bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy evaluation of a bivalent subunit vaccine against epidemic PEDV heterologous strains with low cross-protection
Authors: Song Xu , Li Yunchuan , Wang Chuanhong , Zhao Yongxiang , Yang Shanshan , Guo Rongli , Hu Mi , Sun Min , Zhang Gege , Li Yupeng , Wang Yi , Liu Shiyu , Shen Yaoxin , Li Chengcheng , Zhang Xuehan , Li Jizong , Fan Baochao , Li Bin 
Published: September 2024

ABSTRACT

Variant
Porcine epidemic diarrhea virus
(PEDV), which causes diarrhea and high mortality in piglets, has become a major pathogen, and co-epidemics of different subtypes of the virus have become a very thorny problem for the clinical prevention and control of PEDV. However, cross-protection between epidemic G2a and G2b subtype strains has not been observed, and there is currently no vaccine against both G2a and G2b strains. In this study, we demonstrate the low cross-protection between G2a and G2b strains with piglet immunization and challenge tests. The trimeric full-length S proteins of G2a and G2b variants were purified and a bivalent subunit vaccine against PEDV G2a/G2b-S was developed. In active and passive immune protection tests, the bivalent subunit vaccine produced high neutralizing antibody titers and S-specific immunoglobulin G (IgG) and IgA titers against both the G2a and G2b strains in piglets and sows. In the attack phase of the viruses, the clinical symptoms and microscopic lesions in the immunized groups were significantly alleviated. Importantly, the PEDV G2a/G2b-S bivalent subunit vaccine conferred effective passive immunity against PEDV G2a and G2b challenges in the form of colostrum-derived antibodies from the immunized sows. In conclusion, our data demonstrate the low cross-protection of PEDV epidemic G2a and G2b strains and show that the G2a/G2b-S bivalent subunit vaccine is protective against both G2a and G2b strains. It is therefore a candidate vaccine for PEDV prevention.

IMPORTANCE
The detection rate of PEDV G2a subtype strains is currently increasing. Although commercial vaccines are available, most vaccines do not exert an ideal protective effect against these strains. Furthermore, there is no definitive research into the cross-protection between G2a and G2b strains, and no bivalent vaccine provides joint protection against both. Therefore, in this study, we investigated the cross-protection between PEDV G2a and G2b strains and designed a candidate bivalent subunit vaccine combining the trimeric S proteins of the G2a and G2b subtypes. We demonstrate that the cross-protection between strains G2a and G2b is poor and that this bivalent subunit vaccine protects piglets from viral attack by inducing both active and passive immunity. This study emphasizes the effectiveness of the PEDV G2a/G2b-S bivalent subunit vaccine and provides a feasible method for the development of efficient PEDV vaccines.
Small molecule produced by
Photorhabdus
interferes with ubiquinone biosynthesis in Gram-negative bacteria
Authors: Bargabos Rachel , Iinishi Akira , Hawkins Bryson , Privalsky Thomas , Pitt Norman , Son Sangkeun , Corsetti Rachel , Gates Michael F. , Miller Ryan D. , Lewis Kim 
Published: September 2024

ABSTRACT

We report the identification of 3,6-dihydroxy-1,2-benzisoxazole (DHB) in a screen of
Photorhabdus
and
Xenorhabdus
, whose symbiotic relationship with eukaryotic nematodes favors secondary metabolites that meet several requirements matching those for clinically useful antibiotics. DHB is produced by
Photorhabdus laumondii
and is selective against the Gram-negative species
Escherichia coli, Enterobacter cloacae, Serratia marcescens, Klebsiella pneumoniae, Proteus mirabilis,
and
Acinetobacter baumannii
. It is inactive against anaerobic gut bacteria and nontoxic to human cells. Mutants resistant to DHB map to the ubiquinone biosynthesis pathway. DHB binds to 4-hydroxybenzoate octaprenyltransferase (UbiA) and prevents the formation of 4-hydroxy-3-octaprenylbenzoate. Remarkably, DHB itself is prenylated, forming an unusable chimeric product that likely contributes to the toxic effect of this antimicrobial. DHB appears to be both a competitive enzyme inhibitor and a prodrug; this dual mode of action is unusual for an antimicrobial compound.

IMPORTANCE

The spread of resistant pathogens has led to the antimicrobial resistance crisis, and the need for new compounds acting against Gram-negative pathogens is especially acute. From a screen of
Photorhabdus
symbionts of nematodes, we identified 3,6-dihydroxy-1,2-benzisoxazole (DHB) that acts against a range of Gram-negative bacteria, including
Escherichia coli
,
Enterobacter cloacae
,
Klebsiella pneumoniae
, and
Acinetobacter baumannii
. DHB had previously been isolated from other bacterial species, but its mechanism of action remained unknown. We show that DHB is unique among antimicrobials, with dual action as an inhibitor of an important enzyme, UbiA, in the biosynthesis pathway of ubiquinone and as a prodrug. DHB is a mimic of the natural substrate, and UbiA modifies it into a toxic product, contributing to the antimicrobial action of this unusual antibiotic. We also uncover the mechanism of DHB selectivity, which depends on a particular fold of the UbiA enzyme.
Time-resolved multi-omics reveals diverse metabolic strategies of
Salmonella
during diet-induced inflammation
Authors: Kokkinias Katherine , Sabag-Daigle Anice , Kim Yongseok , Leleiwi Ikaia , Shaffer Michael , Kevorkian Richard , Daly Rebecca A. , Wysocki Vicki H. , Borton Mikayla A. , Ahmer Brian M. M. , Wrighton Kelly C. 
Published: September 2024

ABSTRACT

With a rise in antibiotic resistance and chronic infection, the metabolic response of
Salmonella enterica
serovar Typhimurium to various dietary conditions over time remains an understudied avenue for novel, targeted therapeutics. Elucidating how enteric pathogens respond to dietary variation not only helps us decipher the metabolic strategies leveraged for expansion but also assists in proposing targets for therapeutic interventions. In this study, we use a multi-omics approach to identify the metabolic response of
Salmonella enterica
serovar Typhimurium in mice on both a fibrous diet and high-fat diet over time. When comparing
Salmonella
gene expression between diets, we found a preferential use of respiratory electron acceptors consistent with increased inflammation in high-fat diet mice. Looking at the high-fat diet over the course of infection, we noticed heterogeneity in samples based on
Salmonella
ribosomal activity, which is separated into three infection phases: early, peak, and late. We identified key respiratory, carbon, and pathogenesis gene expressions descriptive of each phase. Surprisingly, we identified genes associated with host cell entry expressed throughout infection, suggesting subpopulations of
Salmonella
or stress-induced dysregulation. Collectively, these results highlight not only the sensitivity of
Salmonella
to its environment but also identify phase-specific genes that may be used as therapeutic targets to reduce infection.

IMPORTANCE

Identifying novel therapeutic strategies for
Salmonella
infection that occur in relevant diets and over time is needed with the rise of antibiotic resistance and global shifts toward Western diets that are high in fat and low in fiber. Mice on a high-fat diet are more inflamed compared to those on a fibrous diet, creating an environment that results in more favorable energy generation for
Salmonella
. We observed differential gene expression across infection phases in mice over time on a high-fat diet. Together, these findings reveal the metabolic tuning of
Salmonella
to dietary and temporal perturbations. Research like this, which explores the dimensions of pathogen metabolic plasticity, can pave the way for rationally designed strategies to control disease.
Development and application of a rapid visual detection technique for VanA gene in vancomycin-resistant
Enterococcus faecium
Authors: Ji Tuo , Wang Wenjun , Wang Li , Gao Yuzhi , Wang Yan , Gao Xuzhu 
Published: September 2024

ABSTRACT

The objective of this study was to establish a rapid visual diagnosis method for vancomycin-resistant
Enterococcus faecium
(VREFm) based on multienzyme isothermal rapid amplification (MIRA) combined with lateral flow strips (LFSs). The MIRA primers and probes were specifically designed to maintain the sequence of the VanA gene of VREFm. We optimized the reaction time and temperature and thoroughly assessed the specificity and sensitivity of the MIRA-LFS system. We also compared the MIRA-LFS method with the polymerase chain reaction (PCR) assay and the disc diffusion method. We then evaluated the MIRA-LFS assay for consistency testing and clinical application. The MIRA-LFS technique completed the amplification process within 30 min, and the results were observed on LFS. The method demonstrated high sensitivity, with a minimum detection limit of 1.066 CFU/µL for VREFm and exhibited specificity without cross-reactivity with other pathogenic bacteria. When applied to the detection of clinical samples, the method exhibited consistency with the PCR and agar dilution methods. The combined use of MIRA and LFS in this study facilitates simplifying the workflow for detecting VREFm, which is of great significance for rapidly detecting the enterococcal infections and preventing and controlling the nosocomial infections.

IMPORTANCE

One of the key approaches to treating and controlling vancomycin-resistant
Enterococcus faecium
(VREFm) is an accurate and rapid diagnosis. To achieve this goal, a simple and rapid method must be constructed for immediate detection in the field. Multienzyme isothermal rapid amplification (MIRA) is an isothermal rapid amplification method that allows amplification reactions to be completed under room temperature conditions. When combined with lateral flow strips (LFSs), MIRA-LFS enables the rapid detection of pathogenic microorganisms. However, the MIRA method often produces false signals. These false signals are eliminated by using base mismatches introduced in primers and probes. The MIRA-LFS system was constructed with high specificity and sensitivity for the detection of VREfm, without the limitation of sophisticated instruments. This enables the prompt formulation of diagnostic and therapeutic decisions.
Inosine reverses multidrug resistance in Gram-negative bacteria carrying mobilized RND-type efflux pump gene cluster
tmexCD-toprJ
Authors: Li Fulei , Xu Tianqi , Fang Dan , Wang Zhiqiang , Liu Yuan 
Published: September 2024

ABSTRACT

Antimicrobial resistance is rapidly increasing worldwide, highlighting the urgent need for pharmaceutical and nonpharmaceutical interventions to tackle different-to-treat bacterial infections. Tigecycline, a semi-synthesis glycylcycline for parenteral administration, is widely recognized as one of the few effective therapies available against pan-drug resistant Gram-negative pathogens. Regrettably, the efficacy of multiple drugs, including tigecycline, is currently being undermined due to the emergence of a recently discovered mobilized resistance-nodulation-division-type efflux pump gene cluster
tmexCD1-toprJ1
. Herein, by employing untargeted metabolomic approaches, we reveal that the expression of
tmexCD1-toprJ1
disrupts bacterial purine metabolism, with inosine being identified as a crucial biomarker. Notably, the supplementation of inosine effectively reverses tigecycline resistance in
tmexCD1-toprJ1
-positive bacteria. Mechanistically, exogenous inosine enhanced bacterial proton motive force, which promotes the uptake of tigecycline. Furthermore, inosine enhances succinate biosynthesis by stimulating the tricarboxylic acid cycle. Succinate interacts with the two-component system EnvZ/OmpR and upregulates OmpK 36, thereby promoting the influx of tigecycline. These actions collectively lead to the increased intracellular accumulation of tigecycline. Overall, our study offers a distinct combinational strategy to manage infections caused by
tmexCD-toprJ
-positive bacteria.

IMPORTANCE

TMexCD1-TOprJ1, a mobilized resistance-nodulation-division-type efflux pump, confers phenotypic resistance to multiple classes of antibiotics. Nowadays,
tmexCD-toprJ
has disseminated among diverse species of clinical pathogens, exacerbating the need for novel anti-infective strategies. In this study, we report that
tmexCD1-toprJ1
-negative and -positive bacteria exhibit significantly different metabolic flux and characteristics, especially in purine metabolism. Intriguingly, the addition of inosine, a purine metabolite, effectively restores the antibacterial activity of tigecycline by promoting antibiotic uptake. Our findings highlight the correlation between bacterial mechanism and antibiotic resistance, and offer a distinct approach to overcome
tmexCD-toprJ
-mediated multidrug resistance.
High-intensity interval training for cardiometabolic health in adults with metabolic syndrome: a systematic review and meta-analysis of randomised controlled trials
Authors: Poon Eric Tsz-Chun , Wongpipit Waris , Li Hong-Yat , Wong Stephen Heung-Sang , Siu Parco M , Kong Alice Pik-Shan , Johnson Nathan A 
Published: September 2024

Objective
To assess the effectiveness of high-intensity interval training (HIIT) compared with traditional moderate-intensity continuous training (MICT) and/or non-exercise control (CON) for modification of metabolic syndrome (MetS) components and other cardiometabolic health outcomes in individuals with MetS.

Design
Systematic review and meta-analysis

Data sources
Five databases were searched from inception to March 2024.

Study appraisal and synthesis
Meta-analyses of randomised controlled trials (RCTs) comparing HIIT with MICT/CON were performed for components of MetS (waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and fasting blood glucose (BG)) and clinically relevant cardiometabolic health parameters. Subgroup moderator analyses were conducted based on the intervention duration and HIIT volume.

Results
Out of 4819 studies, 23 RCTs involving 1374 participants were included (mean age: 46.2–67.0 years, 55% male). HIIT significantly improved WC (weighted mean difference (WMD) –4.12 cm, 95% CI –4.71 to –3.53), SBP (WMD –6.05 mm Hg, 95% CI –8.11 to –4.00), DBP (WMD –3.68 mm Hg, 95% CI –5.70 to –1.65), HDL-C (WMD 0.12 mmol/L, 95% CI 0.04 to 0.20), TG (WMD –0.34 mmol/L, 95% CI –0.41 to –0.27) and BG (WMD –0.35 mmol/L, 95% CI –0.54 to –0.16) compared with CON (all p<0.01). HIIT approaches demonstrated comparable effects to MICT across all parameters. Subgroup analyses suggested that HIIT protocols with low volume (ie, <15 min of high-intensity exercise per session) were not inferior to higher volume protocols for improving MetS components.

Conclusion
This review supports HIIT as an efficacious exercise strategy for improving cardiometabolic health in individuals with MetS. Low-volume HIIT appears to be a viable alternative to traditional forms of aerobic exercise.
Risk of neuropsychiatric adverse events associated with montelukast use in children and adolescents: a population-based case-crossover study
Authors: Kim Jae Won , Kim Mideum , Seo Min Sook , Shin Ju-Young 
Published: September 2024

PurposeMontelukast is used extensively in children and adolescents for allergic rhinitis and asthma. However, concerns have been raised regarding the increased risk of neuropsychiatric adverse events (NPAEs) associated with montelukast use. Therefore, our case-crossover study was conducted to observe whether there is an increased risk of NPAEs associated with montelukast use in children and adolescents.Materials and methodsA population-based case-crossover study using the customised Health Insurance Review and Assessment (HIRA) dataset was conducted. Paediatric patients aged between 0 and 19 years diagnosed with allergic rhinitis and/or asthma with a history of at least one montelukast prescription between 1 January 2018 and 31 December 2021 were included. Exposure to montelukast was assessed during 3-, 7-, 14-, 28- and 56-day hazard periods prior to each patient’s NPAE. Stratified analyses according to age group, gender and season for the risk of NPAEs associated with montelukast use in the previous 7 days and 14 days were performed, respectively. Conditional logistic regression analysis was used to calculate adjusted ORs (aORs) with their corresponding 95% CIs, adjusting for concomitant medications.ResultsA total of 161 386 paediatric patients was identified. An increased risk of NPAEs associated with montelukast was found in all time window periods, including 3-day (aOR 1.28, 95% CI 1.24 to 1.32), 7-day (aOR 1.29, 95% CI 1.26 to 1.33), 14-day (aOR 1.34, 95% CI 1.31 to 1.37), 28-day (aOR 1.38, 95% CI 1.36 to 1.41) and 56-day (aOR 1.21, 95% CI 1.19 to 1.22) preceding hazard periods compared with use in the four control periods.ConclusionChildren and adolescents with allergic rhinitis and/or asthma should be prescribed montelukast with caution considering clinical benefits.
Microbiota-induced S100A11-RAGE axis underlies immune evasion in right-sided colon adenomas and is a therapeutic target to boost anti-PD1 efficacy
Authors: Zhou Qiming , Lei Linhan , Cheng Junhong , Chen Junyou , Du Yuyang , Zhang Xuehua , Li Qing , Li Chuangen , Deng Haijun , Wong Chi Chun , Zhuang Baoxiong , Li Guoxin , Bai Xiaowu 
Published: September 2024

Background
Tumourigenesis in right-sided and left-sided colons demonstrated distinct features.

Objective
We aimed to characterise the differences between the left-sided and right-sided adenomas (ADs) representing the early stage of colonic tumourigenesis.

Design
Single-cell and spatial transcriptomic datasets were analysed to reveal alterations between right-sided and left-sided colon ADs. Cells, animal experiments and clinical specimens were used to verify the results.

Results

Single-cell analysis revealed that in right-sided ADs, there was a significant reduction of goblet cells, and these goblet cells were dysfunctional with attenuated mucin biosynthesis and defective antigen presentation. An impairment of the mucus barrier led to biofilm formation in crypts and subsequent bacteria invasion into right-sided ADs. The regions spatially surrounding the crypts with biofilm occupation underwent an inflammatory response by lipopolysaccharide (LPS) and an apoptosis process, as revealed by spatial transcriptomics. A distinct S100A11
+
epithelial cell population in the right-sided ADs was identified, and its expression level was induced by bacterial LPS and peptidoglycan. S100A11 expression facilitated tumour growth in syngeneic immunocompetent mice with increased myeloid-derived suppressor cells (MDSC) but reduced cytotoxic CD8+ T cells. Targeting S100A11 with well-tolerated antagonists of its receptor for advanced glycation end product (RAGE) (Azeliragon) significantly impaired tumour growth and MDSC infiltration, thereby boosting the efficacy of anti-programmed cell death protein 1 therapy in colon cancer.

Conclusion
Our findings unravelled that dysfunctional goblet cells and consequential bacterial translocation activated the S100A11-RAGE axis in right-sided colon ADs, which recruits MDSCs to promote immune evasion. Targeting this axis by Azeliragon improves the efficacy of immunotherapy in colon cancer.
Youth and young adult flavour expectancies for new ‘non-menthol’ cigarettes introduced following California’s ban on flavoured tobacco products
Authors: Kreslake Jennifer M , Cordova Jamie , Seidenberg Andrew B , Ali Fatma Romeh M , Schillo Barbara , Marynak Kristy 
Published: September 2024

BackgroundFollowing California’s statewide law prohibiting the sale of flavoured tobacco products, some cigarette brands introduced new variants advertised as non-menthol, yet featuring design and text commonly found in menthol cigarette marketing.MethodsData are from the February–May 2023 wave of the Tobacco Epidemic Evaluation Network (TEEN+) national probability-based survey (aged 13–25 years). Respondents (N=10 217) were shown images of two (of four) ‘new non-menthol’ brand ads or packaging and two comparators (‘classic’ non-menthol and menthol cigarette brands). Respondents reported expected taste of each (no or any minty/menthol taste; ‘don’t know’). Multinomial regression models tested associations between predictors (age, gender identity, race and ethnicity, perceived financial situation, smoking status) and expectation of minty/menthol taste.ResultsYounger age was associated with expectations of minty/menthol taste, controlling for covariates. Respondents aged 13–17 years had greater odds of expecting minty/menthol taste than no minty/menthol taste for all tested new non-menthol brands (Camel Crush Oasis adjusted OR (aOR): 1.30, p<0.05; Camel Crisp aOR: 1.47, p<0.001; Kool Non-Menthol Blue aOR: 1.27, p<0.05; Kool Non-Menthol Green aOR: 1.43, p<0.01), compared to respondents aged 21 and older. Respondents aged 18–20 years had greater odds of reporting minty/menthol expectancies than no minty/menthol expectancies for Camel Crush Oasis (aOR: 1.35, p<0.05) and Kool Non-Menthol Green (aOR: 1.29, p<0.05) compared to those aged 21–25 years. Compared to non-Hispanic white respondents, non-Hispanic Asian respondents had greater odds of expecting minty/menthol taste than no minty/menthol taste for Camel Crush Oasis (aOR: 1.89, p<0.01), Kool Non-Menthol Blue (aOR: 1.88, p<0.01) and Kool Non-Menthol Green (aOR: 1.72, p<0.05).DiscussionYounger age was associated with expectations of new non-menthol cigarettes having a minty/menthol taste. Results raise concerns regarding the potential appeal of these products to youth and young adults.
Do Azospirillum brasiliense and Chlorella sp. microalgae benefit the production of Hymenaea courbaril L. seedlings?
Authors: Biazatti Renan Marré , Santos Silvia Correa , Santos Cleberton Correia , Pinheiro Bruno Lenhart , de Carvalho Rafael Lima , de Medeiros Elias Silva , Scalon Silvana de Paula Quintão , Torales Elissandra Pacito 
Published: September 2024

The use of Azospirillum brasiliense and Chlorella sp. has gained popularity in agriculture and forestry due to their benefits to plants. These two biological solutions have demonstrated potential to improve the performance and sustainability of crops and forest species, opening new perspectives for agriculture, and the recovery of degraded areas. Given the importance of establishing management strategies for seedling production and that information on forest essences is insufficient, the aim of this study was to evaluate the effect of intervals of Chlorella sp . microalgae application and inoculation with A. brasiliense doses on the growth and quality of Hymenaea courbaril L. seedlings. The experiment was conducted in a randomized block experimental design, and treatments were arranged in a 5 × 4 factorial scheme, with four replicates, testing five A. brasiliense doses: 0, 3, 6, 9, and 12 mL/plant and four intervals of Chlorella sp. microalgae application: single application and every 7, 14, and 21 days after transplanting, for 120 days. Growth and photosynthetic parameters were evaluated. Inoculation with 6 and 9 mL of Azospirillum brasiliense, regardless of Chlorella sp. microalgae application favored the growth of H. courbaril seedlings. Chlorella sp. microalgae application at intervals of 14 and 21 days favored the responses of seedlings inoculated with A. brasilienses. The association between Azospirillum brasiliense and Chlorella sp. promoted gains in seedling production and quality.
Interpolating gauge-fixing for Yang–Mills–Chern–Simons theory in $$D=3$$
Authors: Azevedo Daniel O. R. , Del Cima Oswaldo M. , Dias Thadeu S. , Pereira Emílio D. 
Published: September 2024

AbstractThe Yang–Mills–Chern–Simons theory in three-dimensional Minkowski space-time is studied in a gauge-fixing scheme which interpolates between the covariant gauge and light-cone gauge, the interpolating gauge-fixing. The ultraviolet finiteness of the theory is proved via the Becchi–Rouet–Stora (BRS) algebraic renormalization procedure, which allows us to demonstrate the vanishing of all $$\beta $$
β
-functions and all anomalous dimensions to all orders in perturbation theory.