bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac-specific PFKFB3 overexpression prevents diabetic cardiomyopathy via enhancing OPA1 stabilization mediated by K6-linked ubiquitination
Authors: Luo Jinlan , Hu Shuiqing , Liu Jingrui , Shi Lili , Luo Liman , Li Wenhua , Cai Yueting , Tang Jiaxin , Liu Siyang , Fu Menglu , Dong Ruolan , Yang Yan , Tu Ling , Xu Xizhen 
Published: May 2024

AbstractDiabetic cardiomyopathy (DCM) is a prevalent complication of type 2 diabetes (T2D). 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) is a glycolysis regulator. However, the potential effects of PFKFB3 in the DCM remain unclear. In comparison to db/m mice, PFKFB3 levels decreased in the hearts of db/db mice. Cardiac-specific PFKFB3 overexpression inhibited myocardial oxidative stress and cardiomyocyte apoptosis, suppressed mitochondrial fragmentation, and partly restored mitochondrial function in db/db mice. Moreover, PFKFB3 overexpression stimulated glycolysis. Interestingly, based on the inhibition of glycolysis, PFKFB3 overexpression still suppressed oxidative stress and apoptosis of cardiomyocytes in vitro, which indicated that PFKFB3 overexpression could alleviate DCM independent of glycolysis. Using mass spectrometry combined with co-immunoprecipitation, we identified optic atrophy 1 (OPA1) interacting with PFKFB3. In db/db mice, the knockdown of OPA1 receded the effects of PFKFB3 overexpression in alleviating cardiac remodeling and dysfunction. Mechanistically, PFKFB3 stabilized OPA1 expression by promoting E3 ligase NEDD4L-mediated atypical K6-linked polyubiquitination and thus prevented the degradation of OPA1 by the proteasomal pathway. Our study indicates that PFKFB3/OPA1 could be potential therapeutic targets for DCM.
Graphical Abstract
Cholesterol neutralized vemurafenib treatment by promoting melanoma stem-like cells via its metabolite 27-hydroxycholesterol
Authors: Wang Xiaohong , Zhong Feiliang , Chen Tingting , Wang Hongbo , Wang Weifang , Jin Hongkai , Li Chouyang , Guo Xuan , Liu Ying , Zhang Yu , Li Bo 
Published: May 2024

AbstractVemurafenib has been used as first-line therapy for unresectable or metastatic melanoma with BRAFV600E mutation. However, overall survival is still limited due to treatment resistance after about one year. Therefore, identifying new therapeutic targets for melanoma is crucial for improving clinical outcomes. In the present study, we found that lowering intracellular cholesterol by knocking down DHCR24, the limiting synthetase, impaired tumor cell proliferation and migration and abrogated the ability to xenotransplant tumors. More importantly, administration of DHCR24 or cholesterol mediated resistance to vemurafenib and promoted the growth of melanoma spheroids. Mechanistically, we identified that 27-hydroxycholesterol (27HC), a primary metabolite of cholesterol synthesized by the enzyme cytochrome P450 27A1 (CYP27A1), reproduces the phenotypes induced by DHCR24 or cholesterol administration and activates Rap1-PI3K/AKT signaling. Accordingly, CYP27A1 is highly expressed in melanoma patients and upregulated by DHCR24 induction. Dafadine-A, a CYP27A1 inhibitor, attenuates cholesterol-induced growth of melanoma spheroids and abrogates the resistance property of vemurafenib-resistant melanoma cells. Finally, we confirmed that the effects of cholesterol on melanoma resistance require its metabolite 27HC through CYP27A1 catalysis, and that 27HC further upregulates Rap1A/Rap1B expression and increases AKT phosphorylation. Thus, our results suggest that targeting 27HC may be a useful strategy to overcome treatment resistance in metastatic melanoma.
Cellular depletion of major cathepsin proteases reveals their concerted activities for lysosomal proteolysis
Authors: Gallwitz Lisa , Bleibaum Florian , Voss Matthias , Schweizer Michaela , Spengler Katharina , Winter Dominic , Zöphel Frederic , Müller Stephan , Lichtenthaler Stefan , Damme Markus , Saftig Paul 
Published: May 2024

AbstractProteins delivered by endocytosis or autophagy to lysosomes are degraded by exo- and endoproteases. In humans 15 lysosomal cathepsins (CTS) act as important physiological regulators. The cysteine proteases CTSB and CTSL and the aspartic protease CTSD are the most abundant and functional important lysosomal proteinases. Whereas their general functions in proteolysis in the lysosome, their individual substrate, cleavage specificity, and their possible sequential action on substrate proteins have been previously studied, their functional redundancy is still poorly understood. To address a possible common role of highly expressed and functional important CTS proteases, we generated CTSB-, CTSD-, CTSL-, and CTSBDL-triple deficient (KO) human neuroblastoma-derived SH-SY5Y cells and CTSB-, CTSD-, CTSL-, CTSZ and CTSBDLZ-quadruple deficient (KO) HeLa cells. These cells with a combined cathepsin deficiency exhibited enlarged lysosomes and accumulated lipofuscin-like storage material. The lack of the three (SH-SY5Y) or four (HeLa) major CTSs caused an impaired autophagic flux and reduced degradation of endocytosed albumin. Proteome analyses of parental and CTS-depleted cells revealed an enrichment of cleaved peptides, lysosome/autophagy-associated proteins, and potentially endocytosed membrane proteins like the amyloid precursor protein (APP), which can be subject to endocytic degradation. Amino- and carboxyterminal APP fragments accumulated in the multiple CTS-deficient cells, suggesting that multiple CTS-mediated cleavage events regularly process APP. In summary, our analyses support the idea that different lysosomal cathepsins act in concert, have at least partially and functionally redundant substrates, regulate protein degradation in autophagy, and control cellular proteostasis, as exemplified by their involvement in the degradation of APP fragments.
Local Spectral Multiplicity of Selfadjoint Couplings with General Interface Conditions
Authors: Simonov Sergey , Woracek Harald 
Published: May 2024

AbstractWe consider selfadjoint operators obtained by pasting a finite number of boundary relations with one-dimensional boundary space. A typical example of such an operator is the Schrödinger operator on a star-graph with a finite number of finite or infinite edges and an interface condition at the common vertex. A wide class of “selfadjoint” interface conditions, subject to an assumption which is generically satisfied, is considered. We determine the spectral multiplicity function on the singular spectrum (continuous as well as point) in terms of the spectral data of decoupled operators.
Quantifying the Potential of Argon Detection Capabilities for Nuclear Explosion Monitoring
Authors: Adhikari Pranshu , Gordon Emily M. , Shah Khiloni A. , Eslinger Paul W. , Miley Harry S. , Bowyer Theodore W. , Haas Derek A. 
Published: May 2024

AbstractCurrent noble gas detection systems for nuclear explosion monitoring are based on the detection of four radioxenon isotopes—Xe-131m, -133, -133m and -135. The data provided by radioxenon detection could be enhanced by other radionuclide signatures such as Ar-37. Activation of Ca-40 in rock by neutrons produces Ar-37, and monitoring for this additional nuclide could help distinguish detections of nuclear explosions from background sources, such as medical isotope production. This work studies the capabilities of a hypothetical argon detection network. A 10 kt explosion was modeled using MCNP and SCALE to determine the inventory of Ar-37 created in a representative granite rock layer, assuming either 0.1, 1 or 10% of the total inventory was released. The Ar-37 inventory was combined with atmospheric transport data from HYSPLIT compiled in a previous study, along with the detection limits of standard Ar-37 detection systems, to determine how many hypothetical monitoring stations would detect Ar-37 from an explosion. This method was repeated for 365 HYSPLIT data sets to create a year’s worth of hypothetical explosions, releases, and detections. The study quantified the average number of detections per release, the number of stations detecting Ar-37, and the possibility of detecting Ar-37 in coincidence with xenon.
Iron bioleaching and polymers accumulation by an extreme acidophilic bacterium
Authors: Marchetti Alessandro , Kupka Daniel , Senatore Vittorio Giorgio , Bártová Zuzana , Branduardi Paola , Hagarová Lenka , Hredzák Slavomír , Lotti Marina 
Published: May 2024

AbstractIn many European regions, both local metallic and non-metallic raw materials are poorly exploited due to their low quality and the lack of technologies to increase their economic value. In this context, the development of low cost and eco-friendly approaches, such as bioleaching of metal impurities, is crucial. The acidophilic strain Acidiphilium sp. SJH reduces Fe(III) to Fe(II) by coupling the oxidation of an organic substrate to the reduction of Fe(III) and can therefore be applied in the bioleaching of iron impurities from non-metallic raw materials. In this work, the physiology of Acidiphilium sp. SJH and the reduction of iron impurities from quartz sand and its derivatives have been studied during growth on media supplemented with various carbon sources and under different oxygenation conditions, highlighting that cell physiology and iron reduction are tightly coupled. Although the organism is known to be aerobic, maximum bioleaching performance was obtained by cultures cultivated until the exponential phase of growth under oxygen limitation. Among carbon sources, glucose has been shown to support faster biomass growth, while galactose allowed highest bioleaching. Moreover, Acidiphilium sp. SJH cells can synthesise and accumulate Poly-β-hydroxybutyrate (PHB) during the process, a polymer with relevant application in biotechnology. In summary, this work gives an insight into the physiology of Acidiphilium sp. SJH, able to use different carbon sources and to synthesise a technologically relevant polymer (PHB), while removing metals from sand without the need to introduce modifications in the process set up.
Anti-classification results for weakly mixing diffeomorphisms
Authors: Kunde Philipp 
Published: May 2024

AbstractWe extend anti-classification results in ergodic theory to the collection of weakly mixing systems by proving that the isomorphism relation as well as the Kakutani equivalence relation of weakly mixing invertible measure-preserving transformations are not Borel sets. This shows in a precise way that classification of weakly mixing systems up to isomorphism or Kakutani equivalence is impossible in terms of computable invariants, even with a very inclusive understanding of “computability”. We even obtain these anti-classification results for weakly mixing area-preserving smooth diffeomorphisms on compact surfaces admitting a non-trivial circle action as well as real-analytic diffeomorphisms on the 2-torus.
Interleukin 1β receptor blocker (Anakinra) and regenerative stem cell therapy: two novel approaches effectively ameliorating diabetic cardiomyopathy
Authors: Mahmoud Lamiaa Mohamed , Mageed Aya Aly Ashraf Abdel , Saadallah Jackline Moawad , Youssef Mira Farouk , Rashed Liala Ahmed , Ammar Hania Ibrahim 
Published: May 2024

AbstractDiabetic cardiomyopathy (DCM) is a serious common complication of diabetes. Unfortunately, there is no satisfied treatment for those patients and more studies are in critical need to cure them. Therefore, we aimed to carry out our current research to explore the role of two novel therapeutic approaches: one a biological drug aimed to block inflammatory signaling of the IL 1beta (IL1β) axis, namely, anakinra; the other is provision of anti-inflammatory regenerative stem cells. Wistar male rats were allocated into four groups: control group: type 2 diabetes mellitus (DM) induced by 6-week high-fat diet (HFD) followed by a single-dose streptozotocin (STZ) 35 mg/kg i.p., then rats were allocated into: DM: untreated; DM BM-MSCs: received a single dose of BM-MSCs (1 × 106 cell/rat) into rat tail vein; DM-Anak received Anak 0.5 μg/kg/day i.p. for 2 weeks. Both therapeutic approaches improved cardiac performance, fibrosis, and hypertrophy. In addition, blood glucose and insulin resistance decreased, while the antioxidant parameter, nuclear factor erythroid 2–related factor 2 (Nrf2) and interleukin 10 (IL10), and anti-inflammatory agent increased. Furthermore, there is a significant reduction in tumor necrosis factor alpha (TNFα), IL1β, caspase1, macrophage marker CD 11b, inducible nitric oxide synthase (iNOS), and T-cell marker CD 8. Both Anak and BM-MSCs effectively ameliorated inflammatory markers and cardiac performance as compared to non-treated diabetics. Improvement is mostly due to anti-inflammatory, antioxidant, anti-apoptotic properties, and regulation of TNFα/IL1β/caspase1 and Nrf2/IL10 pathways.
Thermotolerant acetic acid bacteria in the production of a red wine vinegar by surface culture at different temperatures: volatile and polyphenolic composition
Authors: Chanivet Marina , Es-sbata Ikram , Astola Antonio , Durán-Guerrero Enrique , Castro Remedios 
Published: May 2024

AbstractThis work aims to determine the effect on the aromatic profile and phenolic content of red wine vinegars produced by surface culture at two different temperatures (30 °C and 37 °C) and using different inocula of acetic acid bacteria (Acetobacter malorum, Gluconobacter oxydans and a mixture of bacteria isolated from a Sherry vinegar). Fifty-seven volatile compounds and 23 polyphenolic and furfural compounds were identified. Vinegars obtained at 37 °C had poorer volatile profiles, with no significant influence of the strain of acetic bacteria. For polyphenolic content, temperature was also the most significant variable, so that the vinegars produced at higher temperatures had lower total anthocyanin contents, while no clear trend was observed regarding the influence of temperature on the low-molecular-weight phenolic constituents. The total tannin content in the vinegars obtained experienced slight increases after acetification, although this was not affected by temperature, and it was observed that when using the mixture of acetic acid bacteria from the Sherry vinegar, the total tannin content was significantly higher than when individual bacteria cultures of Acetobacter malorum or Gluconobacter oxydans were used. Temperature appears as a key parameter for the volatile and phenolic composition of red wine vinegar versus the use of different acetic acid bacteria.
Asymptotic behavior of the overlap gap between infinite words
Authors: Costa J. C. , Nogueira C. , Teixeira M. L. 
Published: May 2024

AbstractWe proceed with the study of ultimate periodicity properties related to overlaps between the suffixes of a left-infinite word $$\lambda $$
λ
and the prefixes of a right-infinite word $$\rho $$
ρ
. For a positive integer n, let g(n) be n minus the maximum length of overlaps between the suffix of $$\lambda $$
λ
and the prefix of $$\rho $$
ρ
of length n. In a recent publication we have shown that the function g has finite image if and only if $$\lambda $$
λ
and $$\rho $$
ρ
are ultimately periodic words with a same root. In this paper we give an asymptotic characterization of words $$\lambda $$
λ
and $$\rho $$
ρ
for which the function g has finite image. We prove that this condition is true if and only if the sequence $$\big (g(n)/n\big )_n$$

(

g

(
n
)

/
n

)

n

tends to zero
NP, OP and Derivatives in Freshwater Sediment Downstream of Textile Associated Municipal Wastewater Discharges
Authors: Lalonde Benoit , Garron Christine 
Published: May 2024

AbstractAlkylphenol ethoxylates comprise of many anthropogenic chemicals such as nonylphenol (NP), octylphenol (OP) and nonylphenol ethoxylates (NPEOs). The objectives of this study were to assess the frequency and magnitude of detections of 4-NP, OP and NPEOs in Canadian sediment downstream of textile associated municipal wastewater treatment plants (MWWTPs) to determine if regulatory actions have had a beneficial impact on the receiving environment. Surficial sediments were obtained in four locations in the province of Québec (Canada) and were analyzed for nonylphenol, nonylphenol monoethoxylates (NP1EO), nonylphenol diethoxylates (NP2EO) and octylphenol from 2015 to 2018. Individual concentrations of the compounds varied from non detect to 419 ng/g. Of the four compounds analyzed, NP was detected the most frequently with a 75% detection rate while OPs were not detected in any of the samples. Since the Canadian regulatory actions have drastically reduced NP/NPEOs usage in textile mill factories and manufactured products, the potential source of these compounds in sediment for this study could stem from the outfall from the MWWTPs but not related to textile mills as well as from the usage of these compounds as formulants in pesticide products. Lastly, there were no exceedances to the Canadian Sediment Quality guideline toxic equivalency approach (TEQ) of 1400 ng/g or the 1310 ng/g guideline for NP in freshwater sediment from the European Scientific Committee on Health, Environmental and Emerging Risks. We hypothesize that the significant concentrations of these compounds in sediment may be a relevant and continuous source of 4NP in surface waters due to resuspension of sediment in the water column.
Shear wave elastography and dispersion imaging for hepatic veno-occlusive disease prediction after pediatric hematopoietic stem cell transplantation: a feasibility study
Authors: Lee Seul Bi , Lee Seunghyun , Cho Yeon Jin , Choi Young Hun , Cheon Jung-Eun , Hong Kyung Taek , Choi Jung Yun , Kang Hyoung Jin 
Published: May 2024

Abstract
Background
Non-invasive imaging modalities are warranted for diagnosing and monitoring veno-occlusive disease because early diagnosis and treatment improve the prognosis.

Objective
To evaluate the usefulness of liver shear wave elastography (SWE) and shear wave dispersion (SWD) imaging in diagnosing and monitoring veno-occlusive disease in pediatric patients.

Materials and methods
We conducted a prospective cohort study at a single tertiary hospital from March 2021 to April 2022. The study protocol included four ultrasound (US) sessions: a baseline US and three follow-up US after hematopoietic stem cell transplantation. Clinical criteria, including the European Society for Blood and Marrow Transplantation criteria, were used to diagnose veno-occlusive disease. We compared clinical factors and US parameters between the veno-occlusive disease and non-veno-occlusive disease groups. The diagnostic performance of US parameters for veno-occlusive disease was assessed by plotting receiver operating characteristic (ROC) curves. We describe temporal changes in US parameters before and after veno-occlusive disease diagnosis.

Results
Among the 38 participants (mean age 10.7 years), eight developed veno-occlusive disease occurring 17.0 ± 5.2 days after hematopoietic stem cell transplantation. Liver stiffness, as measured by SWE (15.0 ± 6.2 kPa vs. 5.8 ± 1.8 kPa; P<0.001), and viscosity, as assessed with SWD (17.7 ± 3.1 m/s/kHz vs. 14.3 ± 2.8 m/s/kHz; P=0.015), were significantly higher in the veno-occlusive disease group compared to the non-veno-occlusive disease group at the time of diagnosis. Liver stiffness demonstrated the highest area under the ROC (AUROC) curves at 0.960, with an optimal predictive value of >6.5 kPa, resulting in sensitivity and specificity of 100% and 83.3%, respectively. Viscosity demonstrated an AUROC of 0.783, with an optimal cutoff value of 13.9 m/s/kHz for predicting veno-occlusive disease, with a sensitivity of 100% and specificity of 53.3%, respectively. Liver stiffness increased with disease severity and decreased during post-treatment follow-up.

Conclusion
SWE may be a promising technique for early diagnosis and severity prediction of veno-occlusive disease. Furthermore, liver viscosity assessed by SWD may serve as an additional marker of veno-occlusive disease.

Graphical abstract
Gut Microbial Composition of Cyprinella lutrensis (Red Shiner) and Notropis stramineus (Sand Shiner): Insights from Wild Fish Populations
Authors: Starr Krista , Montesanto Federica , Perisho Esther , Aluthge Nirosh , Pegg Mark , Fernando Samodha C. 
Published: May 2024

AbstractThe gut microbiome is a highly intricate ecosystem that exerts a pivotal influence on the host’s physiology. Characterizing fish microbiomes is critical to understanding fish physiology and health, but little is known about the ecology and colonization dynamics of microorganisms inhabiting fish species. In this study, we investigated the bacterial communities of two small-bodied fish species, Cyprinella lutrensis (red shiner) and Notropis stramineus (sand shiner), two fish species where gut microbiomes have not been investigated previously and surrounding waters, collected from rivers in Nebraska, USA. Our study focused on evaluating microbial diversity in small-bodied fish and identifying autochthonous microbes present within these species irrespective of location to better understand bacterial community composition and possible roles of such bacterial species. Our results revealed that both red shiner and sand shiner exhibited gut bacterial communities dominated by typical bacterial phyla found in freshwater fish. The phylum Bacteroidota was minimally abundant in both species and significantly lower in relative abundance compared to the surrounding water microbial community. Furthermore, we found that the gut microbiomes of red shiner and sand shiner differed from the microbial community in the surrounding water, suggesting that these fish species contain host-associated bacterial species that may provide benefits to the host such as nutrient digestion and colonization resistance of environmental pathogens. The fish gut bacterial communities were sensitive to environmental conditions such as turbidity, dissolved oxygen, temperature, and total nitrogen. Our findings also show bacterial community differences between fish species; although they shared notable similarities in bacterial taxa at phyla level composition, ASV level analysis of bacterial taxa displayed compositional differences. These findings contribute to a better understanding of the gut bacterial composition of wild, freshwater, small-bodied fish and highlight the influence of intrinsic (host) and environmental factors on shaping the bacterial composition.
Turn Your Vision into Reality—AI-Powered Pre-operative Outcome Simulation in Rhinoplasty Surgery
Authors: Knoedler Samuel , Alfertshofer Michael , Simon Siddharth , Panayi Adriana C. , Saadoun Rakan , Palackic Alen , Falkner Florian , Hundeshagen Gabriel , Kauke-Navarro Martin , Vollbach Felix H. , Bigdeli Amir K. , Knoedler Leonard 
Published: May 2024

Abstract

Background
The increasing demand and changing trends in rhinoplasty surgery emphasize the need for effective doctor–patient communication, for which Artificial Intelligence (AI) could be a valuable tool in managing patient expectations during pre-operative consultations.

Objective
To develop an AI-based model to simulate realistic postoperative rhinoplasty outcomes.

Methods
We trained a Generative Adversarial Network (GAN) using 3,030 rhinoplasty patients’ pre- and postoperative images. One-hundred-one study participants were presented with 30 pre-rhinoplasty patient photographs followed by an image set consisting of the real postoperative versus the GAN-generated image and asked to identify the GAN-generated image.

Results
The study sample (48 males, 53 females, mean age of 31.6 ± 9.0 years) correctly identified the GAN-generated images with an accuracy of 52.5 ± 14.3%. Male study participants were more likely to identify the AI-generated images compared with female study participants (55.4% versus 49.6%; p = 0.042).

Conclusion
We presented a GAN-based simulator for rhinoplasty outcomes which used pre-operative patient images to predict accurate representations that were not perceived as different from real postoperative outcomes.

Level of Evidence III
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.