bluuebunny/crossref_metadata_2025_split huggingface dataset:
A CTL − Lys immune function maintains insect metamorphosis by preventing gut bacterial dysbiosis and limiting opportunistic infections
Authors: Xiong Pei , Wang Wen-Wen , Liu Xu-Sheng , Wang Yu-Feng , Wang Jia-Lin 
Published: March 2024

Abstract
Background
Gut bacteria are beneficial to the host, many of which must be passed on to host offspring. During metamorphosis, the midgut of holometabolous insects undergoes histolysis and remodeling, and thus risks losing gut bacteria. Strategies employed by holometabolous insects to minimize this risk are obscure. How gut bacteria affect host insects after entering the hemocoel and causing opportunistic infections remains largely elusive.

Results
We used holometabolous Helicoverpa armigera as a model and found low Lactobacillus load, high level of a C-type lectin (CTL) gene CD209 antigen-like protein 2 (CD209) and its downstream lysozyme 1 (Lys1) in the midgut of the wandering stage. CD209 or Lys1 depletion increased the load of midgut Lactobacillus, which further translocate to the hemocoel. In particular, CD209 or Lys1 depletion, injection of Lactobacillus plantarum, or translocation of midgut L. plantarum into the hemocoel suppressed 20-hydroxyecdysone (20E) signaling and delayed pupariation. Injection of L. plantarum decreased triacylglycerol and cholesterol storage, which may result in insufficient energy and 20E available for pupariation. Further, Lysine-type peptidoglycan, the major component of gram-positive bacterial cell wall, contributed to delayed pupariation and decreased levels of triacylglycerols, cholesterols, and 20E, in both H. armigera and Drosophila melanogaster.

Conclusions
A mechanism by which (Lactobacillus-induced) opportunistic infections delay insect metamorphosis was found, namely by disturbing the homeostasis of lipid metabolism and reducing 20E production. Moreover, the immune function of CTL − Lys was characterized for insect metamorphosis by maintaining gut homeostasis and limiting the opportunistic infections.
Use of the energy waveform electrocardiogram to detect subclinical left ventricular dysfunction in patients with type 2 diabetes mellitus
Authors: Soh Cheng Hwee , de Sá Alex G. C. , Potter Elizabeth , Halabi Amera , Ascher David B. , Marwick Thomas H. 
Published: March 2024

Abstract
Background
Recent guidelines propose N-terminal pro-B-type natriuretic peptide (NT-proBNP) for recognition of asymptomatic left ventricular (LV) dysfunction (Stage B Heart Failure, SBHF) in type 2 diabetes mellitus (T2DM). Wavelet Transform based signal-processing transforms electrocardiogram (ECG) waveforms into an energy distribution waveform (ew)ECG, providing frequency and energy features that machine learning can use as additional inputs to improve the identification of SBHF. Accordingly, we sought whether machine learning model based on ewECG features was superior to NT-proBNP, as well as a conventional screening tool—the Atherosclerosis Risk in Communities (ARIC) HF risk score, in SBHF screening among patients with T2DM.

Methods
Participants in two clinical trials of SBHF (defined as diastolic dysfunction [DD], reduced global longitudinal strain [GLS ≤ 18%] or LV hypertrophy [LVH]) in T2DM underwent 12-lead ECG with additional ewECG feature and echocardiography. Supervised machine learning was adopted to identify the optimal combination of ewECG extracted features for SBHF screening in 178 participants in one trial and tested in 97 participants in the other trial. The accuracy of the ewECG model in SBHF screening was compared with NT-proBNP and ARIC HF.

Results
SBHF was identified in 128 (72%) participants in the training dataset (median 72 years, 41% female) and 64 (66%) in the validation dataset (median 70 years, 43% female). Fifteen ewECG features showed an area under the curve (AUC) of 0.81 (95% CI 0.787–0.794) in identifying SBHF, significantly better than both NT-proBNP (AUC 0.56, 95% CI 0.44–0.68, p < 0.001) and ARIC HF (AUC 0.67, 95%CI 0.56–0.79, p = 0.002). ewECG features were also led to robust models screening for DD (AUC 0.74, 95% CI 0.73–0.74), reduced GLS (AUC 0.76, 95% CI 0.73–0.74) and LVH (AUC 0.90, 95% CI 0.88–0.89).

Conclusions
Machine learning based modelling using additional ewECG extracted features are superior to NT-proBNP and ARIC HF in SBHF screening among patients with T2DM, providing an alternative HF screening strategy for asymptomatic patients and potentially act as a guidance tool to determine those who required echocardiogram to confirm diagnosis.
Trial registration LEAVE-DM, ACTRN 12619001393145 and Vic-ELF, ACTRN 12617000116325
The worsening effect of paroxysmal atrial fibrillation on left ventricular function and deformation in type 2 diabetes mellitus patients: a 3.0 T cardiovascular magnetic resonance feature tracking study
Authors: Li Xue-Ming , Yan Wei-Feng , Shi Ke , Shi Rui , Jiang Li , Gao Yue , Min Chen-Yan , Liu Xiao-Jing , Guo Ying-Kun , Yang Zhi-Gang 
Published: March 2024

Abstract
Background
Atrial fibrillation (AF) has been linked to an increased risk of cardiovascular death, overall mortality and heart failure in patients with type 2 diabetes mellitus (T2DM). The present study investigated the additive effects of paroxysmal AF on left ventricular (LV) function and deformation in T2DM patients with or without AF using the cardiovascular magnetic resonance feature tracking (CMR-FT) technique.

Methods
The present study encompassed 225 T2DM patients differentiated by the presence or absence of paroxysmal AF [T2DM(AF+) and T2DM(AF−), respectively], along with 75 age and sex matched controls, all of whom underwent CMR examination. LV function and global strains, including radial, circumferential and longitudinal peak strain (PS), as well as peak systolic and diastolic strain rates (PSSR and PDSR, respectively), were measured and compared among the groups. Multivariable linear regression analysis was used to examine the factors associated with LV global strains in patients with T2DM.

Results
The T2DM(AF+) group was the oldest, had the highest LV end‑systolic volume index, lowest LV ejection fraction and estimated glomerular filtration rate compared to the control and T2DM(AF−) groups, and presented a shorter diabetes duration and lower HbA1c than the T2DM(AF−) group. LV PS-radial, PS-longitudinal and PDSR-radial declined successively from controls through the T2DM(AF−) group to the T2DM(AF+) group (all p < 0.001). Compared to the control group, LV PS-circumferential, PSSR-radial and PDSR-circumferential were decreased in the T2DM(AF+) group (all p < 0.001) but preserved in the T2DM(AF−) group. Among all clinical indices, AF was independently associated with worsening LV PS-longitudinal (β = 2.218, p < 0.001), PS-circumferential (β = 3.948, p < 0.001), PS-radial (β = − 8.40, p < 0.001), PSSR-radial and -circumferential (β = − 0.345 and 0.101, p = 0.002 and 0.014, respectively), PDSR-radial and -circumferential (β = 0.359 and − 0.14, p = 0.022 and 0.003, respectively).

Conclusions
In patients with T2DM, the presence of paroxysmal AF further exacerbates LV function and deformation. Proactive prevention, regular detection and early intervention of AF could potentially benefit T2DM patients.
Designing and validating an experimental protocol to induce airway narrowing in older adults with and without asthma
Authors: Chavoshian Shaghayegh , Cao Xiaoshu , Thommandram Anirudh , Stanbrook Matthew B. , Tarlo Susan M. , Fossat Yan , Yadollahi Azadeh 
Published: March 2024

Abstract
Background
Persons with asthma may experience excessive airway narrowing due to exercise or exposure to cold air, worsening their daily functionality. Exercise has several benefits for asthma control, but it may induce airway narrowing in some persons with asthma. When combined with cold temperatures, it introduces another layer of challenges. Therefore, managing this interaction is crucial to increase the quality of life in individuals with asthma. The purpose of this study was to develop a reliable experimental protocol to assess the effects of exercise and cold air on airway narrowing in adults with asthma in a controlled and safe environment.

Methods
This study was a randomized cross-over study in adults with and without asthma. Participants underwent a protocol involving a 10-min seated rest, followed by a 10-min cycling on a stationary bike in different temperatures of 0, 10, or 20 $$^{\circ }$$

∘

C. The sequence of room temperatures was randomized, and there was a 30-min interval for recovery between each temperature transition. In each temperature, to measure lung function and respiratory symptoms, oscillometry and a questionnaire were used at 0 min (baseline), after 10 min of sitting and before starting biking (pre-exercise), and after 10 min of biking (post-exercise). At each room temperature, the changes in airway mechanics and asthma symptoms among baseline, pre-exercise, and post-exercise were compared with one-way repeated measures ANOVA or Friedman Rank Test. Within each arm, cardiac and thoraco-abdominal motion respiration signals were also measured continuously using electrodes and calibrated respiratory inductance plethysmographs, respectively.

Results
A total of 23 persons with asthma (11 females, age: 56.3 ± 10.9 years, BMI: 27.4 ± 5.7 kg/m2) and 6 healthy subjects (3 females, age: 61.8 ± 9.1 years, BMI: 28.5 ± 3.1 kg/m2) were enrolled in the study. Cold temperature of 0 $$^{\circ }$$

∘

C induced airway narrowing in those with and without asthma after 10 and 20 min, respectively. Exercise intervention had significant changes in airway narrowing in participants with asthma in the range of 10–20 $$^{\circ }$$

∘

C. Our results showed that in asthma, changes in subjective respiratory symptoms were due to both cold temperatures of 0 and 10 $$^{\circ }$$

∘

C and exercise in the 0–20 $$^{\circ }$$

∘

C range. Respiratory symptoms were not noticed among the healthy participants.

Conclusion
In conclusion, our findings suggest that exposure to cold temperatures of 0 $$^{\circ }$$

∘

C could serve as a reliable method in the experimental protocol for inducing airway narrowing in asthma. The impact of exercise on airway narrowing was more variable among participants. Understanding these triggers in the experimental protocol is essential for the successful management of asthma in future studies.
Quercetin-loaded mesoporous nano-delivery system remodels osteoimmune microenvironment to regenerate alveolar bone in periodontitis via the miR-21a-5p/PDCD4/NF-κB pathway
Authors: Yang Shi-Yuan , Hu Yue , Zhao Ran , Zhou Yu-Ning , Zhuang Yu , Zhu Yan , Ge Xiao-Li , Lu Ting-Wei , Lin Kai-Li , Xu Yuan-Jin 
Published: March 2024

Abstract
Background
Impaired osteo-/angiogenesis, excessive inflammation, and imbalance of the osteoimmune homeostasis are involved in the pathogenesis of the alveolar bone defect caused by periodontitis. Unfortunately, there is still a lack of ideal therapeutic strategies for periodontitis that can regenerate the alveolar bone while remodeling the osteoimmune microenvironment. Quercetin, as a monomeric flavonoid, has multiple pharmacological activities, such as pro-regenerative, anti-inflammatory, and immunomodulatory effects. Despite its vast spectrum of pharmacological activities, quercetin’s clinical application is limited due to its poor water solubility and low bioavailability.

Results
In this study, we fabricated a quercetin-loaded mesoporous bioactive glass (Quercetin/MBG) nano-delivery system with the function of continuously releasing quercetin, which could better promote the bone regeneration and regulate the immune microenvironment in the alveolar bone defect with periodontitis compared to pure MBG treatment. In particular, this nano-delivery system effectively decreased injection frequency of quercetin while yielding favorable therapeutic results. In view of the above excellent therapeutic effects achieved by the sustained release of quercetin, we further investigated its therapeutic mechanisms. Our findings indicated that under the periodontitis microenvironment, the intervention of quercetin could restore the osteo-/angiogenic capacity of periodontal ligament stem cells (PDLSCs), induce immune regulation of macrophages and exert an osteoimmunomodulatory effect. Furthermore, we also found that the above osteoimmunomodulatory effects of quercetin via macrophages could be partially blocked by the overexpression of a key microRNA——miR-21a-5p, which worked through inhibiting the expression of PDCD4 and activating the NF-κB signaling pathway.

Conclusion
In summary, our study shows that quercetin-loaded mesoporous nano-delivery system has the potential to be a therapeutic approach for reconstructing alveolar bone defects in periodontitis. Furthermore, it also offers a new perspective for treating alveolar bone defects in periodontitis by inhibiting the expression of miR-21a-5p in macrophages and thereby creating a favorable osteoimmune microenvironment.

Graphical Abstract
Defects of mitochondria-lysosomes communication induce secretion of mitochondria-derived vesicles and drive chemoresistance in ovarian cancer cells
Authors: Gagliardi Sinforosa , Mitruccio Marco , Di Corato Riccardo , Romano Roberta , Aloisi Alessandra , Rinaldi Rosaria , Alifano Pietro , Guerra Flora , Bucci Cecilia 
Published: March 2024

AbstractBackgroundAmong the mechanisms of mitochondrial quality control (MQC), generation of mitochondria-derived vesicles (MDVs) is a process to avoid complete failure of mitochondria determining lysosomal degradation of mitochondrial damaged proteins. In this context, RAB7, a late endocytic small GTPase, controls delivery of MDVs to late endosomes for subsequent lysosomal degradation. We previously demonstrated that RAB7 has a pivotal role in response to cisplatin (CDDP) regulating resistance to the drug by extracellular vesicle (EVs) secretion.MethodsWestern blot and immunofluorescence analysis were used to analyze structure and function of endosomes and lysosomes in CDDP chemosensitive and chemoresistant ovarian cancer cell lines. EVs were purified from chemosensitive and chemoresistant cells by ultracentrifugation or immunoisolation to analyze their mitochondrial DNA and protein content. Treatment with cyanide m-chlorophenylhydrazone (CCCP) and RAB7 modulation were used, respectively, to understand the role of mitochondrial and late endosomal/lysosomal alterations on MDV secretion. Using conditioned media from chemoresistant cells the effect of MDVs on the viability after CDDP treatment was determined. Seahorse assays and immunofluorescence analysis were used to study the biochemical role of MDVs and the uptake and intracellular localization of MDVs, respectively.ResultsWe observed that CDDP-chemoresistant cells are characterized by increased MDV secretion, impairment of late endocytic traffic, RAB7 downregulation, an increase of RAB7 in EVs, compared to chemosensitive cells, and downregulation of the TFEB-mTOR pathway overseeing lysosomal and mitochondrial biogenesis and turnover. We established that MDVs can be secreted rather than delivered to lysosomes and are able to deliver CDDP outside the cells. We showed increased secretion of MDVs by chemoresistant cells ultimately caused by the extrusion of RAB7 in EVs, resulting in a dramatic drop in its intracellular content, as a novel mechanism to regulate RAB7 levels. We demonstrated that MDVs purified from chemoresistant cells induce chemoresistance in RAB7-modulated process, and, after uptake from recipient cells, MDVs localize to mitochondria and slow down mitochondrial activity.ConclusionsDysfunctional MQC in chemoresistant cells determines a block in lysosomal degradation of MDVs and their consequent secretion, suggesting that MQC is not able to eliminate damaged mitochondria whose components are secreted becoming effectors and potential markers of chemoresistance.
Dysregulated Gab1 signalling in triple negative breast cancer
Authors: Bongartz Hannes , Mehwald Nora , Seiß Elena A. , Schumertl Tim , Naß Norbert , Dittrich Anna 
Published: March 2024

Abstract
Background
Breast cancer is the most common cancer in women worldwide. Triple-negative breast cancer (TNBC) is especially aggressive and associated with high metastasis. The aetiology of TNBC is heterogeneous and characterised by multiple different mutations that amongst others cause constitutive and dysregulated MAPK and PI3K signalling. Additionally, in more than 50% of TNBC patients, the epidermal growth factor receptor (EGFR) is overexpressed and constitutively active. The multi-site docking protein Grb2-associated binder 1 (Gab1) is a central signalling hub that connects MAPK and PI3K signalling.

Methods
Expression and activation of members of the Gab1/PI3K/MAPK signalling network were assessed in cells from different breast cancer subtypes. Influence of short- and long-term inhibition of EGFR, MAPK and PI3K on the activation of the Gab1/PI3K/MAPK signalling network as well as on cell viability, proliferation and migration was determined. Additionally, cellular localisation of Gab1 and Gab1 variants in naive cells and cells treated with the above-mentioned inhibitors was investigated.

Results
We show that, activation of the Gab1/PI3K/MAPK signalling network is heterogeneous between different breast cancer subtypes. Gab1 phosphorylation and plasma membrane recruitment of Gab1 are dysregulated in the EGFRhigh TNBC cell line MDA-MB-468. While the Gab1/MAPK/PI3K signalling network follows canonical Gab1 signalling in naive MDA-MB-468 cells, Gab1 signalling is changed in cells that acquired resistance towards MAPK and PI3K inhibition. In resistant cells, Gab1 is not located at the plasma membrane despite strong activation of PI3K and MAPK. Furthermore, Gab1 tyrosine phosphorylation is uncoupled from plasma membrane recruitment.

Conclusion
Our study indicates that Gab1 signalling changes fundamentally during the acquisition of resistance to pharmacological inhibitors. Given the molecular heterogeneity between breast cancer subtypes, the detailed understanding of dysregulated and aberrant signalling is an absolute necessity in order to develop personalised therapies for patients with TNBC.
WNT-inhibitory factor 1-mediated glycolysis protects photoreceptor cells in diabetic retinopathy
Authors: Chen Bolin , Zou Jing , Xie Lihui , Cai Yinjun , Li Bowen , Tan Wei , Huang Jinhaohao , Li Fangling , Xu Huizhuo 
Published: March 2024

Abstract
Background
In diabetic retinopathy (DR), hypoxia-inducible factor (HIF-1α) induces oxidative stress by upregulating glycolysis. This process leads to neurodegeneration, particularly photoreceptor cell damage, which further contributes to retinal microvascular deterioration. Further, the regulation of Wnt-inhibitory factor 1 (WIF1), a secreted Wnt signaling antagonist, has not been fully characterized in neurodegenerative eye diseases. We aimed to explore the impact of WIF1 on photoreceptor function within the context of DR.

Method
Twelve-week-old C57BL/KsJ-db/db mice were intravitreally injected with WIF1 overexpression lentivirus. After 4 weeks, optical coherence tomography (OCT), transmission electron microscopy (TEM), H&E staining, and electroretinography (ERG) were used to assess the retinal tissue and function. The potential mechanism of action of WIF1 in photoreceptor cells was explored using single-cell RNA sequencing. Under high-glucose conditions, 661 W cells were used as an in vitro DR model. WIF1-mediated signaling pathway components were assessed using quantitative real-time PCR, immunostaining, and western blotting.

Result
Typical diabetic manifestations were observed in db/db mice. Notably, the expression of WIF1 was decreased at the mRNA and protein levels. These pathological manifestations and visual function improved after WIF1 overexpression in db/db mice. TEM demonstrated that WIF1 restored damaged mitochondria, the Golgi apparatus, and photoreceptor outer segments. Moreover, ERG indicated the recovery of a-wave potential amplitude. Single-cell RNA sequencing and in vitro experiments suggested that WIF1 overexpression prevented the expression of glycolytic enzymes and lactate production by inhibiting the canonical Wnt signaling pathway, HIF-1α, and Glut1, thereby reducing retinal and cellular reactive oxygen species levels and maintaining 661 W cell viability.

Conclusions
WIF1 exerts an inhibitory effect on the Wnt/β-catenin-HIF-1α-Glut1 glycolytic pathway, thereby alleviating oxidative stress levels and mitigating pathological structural characteristics in retinal photoreceptor cells. This mechanism helps preserve the function of photoreceptor cells in DR and indicates that WIF1 holds promise as a potential therapeutic candidate for DR and other neurodegenerative ocular disorders.

Graphical Abstract
Resisting stigma: the role of online communities in young mothers’ successful breastfeeding
Authors: Severinsen Christina , Neely Eva , Hutson Rochelle 
Published: March 2024

Abstract
Background
Breastfeeding initiation and continuation rates are shaped by complex and interrelated determinants across individual, interpersonal, community, organisational, and policy spheres. Young mothers, however, face a double burden of stigma, being perceived as immature and incompetent in their mothering and breastfeeding abilities. In this study, we aimed to understand the experiences of young mothers who exclusively breastfed for six months and beyond and explore their experiences of stigma and active resistance through social media.

Methods
In 2020, in-depth telephone interviews about breastfeeding experiences were conducted with 44 young mothers under age 25 in Aotearoa New Zealand who breastfed for six months or longer. Participants were recruited via social media. Interviews were audio-recorded, transcribed and analysed thematically.

Results
Analysis yielded four themes on young mothers’ negotiation of breastfeeding and support. The first three themes revealed young mothers’ encounters with socio-cultural contexts. They faced negative judgments about maturity and competence, adverse guidance to supplement or cease breastfeeding, and an undermining of their breastfeeding efforts. The fourth theme showed how young mothers sought alternative support in online environments to avoid negative interactions. Online spaces provided anonymity, convenience, experiential knowledge and social connections with shared values. This facilitated identity strengthening, empowerment and stigma resistance.

Conclusion
Our research highlights the importance of online communities as a tool for young mothers to navigate and resist the societal stigmas surrounding breastfeeding. Online spaces can provide a unique structure that can help counteract the adverse effects of social and historical determinants on breastfeeding rates by fostering a sense of inclusion and support. These findings have implications for the development of breastfeeding promotion strategies for young mothers and highlight the potential of peer support in counteracting the negative impacts of stigma. The research also sheds light on the experiences of young mothers within the health professional relationship and the effects of stigma and cultural health capital on their engagement and withdrawal from services. Further research should examine how sociocultural barriers to breastfeeding stigmatise and marginalise young mothers and continue to reflect on their socio-political and economic positioning and how it can exacerbate inequities.