibacter. The average nucleotide identity (ANI) value and digital DNA-DNA hybridization (dDDH) estimate between the two strains and N. mangrovi M9-3-2T were 78.5–78.7% and 21.4–21.6%, respectively, indicating that the two strains represent a novel species. The genomes of strain H1-1-2AT (complete genome) and ZN11-R3-1 (draft genome) were 4.7Mbp in length encoding ~4,360 functional genes. The DNA G+C content was 62.7%. Nitrogen fixation genes were found in the two strains, which were responsible for the growth on nitrogen-free medium, whereas denitrification genes found in N. mangrovi M9-3-2T were absent in the two strains. The respiratory quinone was ubiquinone-8. The major polar lipids consisted of phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, and aminophospholipid. The major fatty acids were summed feature 3 (C16:1ω7c and C16:1ω6c), C16:0, C12:0, and C10:0 3-OH. Based on genomic, phenotypic, and chemotaxonomic characterizations, strains H1-1-2AT and ZN11-R3-1 represent a novel species of the genus Nitrogeniibacter, for which the name Nitrogeniibacter aestuarii sp. nov. is proposed. The type strain is H1-1-2AT (=MCCC 1K04284T=KCTC 82672T), and additional strain is ZN11-R3-1 (=MCCC 1A17971=KCTC 82671). Additionally, phylogenomic analysis of the members of the family Zoogloeaceae including type strains and uncultivated bacteria was performed, using the Genome Taxonomic Database toolkit (GTDB-Tk). Combined with the 16S rRNA gene phylogeny, four novel genera, Parazoarcus gen. nov., Pseudazoarcus gen. nov., Pseudothauera gen. nov., and Cognatazoarcus gen. nov., were proposed. This study provided new insights to the taxonomy of the family Zoogloeaceae.
Bioevaluation and Targeted Modification of Temporin-FL From the Skin Secretion of Dark-Spotted Frog (Pelophylax nigromaculatus)
Authors: Wang Wenjie , Yang Wanqing , Du Shouying , Xi Xinping , Ma Chengbang , Wang Lei , Zhou Mei , Chen Tianbao
Published: October 2021

Bioactive proteins secreted by the granular glands of amphibian skin play a self-defensive role, and exhibit various bioactivities in vitro and in vivo. In light of the severity of the problem of antibiotic resistance for treating infections, many antimicrobial peptides (AMPs) have been developed and applied in clinical microbial treatments. We identified a naturally derived and potent antimicrobial peptide, temporin-FL, obtained from the skin secretion of Pelophylax nigromaculatus via “shotgun” cloning. Two truncated analogues of this peptide were chemically synthesized to explore their structural-functional relationships. The results of a functional evaluation showed that all of the tested AMPs were active against Gram-positive bacteria and fungi and demonstrated antibiofilm activity against methicillin-resistant Staphylococcus aureus (MRSA) but did not have an effect on Gram-negative bacteria. Moreover, temporin-FLa demonstrated a higher level of hydrophobicity and enhanced antimicrobial efficiency, as well as hemolytic activity and cell cytotoxicity than the parent peptide. Temporin-FLb, which evidenced significantly less α-helicity, was less potent against various microbes but exhibited lower cytotoxicity relating to mammalian cells. Both of the synthesized analogues possessed a higher therapeutic index than the original peptide. Moreover, the membrane permeability assay and the measuring membrane depolarization assay declared that temporin-FL and its analogues induced membrane fracture and depolarization; the quantitative biofilm formation assay and the observations of MRSA biofilms using scanning electron microscopy revealed that the AMPs caused biofilm disruption and blocked biofilm formation, the former experiments all confirming their antimicrobial and antibiofilm properties. Hence, the optimization of temporin-FL offers insights for the discovery of new drugs for treating MRSA infections.
Association Between Eating Speed and Metabolic Syndrome: A Systematic Review and Meta-Analysis
Authors: Yuan Shu-qian , Liu Ying-ming , Liang Wei , Li Fei-fei , Zeng Yuan , Liu Yin-yue , Huang Shu-zhen , He Quan-yuan , Quach Binh , Jiao Jiao , Baker Julien S. , Yang Yi-de
Published: October 2021

Objective: This review aimed to systematically summarize and meta-analyze the association between eating speed and metabolic syndrome (MetS).

Methods: Following the Preferred Reporting Items for Systematic Reviews, and Meta Analyses (PRISMA) guidelines, four electronic databases (PubMed, Web of Science, MEDLINE, and EMBASE) were searched until March 2021 to identify eligible articles based on a series of inclusion and exclusion criteria. Heterogeneity was examined using I2 statistics. Using random-effects models, the pooled odds ratios (ORs), and 95% CIs were calculated to evaluate the association between eating speed with MetS and its components, including central obesity, blood pressure (BP), high-density lipoprotein cholesterol (HDL), triglyceride (TG), and fasting plasma glucose (FPG).

Results: Of the 8,500 original hits generated by the systematic search, 29 eligible studies with moderate-to-high quality were included, involving 465,155 subjects. The meta-analysis revealed that eating faster was significantly associated with higher risks of MetS (OR = 1.54, 95% CI: 1.27–1.86), central obesity (OR = 1.54, 95% CI: 1.37–1.73), elevated BP (OR = 1.26, 95% CI: 1.13–1.40), low HDL (OR = 1.23, 95% CI: 1.15–1.31), elevated TG (OR = 1.29, 95% CI: 1.18–1.42), and elevated FPG (OR = 1.16, 95% CI: 1.06–1.27) compared to eating slowly.

Conclusions: The results of the review indicated that eating speed was significantly associated with MetS and its components. Interventions related to decreasing eating speed may be beneficial for the management of MetS.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021242213, identifier: CRD42021242213.
Proposed Nutrient Standards for Plant-Based Beverages Intended as Milk Alternatives
Authors: Drewnowski Adam , Henry Christiani Jeyakumar , Dwyer Johanna T.
Published: October 2021

Background: Plant-based beverages (PBB) that are marketed as alternatives to cow milk are gaining in popularity worldwide. Nutrient quality of PBB can be highly variable.

Objective: To develop a set of voluntary or mandatory nutrient standards for the PBB product category in order to assist innovation and guide product development and reformulation.

Methods: The present goal was to develop standards for PBB energy content, minimum protein content and quality, maximum content for added fat, sugar, and salt, and to suggest fortification levels for selected vitamins and minerals. The standards were based on dietary recommendations and guidelines and current practices of federal agencies in the US.

Results: The proposed energy and nutrient content for PBB milk alternatives are maximum 85–100 kcal energy per 100 g; a minimum for 2.2/100 g of high-quality protein, low content of saturated fat (<0.75/100 g) and added sugar (5.3–6.25/100 g) and consistent fortification with calcium, vitamins A, D, B-2, and B-12 at levels comparable to those found in cow milk (1%). Ideally, the protein content ought to be increased (2.8/100 g) and added sugar content reduced even further (2.7–3.1/100 g) for “best of class” products. These proposed standards were applied to the 641 existing PBB products listed in the 2018 version of the USDA Branded Food Products Database (BFPDB). The standards were met by <5% of the PBB on the US market.

Conclusion: Often viewed as equivalent to milk in nutritional value, many PBB are often low in protein and are fortified with varying amounts of calcium, and vitamins A and D. Nutrient standards for this category should be adopted by the food industry, by public health regulatory authorities, and by standardization bodies such as the Codex Alimentarius.
Prognostic Value of CEA, CA19-9, CA125, CA724, and CA242 in Serum and Ascites in Pseudomyxoma Peritonei
Authors: Liang Lei , Fang Jingyang , Han Xuedi , Zhai Xichao , Song Yan , Lu Yiyan , Zhang Qian , Ma Ruiqing
Published: October 2021

Purpose

To investigate the expression of carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), CA19-9, CA724, and CA242 in serum and ascites of pseudomyxoma peritonei (PMP) patients and evaluate the predictive value of these elevated biomarkers in pathological grade, completeness of cytoreduction (CC), and survival.

Methods

From May 2009 to October 2019, a total of 512 patients diagnosed with PMP through pathology in Aerospace Center Hospital were enrolled. The serum and ascites tumor biomarkers were obtained. The diagnostic values between serum and ascites biomarkers in pathology and CC were compared by the receiver operating characteristic (ROC) curves. The correlation between pathology, cytoreduction, and biomarkers was calculated by univariate and multivariate logistic regression. The associations between different numbers of elevated biomarkers and survival status were examined using univariate and multivariate backward Cox proportional hazard regression models.

Results

The results showed that the areas under the ROC curves (AUROC) in the diagnosis of CC were 0.798 (95% CI: 0.760–0.836) and 0.632 (95% CI: 0.588–0.676) in serum and ascites biomarkers, respectively. The elevated serum and ascites biomarkers were independent risk factors for both pathology and CC. The 1-year, 3-year, and 5-year survival rates were 89.07%, 73.22%, and 66.94%, respectively. Longer survival was observed in patients who had less than two elevated serum biomarkers compared with those with 2–3 and 4-5 elevated serum biomarkers (p < 0.001).

Conclusion

CEA, CA125, CA19-9, CA724, and CA242 in serum and ascites can be used to judge the severity and predict the resectability. Furthermore, different numbers of elevated biomarkers can help determine the prognosis of PMP.
Case Report: Targeted Therapy for Metastatic Solid Pseudopapillary Neoplasm of the Pancreas With CTNNB1 and PTEN Mutations
Authors: Wang Xinbo , Zhu Daojun , Bao Wei , Li Min , Wang Sizhen , Shen Rongxi
Published: October 2021

Background

Solid pseudopapillary neoplasm (SPN) of the pancreas shows an indolent clinical behavior in cases undergoing surgical resection. The efficacy of combination therapy in the metastatic extrapancreatic SPN treatment remains largely unknown and a clinical challenge.

Case Presentation

We report a case of a metastatic pancreatic SPN in a 45-year-old woman who presented with an aggressive peritoneal dissemination and hepatic metastases and still showed an indolent clinical course with combination therapy with repeated surgery and targeted therapy. Although the follow-up effect remains to be seen, this is the first report of practical experience of the targeted agents sunitinib and everolimus in metastatic SPN tumors based on the mutation status of PTEN (c.379G>A; p.G127R) and CTNNB1 (c.98C>G; p.S33C). To our knowledge, the PTEN variant identified in this case has not been previously reported in SPN.

Conclusion

Evidence on variant genetics indicates that future molecular studies may not only help to explain the mechanism of SPN occurrence and development but are also more likely to direct to future precision treatments.
CT-Based Peritumoral and Intratumoral Radiomics as Pretreatment Predictors of Atypical Responses to Immune Checkpoint Inhibitor Across Tumor Types: A Preliminary Multicenter Study
Authors: He Shuai , Feng Yuqing , Lin Qi , Wang Lihua , Wei Lijun , Tong Jing , Zhang Yuwei , Liu Ying , Ye Zhaoxiang , Guo Yan , Yu Tao , Luo Yahong
Published: October 2021

Objective

To develop and validate a new strategy based on radiomics features extracted from intra- and peritumoral regions on CT images for the prediction of atypical responses to the immune checkpoint inhibitor (ICI) in cancer patients.

Methods

In total, 135 patients derived from five hospitals with pathologically confirmed malignancies receiving ICI were included in this retrospective study. Atypical responses including pseudoprogression (PsP) and hyperprogression disease (HPD) were identified as their definitions. A subgroup of standard progression disease (sPD) in 2018 was also involved in this study. Based on pretreatment CT imaging, a total of 107 features were extracted from intra- and peri-tumoral regions, respectively. The least absolute shrinkage and selection operator (Lasso) algorithm was used for feature selection, and multivariate logistic analysis was used to develop radiomics signature (RS). Finally, a total of nine RSs, derived from intra-tumoral, peri-tumoral, and combination of both regions, were built respectively to distinguish PsP vs. HPD, PsP vs. sPD, and HPD vs. sPD. The performance of the RSs was evaluated with discrimination, calibration, and clinical usefulness.

Results

No significant difference was found when compared in terms of clinical characteristics of PsP, HPD, and sPD. RS based on combined regions outperformed those from either intra-tumoral or peri-tumoral alone, yielding an AUC (accuracy) of 0.834 (0.827) for PsP vs. HPD, 0.923 (0.868) for PsP vs. sPD, and 0.959 (0.894) for HPD vs. sPD in the training datasets, and 0.835 (0.794) for PsP vs. HPD, 0.919 (0.867) for PsP vs. sPD, and 0.933 (0.842) for HPD vs. sPD in the testing datasets. The combined RS showed good fitness (Hosmer–Lemeshow test p > 0.05) and provided more net benefit than the treat-none or treat-all scheme by decision curve analysis in both training and testing datasets.

Conclusion

Pretreatment radiomics are helpful to predict atypical responses to ICI across tumor types. The combined RS outperformed those from either intra- or peri-tumoral alone which may provide a more comprehensive characterization of atypical responses to ICI.
Novel Natural Inhibitors Targeting Enhancer of Zeste Homolog 2: A Comprehensive Structural Biology Research
Authors: Li Weihang , Ding Ziyi , Zhao Yunlong , Jiang Min , Zhang Shilei , Zhao Hongzhe , Lei Ke , Xu Rui , Zhao Yingjing , Wang Dong , Chao Min , Yin Yanjiang , Yang Changbin , Wang Liang , Yan Ming
Published: October 2021

The enhancer of zeste homolog 2 (EZH2) is a methylated modification enzyme of Histone H3-Lys 27. The high expression of EZH2 in cells is closely related to the progression, invasion, and metastasis of neoplasm. Therefore, this target is gradually becoming one of the research hot spots of tumor pathogenesis, and the inhibitors of the EZH2 enzyme are expected to become new antitumor drugs. This study used a series of virtual screening technologies to calculate the affinity between the compounds obtained from the ZINC15 database and the target protein EZH2, the stability of the ligand–receptor complex. This experiment also predicted the toxicity and absorption, distribution, metabolism, and excretion (ADME) properties of the candidate drugs in order to obtain compounds with excellent pharmacological properties. Finally, the ligand–receptor complex under in vivo situation was estimated by molecular dynamics simulation to observe whether the complex could exist steadily in the body. The experimental results showed that the two natural compounds ZINC000004217536 and ZINC000003938642 could bind tightly to EZH2, and the ligand–receptor complex could exist stably in vivo. Moreover, these two compounds were calculated to be nontoxic. They also had a high degree of intestinal absorption and high bioavailability. In vitro experiments confirmed that drug ZINC000003938642 could inhibit the proliferation and migration of osteosarcoma, which could serve as potential lead compounds. Therefore, the discovery of these two natural products had broad prospects in the development of EZH2 inhibitors, providing new clues for the treatment or adjuvant treatment of tumors.
Tumor-Infiltrating Cytotoxic T Cells and Tumor-Associated Macrophages Correlate With the Outcomes of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer
Authors: Yang Yuqin , Tian Wenjing , Su Liqian , Li Peiqiu , Gong Xiaohua , Shi Lu , Zhang Qingling , Zhao Bin , Zhao Hong
Published: October 2021

Background

Tumor-infiltrating immune cells (TIICs) play a key role in immunoregulatory networks and are related to tumor development. Emerging evidence shows that these cells are associated with sensitivity to chemotherapy and radiotherapy. However, the predictive role of TIICs in the outcomes of neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC) is unclear.

Methods

Imaging mass cytometry (IMC) was performed to comprehensively assess the immune status before nCRT in 6 patients with LARC (3 achieved pathological complete response (pCR), 3 did not) with matched clinicopathological parameters. Immunohistochemistry (IHC) for CD8, CD163 and Foxp3 on biopsy samples from 70 patients prior to nCRT and logistic regression analysis were combined to further evaluate its predictive value for treatment responses in an independent validation group.

Results

A trend of increased CD8+ cytotoxic T lymphocytes (CTLs) and decreased CD163+ tumor-associated macrophages (TAMs) and Foxp3+ regulatory T cells (Tregs) in the pCR group was revealed by IMC. In the validation group, CTLs and TAMs were strong predictors of the clinical response to nCRT. High levels of CTLs were positively associated with the pCR ratio (OR=1.042; 95% CI: 1.015~1.070, p=0.002), whereas TAMs were correlated with a poor response (OR=0.969; 95% CI: 0.941~0.998, p=0.036). A high density of TAMs was also associated with an advanced cN stage.

Conclusion

CTLs in the tumor microenvironment (TME) may improve the response to nCRT, whereas TAMs have the opposite effect. These results suggest that these cells might be potential markers for the clinical outcomes of nCRT and aid in the clinical decision-making of LARC for improved clinical outcomes.