bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contributing roles of mitochondrial dysfunction and hepatocyte apoptosis in liver diseases through oxidative stress, post-translational modifications, inflammation, and intestinal barrier dysfunction
Authors: LeFort Karli R. , Rungratanawanich Wiramon , Song Byoung-Joon 
Published: January 2024

AbstractThis review provides an update on recent findings from basic, translational, and clinical studies on the molecular mechanisms of mitochondrial dysfunction and apoptosis of hepatocytes in multiple liver diseases, including but not limited to alcohol-associated liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), and drug-induced liver injury (DILI). While the ethanol-inducible cytochrome P450-2E1 (CYP2E1) is mainly responsible for oxidizing binge alcohol via the microsomal ethanol oxidizing system, it is also responsible for metabolizing many xenobiotics, including pollutants, chemicals, drugs, and specific diets abundant in n-6 fatty acids, into toxic metabolites in many organs, including the liver, causing pathological insults through organelles such as mitochondria and endoplasmic reticula. Oxidative imbalances (oxidative stress) in mitochondria promote the covalent modifications of lipids, proteins, and nucleic acids through enzymatic and non-enzymatic mechanisms. Excessive changes stimulate various post-translational modifications (PTMs) of mitochondrial proteins, transcription factors, and histones. Increased PTMs of mitochondrial proteins inactivate many enzymes involved in the reduction of oxidative species, fatty acid metabolism, and mitophagy pathways, leading to mitochondrial dysfunction, energy depletion, and apoptosis. Unique from other organelles, mitochondria control many signaling cascades involved in bioenergetics (fat metabolism), inflammation, and apoptosis/necrosis of hepatocytes. When mitochondrial homeostasis is shifted, these pathways become altered or shut down, likely contributing to the death of hepatocytes with activation of inflammation and hepatic stellate cells, causing liver fibrosis and cirrhosis. This review will encapsulate how mitochondrial dysfunction contributes to hepatocyte apoptosis in several types of liver diseases in order to provide recommendations for targeted therapeutics.
Disease-associated nonsense and frame-shift variants resulting in the truncation of the GluN2A or GluN2B C-terminal domain decrease NMDAR surface expression and reduce potentiating effects of neurosteroids
Authors: Kysilov Bohdan , Kuchtiak Viktor , Hrcka Krausova Barbora , Balik Ales , Korinek Miloslav , Fili Klevinda , Dobrovolski Mark , Abramova Vera , Chodounska Hana , Kudova Eva , Bozikova Paulina , Cerny Jiri , Smejkalova Tereza , Vyklicky Ladislav 
Published: January 2024

AbstractN-methyl-d-aspartate receptors (NMDARs) play a critical role in normal brain function, and variants in genes encoding NMDAR subunits have been described in individuals with various neuropsychiatric disorders. We have used whole-cell patch-clamp electrophysiology, fluorescence microscopy and in-silico modeling to explore the functional consequences of disease-associated nonsense and frame-shift variants resulting in the truncation of GluN2A or GluN2B C-terminal domain (CTD). This study characterizes variant NMDARs and shows their reduced surface expression and synaptic localization, altered agonist affinity, increased desensitization, and reduced probability of channel opening. We also show that naturally occurring and synthetic steroids pregnenolone sulfate and epipregnanolone butanoic acid, respectively, enhance NMDAR function in a way that is dependent on the length of the truncated CTD and, further, is steroid-specific, GluN2A/B subunit-specific, and GluN1 splice variant-specific. Adding to the previously described effects of disease-associated NMDAR variants on the receptor biogenesis and function, our results improve the understanding of the molecular consequences of NMDAR CTD truncations and provide an opportunity for the development of new therapeutic neurosteroid-based ligands.
Progression of type 1 diabetes is associated with high levels of soluble PD-1 in islet autoantibody-positive children
Authors: Bruzzaniti Sara , Piemonte Erica , Bruzzese Dario , Lepore Maria Teresa , Strollo Rocky , Izzo Lavinia , Di Candia Francesca , Franzese Adriana , Bifulco Maurizio , Mozzillo Enza , Ludvigsson Johnny , Matarese Giuseppe , Galgani Mario 
Published: January 2024

Abstract
Aims/hypothesis
Type 1 diabetes is an autoimmune disorder that is characterised by destruction of pancreatic beta cells by autoreactive T lymphocytes. Although islet autoantibodies (AAb) are an indicator of disease progression, specific immune biomarkers that can be used as target molecules to halt development of type 1 diabetes have not been discovered. Soluble immune checkpoint molecules (sICM) play a pivotal role in counteracting excessive lymphocyte responses, but their role in type 1 diabetes is unexplored. In this longitudinal study, we measured sICM levels in AAb-positive (AAb+) children to identify molecules related to type 1 diabetes progression.

Methods
We measured the levels of 14 sICM in the sera of AAb+ children (n=57) compared to those with recent-onset type 1 diabetes (n=79) and healthy children (n=44), obtained from two cohorts. AAb+ children were followed up and divided based on their progression to type 1 diabetes (AAbP) or not (AAbNP) (if they lost islet autoimmunity and did not develop disease in subsequent years). sICM were also measured in the sample taken at the visit closest to disease onset in AAbP children.

Results
We found that AAb+ children had a distinct sICM profile compared with healthy children and those with recent-onset type 1 diabetes. In addition, AAb+ children who progressed to type 1 diabetes (AAbP) had higher sICM concentrations than non-progressors (AAbNP). Further, sICM levels decreased in AAbP children close to disease onset. Application of Cox regression models highlighted that high concentrations of soluble programmed cell death protein 1 (sPD-1) are associated with type 1 diabetes progression (HR 1.71; 95% CI 1.16, 2.51; p=0.007).

Conclusions/interpretation
This study reveals an sICM profile that is dysregulated during the preclinical stage of type 1 diabetes, and identifies sPD-1 as a pathophysiologically-relevant molecule that is associated with disease progression, offering a potential target for early interventions in autoimmune diabetes.

Graphical Abstract
Nanosponge hydrogel of octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoate of Alcaligenes faecalis
Authors: El-Sayed Sayed E. , Abdelaziz Neveen A. , El-Housseiny Ghadir S. , Aboshanab Khaled M. 
Published: January 2024

Abstract
Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoate (ODHP) was extracted in a previous study from the culture broth of soil isolate Alcaligenes faecalis MT332429 and showed a promising antimycotic activity. This study was aimed to formulate ODHP loaded β-cyclodextrins (CD) nanosponge (NS) hydrogel (HG) to control skin fungal ailments since nanosponges augment the retention of tested agents in the skin. Box-Behnken design was used to produce the optimized NS formulation, where entrapment efficiency percent (EE%), polydispersity index (PDI), and particle size (PS) were assigned as dependent parameters, while the independent process parameters were polyvinyl alcohol % (w/v %), polymer-linker ratio, homogenization time, and speed. The carbopol 940 hydrogel was then created by incorporating the nanosponges. The hydrogel fit Higuchi’s kinetic release model the best, according to in vitro drug release. Stability and photodegradation studies revealed that the NS-HG remained stable under tested conditions. The formulation also showed higher in vitro antifungal activity against Candida albicans compared to the control fluconazole. In vivo study showed that ODHP-NS-HG increased survival rates, wound contraction, and healing of wound gap and inhibited the inflammation process compared to the other control groups. The histopathological examinations and Masson’s trichrome staining showed improved healing and higher records of collagen deposition. Moreover, the permeability of ODHP-NS-HG was higher through rats’ skin by 1.5-folds compared to the control isoconazole 1%. Therefore, based on these results, NS-HG formulation is a potential carrier for enhanced and improved topical delivery of ODHP. Our study is a pioneering research on the development of a formulation for ODHP produced naturally from soil bacteria.

Key points
• Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoate was successfully formulated as a nanosponge hydrogel and statistically optimized.
• The new formula exhibited in vitro good stability, drug release, and higher antifungal activity against C. albicans as compared to the fluconazole.
• Ex vivo showed enhanced skin permeability, and in vivo analysis showed high antifungal activity as evidenced by measurement of various biochemical parameters and histopathological examination.
CIRSE Standards of Practice on Management of Endoleaks Following Endovascular Aneurysm Repair
Authors: Chun Joo-Young , de Haan Michiel , Maleux Geert , Osman Asaad , Cannavale Alessandro , Morgan Robert 
Published: January 2024

Abstract
Background
Endoleaks represent the most common complication after EVAR. Some types are associated with ongoing risk of aneurysm rupture and necessitate long-term surveillance and secondary interventions.

Purpose
This document, as with all CIRSE Standards of Practice documents, will recommend a reasonable approach to best practices of managing endoleaks. This will include imaging diagnosis, surveillance, indications for intervention, endovascular treatments and their outcomes. Our purpose is to provide recommendations based on up-to-date evidence, updating the guidelines previously published on this topic in 2013.

Methods
The writing group was established by the CIRSE Standards of Practice Committee and consisted of clinicians with internationally recognised expertise in endoleak management. The writing group reviewed the existing literature performing a pragmatic evidence search using PubMed to select publications in English and relating to human subjects up to 2023. The final recommendations were formulated through consensus.

Results
Endoleaks may compromise durability of the aortic repair, and long-term imaging surveillance is necessary for early detection and correct classification to guide potential re-intervention. The majority of endoleaks that require treatment can be managed using endovascular techniques. This Standards of Practice document provides up-to-date recommendations for the safe management of endoleaks.
Numerical Modeling of Distortions and Residual Stresses During Wire Arc Additive Manufacturing of an ER 5183 Alloy with Weaving Deposition
Authors: Drexler Hugo , Haunreiter Fabio , Raberger Lukas , Reiter Leonhard , Hütter Andreas , Enzinger Norbert 
Published: January 2024

AbstractThis study deals with the numerical modelling of residual stresses and distortions occurring during wire arc additive manufacturing of ER 5183 parts with weaving deposition. It is shown that the mesh size, as well as the accurate implementation of the heat source weaving pattern has a significant impact on the results. The mechanical material properties for the simulation are evaluated utilizing in-house standardized test equipment. Validation of the thermo-mechanical simulation is done by monitoring temperatures and distortions during the process. Additionally, 3D scans of the part geometry and residual stress measurements using the hole drilling method are conducted post manufacturing. A good agreement between the experimental measurements and the numerical simulation results is found with the use of an accurate heat source model.
Training a shallow NN to erase ink seepage in historical manuscripts based on a degradation model
Authors: Savino Pasquale , Tonazzini Anna 
Published: January 2024

AbstractIn historical recto–verso manuscripts, very often the text written on the opposite page of the folio penetrates through the fiber of the paper, so that the texts on the two sides appear mixed. This is a very impairing damage that cannot be physically removed, and hinders both the work of philologists and palaeographers and the automatic analysis of linguistic contents. A procedure based on neural networks (NN) is proposed here to clean up the complex background of the manuscripts from this interference. We adopt a very simple shallow NN whose learning phase employs a training set generated from the data itself using a theoretical blending model that takes into account ink diffusion and saturation. By virtue of the parametric nature of the model, various levels of damage can be simulated in the training set, favoring a generalization capability of the NN. More explicitly, the network can be trained without the need for a large class of other similar manuscripts, but is still able, at least to some extent, to classify manuscripts with varying degrees of corruption. We compare the performance of this NN and other methods both qualitatively and quantitatively on a reference dataset and heavily damaged historical manuscripts.
Impact of a gravity wave process on the upper stratospheric ozone valley on the Qinghai-Tibetan Plateau
Authors: Wang Jundong , Wan Lingfeng , Chang Shujie , He Haotian 
Published: January 2024

AbstractAtmospheric gravity waves are essential meso-small-scale oscillations that facilitate material exchange within the atmosphere. These waves can significantly affect the ozone layer in the Upper Troposphere and Lower Stratosphere (UTLS) on the Qinghai-Tibetan Plateau. However, the influence of gravity wave dynamic processes on upper stratospheric ozone has rarely been studied. This paper identifies the gravity waves on the Tibetan Plateau based on ECMWF Reanalysis 5 (ERA5) data, analyzes the response of the upper stratospheric ozone to the event, and simulates the dynamic propagation mechanism of gravity waves by the Weather Research and Forecasting (WRF) model. This analysis reveals that between 15:00 and 21:00 UTC on July 29, 2015, gravity waves propagated from the surface of Tibetan Plateau (450 hPa) up to the upper stratosphere (20 − 3 hPa) in an arc-shaped structure and tilted to the east with height. The gravity wave signals started to weaken at 21:00 UTC on the same day. Influenced by the easterly rapids, gravity waves partially broke near 3 hPa at 02:30 UTC on July 30, but gravity wave signals were still present, and gravity waves completely broke and released energy at 04:00 UTC. During this process, ozone in the 20–3 hPa region (upper stratosphere) on the Qinghai-Tibetan Plateau responds well to gravity waves, and the ozone mixing ratio began to drop in ozone concentration 30 min after the partial breakup (03:00 UTC). The ozone dropped drastically by about 0.014 ppmv from 04:00 to 05:00 UTC. The WRF simulation results agree well with ERA5 and accurately capture the intricate characteristics of gravity waves. Furthermore, the breakup of gravity waves caused a total drop in ozone of 0.024 ppmv.
ZMIZ1 Regulates Proliferation, Autophagy and Apoptosis of Colon Cancer Cells by Mediating Ubiquitin–Proteasome Degradation of SIRT1
Authors: Huang Min , Wang Junfeng , Zhang Zhengrong , Zuo Xueliang 
Published: January 2024

AbstractThere are nearly 1.15 million new cases of colon cancer, as well as 586,858 deaths from colon cancer worldwide in 2020. The aim of this study is to reveal whether ZMIZ1 can control the fate of colon cancer cells and the mechanism by which it functions. Specific shRNA transfection was used to knock down the expression of ZMIZ1 in colon cancer cell lines (HCT116 and HT29), and cell proliferation was detected using EdU and CCK-8 reagents, apoptosis by flow cytometry, and autophagy by western blot. The interaction of ZMIZ1 and SIRT1 was analyzed. Knockdown of ZMIZ1 significantly inhibited autophagy and proliferation, and induced apoptosis of HCT116 and HT29 cells. The mRNA level of SIRT1 was not affected by ZMIZ1 knockdown, but the protein level of SIRT1 was significantly decreased and the protein level of the SIRT1-specific substrate, acetylated FOXO3a, was reduced. Immunoprecipitation assays identified the interaction between SIRT1 and ZMIZ1 in HCT116 and HT29 cells. ZMIZ1 increased intracellular ubiquitination of SIRT1. Knockdown or pharmacological inhibition of SIRT1 neutralized the effects of ZMIZ knockdown on proliferation, autophagy and apoptosis in HCT116 and HT29 cells. ZMIZ1 may control the fate of colon cancer cells through the SIRT1/FOXO3a axis. Targeting ZMIZ1 would be beneficial for the treatment of colon cancer.
Retinopathy of Prematurity in Very Low Birthweight Neonates of Gestation Less Than 32 weeks in Malaysia
Authors: Boo Nem Yun , Ang Ee Lee , Ang Eric Boon-Kuang 
Published: January 2024

Abstract

Objectives
To determine the screening rates and incidence of retinopathy of prematurity (ROP), and risk factors associated with ROP in very low birthweight (VLBW, <1500 g) neonates of gestation <32 wk admitted to neonatal intensive care units (NICUs) in a middle-income country.

Methods
It was a retrospective cohort study of prospectively submitted data by 44 Malaysian NICUs participating in the Malaysian National Neonatal Registry. All VLBW neonates of gestation <32 wk born in 2015–2020 and survived to discharge were included.

Results
Of 11768 survivors, 90.5% (n = 10436) had ROP screening; 16.1% (1685/10436) had ROP. ROP was significantly more common in neonates <28 wk gestation (extremely preterm, EPT) than ≥28 wk gestation (37.7% vs. 9.7%; p <0.001), and more common in those with birthweight <1000 g (extremely low birthweight, ELBW) than ≥1000 g (32.9% vs. 9.1%; p <0.001). Multiple logistic regression analysis showed that the significant independent factors associated with increased risk of ROP were ELBW, EPT, Indian ethnic group, vaginal delivery, mechanical ventilation >5 d, high frequency ventilation, total parenteral nutrition, late-onset sepsis, bronchopulmonary dysplasia, and intraventricular hemorrhage. Receiving oxygen therapy at birth was associated with significantly lower risk of ROP.

Conclusions
The incidence and severity of ROP increased with decreasing gestation and birthweight. Prolonged duration of oxygen therapy, infection, invasive respiratory support, and conditions commonly causing fluctuations of oxygenation were significant factors associated with increased risk of ROP. Receiving oxygen at birth did not increase risk.
Precision enzyme discovery through targeted mining of metagenomic data
Authors: Ariaeenejad Shohreh , Gharechahi Javad , Foroozandeh Shahraki Mehdi , Fallah Atanaki Fereshteh , Han Jian-Lin , Ding Xue-Zhi , Hildebrand Falk , Bahram Mohammad , Kavousi Kaveh , Hosseini Salekdeh Ghasem 
Published: January 2024

AbstractMetagenomics has opened new avenues for exploring the genetic potential of uncultured microorganisms, which may serve as promising sources of enzymes and natural products for industrial applications. Identifying enzymes with improved catalytic properties from the vast amount of available metagenomic data poses a significant challenge that demands the development of novel computational and functional screening tools. The catalytic properties of all enzymes are primarily dictated by their structures, which are predominantly determined by their amino acid sequences. However, this aspect has not been fully considered in the enzyme bioprospecting processes. With the accumulating number of available enzyme sequences and the increasing demand for discovering novel biocatalysts, structural and functional modeling can be employed to identify potential enzymes with novel catalytic properties. Recent efforts to discover new polysaccharide-degrading enzymes from rumen metagenome data using homology-based searches and machine learning-based models have shown significant promise. Here, we will explore various computational approaches that can be employed to screen and shortlist metagenome-derived enzymes as potential biocatalyst candidates, in conjunction with the wet lab analytical methods traditionally used for enzyme characterization.
Koningipyridines A and B, two nitrogen-containing polyketides from the fungus Trichoderma koningiopsis SC-5
Authors: Peng Weiwei , Huang Qi , Ke Xin , Wang Wenxuan , Chen Yan , Sang Zihuan , Chen Chen , Qin Siyu , Zheng Yuting , Tan Haibo , Zou Zhenxing 
Published: January 2024

AbstractTwo novel koninginin derivatives, koningipyridines A and B (1 and 2), along with four known compounds (3˗6) were isolated from the EtOAc extract of the endophytic fungus Trichoderma koningiopsis SC-5. Among them, koningipyridine A featured an unprecedented pentacyclic ketal skeleton with the formation of a fascinating 6/6/5/6/5 fused ring system and shared a characteristic pyridine core, which represents the first example of nitrogen-containing koninginin-type natural product. Moreover, koningipyridine B was the first member in the koninginin family sharing a unique 6/6/5 dihydropyridine skeleton, and it was suggested to be the critical biosynthetic precursor of koningipyridine A. The structures of 1 and 2 were elucidated by the interpretation of 1D and 2D NMR spectroscopy, HRESIMS data, as well as theoretical calculations of 13C NMR and electronic circular dichroism (ECD). Moreover, all isolates were screened for antimicrobial activities against Staphylococcus aureus, MRSA, and Escherichia coli as well as the cytotoxic effects against three cancer cell lines (A549, Hela, and HepG2).
Graphical Abstract
The Impact of HIP Process and Heat Treatment on the Mechanical Behaviour of an Al–Si–Mg Alloy Component
Authors: Bogdanoff Toni , Ghassemali Ehsan , Jarfors Anders E. W. , Seifeddine Salem 
Published: January 2024

AbstractThis study investigates the effect of hot isostatic pressing (HIPping) on the static and fatigue properties of sand-casting A356 aluminium alloys. HIPping is a method to improve the fatigue properties in aluminium cast material by reducing or eliminating the inner porosities. Investigation of the complex interaction between the microstructural features on mechanical properties before and after the HIPping process was examined using computed tomography and scanning electron microscopy (SEM). Castings generally contain pores and defects that have a detrimental impact on the fatigue properties. The HIPping process closes the porosities in all investigated samples with an increase in density. Without significant defects, the mechanical performance improved in the finer microstructure. However, a considerable variation in the results was found between the different conditions, whereas the coarser microstructure with larger porosities before HIPping showed remarkably reduced results. The high-cycle fatigue-tested samples showed reduced fatigue propagation zone in the coarser microstructure. Moreover, large cleavage areas containing bifilms in the fracture surfaces indicate that the healing process of porosities is inefficient. These porosities are closed but not healed, resulting in a detrimental effect on the static and dynamic properties.