bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of an anisokinetic particle sampling probe for use in a gas turbine engine compressor
Authors: Olshefski Kristopher , Collins Addison , Coulon Thomas , Lowe Todd , Ng Wing
Published: September 2022

Sand and dust particle ingestion is an inevitability for aircraft operating in arid environments. For conventional takeoff and landing aircraft, significant dust can be ingested into the gas turbine powerplant. Helicopters and vertical takeoff and landing (VTOL) aircraft are at especially high risk due to their tendency to blow significant debris into the air during takeoff and landing operations. The present study highlights the development of an anisokinetic particle sampling probe for use in aircraft engines to obtain real-time measurement of ingested particles often present in these harsh environments. Offtake of particles during engine operation in dusty conditions will provide researchers with an improved understanding of particle breakage tendency and component erosion susceptibility. Three foundational studies were conducted to establish a baseline understanding of probe performance: an aerodynamic study, a particle tracking study, and a particle sampling study. These studies were performed using the Free Jet rig at the Advanced Propulsion and Power Laboratory at Virginia Tech. Particles as large as 1.3 mm were sampled at Mach numbers where M = (0.25, 0.70) and yaw angles ranging from 0° to 45° relative to freestream, conditions not previously investigated. Results indicate that the probe operates sub-isokinetically throughout the full range of test conditions and that probe aerodynamic capture efficiency is inversely proportional to both Mach number and yaw angle. However, this efficiency limitation does not notably influence the sampling probe’s ability to capture the test dust of interest. While the presence of the probe in the flow does result in an airflow velocity reduction of up to 55%, due to their relatively large Stokes numbers the particles of interest only experience a decrease of roughly 5%. These results indicate that this probe is capable of providing researchers with valuable particle size and shape information through effective particle sampling at particle sizes (100 μm ≤ dp ≤ 1,300 μm) and speeds (M ≥ 0.25) not previously investigated.
Cilgavimab/Tixagevimab as alternative therapeutic approach for BA.2 infections
Authors: Dichtl Stefanie , Zaderer Viktoria , Kozubowski Viktoria , Abd El Halim Hussam , Lafon Eliott , Lanser Lukas , Weiss Günter , Lass-Flörl Cornelia , Wilflingseder Doris , Posch Wilfried
Published: September 2022

Objectives

The identification of the SARS-CoV-2 Omicron variants BA.1 and BA.2 immediately raised concerns about the efficacy of currently used monoclonal antibody therapies. Here, we analyzed the activity of Sotrovimab and Regdanvimab, which are used in clinics for treatment of moderate to severe SARS-CoV-2 infections, and Cilgavimab/Tixagevimab, which are approved for prophylactic use, against BA.1 and BA.2 in a 3D model of primary human bronchial epithelial cells.

Methods

Primary human airway epithelia (HAE) cells in a 3D tissue model were infected with clinical isolates of SARS-CoV-2 Delta, BA.1 or BA.2. To mimic the therapeutic use of mAbs, we added Regdanvimab, Sotrovimab or Cilgavimab/Tixagevimab 6 h after infection. In order to mirror the prophylactic use of Cilgavimab/Tixagevimab, we added this compound 6 h prior to infection to the fully differentiated, pseudostratified epithelia cultured in air-liquid interphase (ALI).

Results

We observed that Sotrovimab, but not Regdanvimab, is active against BA.1; however, both antibodies lose their efficacy against BA.2. In contrast, we found that BA.2 was sensitive to neutralization by the approved prophylactic administration and the therapeutic use, which is not yet permitted, of Cilgavimab/Tixagevimab.

Conclusion

Importantly, while the use of Tixagevimab/Cilgavimab is effective in controlling BA.2 but not BA.1 infection, monoclonal antibodies (mAbs) with efficacy against BA.1 are ineffective to reduce BA.2 virus replication in a human lung model. Our data may have implications on the variant specific clinical use of monoclonal antibodies.
Diagnostic accuracy of prenatal imaging for the diagnosis of congenital Zika syndrome: Systematic review and meta-analysis
Authors: Herrera Tania T. , Cubilla-Batista Idalina , Goodridge Amador , Pereira Tiago V.
Published: September 2022

Objective

The aim of this study was to assess the accuracy of prenatal imaging for the diagnosis of congenital Zika syndrome.

Data sources

Medline (via Pubmed), PubMed, Scopus, Web of Science, and Google Scholar from inception to March 2022. Two researchers independently screened study titles and abstracts for eligibility.

Study eligibility criteria

Observational studies with Zika virus-infected pregnant women were included. The index tests included ultrasound and/or magnetic resonance imaging. The reference standard included (1) Zika infection-related perinatal death, stillbirth, and neonatal death within the first 48 h of birth, (2) neonatal intensive care unit admission, and (3) clinically defined adverse perinatal outcomes.

Synthesis methods

We extracted 2 × 2 contingency tables. Pooled sensitivity and specificity were estimated using the random-effects bivariate model and assessed the summary receiver operating characteristic (ROC) curve. Risk of bias was assessed using QUADAS 2 tool. The certainty of the evidence was evaluated with grading of recommendations.

Results

We screened 1,459 references and included 18 studies (2359 pregnant women, 347 fetuses with confirmed Zika virus infection). Twelve studies (67%) were prospective cohorts/case series, and six (37%) were retrospective cohort/case series investigations. Fourteen studies (78%) were performed in endemic regions. Ten studies (56%) used prenatal ultrasound only, six (33%) employed ultrasound and fetal MRI, and two studies (11%) used prenatal ultrasound and postnatal fetal MRI. A total of six studies (ultrasound only) encompassing 780 pregnant women (122 fetuses with confirmed Zika virus infection) reported relevant data for meta-analysis (gestation age at which ultrasound imagining was captured ranged from 16 to 34 weeks). There was large heterogeneity across studies regarding sensitivity (range: 12 to 100%) and specificity (range: 50 to 100%). Under a random-effects model, the summary sensitivity of ultrasound was 82% (95% CI, 19 to 99%), and the summary specificity was 97% (71 to 100%). The area under the ROC curve was 97% (95% CI, 72 to 100%), and the summary diagnostic odds ratio was 140 (95% CI, 3 to 7564, P < 0.001). The overall certainty of the evidence was “very low”.

Conclusion

Ultrasound may be useful in improving the diagnostic accuracy of Zika virus infection in pregnancy. However, the evidence is still substantially uncertain due to the methodological limitations of the available studies. Larger, properly conducted diagnostic accuracy studies of prenatal imaging for the diagnosis of congenital Zika syndrome are warranted.

Systematic review registration

Identifier [CRD42020162914].
A non-human primate model of acute liver failure suitable for testing liver support systems
Authors: Kalsi Ranjeet S. , Ostrowska Alina , Olson Adam , Quader Mubina , Deutsch Melvin , Arbujas-Silva Norma J. , Symmonds Jen , Soto-Gutierrez Alejandro , Crowley John J. , Reyes-Mugica Miguel , Sanchez-Guerrero Giselle , Jaeschke Hartmut , Amiot Bruce P. , Cascalho Marilia , Nyberg Scott L. , Platt Jeffrey L. , Tafaleng Edgar N. , Fox Ira J.
Published: September 2022

Acute hepatic failure is associated with high morbidity and mortality for which the only definitive therapy is liver transplantation. Some fraction of those who undergo emergency transplantation have been shown to recover native liver function when transplanted with an auxiliary hepatic graft that leaves part of the native liver intact. Thus, transplantation could have been averted with the development and use of some form of hepatic support. The costs of developing and testing liver support systems could be dramatically reduced by the availability of a reliable large animal model of hepatic failure with a large therapeutic window that allows the assessment of efficacy and timing of intervention. Non-lethal forms of hepatic injury were examined in combination with liver-directed radiation in non-human primates (NHPs) to develop a model of acute hepatic failure that mimics the human condition. Porcine hepatocyte transplantation was then tested as a potential therapy for acute hepatic failure. After liver-directed radiation therapy, delivery of a non-lethal hepatic ischemia-reperfusion injury reliably and rapidly generated liver failure providing conditions that can enable pre-clinical testing of liver support or replacement therapies. Unfortunately, in preliminary studies, low hepatocyte engraftment and over-immune suppression interfered with the ability to assess the efficacy of transplanted porcine hepatocytes in the model. A model of acute liver failure in NHPs was created that recapitulates the pathophysiology and pathology of the clinical condition, does so with reasonably predictable kinetics, and results in 100% mortality. The model allowed preliminary testing of xenogeneic hepatocyte transplantation as a potential therapy.
FTX271: A potential gene resource for plant antiviral transgenic breeding
Authors: Zhang Yuhan , Gao Chaoming , Zhang Yahong , Huang Hang , Du Yameng , Wu Lan , Wu Liping
Published: September 2022

Flammutoxin (FTX), as well as its precursor TDP, is a protein from Flammulina velutipes with antiviral activity. Transgenic tobacco with the FTX271 (gene of FTX or TDP) can not only delay the onset time of symptoms but also alleviate the symptoms caused by tobacco mosaic virus (TMV), but the mechanism is still unclear. In this study, FTX271 was introduced into Nicotiana benthamiana, and the disease resistance mechanism activated by FTX271 was speculated by transcriptomic and proteomic techniques. The results showed that TDP was detected, and some genes, proteins and pathways were significant upregulated or enriched in transgenic tobacco, including the mitogen-activated protein kinase (MAPK) cascade signal transduction pathway, the expression of hypersensitive response (HR) marker genes H1N1 and HSR203J, pathogenesis-related (PR) genes, and the key genes COI1 and lipoxygenase gene LOX2 of the jasmonic acid (JA) signaling pathway, indicating FTX271 may activate the MAPK pathway and increase the content of reactive oxygen species (ROS) and JA, which promoted the HR and inducible systemic resistance (ISR). ISR caused increased expression of peroxidase (POD) and other proteins involved in pathogen defense. In addition, transgenic tobacco may use sHSP-assisted photoreparation to alleviate the symptoms of TMV. In conclusion, JA-mediated ISR and sHSP-assisted photoreparation are activated by FTX271 to protect tobacco from TMV infection and alleviate the symptoms caused by the virus. The study provided a theoretical basis for the TMV resistance mechanism of FTX271, which may represent a potential gene resource for plant antiviral transgenic breeding.
Global research trends on the links between the gut microbiota and diabetes between 2001 and 2021: A bibliometrics and visualized study
Authors: Zhang Boxun , Jin Zishan , Zhai Tiangang , Ding Qiyou , Yang Haoyu , Wang Jia , Zhang Lili , Zhao Linhua
Published: September 2022

Background

Over the past 20 years, evidence has suggested that gut microbiota plays an important role in metabolic homeostasis. The relationship between gut microbiota and diabetes has become the focus of considerable scientific interest. With the sharp increase in publications in this area, it is imperative to analyze the relevant articles using bibliometrics methods.

Methods

Publications on “the gut microbiota and diabetes” were retrieved and downloaded from the Web of Science Core Collection database. Microsoft Excel 2020, VOSviewer, CiteSpace 5.8.R3 and Co-Occurrence 9.94 software were used for data analysis and visualization. Country/academic institution, journal, author, subject category, keyword and reference were analyzed thoroughly. The cutting-edge directions in this field were also determined by analyzing keywords and key articles.

Results

A total of 2,342 documents were included in the analysis; the number of articles in this field has increased yearly, particularly after 2010. China and the University of Copenhagen are the country and research institution associated with the largest number of publications. Nutrients have published 191 articles in this field, ranking first among highly productive journals in the number of publications. The researcher Cani PD affiliated with the University of Leuven, Belgium, published the greatest number of articles in this field between 2001 and 2021 and was also ranked as the first co-cited author and the largest contributor of highly cited papers in this field. Endocrinology & Metabolism was the most common subject category. Three of the most frequently found keywords, besides terms related to “microbiota” and “diabetes,” were “obesity,” “probiotics,” and “inflammation.” Akkermansia muciniphila, Faecalibacterium prausnitzii, trimethylamine n-oxide and branched-chain amino acids are intestinal bacteria or metabolites that have attracted more attention in recent years. Natural products represented by Chinese herbal medicine and some protein receptors or signaling pathways such as aryl hydrocarbon receptor, farnesoid X receptor and AMP-activated protein kinase were frontiers in this field.

Conclusion

Over the past two decades, the rapid development of research on the gut microbiota has deepened the understanding of the physiology and pathology of diabetes, providing new insights into different approaches to treatment. In the future, further interdisciplinary innovation, clinical transformation, and application may receive more attention.
The two-component regulatory system CenK–CenR regulates expression of a previously uncharacterized protein required for salinity and oxidative stress tolerance in Sinorhizobium meliloti
Authors: Bensig Eukene O. , Valadez-Cano Cecilio , Kuang ZiYu , Freire Isabela R. , Reyes-Prieto Adrian , MacLellan Shawn R.
Published: September 2022

Genes of unknown function constitute a considerable fraction of most bacterial genomes. In a Tn5-based search for stress response genes in the nitrogen-fixing facultative endosymbiont Sinorhizobium (Ensifer) meliloti, we identified a previously uncharacterized gene required for growth on solid media with increased NaCl concentrations. The encoded protein carries a predicted thioredoxin fold and deletion of the gene also results in increased sensitivity to hydrogen peroxide and cumene hydroperoxide. We have designated the gene srlA (stress resistance locus A) based on these phenotypes. A deletion mutant yields phenotypic revertants on high salt medium and genome sequencing revealed that all revertants carry a mutation in genes homologous to either cenK or cenR. srlA promoter activity is abolished in these revertant host backgrounds and in a strain carrying a deletion in cenK. We also observed that the srlA promoter is autoregulated, displaying low activity in a wildtype (wt) host background and high activity in the srl deletion mutant background. The srlA promoter includes a conserved inverted repeat directly upstream of the predicted −35 subsequence. A mutational analysis demonstrated that the site is required for the high promoter activity in the srlA deletion background. Electromobility shift assays using purified wildtype CenR response regulator and a D55E phosphomimetic derivative suggest this protein acts as a likely Class II activator by binding promoter DNA. These results document the first identified CenK–CenR regulon member in S. meliloti and demonstrate this two-component regulatory system and gene srlA influences cellular growth and persistence under certain stress-inducing conditions.
Synthesis of the cyanobacterial halometabolite Chlorosphaerolactylate B and demonstration of its antimicrobial effect in vitro and in vivo
Authors: Jensen Nikoline , Jensen Henrik Elvang , Aalbaek Bent , Blirup-Plum Sophie Amalie , Soto Sara M. , Cepas Virginio , López Yuly , Gabasa Yaiza , Gutiérrez-del-Río Ignacio , Villar Claudio J. , Lombó Felipe , Iglesias María José , Soengas Raquel , López Ortiz Fernando , Jensen Louise Kruse
Published: September 2022

Chlorosphaerolactylate B, a newly discovered antimicrobial halometabolite from the cyanobacterium Sphaerospermopsis sp. LEGE 00249 has been synthesized in three steps by using 12-bromododecanoic acid as starting material. A total of 0.5 g was produced for in vitro and in vivo antimicrobial efficacy testing. In vitro, the minimal inhibitory concentration (MIC) was estimated to be 256 mg/L for Staphylococcus aureus, while the minimal biofilm inhibitory concentration (MBIC) was estimated to be 74 mg/L. The in vivo study utilized a porcine model of implant-associated osteomyelitis. In total, 12 female pigs were allocated into 3 groups based on inoculum (n = 4 in each group). An implant cavity (IC) was drilled in the right tibia and followed by inoculation and insertion of a steel implant. All pigs were inoculated with 10 μL containing either: 11.79 mg synthetic Chlorosphaerolactylate B + 104 CFU of S. aureus (Group A), 104 CFU of S. aureus (Group B), or pure saline (Group C), respectively. Pigs were euthanized five days after inoculation. All Group B animals showed macroscopic and microscopic signs of bone infection and both tissue and implant harbored S. aureus bacteria (mean CFU on implants = 1.9 × 105). In contrast, S. aureus could not be isolated from animals inoculated with saline. In Group A, two animals had a low number of S. aureus (CFU = 6.7 × 101 and 3.8 × 101, respectively) on the implants, otherwise all Group A animals were similar to Group C animals. In conclusion, synthetic Chlorosphaerolactylate B holds potential to be a novel antimicrobial and antibiofilm compound.
RNA-Seq transcriptomic analysis reveals gene expression profiles of acetic acid bacteria under high-acidity submerged industrial fermentation process
Authors: Yang Haoran , He Yating , Liao Jing , Li Xin , Zhang Junhong , Liebl Wolfgang , Chen Fusheng
Published: September 2022

Acetic acid bacteria (AAB) are Gram-negative obligate aerobics in Acetobacteraceae family. Producing acetic acid and brewing vinegars are one of the most important industrial applications of AAB, attributed to their outstanding ability to tolerate the corresponding stresses. Several unique acid resistance (AR) mechanisms in AAB have been revealed previously. However, their overall AR strategies are still less-comprehensively clarified. Consequently, omics analysis was widely performed for a better understanding of this field. Among them, transcriptome has recently obtained more and more attention. However, most currently reported transcriptomic studies were conducted under lab conditions and even in low-acidity environment, which may be unable to completely reflect the conditions that AAB confront under industrialized vinegar-brewing processes. In this study, we performed an RNA-Seq transcriptomic analysis concerning AAB’s AR mechanisms during a continuous and periodical industrial submerged vinegar fermentation process, where a single AAB strain performed the fermentation and the acetic acid concentration fluctuated between ~8% and ~12%, the highest acidity as far we know for transcriptomic studies. Samples were directly taken from the initial (CK), mid, and final stages of the same period of the on-going fermentation. 16S rRNA sequence analysis indicated the participation of Komagataeibacter europaeus in the fermentation. Transcriptomic results demonstrated that more genes were downregulated than upregulated at both mid and final stages. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrich analysis reflected that the upregulated genes mainly carried out tricarboxylic acid cycle and oxidative phosphorylation processes, probably implying a considerable role of acetic acid overoxidation in AR during fermentation. Besides, upregulation of riboflavin biosynthesis pathway and two NAD+-dependent succinate-semialdehyde dehydrogenase-coding genes suggested a critical role of succinate oxidation in AR. Meanwhile, downregulated genes were mainly ribosomal protein-coding ones, reflecting that the adverse impact on ribosomes initiates at the transcription level. However, it is ambiguous whether the downregulation is good for stress responding or it actually reflects the stress. Furthermore, we also assumed that the fermentation stages may have a greater effect on gene expression than acidity. Additionally, it is possible that some physiological alterations would affect the AR to a larger extent than changes in gene expression, which suggests the combination of molecular biology and physiology research will provide deeper insight into the AR mechanisms in AAB.
Effects of high concentrate rations on ruminal fermentation and microbiota of yaks
Authors: Pang Kaiyue , Dai Dongwen , Yang Yingkui , Wang Xun , Liu Shujie , Huang Weihua , Xue Bin , Chai Shatuo , Wang ShuXiang
Published: September 2022

Ruminal microflora is closely correlated with the ruminant’s diet. However, information regarding the effect of high concentrate diets on rumen microflora in yaks is lacking. In the current study, 24 healthy male yaks were randomly assigned to two groups, each fed with different diets: less concentrate (LC; concentrate: coarse = 40: 60) and high concentrate (HC; concentrate: coarse = 80: 20) diets. Subsequently, a 21-day feeding trial was performed with the yaks, and rumen fluid samples were collected and compared using 16 s rRNA sequencing. The results showed that NH3-N, total VFA, acetate, butyrate, isobutyrate, and isovalerate were significantly higher in the HC group than that in the LC group (p < 0.05), while microbial diversity and richness were significantly lower in the HC group (p < 0.05). Principal coordinate analysis indicated that rumen microflora was significantly different in LC and HC groups (p < 0.05). In the rumen, phyla Firmicutes and Bacteroidota were the most abundant bacteria, with Firmicutes being more abundant, and Bacteroidota being less abundant in the HC group than those found in the LC group. Christensenellaceae_R-7_group and Prevotella are the highest abundant ones at the genus level. The relative abundance of Acetitomaculum, Ruminococcus, and Candidatus_Saccharimonas were significantly higher in the HC group than that in the LC group (p < 0.05), while the relative abundance of Olsenella was significantly lower in the HC group than in the LC group (p < 0.05). Compared to the LC group, the relative abundance of Prevotella, Ruminococcus, and Candidatus_Saccharimonas was significantly higher in the HC group. The relative abundances of Prevotella, Prevotellaceae_UCG-003, Olsenella, Ruminococcus, Acetitomaculum, Candidatus_Saccharimonas, and NK4A214_group were correlated with ruminal fermentation parameters (p < 0.05). Furthermore, PICRUSt 2 estimation indicated that microbial genes associated with valine, leucine, and isoleucine biosynthesis were overexpressed in the rumen microflora of yaks in the HC group (p < 0.05). Conclusively, our results suggest that high concentrate diets affect the microflora composition and fermentation function in yak rumen. The present findings would provide new insights into the health of yaks under high concentrate feeding conditions and serve as a potent reference for the short-term fattening processes of yaks.
Multilocus sequence typing of diverse phytoplasmas using hybridization probe-based sequence capture provides high resolution strain differentiation
Authors: Pusz-Bochenska Karolina , Perez-Lopez Edel , Wist Tyler J. , Bennypaul Harvinder , Sanderson Daniel , Green Margaret , Dumonceaux Tim J.
Published: September 2022

Phytoplasmas are insect-vectored, difficult-to-culture bacterial pathogens that infect a wide variety of crop and non-crop plants, and are associated with diseases that can lead to significant yield losses in agricultural production worldwide. Phytoplasmas are currently grouped in the provisional genus ‘Candidatus Phytoplasma’, which includes 49 ‘Candidatus’ species. Further differentiation of phytoplasmas into ribosomal groups is based on the restriction fragment length polymorphism (RFLP) pattern of the 16S rRNA-encoding operon, with more than 36 ribosomal groups (16Sr) and over 100 subgroups reported. Since disease symptoms on plants are not associated with phytoplasma identity, accurate diagnostics is of critical importance to manage disease associated with these microorganisms. Phytoplasmas are typically detected from plant and insect tissue using PCR-based methods targeting universal taxonomic markers. Although these methods are relatively sensitive, specific and are widely used, they have limitations, since they provide limited resolution of phytoplasma strains, thus necessitating further assessment of biological properties and delaying implementation of mitigation measures. Moreover, the design of PCR primers that can target multiple loci from phytoplasmas that differ at the sequence level can be a significant challenge. To overcome these limitations, a PCR-independent, multilocus sequence typing (MLST) assay to characterize an array of phytoplasmas was developed. Hybridization probe s targeting cpn60, tuf, secA, secY, and nusA genes, as well as 16S and rp operons, were designed and used to enrich DNA extracts from phytoplasma-infected samples for DNA fragments corresponding to these markers prior to Illumina sequencing. This method was tested using different phytoplasmas including ‘Ca. P. asteris’ (16SrI-B), ‘Ca. P. pruni’ (16SrIII-A),‘Ca. P. prunorum’ (16SrX-B), ‘Ca. P. pyri’ (16SrX-C), ‘Ca. P. mali’ (16SrX-A), and ‘Ca. P. solani’ (16SrXII-A). Thousands of reads were obtained for each gene with multiple overlapping fragments, which were assembled to generate full-length (typically >2 kb), high-quality sequences. Phytoplasma groups and subgroups were accurately determined based on 16S ribosomal RNA and cpn60 gene sequences. Hybridization-based MLST facilitates the enrichment of target genes of phytoplasmas and allows the simultaneous determination of sequences corresponding to seven different markers. In this proof-of-concept study, hybridization-based MLST was demonstrated to be an efficient way to generate data regarding ‘Ca. Phytoplasma’ species/strain differentiation.
Control of Listeria monocytogenes in chicken dry-fermented sausages with bioprotective starter culture and high-pressure processing
Authors: Austrich-Comas Anna , Serra-Castelló Cristina , Jofré Anna , Gou Pere , Bover-Cid Sara
Published: September 2022

Listeria monocytogenes is one of the most relevant pathogens for ready-to-eat food, being a challenge for the food industry to comply with microbiological criteria. The aim of the work was to assess the behavior of L. monocytogenes in two types of chicken-based dry-fermented sausages during the fermentation and ripening, with or without a bioprotective starter culture (Latilactobacillus sakei CTC494). To complement the challenge testing approach, simulations with different predictive models were performed to better understand the role of contributing factors. The impact of post-processing strategies, such as high-pressure processing and/or corrective storage was assessed. The chicken meat was inoculated with a cocktail of three L. monocytogenes strains, mixed with other ingredients/additives and stuffed into small (snack-type) or medium (fuet-type) casings. Snack-type was fermented (22°C/3 days) and ripened (14°C/7 days), while fuet-type was ripened (13°C/16 days). At the end of ripening, HPP (600 MPa/5 min) and/or corrective storage (4 or 15°C/7 days) were applied. The suitability of HPP after fermentation was evaluated in the snack-type sausages. Pathogen growth (>3 Log10) was observed only during the fermentation of the snack type without a starter. The bioprotective starter prevented the growth of L. monocytogenes in the snack-type sausages and enhanced the inactivation (1.55 Log10) in fuet-type sausages, which could be related to the higher lactic acid production and consequent decrease of pH, but also the production of the antilisterial bacteriocin sakacin k. The gamma concept model allowed us to identify the main factors controlling the L. monocytogenes’ growth, i.e., the temperature during the early stages and aw at the end of the production process. The earlier acidification linked with the addition of starter culture made the interaction with the other factors (undissociated lactic acid, aw and temperature) to be the growth-preventing determinants. High-pressure processing only caused a significant reduction of L. monocytogenes in snack-type, which showed higher aw. The application of HPP after fermentation did not offer a relevant advantage in terms of efficacy. Corrective storage did not promote further pathogen inactivation. The findings of the work will guide the food industry to apply effective strategies (e.g., fermentation temperature and bioprotective starter cultures) to control L. monocytogenes in chicken dry-fermented sausages.
Taxonomy and control of Trichoderma hymenopellicola sp. nov. responsible for the first green mold disease on Hymenopellis raphanipes
Authors: Zeng Xiang-Yu , Yuan Xiao-Xiao , Peng Ke-Qin , Pan Yin-Tao , Tan Ting-Jun , Wu Nan , Tian Feng-Hua
Published: September 2022

Trichodermaspp. are a group of widespread fungi with important applications in many aspects of human life, but they are also pathogens that cause green mold disease on mushrooms. During a survey of mushroom cultivation in Guizhou, China, five strains ofTrichodermafrom three different localities were isolated from soil in mushroom bags ofHymenopellis raphanipes. The typical morphology of having gregarious, reddish stromata and gregarious phialides and the results of phylogenetic analyses based on a combined dataset of RPB2, TEF, and ITS gene sequences demonstrated that these green-sporedTrichodermabelong to a new taxon,Trichoderma hymenopellicola. Pathogenicity tests by covering fungal mycelial blocks or soil mixed with spore suspension in mushroom bags showed similar symptoms to those in the field, and the same fungal pathogen had been observed and re-isolated from these symptoms, which fulfill Koch’s postulates. A primary screening test of nine common fungicides indicated that prochloraz-manganese chloride complex and propiconazole are the top two effective fungicides inhibiting the pathogen, whereas the former was further indicated as a suitable fungicide to controlTrichoderma hymenopellicola, with a high inhibition ratio to the pathogen and low toxicity to the mushroom.
Advance in remediated of heavy metals by soil microbial fuel cells: Mechanism and application
Authors: Sun Yingying , Wang Hui , Long Xizi , Xi Hui , Biao Peng , Yang Wei
Published: September 2022

In the past decade, studies on the remediation of heavy metals contaminated soil by microbial fuel cells (MFCs) have attracted broad attention because of the self-generated power and their multifield principles such as the extracellular electron transfer (EET) reduction, electromigration for heavy metals removal. However, given the bio electro-motive power from soil MFCs is weak and fluctuated during the remediation, we need to comprehensively understand the origination of driving force in MFC based on the analysis of the fundamental rationale of ion moving in cells and improve the performance via the appropriate configurations and operations. In this review, we first described the structures of soil MFCs for heavy metals remediation and compared the advantages of different types of configurations. Then, based on the theoretical models of heavy metal migration, enrichment, and reduction in soil MFCs, the optimization of soil MFCs including the length of the remediation area, soil conductivity, control of electrode reaction, and modification of electrodes were proposed. Accordingly, this review contributes to the application of bioelectrochemistry to efficiently remove heavy metals from soils.
A novel cuproptosis-related prognostic signature and potential value in HCC immunotherapy
Authors: Wang Xiang-Xu , Wu Li-Hong , Ji Hongchen , Liu Qing-Qing , Deng Shi-Zhou , Dou Qiong-Yi , Ai Liping , Pan Wei , Zhang Hong-Mei
Published: September 2022

Background: Copper metabolism plays an important role in the tumor microenvironment, and cuproptosis is the last discovered programmed cell death process. However, the potential mechanism of cuproptosis in regulating the immune microenvironment of HCC remains unclear.

Methods: A total of 716 HCC patients with complete mRNA expression and survival information were collected from three public HCC cohorts (TCGA-LIHC cohort, n = 370; GSE76427 cohort, n = 115; ICGC-LIRI cohort, n = 231). The unsupervised clustering analysis (NMF) was performed to identify three different cuproptosis-related subtypes. The univariate-Cox, lasso-Cox and multivariate-Cox regression analyses were performed to screen the cuproptosis related and construct the cuproptosis-related prognosis signature (Cu-PS). The immune cell infiltration was estimated by both CIBERSORT and MCPcounter algorithms.

Results: This study identified three distinct cuproptosis-related metabolic patterns, which presented different pathway enrichment and immune cell infiltration. The Cu-PS, a 5-genes (C7, MAGEA6, HK2, CYP26B1 and EPO) signature, was significantly associated with TNM stage, tumor mutational burden (TMB), drugs sensitivity, and immunotherapies response.

Conclusion: This study performed a multi-genetic analysis of cuproptosis-related genes and further explored the regulatory mechanism of cuproptosis in HCC. The Cu-PS might be a useful biomarker for predicting immunotherapy response and enhancing the diagnosis and treatment of HCC.
GPI-anchored glutathione S-transferase as marker allows affinity sorting of transfection-positive cells
Authors: Ma Shumin , Yang Lele , Zuo Qingqing , Huang Qilai
Published: September 2022

Cell transfection efficiency is still a limiting factor in gene function research. A method that allows isolation and enrichment of the transfection-positive cells is an effective solution. Here, we report a transfection-positive cell sorting system that utilizes GPI-anchored GST (Glutathione S-transferase) as a plasmid marker. The Glutathione S-transferase fusion protein will be expressed and displayed on the cell surface through GPI anchor, and hence permits the positive cells to be isolated using Glutathione (GSH) Magnetic Beads. We prove that the system works efficiently in both the adherent Lenti-X 293T cells and the suspension K-562 cells. The affinity cell sorting procedure efficiently enriched positive cells from 20% to 98% in K-562 cells. The applications in gene knockdown and overexpression experiments in K-562 cells dramatically enhanced the extent of gene alteration, with the gene knockdown efficiency increasing from 7% to 60% and the gene overexpression level rising from 47 to 253 times. This Glutathione S-transferase affinity transfection-positive cell sorting method is simple and fast to operate, large-instrument free, low cost, and hence possesses great potential in gene function study in vitro.
Effects of a plant cyclotide on conformational dynamics and destabilization of β-amyloid fibrils through molecular dynamics simulations
Authors: Kalmankar Neha V. , Gehi Bhuvaneshwari Rajendrakumar , Sowdhamini Ramanathan
Published: September 2022

Aggregation of β-amyloid (Aβ) peptide is one of the hallmarks of Alzheimer’s disease (AD) which results in chronic and progressive neurodegeneration of the brain. A recent study by our group have shown the ability of cyclic disulfide-rich peptides (“cyclotides”) isolated from a medicinal plant, Clitoria ternatea, to inhibit the aggregation of Aβ peptides and reduce oxidative stress caused by reactive oxygen species using in vivo models of transgenic Caenorhabditis elegans. In the present study, through extensive computational docking and multi-ns molecular dynamics (MD) simulation, we evaluated if cyclotides can stably bind to Aβ molecules and/or destabilize the Aβ fibril by preventing conformational changes from α-helical to β-sheet rich structures. We demonstrate that cyclotides bind effectively and stably to different forms of Aβ structures via hydrogen bonding and hydrophobic interactions. One of the conserved hydrophobic interface residues, Tyr10 was mutated to Ala and the impact of this virtual mutation was estimated by additional MD simulations for the wild-type (WT) and mutant protein-peptide complexes. A detailed MD simulation analyses revealed that cyclotides form hydrogen bonds with the toxic amyloid assemblies thereby weakening the inter-strand hydrogen bonds between the Aβ peptide. The φ-ѱ distribution map of residues in the cyclotide binding pocket that ideally adopt β-sheet conformation show deviation towards right-handed ɑ-helical (ɑR) conformation. This effect was similar to that observed for the Tyr10Ala mutant and doubly so, for the cyclotide bound form. It is therefore possible to hypothesise that the opening up of amyloid β-sheet is due to an unfolding process occurring in the Aβ caused by cyclotide binding and inhibition. Our current findings provide novel structural insights on the mode of interaction between cyclotides and Aβ fibrils and describe their anti-amyloid aggregation potential. This sheds light on the future of cyclotide-based drug design against protein aggregation, a hallmark event in many neurodegenerative diseases.
Pharmacological determination of the fractional block of Nav channels required to impair neuronal excitability and ex vivo seizures
Authors: Thouta Samrat , Waldbrook Matthew G. , Lin Sophia , Mahadevan Arjun , Mezeyova Janette , Soriano Maegan , Versi Pareesa , Goodchild Samuel J. , Parrish R. Ryley
Published: September 2022

Voltage-gated sodium channels (Nav) are essential for the initiation and propagation of action potentials in neurons. Of the nine human channel subtypes, Nav1.1, Nav1.2 and Nav1.6 are prominently expressed in the adult central nervous system (CNS). All three of these sodium channel subtypes are sensitive to block by the neurotoxin tetrodotoxin (TTX), with TTX being almost equipotent on all three subtypes. In the present study we have used TTX to determine the fractional block of Nav channels required to impair action potential firing in pyramidal neurons and reduce network seizure-like activity. Using automated patch-clamp electrophysiology, we first determined the IC50s of TTX on mouse Nav1.1, Nav1.2 and Nav1.6 channels expressed in HEK cells, demonstrating this to be consistent with previously published data on human orthologs. We then compared this data to the potency of block of Nav current measured in pyramidal neurons from neocortical brain slices. Interestingly, we found that it requires nearly 10-fold greater concentration of TTX over the IC50 to induce significant block of action potentials using a current-step protocol. In contrast, concentrations near the IC50 resulted in a significant reduction in AP firing and increase in rheobase using a ramp protocol. Surprisingly, a 20% reduction in action potential generation observed with 3 nM TTX resulted in significant block of seizure-like activity in the 0 Mg2+ model of epilepsy. Additionally, we found that approximately 50% block in pyramidal cell intrinsic excitability is sufficient to completely block all seizure-like events. Furthermore, we also show that the anticonvulsant drug phenytoin blocked seizure-like events in a manner similar to TTX. These data serve as a critical starting point in understanding how fractional block of Nav channels affect intrinsic neuronal excitability and seizure-like activity. It further suggests that seizures can be controlled without significantly compromising intrinsic neuronal activity and determines the required fold over IC50 for novel and clinically relevant Nav channel blockers to produce efficacy and limit side effects.
Serum glial fibrillary acidic protein and neurofilament light chain in patients with early treated phenylketonuria
Authors: Lotz-Havla Amelie S. , Katzdobler Sabrina , Nuscher Brigitte , Weiß Katharina , Levin Johannes , Havla Joachim , Maier Esther M.
Published: September 2022

To pave the way for healthy aging in early treated phenylketonuria (ETPKU) patients, a better understanding of the neurological course in this population is needed, requiring easy accessible biomarkers to monitor neurological disease progression in large cohorts. The objective of this pilot study was to investigate the potential of glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) as blood biomarkers to indicate changes of the central nervous system in ETPKU. In this single-center cross-sectional study, GFAP and NfL concentrations in serum were quantified using the Simoa® multiplex technology in 56 ETPKU patients aged 6–36 years and 16 age matched healthy controls. Correlation analysis and hierarchical linear regression analysis were performed to investigate an association with disease-related biochemical parameters and retinal layers assessed by optical coherence tomography. ETPKU patients did not show significantly higher GFAP concentrations (mean 73 pg/ml) compared to healthy controls (mean 60 pg/ml, p = 0.140). However, individual pediatric and adult ETPKU patients had GFAP concentrations above the healthy control range. In addition, there was a significant association of GFAP concentrations with current plasma tyrosine concentrations (r = −0.482, p = 0.036), a biochemical marker in phenylketonuria, and the retinal inner nuclear layer volume (r = 0.451, p = 0.04). There was no evidence of NfL alterations in our ETPKU cohort. These pilot results encourage multicenter longitudinal studies to further investigate serum GFAP as a complementary tool to better understand and monitor neurological disease progression in ETPKU. Follow-up investigations on aging ETPKU patients are required to elucidate the potential of serum NfL as biomarker.
Examining racial and ethnic disparities in adult emergency department patient visits for concussion in the United States
Authors: Lempke Landon B. , Kerr Zachary Yukio , Melvin Patrice , Walton Samuel R. , Wallace Jessica S. , Mannix Rebekah C. , Meehan William P. , Ward Valerie L.
Published: September 2022

Background

Racial and ethnic differences in emergency department (ED) visits have been reported among adolescent patients but are unsubstantiated among adults. Therefore, our purpose in this study was to examine the relationship between race/ethnicity and adult ED visits for concussions, their injury mechanisms, and computed tomography (CT) scan use among a nationally representative sample.

Methods

We used the National Hospital Ambulatory Medical Care Survey database from 2010–2015 to examine 63,725 adult (20–45 years old) patient visits, representing an estimated 310.6 million visits presented to EDs. Of these visits, 884 (4.5 million national estimate) were diagnosed with a concussion. Visit records detailed patient information (age, sex, race/ethnicity, geographic region, primary payment type), ED visit diagnoses, injury mechanism (sport, motor vehicle, fall, struck by or against, “other”), and head CT scan use. The primary independent variable was race/ethnicity (non-Hispanic Asian, non-Hispanic Black or African American, Hispanic/Latinx, non-Hispanic multiracial or another, and non-Hispanic White). We used multivariable logistic and multinomial regression models with complex survey sampling design weighting to examine the relationship between concussion ED visits, injury mechanisms, and CT scan use separately by race/ethnicity while accounting for covariates.

Results

There were no associations between race/ethnicity and concussion diagnosis among adult ED visits after accounting for covariates. Relative to sports-related injuries, non-Hispanic Black or African American patient visits were associated with a motor vehicle (OR = 2.69, 95% CI: 1.06–6.86) and “other” injury mechanism (OR = 4.58, 95% CI: 1.34–15.69) compared to non-Hispanic White patients. Relative to sports-related injuries, non-Hispanic Asian, multiracial, or patients of another race had decreased odds of falls (OR = 0.20, 95% CI: 0.04–0.91) and “other” injuries (OR = 0.09, 95% CI: 0.01–0.55) compared to non-Hispanic White patients. The odds of a CT scan being performed were significantly lower among Hispanic/Latinx patient visits relative to non-Hispanic White patients (OR = 0.52, 95% CI: 0.30–0.91), while no other race/ethnicity comparisons differed.

Conclusion

Our findings indicate that the overarching concussion ED visit likelihood may not differ by race/ethnicity in adults, but the underlying mechanism causing the concussion and receiving a CT scan demonstrates considerable differences. Prospective future research is warranted to comprehensively understand and intervene in the complex, multi-level race/ethnicity relationships related to concussion health care to ensure equitable patient treatment.
Influence of oxygen concentration on the neuroprotective effect of hydrogen inhalation in a rat model of cardiac arrest
Authors: Wang Jianjie , Shen Yiming , Li Jingru , Chen Bihua , Yin Changlin , Li Yongqin
Published: September 2022

Background

Post-cardiac arrest (CA) brain injury is the main cause of death in patients resuscitated from CA. Previous studies demonstrated that hydrogen inhalation mitigates post-CA brain injury. However, factors affecting the efficacy of hydrogen remain unknown. In the present study, we investigated the influence of oxygen concentration and targeted temperature on neuroprotective effect in a CA rat model of ventricular fibrillation (VF).

Methods

Cardiopulmonary resuscitation (CPR) was initiated after 7 min of untreated VF in adult male Sprague–Dawley rats. Immediately following successful resuscitation, animals were randomized to be ventilated with 21% oxygen and 79% nitrogen (21%O2); 2% hydrogen, 21% oxygen, and 77% nitrogen (2%H2 + 21%O2); 2% hydrogen, 50% oxygen, and 48% nitrogen (2%H2 + 50%O2); or 2% hydrogen and 98% oxygen (2%H2 + 98%O2) for 3 h. For each group, the target temperature was 37.5°C for half of the animals and 35.0°C for the other half.

Results

No statistical differences in baseline measurements and CPR characteristics were observed among groups. For animals with normothermia, 2%H2 + 50%O2 (123 [369] vs. 500 [393], p = 0.041) and 2%H2 + 98%O2 (73 [66] vs. 500 [393], p = 0.002) groups had significantly lower neurological deficit scores (NDSs) at 96 h and significantly higher survival (75.0 vs. 37.5%, p = 0.033 and 81.3 vs. 37.5%, p = 0.012) than 21%O2 group. For animals with hypothermia, no statistical difference in NDS among groups but 2%H2 + 98%O2 has significantly higher survival than the 21%O2 group (93.8 vs. 56.3%, p = 0.014).

Conclusion

In this CA rat model, inhaling 2% hydrogen combined with a high concentration of oxygen improved 96-h survival, either under normothermia or under hypothermia.
The modularization design and autonomous motion control of a new baby stroller
Authors: Zhang Chunhong , He Zhuoting , He Xiaotong , Shen Weifeng , Dong Lin
Published: September 2022

The increasing number of newborns has stimulated the infant market. In particular, the baby stroller, serving as an important life partner for both babies and parents, has attracted more attention from society. Stroller design and functionality are of vital importance to babies' physiological and psychological health as well as brain development. Therefore, in this paper, we propose a modularization design method for the novel four-wheeled baby stroller based on the KANO model to ensure the mechanical safety and involve more functionalities. Manual control of the baby stroller requires the rapid response of human motor systems in a completely controlled manner, which could be a potential risk. To enhance the safety and stability of the stroller motion, especially in situations where manual control is hard to achieve (e.g., sharp turns), we propose an autonomous motion control scheme based on model predictive control. Both the modularization design and the motion controller are verified in the MATLAB simulation environment through path tracking tasks. The feasibility is validated by the satisfactory experimental results with lateral position error in a reasonable range and good trajectory smoothness.