bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interplay between gut microbiota and tryptophan metabolism in type 2 diabetic mice treated with metformin
Authors: Xie Yvhao , Li Xinxin , Meng Qingshi , Li Jinjun , Wang Xin , Zhu Liying , Wang Weiwei , Li Xiaoqiong 
Published: August 2024

ABSTRACT

Tryptophan (TRP) metabolites have been identified as potent biomarkers for complications of type 2 diabetes mellitus (T2DM). However, it remains unclear whether the therapeutic effect of metformin in T2DM is related to the modulation of TRP metabolic pathway. This study aims to investigate whether metformin affects TRP metabolism in T2DM mice through the gut microbiota. A liquid chromatography-tandem mass spectrometry method was established to determine 16 TRP metabolites in the serum, colon content, urine, and feces of T2DM mice, and the correlations between metabolites and the T2DM mice gut microbiota were performed. The method demonstrated acceptable linearity (
R
2
> 0.996), with the limit of quantification ranging from 0.29 to 69.444 nmol/L for 16 analytes, and the limit of detection ranging from 0.087 to 20.833 nmol/L. In T2DM mice, metformin treatment effectively restored levels of indole-3-lactic acid (ILA), indole-3-propionic acid (IPA), and the ILA/IPA ratio, along with several aryl hydrocarbon receptor ligands in the serum, with a notable impact in the colon but not in the urine. This restoration was accompanied by a shift in the relative abundance of
Dubosiella
,
Turicibacter
,
RF39
,
Clostridia_UCG-014
,
and Alistipes
. Spearman’s correlation analysis revealed positive correlations between
Turicibacter
and
Alistipes
with IPA and indole-3-acetic acid. Conversely, these genera displayed negative correlations with ILA and kynurenine. In addition, our study revealed the presence of endogenous indole pathway in germ-free mice, and the impact of metformin on endogenous TRP metabolism in T2DM mice cannot be disregarded. Further research is needed to investigate the regulation of TRP metabolism by metformin.

IMPORTANCE
This study provides valuable insights into the interrelationship between metformin administration, changes in the tryptophan (TRP) metabolome, and gut microbiota in type 2 diabetes mellitus (T2DM) mice. Indole-3-lactic acid (ILA)/indole-3-propionic acid (IPA) emerges as a potential biomarker for the development of T2DM and prediction of therapeutic response. While the indole metabolic pathway has long been associated exclusively with the gut microbiome, recent research has demonstrated the ability of host interleukin-4-induced-1 to metabolize TRP. The detection of indole derivatives in the serum of germ-free mice suggests the existence of inherent endogenous indole metabolic pathways. These findings deepen our understanding of metformin's efficacy in correcting TRP metabolic disorders and provide valuable directions for further investigation. Moreover, this knowledge may pave the way for the development of targeted treatment strategies for T2DM, focusing on the gut microbiome and restoration of associated TRP metabolism.
Inhibition of SARS-CoV-2 infection by
Porphyromonas gingivalis
and the oral microbiome
Authors: Bontempo Alexander , Chirino Alexandra , Heidari Alireza , Lugo Alexandra , Shindo Satoru , Pastore Maria R. , Madonia Riccardo , Antonson Sibel A. , Godoy Cristina , Nichols Frank C. , Potempa Jan , Davey Mary Ellen , Kawai Toshihisa , Cayabyab Mark J. 
Published: August 2024

ABSTRACT

The COVID-19 pandemic persists despite the availability of vaccines, and it is, therefore, crucial to develop new therapeutic and preventive approaches. In this study, we investigated the potential role of oral microbiome in SARS-CoV-2 infection. Using an
in vitro
SARS-CoV-2 pseudovirus infection assay, we found a potent inhibitory effect exerted by
Porphyromonas gingivalis
on SARS-CoV-2 infection mediated by known
P. gingivalis
compounds such as phosphoglycerol dihydroceramide (PGDHC) and gingipains as well as by unknown bacterial factors. We found that the gingipain-mediated inhibition of infection is likely due to cytotoxicity, whereas PGDHC inhibited virus infection by an unknown mechanism. Unidentified factors present in
P. gingivalis
supernatant inhibited SARS-CoV-2 likely via the fusion step of the virus life cycle. We addressed the role of other oral bacteria and found certain periodontal pathogens capable of inhibiting SARS-CoV-2 pseudovirus infection by inducing cytotoxicity on target cells. In the human oral cavity, we observed that the modulatory activity of oral microbial communities varied among individuals, in that some saliva-based cultures were capable of inhibiting while others were enhancing infection. These findings contribute to our understanding of the complex relationship between the oral microbiome and viral infections, offering potential avenues for innovative therapeutic strategies in combating COVID-19.

IMPORTANCE

The oral microbiome is important in health and disease, and in this study, we addressed the potential role of the oral microbiome in COVID-19 infection. Our
in vitro
studies suggest that certain bacteria of the oral microbiome such as
P. gingivalis
produce compounds that could potentially inhibit SARS-CoV-2 infection. These findings elucidating the interactions between the oral microbiome and SARS-CoV-2 infection will be important in our understanding of COVID-19 pathogenesis and the development of innovative therapeutic and preventive strategies against COVID-19 infection.
Core microbes in
Cordyceps militaris
sclerotia and their nitrogen metabolism-related ecological functions
Authors: Luo Li , Dai Fei , Xu Zhongshun , Guan Jingqiang , Fei Gangxiang , Qu Jiaojiao , Yao Min , Xue Yuan , Zhou Yeming , Zou Xiao 
Published: August 2024

ABSTRACT

Cordyceps militaris
infects insects and forms sclerotia within the insect remains, establishing insect–microbe complexes. Here,
C
.
militaris
sclerotia samples from a single location in China over a 5-year period were subjected to high-throughput DNA sequencing, and the core microbes (which were stably enriched in the sclerotia over the 5 years) were identified. Next, seven bacterial strains were isolated from the
C. militaris
sclerotia, their biochemical characteristics were assessed, and they were co-cultured with
C. militaris
to study their effects on
C. militaris
metabolite production and biomass. Furthermore, the effects of NH
4
, NO
3
, and peptone media on
C. militaris
were compared. The results showed that
Rhodococcus
,
Phyllobacterium
,
Pseudomonas
,
Achromobacter
,
Ensifer
,
Stenotrophomonas
,
Sphingobacterium
,
Variovorax
, and
Acinetobacter
were the core microbes. Although co-culture of
C. militaris
with the seven bacterial strains isolated from the sclerotia did not directly increase the cordycepin level, they all had NO
3
reduction ability, and four had urea decomposition ability. Meanwhile,
C. militaris
in NH
4
medium had an increased cordycepin level compared to
C. militaris
in the other two media. From this, we inferred that bacteria in the sclerotia can convert NO
3
to NH
4
, and then cordycepin is produced using NH
4
, which was confirmed by RNA-seq and real-time fluorescence quantitative PCR. Thus, bacteria in the sclerotia may indirectly affect the
C. militaris
metabolite production by regulating nitrogen metabolism. In summary, there are stable core microbes in the
C. militaris
sclerotia, and they may directly and indirectly affect the growth and metabolite production of
C. militaris
.

IMPORTANCE

The model
Cordyceps
species
Cordyceps militaris
is rich in therapeutic compounds. It has recently been demonstrated that symbiotic microbes in sclerotia affect
Cordyceps’
growth, development, and secondary metabolite production. In this study, core microbes were identified based on
C. militaris
sclerotia samples obtained from the same site over 5 years. Additionally, bacterial strains isolated from
C. militaris
sclerotia were found to affect metabolite production and nitrogen utilization, based on functional tests. Moreover, based on the bacterial nitrogen metabolism capacity in the sclerotia and its influence on
C. militaris
metabolite production, we deduced that bacteria in the sclerotia can indirectly affect
C. militaris
metabolite production by regulating nitrogen metabolism. This is the first report on how bacteria in the sclerotia affect
C. militaris
metabolite production from the perspective of the nitrogen cycle. The results increase our understanding of microbial functions in
C. militaris
sclerotia.
Mutation of
Pseudomonas aeruginosa lasI/rhlI
diminishes its cytotoxicity, oxidative stress, inflammation, and apoptosis on THP-1 macrophages
Authors: Ren Yanying , You Xiaojuan , Zhu Rui , Li Dengzhou , Wang Chunxia , He Zhiqiang , Hu Yue , Li Yifan , Liu Xinwei , Li Yongwei 
Published: August 2024

ABSTRACT

The management of
Pseudomonas aeruginosa
(
P. aeruginosa
) infections presents a substantial challenge to clinics and public health, emphasizing the urgent need for innovative strategies to address this issue. Quorum sensing (QS) is an intercellular communication mechanism that coordinates bacterial activities involved in various virulence mechanisms, such as acquiring host nutrients, facilitating biofilm formation, enhancing motility, secreting virulence factors, and evading host immune responses, all of which play a crucial role in the colonization and infection of
P. aeruginosa
. The LasI/R and RhlI/R sub-systems dominate in the QS system of
P. aeruginosa
. Macrophages play a pivotal role in the host’s innate immune response to
P. aeruginosa
invasion, particularly through phagocytosis as the initial host defense mechanism. This study investigated the effects of
P. aeruginosa
’s QS system on THP-1 macrophages. Mutants of PAO1 with
lasI/rhlI
deletion, as well as their corresponding complemented strains, were obtained, and significant downregulation of QS-related genes was observed in the mutants. Furthermore, the
ΔlasI
and
ΔlasIΔrhlI
mutants exhibited significantly attenuated virulence in terms of biofilm formation, extracellular polymeric substances synthesis, bacterial adhesion, motility, and virulence factors production. When infected with
ΔlasI
and
ΔlasIΔrhlI
mutants, THP-1 macrophages exhibited enhanced scavenging ability against the mutants and demonstrated resistance to cytotoxicity, oxidative stress, inflammatory response, and apoptosis induced by the culture supernatants of these mutant strains. These findings offer novel insights into the mechanisms underlying how the
lasI/rhlI
mutation attenuates cytotoxicity, oxidative stress, inflammation, and apoptosis in macrophages induced by
P. aeruginosa
.

IMPORTANCE

P. aeruginosa
is classified as one of the ESKAPE pathogens and poses a global public health concern. The QS system of this versatile pathogen contributes to a broad spectrum of virulence, thereby constraining therapeutic options for serious infections. This study illustrated that the
lasI/rhlI
mutation of the QS system plays a prominent role in attenuating the virulence of
P. aeruginosa
by affecting bacterial adhesion, biofilm formation, extracellular polymeric substances synthesis, bacterial motility, and virulence factors’ production. Notably, THP-1 macrophages infected with mutant strains exhibited increased phagocytic activity in eliminating intracellular bacteria and enhanced resistance to cytotoxicity, oxidative stress, inflammation, and apoptosis. These findings suggest that targeted intervention toward the QS system is anticipated to diminish the pathogenicity of
P. aeruginosa
to THP-1 macrophages.
Using a landscape fingerprint to identify changes in fault-slip behavior
Authors: Ross Emily O. , Reber Jacqueline E. , Titus Sarah J. , García Antonio F. 
Published: August 2024

Abstract
The Gabilan mesa tilts gently southwest away from the San Andreas fault in central California (western United States). Rather than attributing its existence to plate convergence, we argue that this large landform developed in response to a change in slip behavior along the San Andreas fault. Our interpretation is based on results from physical experiments. When we isolate a change in slip behavior (i.e., creeping to locked) as the only variable influencing deformation, a half-dome feature forms alongside the slip transition and mimics the shape and location of the Gabilan mesa adjacent to the San Andreas fault. We show other examples of half-dome features along the North Anatolian (Turkey), Philippine, and Chaman (Afghanistan-Pakistan) faults, suggesting that these domed landforms may provide indications of slip behavior transitions on poorly monitored faults.
Predicting extubation failure in preterm infants using lung ultrasound: a diagnostic accuracy study
Authors: Sett Arun , Foo Gillian , Ngeow Alvin , Thomas Niranjan , Kee Penny P L , Zayegh Amir , Hodgson Kate A , Donath Susan M , Tingay David G , Davis Peter G , Manley Brett J , Rogerson Sheryle R 
Published: August 2024

Objective
To determine the accuracy of pre-extubation lung ultrasound (LUS) to predict reintubation in preterm infants born <32 weeks’ gestation.

Design
Prospective diagnostic accuracy study.

Setting
Two neonatal intensive care units.

Methods
Anterior and lateral LUS was performed pre-extubation. The primary outcome was the accuracy of LUS scores (range 0–24) to predict reintubation within 72 hours. Secondary outcomes were accuracy in predicting (1) reintubation within 7 days, (2) reintubation stratified by postnatal age and (3) accuracy of lateral imaging only (range 0–12). Pre-specified subgroup analyses were performed in extremely preterm infants born <28 weeks’ gestation. Cut-off scores, sensitivities and specificities were calculated using receiver operating characteristic analysis and reported as area under the curves (AUCs).

Results
One hundred preterm infants with a mean (SD) gestational age of 27.4 (2.2) weeks and birth weight of 1059 (354) g were studied. Thirteen were subsequently reintubated. The AUC (95% CI) of the pre-extubation LUS score for predicting reintubation was 0.63 (0.45–0.80). Accuracy was greater in extremely preterm infants: AUC 0.70 (0.52–0.87) and excellent in infants who were <72 hours of age at the time of extubation: AUC 0.90 (0.77–1.00). Accuracy was poor in infants who were >7 days of age. Lateral imaging alone demonstrated similar accuracy to scanning anterior and lateral regions.

Conclusions
In contrast to previous studies, LUS was not a strong predictor of reintubation in preterm infants. Accuracy is increased in extremely preterm infants. Future research should focus on infants at highest risk of extubation failure and consider simpler imaging protocols.

Trial registration number
Australian New Zealand Clinical Trials Registry: ACTRN12621001356853.
Qualitative exploration of patients’ experiences with Intrabeam TARGeted Intraoperative radioTherapy (TARGIT-IORT) and External-Beam RadioTherapy Treatment (EBRT) for breast cancer
Authors: Bagga Sandeep Kumar , Swiderska Natalie , Hooker Charlotte , Royle Jennifer , Ennis-O'Connor Marie , Freeney Siobhan , Watson Dympna , Woolcock Robin , Lodge George , Laws Siobhan , Vaidya Jayant S 
Published: August 2024

ObjectiveTo gather a deep qualitative understanding of the perceived benefits and impacts of External-Beam RadioTherapy (EBRT) and TARGeted Intraoperative radioTherapy (TARGIT-IORT) using Intrabeam to assess how the treatments affected patient/care partner experiences during their cancer treatment and beyond.Design and participantsA patient-led working group was established to guide study design and to help validate findings. Patients with experience of receiving EBRT or TARGIT-IORT were purposively sampled by Hampshire Hospitals NHS Foundation Trust. These patients had been offered both regimens as per their clinical features and eligibility. Semistructured interviews were conducted with 29 patients and care partners with lived experience of either EBRT (n=12, 5-day FAST-Forward regimen and n=3, 3-week regimen) or TARGIT-IORT (n=14). Thematic analysis was then carried out by two coders generating 11 themes related to EBRT or TARGIT-IORT.SettingSemistructured interviews were conducted virtually via Zoom during February and March 2023.ResultsA number of procedural grievances were noted among EBRT patients. EBRT was perceived as being disruptive to normal routines (work, home and travel) and caused discomfort from side effects. TARGIT-IORT was perceived by patients and care partners as the safer option and efficient with minimal if any disruptions to quality of life. The need for timely accessible information to reduce anxieties was noted in both cohorts.ConclusionsThis qualitative study found that patients perceived EBRT as being greatly disruptive to their lives. In contrast, the one-off feature of TARGIT-IORT given while they are asleep during surgery gives them the feeling of stamping out the cancer without conscious awareness. These insights can help healthcare staff and policy-makers further justify the incorporation of the treatment favoured by these patient perceptions (TARGIT-IORT) more widely in routine practice. Further research is planned to explore TARGIT-IORT in more diverse populations and in the 35 countries where it is an established treatment option.
Behavioural attitudes of three-wheeled taxi drivers towards mitigation of on-road air pollution in urban cities in Sri Lanka: a qualitative study from South Asia
Authors: Adikaram W D C Niroshini , Arambepola Carukshi 
Published: August 2024

ObjectivesIn recent years, urban areas across South Asia have experienced alarming levels of air pollution, primarily attributed to the rapid growth of motorised transportation. Three-wheeled taxis, commonly known as ‘tuk-tuks’, constitute a significant portion of the public transport system in Sri Lankan cities, making it crucial to understand the behavioural attitudes of their drivers in addressing on-road air pollution as they are key stakeholders in urban mobility and environmental sustainability. Therefore, this research aimed to contribute valuable insights into the behavioural attitudes of three-wheeled taxi drivers towards mitigation of on-road air pollution.MethodsWe recruited 67 three-wheeled taxi drivers to participate in semi-structured focus group interviews and in-depth interviews through purposive sampling. The sample size was determined on the basis of data saturation. We collected data from on-site note-taking, audio recording and transcribing the interviews, and subjected them to content thematic analysis manually.ResultBehavioural attitudes for mitigation were mainly based on efforts to minimise on-road air pollution, perception of minimising on-road air pollution, knowledge, socio-demographic and legislative factors related to behaviour.ConclusionBehavioural attitudes on mitigation were multi-faceted. To minimise the hazards as well as mitigate air pollution, educating and supporting them financially and by inducing a behavioural change are recommended to safeguard their health.
The need for thoracic magnetic resonance imaging before vertebral augmentation surgery in patients with lumbar vertebral fractures
Authors: Zhang Yuye , Tang Wenxiang , Niu Yanping , Zhao Xushen , Hua Jun , Zhou Xiaozhong , Lin Fanguo 
Published: August 2024

BackgroundOsteoporotic vertebral compression fractures (OVCFs) of the lumbar region may be accompanied by thoracic fractures. Treating only the lumbar fractures can lead to worsening of the thoracic fractures or unresolved postoperative symptoms. This study aims to investigate the need to perform thoracic MRI before vertebral augmentation (including percutaneous vertebroplasty and percutaneous kyphoplasty) in patients with lumbar OVCF.MethodsThis study retrospectively analyzed patients with lumbar OVCF who were scheduled for surgical treatment. All patients underwent thoracic and lumbar MRI before surgery. We evaluated the proportion of thoracic fractures accompanying lumbar fractures at each segment and identified the common locations of these accompanying fractures. Univariate and multivariate analyses were conducted to determine the risk factors and optimal thresholds for predicting accompanying thoracic fractures.ResultsThe study recruited 700 patients, of whom 96 (13.71%) had new thoracic fractures along with lumbar fractures. The most common thoracic segments affected were T10 (22.50%), T9 (19.17%), T8 (26.67%), and T7 (20.83%). Univariate analysis showed significant differences in age and cause of injury between the thoracic fracture group and the control group. The bone density of the thoracic fracture group was significantly lower than that of the control group. Multivariate logistic regression analysis indicated that lifting heavy objects, sprains, and low bone density are risk factors for thoracic fractures in patients with lumbar OVCF.ConclusionIt is crucial to perform thoracic MRI before surgery in patients with lumbar OVCF. This helps to avoid missing thoracic fractures, prevent the worsening of injuries, and ensure better postoperative outcomes.
Yukawa–Casimir wormholes in the framework of f(R) gravity
Authors: Venkatesha V. , Chalavadi Chaitra Chooda , Malik Adnan 
Published: August 2024

AbstractIn this article, we explore the Yukawa modification of the Casimir wormhole within the framework of f(R) gravity. To accomplish this, we adopt an approach proposed by Garattini (Eur Phys J C 81:824, 2021), wherein the original Casimir source is modified by a Yukawa term in three distinct scenarios. We utilize these Yukawa Casimir energy densities to assess the feasibility of traversable wormholes. The resulting shape function satisfies the criteria for traversability under the specified parameter values. Furthermore, we scrutinize the energy conditions and the violation of the null energy conditions suggests the presence of exotic matter within the Yukawa Casimir wormholes. Additionally, we analyze the embedding procedures for the wormhole geometry.
Nonlinear chiral forms in the Sen formulation
Authors: Janaun Sujiphat , Phonchantuek Anajak , Vanichchapongjaroen Pichet 
Published: August 2024

AbstractThe Sen formulation for chiral (2p)-form in $$4p+2$$

4
p
+
2

dimensions describes a system with two separate sectors, one is physical while the other is unphysical. Each contains a chiral form and a metric. In this paper, we focus on the cases where the self-duality condition for the unphysical sector is linear while for the physical sector can be nonlinear. We show the decoupling at the Hamiltonian and Lagrangian levels. The decoupling at the Hamiltonian level follows the idea in the literature. Then by an appropriate field redefinition of the corresponding first-order Lagrangian, the separation at the Lagrangian level follows. We derive the diffeomorphism of the theory in the case where the chiral form in the physical sector has nonlinear self-dual field strength and couples to external $$(2p+1)$$

(
2
p
+
1
)

-form field. Explicit forms of Sen theories are also discussed. The Lagrangian for the quadratic theory is separated into two Henneaux–Teitelboim Lagrangians. We also discuss the method of generating explicit nonlinear theories with $$p=1$$

p
=
1

. Finally, we also show that the M5-brane action in the Sen formulation is separated into a Henneaux–Teitelboim action in unphysical sector and a gauge-fixed PST in physical sector.