bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of sub-micron grains and defect-dipole interactions on dielectric properties of iron, cobalt, and copper doped barium titanate ceramics
Authors: Mills Sara C. , Patterson Eric A. , Staruch Margo L.
Published: September 2023

Introduction: Dilutely doped ferroelectric materials are of interest, as engineering these materials by introducing point defects via doping often leads to unique behavior not otherwise achievable in the undoped material. For example, B-site doping with transition metals in barium titanate (BaTiO3, or BTO) creates defect dipoles via oxygen vacancies leading enhanced polarization, strain, and the ability to tune dielectric properties. Though defect dipoles should lead to dielectric property enhancements, the effect of grain size in polycrystalline ferroelectrics such as BTO plays a significant role in those properties as well.

Methods: Herein, doped BTO with 1.0% copper (Cu), iron (Fe), or cobalt (Co) was synthesized using traditional solid-state processing to observe the contribution of both defect-dipole formation and grain size on the ferroelectric and dielectric properties.

Results and discussion: 1.0% Cu doped BTO showed the highest polarization and strain (9.3 μC/cm2 and 0.1%, respectively) of the three doped BTO samples. While some results, such as the aforementioned electrical properties of the 1.0% Cu doped BTO can be explained by the strong chemical driving force of the Cu atoms to form defect dipoles with oxygen vacancies and copper’s consistent +2 valency leading to stable defect-dipole formation (versus the readily mixed valency states of Fe and Co at +2/+3), other properties cannot. For instance, all three Tc values should fall below that of undoped BTO (typically 120°C–135°C), but the Tc of 1.0% Cu BTO actually exceeds that range (139.4°C). Data presented on the average grain size and distribution of grain sizes provides insight allowing us to decouple the effect of defect dipoles and the effect of grain size on properties such as Tc, where the 1.0% Cu BTO was shown to possess the largest overall grains, leading to its increase in Tc.

Conclusion/future work: Overall, the 1% Cu BTO possessed the highest polarization, strain, and Tc and is a promising dopant for engineering the performance of the material. This work emphasizes the challenge of extricating one effect (such as defect-dipole formation) from another (grain size modification) inherent to doping polycrystalline BTO.
Invasive Fusarium rhinosinusitis in COVID-19 patients: report of three cases with successful management
Authors: Erami Mahzad , Aboutalebian Shima , Hashemi Hezaveh Seyed Jamal , Matini Amir Hassan , Momen-Heravi Mansooreh , Ahsaniarani Amir Hossein , Arani Shirin Shafaee , Ganjizadeh Mohsen , Mirhendi Hossein
Published: September 2023

Invasive fungal rhinosinusitis (IFRS) is a life-threatening infection that can occur in immunocompromised patients, including those with COVID-19. Although Mucorales and Aspergillus species are the most common causes of IFRS, infections caused by other fungi such as Fusarium are rare. In this report, we present three cases of proven rhinosinusitis fusariosis that occurred during or after COVID-19 infection. The diagnosis was confirmed through microscopy, pathology, and culture, and species identification of the isolates was performed by DNA sequencing the entire ITS1-5.8 rRNA-ITS2 region and translation elongation factor 1-alpha (TEF-1α). Antifungal susceptibility testing was conducted according to CLSI guidelines. The causative agents were identified as Fusarium proliferatum, F. oxysporum + Aspergillus flavus, and F. solani/falciforme. Treatment involved the administration of antifungal medication and endoscopic sinus surgery to remove the affected mucosa, leading to the successful resolution of the infections. However, one patient experienced a recurrence of IFRS caused by A. flavus 15 months later. Early diagnosis and timely medical and surgical treatment are crucial in reducing mortality rates associated with invasive fusariosis. Additionally, the cautious use of corticosteroids in COVID-19 patients is highly recommended.
Case report: Unveiling the unforeseen: a catastrophic encounter of giant aortic aneurysm rupture during re-sternotomy in a patient with bicuspid aortic valve and previous surgical aortic valve replacement
Authors: Niu Hao , Liu Lu , Gong Xiangfeng , Wang Haochen , Guo Yingqiang , Zhang Eryong , Xiao Zhenghua
Published: September 2023

Due to structural abnormalities in the leaflets, patients with bicuspid aortic valve (BAV) may develop isolated aortic valve disease, such as aortic regurgitation, aortic stenosis, or a combination of both. In addition to valvular pathology, numerous studies have indicated that approximately 40% of BAV patients exhibit aortic pathologies characterized by aortic dilatation. According to guidelines for valvular diseases, patients with BAV who require surgical aortic valve replacement (SAVR) and have a diameter of the aortic sinuses or ascending aorta ≥4.5 cm are recommended to undergo concomitant replacement of the aortic sinuses or ascending aorta. However, we encountered a case in 2020 involving a patient with severe aortic regurgitation due to BAV and an ascending aortic diameter of 4.2 cm. This patient underwent SAVR and ascending aortoplasty surgery at our center. Remarkably, three years postoperatively, the patient's aortic diameter rapidly expanded by nearly threefold, which also suggests the risk of encountering a giant aortic root aneurysm during reoperation. Unfortunately, a fatal rupture of a giant aortic root aneurysm was encountered during re-sternotomy. Fortunately, with adequate preoperative planning, we successfully managed to avert this perilous situation. The patient recovered without complications and was discharged on the 8th day. Individualized surgical plans were formulated based on a comprehensive evaluation of the perioperative conditions.
First assessment of hydrogen/brine/Saudi basalt wettability: implications for hydrogen geological storage
Authors: Alanazi Amer , Al-Yaseri Ahmed , Mowafi Mahmoud , Leila Mahmoud , Hoteit Hussein
Published: September 2023

Introduction: Underground hydrogen (H2) storage is a prominent technique to enable a large-scale H2-based economy as part of the global energy mix for net-zero carbon emission. Recently, basalts have gained interest as potential caprocks for subsurface H2 storage due to their low permeability, vast extension, and potential volumetric capacity induced by structural entrapment of the buoyant H2. Wettability represents a fundamental parameter which controls the capillary-entrapment of stored gases in porous media.

Methods: The present study evaluates the wettability of basalt/H2/brine system of two basalt samples from Harrat Uwayrid, a Cenozoic volcanic field, in Saudi Arabia. The H2/basalt contact angle was measured using a relevant reservoir brine (10% NaCl) under storage conditions of 323K temperature and pressure ranges from 3 to 28 MPa using the modified sessile drop method. The surface roughness of the basaltic rocks was determined to ensure accurate results.

Results: The investigated Saudi basalt samples are water-wet, thereby they did not achieve a 100% hydrogen wetting phase even at 28 MPa pressure. The measured contact angles slightly decrease as pressure increases, thereby pressure did not significantly influences the height of the H2 column.

Discussion: We interpret this trend to the slight increase in H2 density with increasing pressure as well as to the olivine-rich mineralogical composition of the Saudi basalt. Thus, from the wettability aspects, Saudi basalt has the potential to store a large volume of H2 (>1,400 m height) and maintain its excellent storage capacity even in deep, high-pressure regimes. This study demonstrates that the basalt rock texture (pore throat radii) and mineralogy control their capacity for subsurface H2 storage.
Spotlight on iron and ferroptosis: research progress in diabetic retinopathy
Authors: Ouyang Junlin , Zhou Ling , Wang Qing
Published: September 2023

Iron, as the most abundant metallic element within the human organism, is an indispensable ion for sustaining life and assumes a pivotal role in governing glucose and lipid metabolism, along with orchestrating inflammatory responses. The presence of diabetes mellitus (DM) can induce aberrant iron accumulation within the corporeal system. Consequentially, iron overload precipitates a sequence of important adversities, subsequently setting in motion a domino effect wherein ferroptosis emerges as the utmost pernicious outcome. Ferroptosis, an emerging variant of non-apoptotic regulated cell death, operates independently of caspases and GSDMD. It distinguishes itself from alternative forms of controlled cell death through distinctive morphological and biochemical attributes. Its principal hallmark resides in the pathological accrual of intracellular iron and the concomitant generation of iron-driven lipid peroxides. Diabetic retinopathy (DR), established as the predominant cause of adult blindness, wields profound influence over the well-being and psychosocial strain experienced by afflicted individuals. Presently, an abundance of research endeavors has ascertained the pervasive engagement of iron and ferroptosis in the microangiopathy inherent to DR. Evidently, judicious management of iron overload and ferroptosis in the early stages of DR bears the potential to considerably decelerate disease progression. Within this discourse, we undertake a comprehensive exploration of the regulatory mechanisms governing iron homeostasis and ferroptosis. Furthermore, we expound upon the subsequent detriments induced by their dysregulation. Concurrently, we elucidate the intricate interplay linking iron overload, ferroptosis, and DR. Delving deeper, we engage in a comprehensive deliberation regarding strategies to modulate their influence, thereby effecting prospective interventions in the trajectory of DR’s advancement or employing them as therapeutic modalities.
Methylmercury content in soil and litter from the Amazonian rainforest and its potential fate during forest fires
Authors: Fostier Anne Helene , Amouroux David , Tessier Emmanuel , Viana José Lucas Martins , Richter Larissa
Published: September 2023

Methylmercury in soils and vegetation from the Amazonian rainforest is still poorly studied. Hence, the aim of this work was to determine the total mercury [THg] and methylmercury [MeHg] concentrations in litter and surface soil, MeHg deposition via litterfall, and the MeHg fate during a forest fire in the Amazonian rainforest. Sampling of litter, soil (0–1, 1–2, and 2–5 cm), and ash was carried out before (BB) and after (AB) a prescribed forest fire. The results showed a low [THg] (34 ± 8 ng g-1) and [MeHg] (0.16 ± 0.03 ng g-1) value in litter, with a correspondingly low estimate of the MeHg litterfall flux (0.13 ± 0.03 μgm-2yr-1) which has been probably underestimated due to potential losses during the field experiment. In ashes, [THg] and [MeHg] values were 23 ± 8 ng g-1and 0.11 ± 0.04 ng g-1, respectively. Although a significant part of Hg contained in the biomass was lost during the fire, the [MeHg]/[THg] ratio was not affected by it and was the same in litterfall and ash (∼0.5%). In soil, the average [THg] BB value was 149 ± 12 ng g-1in the three layers and [MeHg] was between 0.8 and 1.0 ng g-1. The forest fire only affected the superficial soil, with a significant decrease of [THg] and [MeHg] in the 0-1 cm layer. Similarly, the decrease of the [MeHg]/[THg] ratio in the surface soil layer suggested that MeHg was more readily emitted or degraded than the other Hg species present.
Relationship between tropical leaf phenology and ecosystem productivity using phenocameras
Authors: Alberton Bruna , Martin Thomas C. M. , Da Rocha Humberto R. , Richardson Andrew D. , Moura Magna S. B. , Torres Ricardo S. , Morellato Leonor Patricia Cerdeira
Published: September 2023

Introduction: The interplay of water and light, regarded as the main driver of tropical plant dynamics, determines leaf phenology and ecosystem productivity. Leaf phenology has been discussed as a key variable to explain photosynthetic seasonality in evergreen tropical forests, but the question is still open for seasonally tropical ecosystems. In the search for implementing long-term phenology monitoring in the tropics, phenocameras have proven to be an accurate method to estimate vegetative phenology in tropical communities. Here, we investigated the temporal patterns of leaf phenology and their relation to gross primary productivity (GPP) in a comparative study across three contrasting tropical biomes: dry forest (caatinga), woodland savanna (cerrado), and rainforest (Atlantic Forest).

Methods: We monitored leaf phenology (phenocameras) and estimated gross primary productivity (eddy-covariance) continuously over time at three study sites. We investigated the main drivers controlling leaf phenology and tested the performance of abiotic (climate) and biotic (phenology) factors to explain gross primary productivity across sites.

Results: We found that camera-derived indices presented the best relationships with gross primary productivity across all sites. Gross primary productivity seasonality was controlled by a gradient of water vs. light, where caatinga dry forest was water-limited, cerrado vegetation responded to water seasonality and light, and rainforest was mainly controlled by light availability. Vegetation phenology was tightly associated with productivity in the driest ecosystem (caatinga), where productivity was limited to the wet season, and the camera-derived index (Gcc) was the best proxy for gross primary productivity.

Discussion: Leaf phenology increased their relative importance over gross primary productivity seasonality at less seasonal sites (cerrado and rainforest), where multiple leafing strategies influenced carbon exchanges. Our multi-site comparison, along with fine-scale temporal observations of leaf phenology and gross primary productivity patterns, uncovered the relationship between leafing and productivity across tropical ecosystems under distinct water constraints.
Elucidating the molecular mechanisms of ozone therapy for neuropathic pain management by integrated transcriptomic and metabolomic approach
Authors: Yang Xiaolan , Chen Chaoming , Wang Keyang , Chen Min , Wang Yong , Chen Zhengping , Zhao Wang , Ou Shu
Published: September 2023

Introduction: Neuropathic pain remains a prevalent and challenging condition to treat, with current therapies often providing inadequate relief. Ozone therapy has emerged as a promising treatment option; however, its mechanisms of action in neuropathic pain remain poorly understood.

Methods: In this study, we investigated the effects of ozone treatment on gene expression and metabolite levels in the brainstem and hypothalamus of a rat model, using a combined transcriptomic and metabolomic approach.

Results: Our findings revealed significant alterations in key genes, including DCST1 and AIF1L, and metabolites such as Aconitic acid, L-Glutamic acid, UDP-glucose, and Tyrosine. These changes suggest a complex interplay of molecular pathways and region-specific mechanisms underlying the analgesic effects of ozone therapy.

Discussion: Our study provides insights into the molecular targets of ozone treatment for neuropathic pain, laying the groundwork for future research on validating these targets and developing novel therapeutic strategies.
CD11a regulates hematopoietic stem and progenitor cells
Authors: Hou Lifei , Yuki Koichi
Published: September 2023

Integrin αLβ2 (CD11a/CD18, CD11a) is a critical leukocyte adhesion molecule in leukocyte arrest and immunological synapse formation. However, its role in the bone marrow has not been investigated in depth. Here we showed that CD11a was expressed on all subsets of hematopoietic stem and progenitor cells (HPSCs). CD11a deficiency enhanced HSPCs activity under lipopolysaccharide (LPS) stimulation as demonstrated by a higher HSPC cell count along with an increase in cell proliferation. However, our mixed chimera experiment did not support that this phenotype was driven in a cell-intrinsic manner. Rather we found that the production of IL-27, a major cytokine that drives HSPC proliferation, was significantly upregulated both in vivo and in vitro. This adds a novel role of CD11a biology.
Comprehensive single-cell analysis reveals novel anergic antigen-presenting cell subtypes in human sepsis
Authors: Zhang Tuo , Lian Guodong , Fang Wei , Tian Lei , Ma Wenhao , Zhang Jicheng , Meng Zhaoli , Yang Hongna , Wang Chunting , Wei Chengguo , Chen Man
Published: September 2023

Background

Sepsis is a life-threatening condition with high mortality. A few studies have emerged utilizing single-cell RNA sequencing (scRNA-seq) to analyze gene expression at the single-cell resolution in sepsis, but a comprehensive high-resolution analysis of blood antigen-presenting cells has not been conducted.

Methods

All published human scRNA-seq data were downloaded from the single cell portal database. After manually curating the dataset, we extracted all antigen-presenting cells, including dendritic cells (DCs) and monocytes, for identification of cell subpopulations and their gene profiling and intercellular interactions between septic patients and healthy controls. Finally, we further validated the findings by performing deconvolution analysis on bulk RNA sequencing (RNA-seq) data and flow cytometry.

Results

Within the traditional DC populations, we discovered novel anergic DC subtypes characterized by low major histocompatibility complex class II expression. Notably, these anergic DC subtypes showed a significant increase in septic patients. Additionally, we found that a previously reported immunosuppressive monocyte subtype, Mono1, exhibited a similar gene expression profile to these anergic DCs. The consistency of our findings was confirmed through validation using bulk RNA-seq and flow cytometry, ensuring accurate identification of cell subtypes and gene expression patterns.

Conclusions

This study represents the first comprehensive single-cell analysis of antigen-presenting cells in human sepsis, revealing novel disease-associated anergic DC subtypes. These findings provide new insights into the cellular mechanisms of immune dysregulation in bacterial sepsis.
The benthic-pelagic coupling affects the surface water carbonate system above groundwater-charged coastal sediments
Authors: Szymczycha Beata , Böttcher Michael Ernst , Diak Magdalena , Koziorowska-Makuch Katarzyna , Kuliński Karol , Makuch Przemysław , von Ahn Cátia Milene Ehlert , Winogradow Aleksandra
Published: September 2023

Submarine groundwater discharge (SGD) can be a significant source of dissolved nutrients, inorganic and organic carbon, and trace metals in the ocean and therefore can be a driver for the benthic-pelagic coupling. However, the influence of hypoxic or anoxic SGD on the carbonate system of coastal seawater is still poorly understood. In the present study, the production of dissolved inorganic carbon (DIC) and alkalinity (AT) in coastal sediments has been investigated under the impact of oxygen-deficient SGD and was estimated based on the offset between the measured data and the conservative mixing of the end members. Production of ATand DIC was primarily caused by denitrification and sulphate reduction. The ATand DIC concentrations in SGD decreased by approximately 32% and 37% mainly due to mixing with seawater counterbalanced by reoxidation and CO2release into the atmosphere. Total SGD-ATand SGD-DIC fluxes ranged from 0.1 to 0.2mol m-2d-1and from 0.2 to 0.3mol m-2d-1, respectively. These fluxes are probably the reason why the seawater in the Bay of Puck is enriched in ATand DIC compared to the open waters of the Baltic Sea. Additionally, SGD had low pH and was undersaturated with respect to the forms of the aragonite and calcite minerals of CaCO3. The seawater of the Bay of Puck also turned out to be undersaturated in summer (Inner Bay) and fall (Outer Bay). We hypoth​e​size that SGD can potentially contribute to ocean acidification and affect the functioning of the calcifying invertebrates.
Hyperarid soil microbial community response to simulated rainfall
Authors: Demergasso Cecilia , Neilson Julia W. , Tebes-Cayo Cinthya , Véliz Roberto , Ayma Diego , Laubitz Daniel , Barberán Albert , Chong-Díaz Guillermo , Maier Raina M.
Published: September 2023

The exceptionally long and protracted aridity in the Atacama Desert (AD), Chile, provides an extreme, terrestrial ecosystem that is ideal for studying microbial community dynamics under hyperarid conditions. Our aim was to characterize the temporal response of hyperarid soil AD microbial communities to ex situ simulated rainfall (5% g water/g dry soil for 4 weeks) without nutrient amendment. We conducted replicated microcosm experiments with surface soils from two previously well-characterized AD hyperarid locations near Yungay at 1242 and 1609 masl (YUN1242 and YUN1609) with distinct microbial community compositions and average soil relative humidity levels of 21 and 17%, respectively. The bacterial and archaeal response to soil wetting was evaluated by 16S rRNA gene qPCR, and amplicon sequencing. Initial YUN1242 bacterial and archaeal 16S rRNA gene copy numbers were significantly higher than for YUN1609. Over the next 4 weeks, qPCR results showed significant increases in viable bacterial abundance, whereas archaeal abundance decreased. Both communities were dominated by 10 prokaryotic phyla (Actinobacteriota, Proteobacteria, Chloroflexota, Gemmatimonadota, Firmicutes, Bacteroidota, Planctomycetota, Nitrospirota, Cyanobacteriota, and Crenarchaeota) but there were significant site differences in the relative abundances of Gemmatimonadota and Chloroflexota, and specific actinobacterial orders. The response to simulated rainfall was distinct for the two communities. The actinobacterial taxa in the YUN1242 community showed rapid changes while the same taxa in the YUN1609 community remained relatively stable until day 30. Analysis of inferred function of the YUN1242 microbiome response implied an increase in the relative abundance of known spore-forming taxa with the capacity for mixotrophy at the expense of more oligotrophic taxa, whereas the YUN1609 community retained a stable profile of oligotrophic, facultative chemolithoautotrophic and mixotrophic taxa. These results indicate that bacterial communities in extreme hyperarid soils have the capacity for growth in response to simulated rainfall; however, historic variations in long-term hyperaridity exposure produce communities with distinct putative metabolic capacities.
Microbial proteases and their applications
Authors: Song Peng , Zhang Xue , Wang Shuhua , Xu Wei , Wang Fei , Fu Rongzhao , Wei Feng
Published: September 2023

Proteases (proteinases or peptidases) are a class of hydrolases that cleave peptide chains in proteins. Endopeptidases are a type of protease that hydrolyze the internal peptide bonds of proteins, forming shorter peptides; exopeptidases hydrolyze the terminal peptide bonds from the C-terminal or N-terminal, forming free amino acids. Microbial proteases are a popular instrument in many industrial applications. In this review, the classification, detection, identification, and sources of microbial proteases are systematically introduced, as well as their applications in food, detergents, waste treatment, and biotechnology processes in the industry fields. In addition, recent studies on techniques used to express heterologous microbial proteases are summarized to describe the process of studying proteases. Finally, future developmental trends for microbial proteases are discussed.
Interkingdom multi-omics analysis reveals the effects of nitrogen application on growth and rhizosphere microbial community of Tartary buckwheat
Authors: Qiu Qingcheng , Xiang Dabing , Li Qiang , Wang Hanlin , Wan Yan , Wu Qi , Ye Xueling , Jiang Liangzhen , Fan Yu , Liu Bingliang , Liu Yanxia , Li Han , Liu Changying
Published: September 2023

Tartary buckwheat (Fagopyrum tataricum Gaertn.) is an important pseudocereal crop with excellent edible, nutritional and medicinal values. However, the yield of Tartary buckwheat (TB) is very low due to old-fashioned cultivation techniques, particularly unreasonable application of nitrogen fertilizer. To improve the understanding on the theories of nitrogen use in TB, the effects of nitrogen application on growth, as well as chemical properties and microbial community of rhizosphere soil were investigated in this study. Nitrogen application could promote the plant height, stem diameter, nitrogen accumulation and yield of TB. The relative abundance and diversity of bacteria and fungi in the rhizosphere soil of TB were improved by nitrogen fertilizer. Nitrogen application increased the abundance of beneficial bacteria such as Lysobacter and Sphingomonas in rhizosphere soil, and decreased the abundance of pathogenic fungi such as Fusarium and Plectosphaerella. The results indicated that nitrogen application changed the distribution of microbial communities in TB rhizosphere soil. Furthermore, the specific enriched or depleted microorganisms in the rhizosphere soil of four TB varieties were analyzed at OTU level. 87 specific nitrogen-responsive genes with sequence variation were identified in four varieties by integrating genomic re-sequencing and transcriptome analysis, and these genes may involve in the recruitment of specific rhizosphere microorganisms in different TB varieties. This study provided new insights into the effects of nitrogen application on TB growth and rhizosphere microbial community, and improved the understanding on the mechanisms of TB root–microbe interactions.
Research progress on alternative kombucha substrate transformation and the resulting active components
Authors: Su Jingqian , Tan Qingqing , Tang Qian , Tong Zhiyong , Yang Minhe
Published: September 2023

Kombucha is a customary tea-based beverage that is produced through the process of fermenting a mixture of tea and sugar water with symbiotic culture of bacteria and yeast (SCOBY). Traditional kombucha has various beneficial effects and can improve immunity. The significant market share of Kombucha can be attributed to the growing consumer inclination towards healthy foods within the functional beverage industry. The research focus has recently expanded from the probiotics of traditional black tea kombucha to encompass other teas, Chinese herbs, plant materials, and alternative substrates. There is a lack of comprehensive literature reviews focusing on substance transformation, functional, active substances, and efficacy mechanisms of alternative kombucha substrates. This article aimed to bridge this gap by providing an in-depth review of the biological transformation pathways of kombucha metabolites and alternative substrates. The review offers valuable insights into kombucha research, including substance metabolism and transformation, efficacy, pharmacological mechanism, and the purification of active components, offering direction and focus for further studies in this field.
Longitudinal trajectories of memory among middle-aged and older people with hearing loss: the influence of cochlear implant use on cognitive functioning
Authors: Völter Christiane , Götze Lisa , Dazert Stefan , Thomas Jan Peter , Kamin Stefan Thomas
Published: September 2023

Introduction

Cochlear implants (CI) are the gold standard intervention for severe to profound hearing loss, a known modifiable risk factor for dementia. However, it remains unknown whether CI use might prevent the age-related cognitive decline. Recent studies are encouraging but are limited, mainly by short follow-up periods and, for ethical reasons, lack of appropriate control groups. Further, as age-related cognitive decline is multifaceted and not linear, other statistical approaches have to be evaluated.

Materials and methods

Immediate and delayed recall as measures of cognitive function were assessed in 75 newly implanted CI users (mean age 65.41 years ± 9.19) for up to 5 years (mean 4.5 ± 0.5) of CI use and compared to 8,077 subjects of the same age range from two longitudinal cohort studies, the Health and Retirement Study (HRS) and the English Longitudinal Study of Aging (ELSA). Linear and quadratic changes in cognitive trajectories were analyzed in detail using mixed growth models, considering possible confounders.

Results

For CI users, the linear time slope showed a significant improvement in the specific domains (recall and delayed recall) over time. The quadratic time slope clearly indicated that the predicted change after CI provision followed an inverted U-shape with a predicted decline 2 years after CI provision. In the hearing-impaired group, a significant decline over time was found, with steeper declines early on and the tendency to flatten out in the follow-up.

Conclusion

Cochlear implant use seems to boost cognitive trajectories in the first years after implantation. However, long-term prevention of dementia seems to need far more than restoration of hearing loss.
NADPH oxidase 4 inhibition is a complementary therapeutic strategy for spinal muscular atrophy
Authors: El Khoury Mirella , Biondi Olivier , Bruneteau Gaelle , Sapaly Delphine , Bendris Sabrina , Bezier Cynthia , Clerc Zoé , Akar Elias Abi , Weill Laure , Eid Assaad A. , Charbonnier Frédéric
Published: September 2023

Introduction

Spinal muscular atrophy (SMA) is a fatal neurodegenerative disorder, characterized by motor neuron (MN) degeneration and severe muscular atrophy and caused by Survival of Motor Neuron (SMN) depletion. Therapies aimed at increasing SMN in patients have proven their efficiency in alleviating SMA symptoms but not for all patients. Thus, combinational therapies are warranted. Here, we investigated the involvement of NADPH oxidase 4 (NOX4) in SMA-induced spinal MN death and if the modulation of Nox4 activity could be beneficial for SMA patients.

Methods

We analysed in the spinal cord of severe type SMA-like mice before and at the disease onset, the level of oxidative stress and Nox4 expression. Then, we tested the effect of Nox4 inhibition by GKT137831/Setanaxib, a drug presently in clinical development, by intrathecal injection on MN survival and motor behaviour. Finally, we tested if GKT137831/Setanaxib could act synergistically with FDA-validated SMN-upregulating treatment (nusinersen).

Results

We show that NOX4 is overexpressed in SMA and its inhibition by GKT137831/Setanaxib protected spinal MN from SMA-induced degeneration. These improvements were associated with a significant increase in lifespan and motor behaviour of the mice. At the molecular level, GKT137831 activated the pro-survival AKT/CREB signaling pathway, leading to an increase in SMN expression in SMA MNs. Most importantly, we found that the per os administration of GKT137831 acted synergistically with a FDA-validated SMN-upregulating treatment.

Conclusion

The pharmacological inhibition of NOX4 by GKT137831/Setanaxib is neuroprotector and could represent a complementary therapeutic strategy to fight against SMA.
Bilateral tonic seizures probably induced by eperisone hydrochloride: a case report
Authors: Luo Long , Yin Jun , Li Zhigang , Zhang Wei , Yuan Ying , Tang Ying , Deng Ye , Zhu Ling
Published: September 2023

Eperisone hydrochloride is a central muscle relaxant used to treat osteoporosis. Seizures are rare side effects of eperisone hydrochloride and have been previously reported in the medical literature in overdose situations but not at regular doses. This case report describes a 42-year-old male painter who developed severe bilateral tonic seizures after the initiation of eperisone hydrochloride at regular doses for low back pain. Symptoms gradually eased in the days following the discontinuation of eperisone hydrochloride and antiepileptic treatment, with no recurrence. This rare adverse drug reaction warrants clinical awareness; however, the mechanisms underlying these adverse reactions remain to be clarified.
Association between the dietary inflammatory index and markers of endothelial and systemic inflammation in hemodialysis patients
Authors: Arab Arman , Karimi Elham , Nazari Maryam , Tabibi Hadi , As’habi Atefeh
Published: September 2023

Objectives

The current survey aimed to investigate the link between energy-adjusted dietary inflammatory index (E-DII) and risk factors for CVD including markers of endothelial and systemic inflammation in Iranian hemodialysis patients.

Methods

Patients on hemodialysis for at least 6 months prior to enrollment were considered eligible in this cross-sectional study. The usual dietary intakes of the hemodialysis individuals were examined through 4 non-consecutive days including 2 dialysis days and 2 non-dialysis days using a 24-h recall approach to calculate E-DII. Multiple linear regression analysis was utilized to investigate the link between E-DII and selected biomarkers of inflammation and oxidative stress including high-sensitive C reactive protein (hs-CRP), serum intercellular adhesion molecule (sICAM), serum vascular cell adhesion molecule (sVCAM), malondialdehyde, and nitric oxide (NO), sE-selectin, and endothelin-1, and beta (β) and 95% confidence interval (CI) was reported. Value of p < 0.05 was considered statistically significant.

Results

Overall, 291 hemodialysis patients make up our study population. In the crude model, the E-DII score was positively associated with a higher sVCAM-1 (β = 177.39; 95% CI: 60.51, 294.26; ptrend = 0.003). Further adjustment for potential confounders attenuated the findings in a way that an increase of 128.72 in the sVCAM-1 was observed when the E-DII score increased from −2.68 to −1.14 (95% CI: 13.50, 243.94). After controlling for potential confounders, E-DII was associated with sE-selectin in hemodialysis patients in the highest category of E-DII as compared to the lowest category (β = 4.11; 95% CI: 0.22, 8.00; ptrend = 0.039).

Conclusion

The present findings suggest that adherence to a pro-inflammatory diet among hemodialysis patients is associated with a higher inflammatory status as evidenced by sVCAM-1 and sE-selectin; however, bidirectionality may exist and the role of residual confounders should be taken into account. Therefore, more longitudinal investigations are needed to elucidate the role of diet on the inflammatory status of hemodialysis patients.
Exploration of the mechanism of aloin ameliorates of combined allergic rhinitis and asthma syndrome based on network pharmacology and experimental validation
Authors: Feng Yan , Qiao Han , Liu Hongyun , Wang Jvfei , Tang Huaping
Published: September 2023

Background: Aloin, as a bioactive compound, has a variety of pharmacological functions, but its effects on combined allergic rhinitis and asthma syndrome (CARAS) have not been studied. To clarify the protective effect and mechanism of aloin in the treatment of CARAS by network pharmacology, molecular dynamics simulation and experiment.

Methods: The targets of aloin, allergic rhinitis and asthma were obtained from various databases. The protein interaction network was constructed for the common targets, and molecular docking and molecular dynamics simulations were performed for the core targets. Functional and pathway enrichment analysis of common targets was also performed using R software. Varieties of biological experiments were conducted to verify the effect of aloin on the inflammatory changes of CARAS and its regulatory mechanism.

Results: A total of 42 anti-allergic rhinitis and 58 anti-asthma targets were obtained, and 5 core anti-allergic rhinitis and 6 core anti-asthma targets were identified using topological analysis. GO and KEGG analyses showed that endopeptidase activity and MAPK signaling pathway played important roles in allergic rhinitis and asthma. Molecular docking and molecular dynamics simulations showed that aloin could stably bind to the core target proteins. Experimental verification showed that aloin significantly inhibited the expression of inflammatory factors, and may regulate CARAS by down-regulating MAPK signaling related proteins.

Conclusion: This study identified the protective effect, potential target and mechanism of aloin on CARAS. It provides reference for understanding the molecular mechanism and clinical application of aloin in the ameliorates of CARAS.
Study of the mass balance, biotransformation and safety of [14C]SHR8554, a novel μ-opioid receptor injection, in healthy Chinese subjects
Authors: Shi Rupeng , Chai Yi , Feng Hao , Xie Lijun , Zhang Lulu , Zhong Tianqi , Chen Juan , Yan Peng , Zhu Bei , Zhao Jun , Zhou Chen
Published: September 2023

Background: SHR8554 is a novel μ-opioid receptor-biased agonist. It has analgesic effects by selectively activating the G protein-coupled pathway. Additionally, it can weakly activate the ß-arrestin-2 pathway, resulting in a limited number of side effects, such as gastrointestinal inhibition. Previous studies have shown that SHR8554 has good analgesic effects, safety and tolerability, but the pharmacokinetic characteristics of SHR8554 in humans have not been reported. This study was designed to investigate the pharmacokinetics and safety of SHR8554 in healthy Chinese male subjects.

Methods: A single 1 mg/41.3 μCi intravenous dose of [14C]SHR8554 was administered to six healthy male subjects. Blood, urine and faecal samples were collected at continuous time points to analyse SHR8554 parent drug levels and their metabolites. The total radioactivity in blood, plasma, urine and faeces was detected by using a liquid scintillation counter. The dynamic changes of SHR8554 and its metabolite concentration were by liquid chromatography-tandem mass spectrometry (LC/MS), and then pharmacokinetic analysis. The safety of the drug on the subjects was also observed after a single intravenous injection.

Results: The total recovery of radioactivity in urine and faeces was 99.68% ± 0.79% in 216 h, including 76.22% ± 1.12% in urine and 23.46% ± 1.36% in faeces. Seventeen major metabolites in blood, urine and faeces were analysed and identified. The main metabolic pathways of SHR8554 in the human body involve 1) N-dealkylation; 2) O-deethylation; 3) mono-oxidation; 4) glucuronidation, etc. The primary mechanism of SHR8554 clearance in the human body is through urinary excretion, primarily in its parent drug and metabolite forms. The drug has good safety, and no serious adverse effects were observed.

Conclusion: SHR8554 showed favourable pharmacokinetic characteristics and safety profiles in this study. SHR8554 is extensively metabolized in human body. The main metabolic pathways include N-dealkylation and O-deethylation, as well as mono-oxidation and glucuronidation. The main excretion route of SHR8554 and its metabolites is through urine.

Clinical Trial Registration:http://www.chinadrugtrials.org.cn/, identifier CTR20220450
Epirubicin and gait apraxia: a real-world data analysis of the FDA Adverse Event Reporting System database
Authors: Wang Wei , Guan Xin , Wang Shuang , Shi Lipeng , Zhu Yanfei , Hua Pengbo , Guo Qiang , Wang Jingqi
Published: September 2023

Introduction: Epirubicin is widely used in many malignancies with good efficacy and tolerability. However, investigations about adverse events (AEs) using real-world information are still insufficient.

Methods: We extracted Epirubicin-related reports submitted between the first quarter of 2014 and first quarter of 2023 from FAERS database. Four algorithms were utilized to evaluate whether there was a significant correlation between Epirubicin and AEs.

Results: After de-duplicating, a total of 3919 cases were extracted. Among the 3919 cases, we identified 1472 AEs, 253 of which were found to be adverse drug reactions (ADRs) associated with Epirubicin. We analysed the occurrence of Epirubicin-induced ADRs and found several unexpected significant ADRs, such as hepatic artery stenosis, hepatic artery occlusion, intestinal atresia and so on. Interestingly, we found gait apraxia, a neurological condition, was also significantly associated with Epirubicin. To our knowledge, there haven't studies that have reported an association between gait disorders and the usage of epirubicin.

Discussion: Our study identified new unexpected significant ADRs related to Epirubicin, providing new perspectives to the clinical use of Epirubicin.
The impact of statin use before intensive care unit admission on patients with acute kidney injury after cardiac surgery
Authors: Li Shishi , Zhang Youlin , Yang Yan , Chen Sining , Yang Zhiqian , Kuang Chaoying , Zhong Yuzhen , Liu Fanna
Published: September 2023

Background: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common and serious complication after cardiac surgery. The influence of statin use before surgery on the renal outcome of patients undergoing cardiac surgery is controversial. The purpose of this study was to evaluate the effect of statins on postoperative renal outcomes in patients undergoing cardiac surgery.

Methods: We included CSA-AKI patients in the Medical Information Mart for Intensive Care (MIMIC)—IV database and were divided into statin group and non-statin group according to whether they used statins before entering intensive care units (ICU). The main outcomes were hospitalization and 30-day mortality, and the secondary outcomes were 60-day mortality and 90-day mortality. We used propensity score matching (PSM) to adjust for confounding factors. The 95% confidence interval (CI) and risk ratio (RO) were calculated by the COX proportional regression model. At the same time, stratified analysis was used to explore whether the relationship between the statins use before intensive care units and mortality was different in each subgroup and whether the relationship between different doses of Atorvastatin and mortality was different.

Result: We identified 675 pre-ICU statin users and 2095 non-statin users. In the COX proportional regression model, pre-ICU statin use was associated with decreased in-hospital (HR = 0.407, 95%confidence interval 0.278–0.595, p < 0.001) and 30-day mortality (HR = 0.407, 95%CI 0.279–0.595, p < 0.001). The survival rate of patients who took statins before entering ICU was significantly higher than that of those who did not use statins at 30 days, 60 days and 90 days. There is a significant interaction between patients with aged>65 years (HR = 0.373, 95%CI 0.240–0.581, p < 0.001), Acute kidney injury grade I (HR = 0.244, 95%CI 0.118–0.428, p < 0.001), and without post-myocardial infarction syndrome (HR = 0.344, 95%CI 0.218–0.542, p < 0.001). The mortality in hospital and 60 days of CSA-AKI patients treated with ≥80 mg Atorvastatin before operation was significantly reduced (p < 0.05).

Conclusion: The pre-ICU statin use was significantly associated with decreased risk in hospital and 30-day mortality. The preoperative use of ≥80 mg Atorvastatin may improve the prognosis of CSA-AKI.
Analysis of the influence of different initial velocities on dynamic performance of multi-layer hard target penetration process
Authors: Liu Peng , Li Jian , Li Changsheng , Li Haojie , Zhang Jinming , Zhang He
Published: September 2023

To determine the overload characteristics of the internal system of a fuze that penetrates multilayer hard targets using different fixed-link structures, a finite element model consisting of two fixed-link structures (a compression screw and a body screw) is adopted in this paper to simulate the penetration process of a three-layer concrete target plate with corresponding initial velocities. The peak amplification coefficient and vibration coefficient are used to analyze the time-domain characteristics of the penetration process signal during segmented analysis. The extracted acceleration signals of the projectile and sensor are processed by fast Fourier transform to obtain the frequency spectrum analysis results. The simulation results show that under the same working conditions, the sensor’s ability to amplify the peak acceleration of the projectile is 17.77% higher for the body screw fixed-link structure, and the average vibration coefficient is also 9.55% higher. Compared with that of the body screw fixed-link structure, the performance of the compression screw fixed-link structure is better under different initial velocity conditions. The initial penetration velocity affects mainly the amplitude of each frequency corresponding to the acceleration signals of the two fixed-link fuze structure projectiles and sensors while having a relatively small influence on the frequency distribution position.
Biostimulant activity of Galaxaura rugosa seaweed extracts against water deficit stress in tomato seedlings involves activation of ABA signaling
Authors: Morales-Sierra Sarai , Luis Juan Cristo , Jiménez-Arias David , Rancel-Rodríguez Nereida M. , Coego Alberto , Rodriguez Pedro L. , Cueto Mercedes , Borges Andrés A.
Published: September 2023

Water scarcity is a serious constraint for agriculture, and global warming and climate change can exacerbate it in many areas. Therefore, sustainable approaches must be implemented to deal with current and future water scarcity scenarios. Genetic and chemical approaches are being applied to manage this limitation and maintain crop yields. In particular, biostimulants obtained from natural sources such as marine algae are promising aids for coping with water deficit stress in agriculture. Here we present a bioprospection study of extracts of the macroalgae Bonnemaisonia hamifera, Galaxaura rugosa, Dasycladus vermicularis, Ulva clathrata, Cystoseira foeniculacea, Cystoseira humilis, Lobophora dagamae, Colpomenia sinuosa and Halopteris scoparia from the north coast of Tenerife, in the Canary Islands. The aqueous extracts of Bonnemaisonia hamifera, Galaxaura rugosa, Dasycladus vermicularis and Cystoseira humilis show biostimulant activity against water deficit stress in tomato seedlings under controlled conditions, providing higher tolerance than the mock-treated control. The Galaxaura rugosa extract showed the highest biostimulant activity against water deficit stress. We demonstrate that this positive effect involves the activation of the abscisic acid (ABA) pathway in Arabidopsis thaliana (arabidopsis) and Solanum lycopersicum (tomato). Application of G. rugosa extract to the root system by drenching tomato seedlings subjected to water deficit leads to improved CO2 assimilation and water use efficiency (WUEp), compared to mock-treated plants. These results highlight a new potential seaweed source of substances with osmoprotectant properties, useful for biostimulant development. Future studies may provide further insight into which components of the seaweed extract induce activation of the ABA pathway.