bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Alchemy unveiled: MicroRNA-mediated gene therapy as the Artisan craft in the battlefront against hepatocellular carcinoma—a comprehensive chronicle of strategies and innovations
Authors: Murshed Abduh , Alnoud Mohammed A. H. , Ahmad Saleem , Khan Safir Ullah , Alissa Mohammed , Alsuwat Meshari A. , Ahmed Ahmed Ezzat , Khan Munir Ullah
Published: June 2024

Investigating therapeutic miRNAs is a rewarding endeavour for pharmaceutical companies. Since its discovery in 1993, our understanding of miRNA biology has advanced significantly. Numerous studies have emphasised the disruption of miRNA expression in various diseases, making them appealing candidates for innovative therapeutic approaches. Hepatocellular carcinoma (HCC) is a significant malignancy that poses a severe threat to human health, accounting for approximately 70%–85% of all malignant tumours. Currently, the efficacy of several HCC therapies is limited. Alterations in various biomacromolecules during HCC progression and their underlying mechanisms provide a basis for the investigation of novel and effective therapeutic approaches. MicroRNAs, also known as miRNAs, have been identified in the last 20 years and significantly impact gene expression and protein translation. This atypical expression pattern is strongly associated with the onset and progression of various malignancies. Gene therapy, a novel form of biological therapy, is a prominent research area. Therefore, miRNAs have been used in the investigation of tumour gene therapy. This review examines the mechanisms of action of miRNAs, explores the correlation between miRNAs and HCC, and investigates the use of miRNAs in HCC gene therapy.
Geochemical and mineralogical heterogeneity of the Cantung mine tailings: implications for remediation and reprocessing
Authors: Surrette A. , Dobosz A. , Lambiv Dzemua G. , Falck H. , Jamieson H. E.
Published: June 2024

Reprocessing tailings to recover minerals of economic interest and environmental concern can add value to a project and decrease environmental risk, but dealing with heterogeneity within tailings facilities is a challenge. This study investigates the heterogeneity of the Cantung Mine tailings to assess the potential for reprocessing for both value recovery and remediation purposes. The Cantung Mine, Northwest Territories, was a world-class tungsten (W) deposit that was mined periodically from 1962 to 2015. Geochemical analysis of 196 tailings samples shows substantial heterogeneity in the elements of value (tungsten and copper (Cu)) and elements of environmental concern for acid rock drainage (iron (Fe) and sulfur (S)). Tungsten and copper concentrations range from 0.06 to 1.06 wt% W (average 0.32 wt% W) and 0.05 to 0.48 wt% Cu (average 0.23 wt% Cu). Iron and sulfur concentrations range from 8.25 to 34.08 wt% Fe (average 17.14 wt% Fe) and 2.20 to 19.70 wt% S (average 6.7 wt% S). Characterization of 29 samples by scanning electron microscope with automated mineralogy software shows that geochemical heterogeneity corresponds to mineralogical heterogeneity with variability in the concentrations of scheelite (CaWO4), chalcopyrite (CuFeS2) and pyrrhotite (Fe(1-x)S). Liberation analyses indicate that additional grinding would be necessary to recover scheelite, chalcopyrite or pyrrhotite. Pyrrhotite with monoclinic and hexagonal-orthorhombic forms were identified. Overall, the Cantung tailings display considerable heterogeneity, which could lead to difficulties in reprocessing for economic or environmental benefit, but characterizing the heterogeneity allows for systems to be optimized.
Aging is associated with an insufficient early inflammatory response of lung endothelial cells in SARS-CoV-2 infection
Authors: Subramaniam Saravanan , Kenney Devin , Jayaraman Archana , O’Connell Aoife Kateri , Walachowski Sarah , Montanaro Paige , Reinhardt Christoph , Colucci Giuseppe , Crossland Nicholas A. , Douam Florian , Bosmann Markus
Published: June 2024

Advanced age is associated with an increased susceptibility to Coronavirus Disease (COVID)-19 and more severe outcomes, although the underlying mechanisms are understudied. The lung endothelium is located next to infected epithelial cells and bystander inflammation may contribute to thromboinflammation and COVID-19-associated coagulopathy. Here, we investigated age-associated SARS-CoV-2 pathogenesis and endothelial inflammatory responses using humanized K18-hACE2 mice. Survival was reduced to 20% in aged mice (85–112 weeks) versus 50% in young mice (12–15 weeks) at 10 days post infection (dpi). Bulk RNA-sequencing of endothelial cells from mock and infected mice at 2dpi of both age groups (aged: 72–85 weeks; young: 15 weeks) showed substantially lower significant differentially regulated genes in infected aged mice than in young mice (712 versus 2294 genes). Viral recognition and anti-viral pathways such as RIG-I-like receptor signaling, NOD-like receptor signaling and interferon signaling were regulated in response to SARS-CoV-2. Young mice showed several fold higher interferon responses (Ifitm3, Ifit1, Isg15, Stat1) and interferon-induced chemokines (Cxcl10 and Cxcl11) than aged mice. Endothelial cells from infected young mice displayed elevated expression of chemokines (Cxcl9, Ccl2) and leukocyte adhesion markers (Icam1) underscoring that inflammation of lung endothelium during infection could facilitate leukocyte adhesion and thromboinflammation. TREM1 and acute phase response signaling were particularly prominent in endothelial cells from infected young mice. Immunohistochemistry was unable to detect viral protein in pulmonary endothelium. In conclusion, our data demonstrate that the early host response of the endothelium to SARS-CoV-2 infection declines with aging, which could be a potential contributor to disease severity.
Toll-like receptors in breast cancer immunity and immunotherapy
Authors: Zhou Joseph , Zhang Lin , Liu Siyao , DeRubeis David , Zhang Dekai
Published: June 2024

Toll-like receptors (TLRs) are a key family of pattern recognition receptors (PRRs) in the innate immune system. The activation of TLRs will not only prevent pathogen infection but also respond to damage-induced danger signaling. Increasing evidence suggests that TLRs play a critical role in breast cancer development and treatment. However, the activation of TLRs is a double-edged sword that can induce either pro-tumor activity or anti-tumor effect. The underlying mechanisms of these opposite effects of TLR signaling in cancer are not fully understood. Targeting TLRs is a promising strategy for improving breast cancer treatment, either as monotherapies or by improving other current therapies. Here we provide an update on the role of TLRs in breast cancer immunity and immunotherapy.
The declining availability of wild mussel seed for aquaculture in a coastal upwelling system
Authors: Padin Xosé A. , Babarro José M. F. , Otero Pablo , Gilcoto Miguel , Rellán Trinidad , Suárez Lino , Velo Anton , Peteiro Laura G.
Published: June 2024

A general decline in foundation species at the rocky intertidal has been observed during the last decades all around the world and primarily related to climate change. In agreement with that trend, the mussel aquaculture sector in Galicia (NW Spain), the main production area in Europe, has warned over the last years about a decline in the availability of wild mussel seed from the rocky coast. Here we compile for the first time, mussel seed collection reports by mussel farmers in Galicia for the period 2006–2021. We employed that dataset as a proxy of mussel recruitment evolution in the rocky shore for the last 16 years. Temporal analysis of our data confirmed the reported decline (-148 t yr-1), particularly pronounced from 2012 onwards. The data base also allowed us to analyze inter-annual variability according to both, climatic variations and management scenarios. Since cultivated mussels conform a meta-population with wild mussels from the rocky shore, alterations on the market preferences towards smaller individuals at harvest, could also contribute to a reduction in reproductive output. Our results show a decrease in life-time egg production under certain scenarios. Nonetheless, coastal upwelling seems to be the largest factor conditioning recruitment abundance, explaining as much as 60% of the variability observed. Decline on recruitment abundance was highly modulated by the observed increment in frequency of intense upwelling events, exceeding 500 m3 km-1 s-1 between July and November. Meridional winds also determined the spatial recruitment patterns, pointing to the large role of wind forcing on mussel larval dispersal. Our results highlights how alterations on upwelling regimes related to climate change can interact with mussel population dynamics and also condition aquaculture sustainability and food security.
Addressing illegal longlining and ghost fishing in the Galapagos marine reserve: an overview of challenges and potential solutions
Authors: Castrejón Mauricio , Defeo Omar
Published: June 2024

Despite regulations aimed at curbing shark finning and bycatch, shark fishing mortality rates continue to escalate, partly due to unintended consequences of these policies which, along with illegal, unreported, and unregulated fishing and ghost fishing, undermine conservation efforts. The ineffectiveness of current regulations to curb shark mortality highlights the pressing need for reevaluating shark conservation strategies, especially in ecologically sensitive areas. In this context, the debate on enforcing longlining bans in multiple-use marine protected areas, including shark sanctuaries, is intensifying. Some argue for total bans to minimize incidental shark mortalities, while others highlight the socioeconomic importance of longlining, advocating for alternative conservation measures. In 2000, longline fishing was banned in the Galapagos Marine Reserve (GMR) as a precautionary measure to prevent illegal fishing of sharks and bycatch of endangered, threatened, and protected species. After 24 years of enforcement, official and anecdotal evidence indicate that illegal small-scale tuna longlining and ghost fishing are increasing threats across the reserve. This paper provides an overview of the longline fishing controversy within the GMR, incorporating scientific evidence, legal and socioeconomic considerations, and perceptions from the Galapagos small-scale fishing community. We offer novel insights and recommendations for the development of the Galapagos small-scale tuna fishery within an ecosystem approach to fisheries. This approach aims to reconcile conservation goals with the needs of local communities, while also proposing innovative solutions to address the longstanding debate surrounding longlining in the GMR.
Diverse nitrogen enrichments enhance photosynthetic resistance of Sargassum horneri to ultraviolet radiation
Authors: Li Baoqi , Xu Zhiguang , Jiang Xiaotong , Wu Hongyan , Bao Menglin , Zang Shasha , Yan Fang , Yuan Tingzhu
Published: June 2024

In recent years, golden tides caused by floating Sargassum have induced severe ecological disasters globally. Eutrophication is a significant factor contributing to the massive spread of Sargassum golden tides. Furthermore, the thalli of Sargassum that float on the ocean surface are subjected to more ultraviolet radiation (UVR). The coupled impact of eutrophication and UVR on the photosynthetic physiology of golden tide species remains unclear. In this study, the thalli of Sargassum horneri, known to cause golden tide, were cultured and acclimated to three distinct nitrogen (N) conditions (natural seawater, NSW; NH4+-N enrichment; and NO3–N enrichment) for 6 days. Subsequently, the thalli were exposed to two different radiation treatments (photosynthetically active radiation (150 W m-2), PAR, 400–700 nm; PAR (150 W m-2) + UVR (28 W m-2), 280–700 nm) for 120 min, to investigate the photosynthetic effects of UVR and N on this alga. The findings demonstrated that exposure to UVR impeded the photosynthetic capacity of S. horneri, as evidenced by a decrease in the maximum photochemical quantum yield (Fv/Fm), photosynthetic efficiency (α) and chlorophyll content. Under diverse N-enrichment conditions, the alga tended to adopt various strategies to mitigate the adverse effects of UVR. NH4+-enrichment dissipated excess UVR energy through a greater increase in non-photochemical quenching (NPQ). While NO3–enrichment protected alga by enhancing N assimilation (higher nitrate reductase activity (NRA) and soluble protein content), and maintained a stable energy captured per unit reaction center for electron transfer (ET0/RC) and a higher net photosynthetic rate. Although different N enrichments could not completely offset the damage caused by UV radiation, they secured the photoprotective ability of S. horneri in several ways.
Design and pilot test of an implicit bias mitigation curriculum for clinicians
Authors: Svetkey Laura P. , Bennett Gary G. , Reese Benjamin , Corsino Leonor , Pinheiro Sandro O. , Fischer Jonathan E. , Seidenstein Judy , Olsen Maren K. , Brown Tyson , Ezem Natalie , Liu Evan , Majors Alesha , Steinhauser Karen E. , Sullivan Brandy H. , van Ryn Michelle , Wilson Sarah M. , Yang Hongqiu , Johnson Kimberly S.
Published: June 2024

Introduction

Clinician implicit racial bias (IB) may lead to lower quality care and adverse health outcomes for Black patients. Educational efforts to train clinicians to mitigate IB vary widely and have insufficient evidence of impact. We developed and pilot-tested an evidence-based clinician IB curriculum, “REACHing Equity.”

Methods

To assess acceptability and feasibility, we conducted an uncontrolled one-arm pilot trial with post-intervention assessments. REACHing Equity is designed for clinicians to: (1) acquire knowledge about IB and its impact on healthcare, (2) increase awareness of one's own capacity for IB, and (3) develop skills to mitigate IB in the clinical encounter. We delivered REACHing Equity virtually in three facilitated, interactive sessions over 7–9 weeks. Participants were health care providers who completed baseline and end-of-study evaluation surveys.

Results

Of approximately 1,592 clinicians invited, 37 participated, of whom 29 self-identified as women and 24 as non-Hispanic White. Attendance averaged 90% per session; 78% attended all 3 sessions. Response rate for evaluation surveys was 67%. Most respondents agreed or strongly agreed that the curriculum objectives were met, and that REACHing Equity equipped them to mitigate the impact of implicit bias in clinical care. Participants consistently reported higher self-efficacy for mitigating IB after compared to before completing the curriculum.

Conclusions

Despite apparent barriers to clinician participation, we demonstrated feasibility and acceptability of the REACHing Equity intervention. Further research is needed to develop objective measures of uptake and clinician skill, test the impact of REACHing Equity on clinically relevant outcomes, and refine the curriculum for uptake and dissemination.

ClinicalTrials.gov ID: NCT03415308.
Epitope screening and self-assembled nanovaccine molecule design of PDCoV-S protein based on immunoinformatics
Authors: Chen Yaping , Song Xinqi , Chen Wenshuang , Zhao Xinyi , Yang Li , Liu Dongyu
Published: June 2024

Based on the whole virus or spike protein of pigs, δ coronavirus (PDCoV) as an immunogen may have unrelated antigenic epitope interference. Therefore, it is essential for screening and identifying advantageous protective antigen epitopes. In addition, immunoinformatic tools are described as an important aid in determining protective antigenic epitopes. In this study, the primary, secondary, and tertiary structures of vaccines were measured using ExPASy, PSIPRED 4.0, and trRosetta servers. Meanwhile, the molecular docking analysis and vector of the candidate nanovaccine were constructed. The immune response of the candidate vaccine was simulated and predicted using the C-ImmSim server. This experiment screened B cell epitopes with strong immunogenicity and high conservation, CTL epitopes, and Th epitopes with IFN-γ and IL-4 positive spike proteins. Ferritin is used as a self-assembled nanoparticle element for designing candidate nanovaccine. After analysis, it has been found to be soluble, stable, non-allergenic, and has a high affinity for its target receptor, TLR-3. The preliminary simulation analysis results show that the candidate nanovaccine has the ability to induce a humoral and cellular immune response. Therefore, it may provide a new theoretical basis for research on coronavirus self-assembled nanovaccines. It may be an effective candidate vaccine for controlling and preventing PDCoV.
Brain and serum lipidomic profiles implicate Lands cycle acyl chain remodeling association with APOEε4 and mild cognitive impairment
Authors: Mares Jason , Costa Ana Paula , Dartora William J. , Wartchow Krista M. , Lazarian Artur , Bennett David A. , Nuriel Tal , Menon Vilas , McIntire Laura Beth J.
Published: June 2024

Introduction

At least one-third of the identified risk alleles from Genome-Wide Association Studies (GWAS) of Alzheimer’s disease (AD) are involved in lipid metabolism, lipid transport, or direct lipid binding. In fact, a common genetic variant (ε4) in a cholesterol and phospholipid transporter, Apolipoprotein E (APOEε4), is the primary genetic risk factor for late-onset AD. In addition to genetic variants, lipidomic studies have reported severe metabolic dysregulation in human autopsy brain tissue, cerebrospinal fluid, blood, and multiple mouse models of AD.

Methods

We aimed to identify an overarching metabolic pathway in lipid metabolism by integrating analyses of lipidomics and transcriptomics from the Religious Order Study and Rush Memory Aging Project (ROSMAP) using differential analysis and network correlation analysis.

Results

Coordinated differences in lipids were found to be dysregulated in association with both mild cognitive impairment (MCI) and APOEε4 carriers. Interestingly, these correlations were weakened when adjusting for education. Indeed, the cognitively non-impaired APOEε4 carriers have higher education levels in the ROSMAP cohort, suggesting that this lipid signature may be associated with a resilience phenotype. Network correlation analysis identified multiple differential lipids within a single module that are substrates and products in the Lands Cycle for acyl chain remodeling. In addition, our analyses identified multiple genes in the Lands Cycle acyl chain remodeling pathway, which were associated with cognitive decline independent of amyloid-β (Aβ) load and tau tangle pathologies.

Discussion

Our studies highlight the critical differences in acyl chain remodeling in brain tissue from APOEε4 carriers and individual non-carriers with MCI. A coordinated lipid profile shift in dorsolateral prefrontal cortex from both APOEε4 carriers and MCI suggests differences in lipid metabolism occur early in disease stage and highlights lipid homeostasis as a tractable target for early disease modifying intervention.
Structures and functions of the normal and injured human olfactory epithelium
Authors: Kikuta Shu , Nagayama Shin , Hasegawa-Ishii Sanae
Published: June 2024

The olfactory epithelium (OE) is directly exposed to environmental agents entering the nasal cavity, leaving OSNs prone to injury and degeneration. The causes of olfactory dysfunction are diverse and include head trauma, neurodegenerative diseases, and aging, but the main causes are chronic rhinosinusitis (CRS) and viral infections. In CRS and viral infections, reduced airflow due to local inflammation, inflammatory cytokine production, release of degranulated proteins from eosinophils, and cell injury lead to decreased olfactory function. It is well known that injury-induced loss of mature OSNs in the adult OE causes massive regeneration of new OSNs within a few months through the proliferation and differentiation of progenitor basal cells that are subsequently incorporated into olfactory neural circuits. Although normal olfactory function returns after injury in most cases, prolonged olfactory impairment and lack of improvement in olfactory function in some cases poses a major clinical problem. Persistent inflammation or severe injury in the OE results in morphological changes in the OE and respiratory epithelium and decreases the number of mature OSNs, resulting in irreversible loss of olfactory function. In this review, we discuss the histological structure and distribution of the human OE, and the pathogenesis of olfactory dysfunction associated with CRS and viral infection.
A phase 1 proof-of-concept study evaluating safety, tolerability, and biological marker responses with combination therapy of CTLA4-Ig and interleukin-2 in amyotrophic lateral sclerosis
Authors: Thonhoff Jason R. , Beers David R. , Zhao Weihua , Faridar Alireza , Thome Aaron , Wen Shixiang , Zhang Aijun , Wang Jinghong , Appel Stanley H.
Published: June 2024

Objective

To determine whether a combination therapy with abatacept (CTLA4-Ig) and interleukin-2 (IL-2) is safe and suppresses markers of oxidative stress, inflammation, and degeneration in ALS.

Methods

In this open-label study, four participants with ALS received subcutaneous injections of low dose IL-2 (1 × 106 IU/injection/day) for 5 consecutive days every 2 weeks and one subcutaneous injection of CTLA4-Ig (125 mg/mL/injection) every 2 weeks coinciding with the first IL-2 injection of each treatment cycle. Participants received a total of 24 treatment cycles during the first 48 weeks in this 56-week study. They were closely monitored for treatment-emergent adverse events (TEAEs) and disease progression with the ALSFRS-R. Phenotypic changes within T cell populations and serum biological markers of oxidative stress [4-hydroxynonenal (4-HNE) and oxidized-LDL (ox-LDL)], inflammation (IL-18), and structural neuronal degeneration [neurofilament light chain (Nf-L)] were assessed longitudinally.

Results

CTLA4-Ig/IL-2 therapy was safe and well-tolerated in all four participants over the 56-week study. During the first 24 weeks, the average rate of change in the ALSFRS-R was +0.04 points/month. Over the 48-week treatment period, the average rate of change was −0.13 points/month with one participant improving by 0.9 points/month while the other three participants experienced an average decrease of −0.47 points/month, which is slower than the average − 1.1 points/month prior to initiation of therapy. Treg suppressive function and numbers increased during treatment. Responses in the biological markers during the first 16 weeks coincided with minimal clinical progression. Mean levels of 4-HNE decreased by 30%, ox-LDL decreased by 19%, IL-18 decreased by 23%, and Nf-L remained the same, on average, in all four participants. Oxidized-LDL levels decreased in all four participants, 4-HNE and IL-18 levels decreased in three out of four participants, and Nf-L decreased in two out of four participants.

Conclusion

The combination therapy of CTLA4-Ig and IL-2 in ALS is safe and well-tolerated with promising results of clinical efficacy and suppression of biomarkers of oxidative stress, neuroinflammation and neuronal degeneration. In this open-label study, the efficacy as measured by the ALSFRS-R and corresponding biomarkers suggests the therapeutic potential of this treatment and warrants further study in a phase 2 double-blind, placebo-controlled trial.

Clinical trial registration

ClinicalTrials.gov, NCT06307301.
Validity and agreement between dual-energy X-ray absorptiometry, anthropometry and bioelectrical impedance in the estimation of fat mass in young adults
Authors: Mecherques-Carini Malek , Albaladejo-Saura Mario , Vaquero-Cristóbal Raquel , Baglietto Nicolás , Esparza-Ros Francisco
Published: June 2024

Introduction

Assessment of fat mass has historically employed various methods like Dual-energy X-ray Absorptiometry (DXA), and bioelectrical impedance (BIA), and anthropometry with its set of formulas. However, doubts persist regarding their validity and interchangeability to evaluate fat mass. This research aimed to determine the validity of anthropometry, and BIA in estimating fat mass Vs DXA, considering the influence of sex and hydration status.

Methods

A descriptive, cross-sectional study included 265 young adults (161 males and 104 females), assessed through DXA, BIA in a standing position, and anthropometry. A fat mass estimation formula with DXA, a fat mass estimation formula with BIA and 10 fat mass estimation formulas with anthropometry were calculated.

Results

Significant differences were found across DXA, BIA and anthropometry in both kilograms and percentages for the overall sample (p<0.001), and when the covariable sex was included (p<0.001), with no significant effect of hydration status (p=0.332-0.527). Bonferroni-adjusted analyses revealed significant differences from DXA with anthropometry and BIA in most cases for the overall sample (p<0.001), as well as when stratified by sex (p<0.001–0.016). Lin’s coefficient indicated poor agreement between most of the formulas and methods both in percentage and kilograms of fat mass (CCC=0.135–0.892). In the Bland-Altman analysis, using the DXA fat mass values as a reference, lack of agreement was found in the general sample (p<0.001-0.007), except for Carter’s formula in kilograms (p=0.136) and percentage (p=0.929) and Forsyth for percentage (p=0.365). When separating the sample by sex, lack of agreement was found in males for all methods when compared with both percentage and kilograms calculated by DXA (p<0.001). In the female sample, all methods and formulas showed lack of agreement (p<0.001–0.020), except for Evans’s in percentage (p=0.058).

Conclusion

The formulas for fat mass assessment with anthropometry and BIA may not be valid with respect to the values reported with DXA, with the exception of Carter’s anthropometry formula for general sample and Evans’s anthropometry formula for female sample. BIA could also be an alternative if what is needed is to assess fat mass in women as a group.
Interleukin-1β activates matrix metalloproteinase-2 to alter lacrimal gland myoepithelial cell structure and function
Authors: Morokuma Junji , Gárriz Angela , Toribio Danny , Pagni Sarah , Zoukhri Driss
Published: June 2024

The aim of the present study is to investigate the role of c-Jun N-terminal kinase (JNK) and matrix metalloproteinase-2 (MMP-2) in mediating the effects of interleukin-1β (IL-1β) on the function of lacrimal gland myoepithelial cells (MECs). MECs isolated from an α-smooth muscle actin–green fluorescent protein (SMA-GFP) transgenic mouse were treated with IL-1β alone or in the presence of SP600125, a JNK inhibitor, or ARP100, an MMP-2 inhibitor. The GFP intensity and the cell size/area were measured, and on day 7, the SMA, calponin, and pro-MMP-2 protein levels and the MEC contraction were assessed. At baseline, the control and treated cells showed no differences in GFP intensity or cell size. Starting on day 2 and continuing on days 4 and 7, the GFP intensity and cell size were significantly lower in the IL-1β-treated samples, and these effects were alleviated following inhibition of either JNK or MMP-2. Compared with the control, the levels of SMA and calponin were lower in the IL-1β-treated samples, and both the JNK and MMP-2 inhibitors reversed this trend. The pro-MMP-2 protein level was elevated in the IL-1β-treated samples, and this effect was abolished by the JNK inhibitor. Finally, oxytocin-induced MEC contraction was diminished in the IL-1β-treated samples, and both the JNK and MMP-2 inhibitors reversed this effect. Our data suggest that IL-1β uses the JNK/MMP-2 pathways to alter MEC functions, which might account for the diminished tears associated with aqueous-deficient dry eye disease.
Direct modulation of G protein-gated inwardly rectifying potassium (GIRK) channels
Authors: Nguyen Ha , Glaaser Ian W. , Slesinger Paul A.
Published: June 2024

Ion channels play a pivotal role in regulating cellular excitability and signal transduction processes. Among the various ion channels, G-protein-coupled inwardly rectifying potassium (GIRK) channels serve as key mediators of neurotransmission and cellular responses to extracellular signals. GIRK channels are members of the larger family of inwardly-rectifying potassium (Kir) channels. Typically, GIRK channels are activated via the direct binding of G-protein βγ subunits upon the activation of G-protein-coupled receptors (GPCRs). GIRK channel activation requires the presence of the lipid signaling molecule, phosphatidylinositol 4,5-bisphosphate (PIP2). GIRK channels are also modulated by endogenous proteins and other molecules, including RGS proteins, cholesterol, and SNX27 as well as exogenous compounds, such as alcohol. In the last decade or so, several groups have developed novel drugs and small molecules, such as ML297, GAT1508 and GiGA1, that activate GIRK channels in a G-protein independent manner. Here, we aim to provide a comprehensive overview focusing on the direct modulation of GIRK channels by G-proteins, PIP2, cholesterol, and novel modulatory compounds. These studies offer valuable insights into the underlying molecular mechanisms of channel function, and have potential implications for both basic research and therapeutic development.
Exploring the potentials of Sesuvium portulacastrum L. for edibility and bioremediation of saline soils
Authors: Zhang Wenbin , Wang Dan , Cao Dingding , Chen Jianjun , Wei Xiangying
Published: June 2024

Sesuvium portulacastrum L. is a flowering succulent halophyte in the ice plant family Aizoaceae. There are various ecotypes distributed in sandy coastlines and salty marshlands in tropical and subtropical regions with the common name of sea purslane. These plants are tolerant to salt, drought, and flooding stresses and have been used for the stabilization of sand dunes and the restoration of coastal areas. With the increased salinization of agricultural soils and the widespread pollution of toxic metals in the environment, as well as excessive nutrients in waterbodies, S. portulacastrum has been explored for the desalination of saline soils and the phytoremediation of metals from contaminated soils and nitrogen and phosphorus from eutrophic water. In addition, sea purslane has nutraceutical and pharmaceutical value. Tissue analysis indicates that many ecotypes are rich in carbohydrates, proteins, vitamins, and mineral nutrients. Native Americans in Florida eat it raw, pickled, or cooked. In the Philippines, it is known as atchara after being pickled. S. portulacastrum contains high levels of ecdysteroids, which possess antidiabetic, anticancer, and anti-inflammatory activities in mammals. In this review article, we present the botanical information, the physiological and molecular mechanisms underlying the tolerance of sea purslane to different stresses, its nutritional and pharmaceutical value, and the methods for its propagation and production in saline soils and waterbodies. Its adaptability to a wide range of stressful environments and its role in the production of valuable bioactive compounds suggest that S. portulacastrum can be produced in saline soils as a leafy vegetable and is a valuable genetic resource that can be used for the bioremediation of soil salinity and eutrophic water.
Effects of physical activity on depression, anxiety, and stress in college students: the chain-based mediating role of psychological resilience and coping styles
Authors: Liu Ming , Liu Huanju , Qin Zhuzhu , Tao Yining , Ye Wan , Liu Renyang
Published: June 2024

Background

Physical activity can alleviate negative emotions in college students by enhancing mood and cognitive functions. Yet, the mechanisms underlying these benefits remain unclear.

Purpose

This study examines the association between physical activity and negative emotions—specifically, depression, anxiety, and stress—in college students. Additionally, we explore the mediating effects of psychological resilience and coping styles to offer theoretical and practical insights for mitigating students’ negative emotions.

Methods

Using a stratified random sampling approach, a total of 1,380 college students, from five universities in Hangzhou, Nanjing, and Wenzhou, were included in the analysis. The survey instruments included the Physical Activity Rating Scale, Connor-Davidson Resilience Scale, Simple Coping Style Scale, and Depression-Anxiety Stress Scale. The data were statistically analyzed using multivariate methods with IBM SPSS 25.0 and the PROCESS V3.3 plug-in.

Results

(1) College students engage in a low level of physical activity, with male students participating significantly more than female students (p < 0.001). (2) Physical activity was significantly positively correlated with psychological resilience and positive coping styles (t = 9.126, p < 0.001; t = 23.087, p < 0.001) and overall negative correlated with negative emotions in college students (t = −3.601, p < 0.001). (3) Psychological resilience and positive coping styles were found to play a chain mediating role between physical activity and negative emotions. The mediation effect consists of two paths: physical activity → psychological resilience → negative emotions (effect value: −0.0324), and physical activity → psychological resilience → positive coping → negative emotions (effect value: −0.0099). (4) Female students demonstrated higher levels of positive coping (p < 0.001), while male students exhibited more negative emotions (p < 0.001).

Conclusion

Our study identifies a significant indirect link, mediated by psychological resilience and positive coping styles, between physical activity and the reduction of negative emotions. Targeted interventions addressing gender differences, such as offering special courses and providing specialized exercise programs and emotional management strategies, can enhance psychological resilience and positive coping mechanisms. Consequently, these measures can alleviate the adverse effects of negative emotions. Our findings have broader implications for both research and practical interventions in promoting mental health among college students.
Risk of major depressive increases with increasing frequency of alcohol drinking: a bidirectional two-sample Mendelian randomization analysis
Authors: Feng Weiyu , Zhang Bing , Duan Pengyu , Bi Yong-hong , Jin Zhehao , Li Xiaoyan , Zhao Xiangcheng , Zuo Kun
Published: June 2024

Introduction

A growing body of evidence suggests that alcohol use disorders coexist with depression. However, the causal relationship between alcohol consumption and depression remains a topic of controversy.

Methods

We conducted a two-sample two-way Mendelian randomization analysis using genetic variants associated with alcohol use and major depressive disorder from a genome-wide association study.

Results

Our research indicates that drinking alcohol can reduce the risk of major depression (odds ratio: 0.71, 95% confidence interval: 0.54~0.93, p = 0.01), while increasing the frequency of drinking can increase the risk of major depression (odds ratio: 1.09, 95% confidence interval: 1.00~1.18, p = 0.04). Furthermore, our multivariate MR analysis demonstrated that even after accounting for different types of drinking, the promoting effect of drinking frequency on the likelihood of developing major depression still persists (odds ratio: 1.13, 95% confidence interval: 1.04~1.23, p = 0.005). Additionally, mediation analysis using a two-step MR approach revealed that this effect is partially mediated by the adiposity index, with a mediated proportion of 37.5% (95% confidence interval: 0.22 to 0.38).

Discussion

In this study, we found that alcohol consumption can alleviate major depression, while alcohol intake frequency can aggravate it.These findings have important implications for the development of prevention and intervention strategies targeting alcohol-related depression.
A systematic review of collaborative robots for nurses: where are we now, and where is the evidence?
Authors: Babalola Grace Titilayo , Gaston Jenna-Marie , Trombetta Joseph , Tulk Jesso Stephanie
Published: June 2024

Introduction: Robots present an opportunity to enhance healthcare delivery. Rather than targeting complete automation and nurse replacement, collaborative robots, or “cobots”, might be designed to allow nurses to focus on high-value caregiving. While many institutions are now investing in these platforms, there is little publicly available data on how cobots are being developed, implemented, and evaluated to determine if and how they support nursing practice in the real world.

Methods: This systematic review investigates the current state of cobotic technologies designed to assist nurses in hospital settings, their intended applications, and impacts on nurses and patient care. A comprehensive database search identified 28 relevant peer-reviewed articles published since 2018 which involve real studies with robotic platforms in simulated or actual clinical contexts.

Results: Few cobots were explicitly designed to reduce nursing workload through administrative or logistical assistance. Most included studies were designed as patient-centered rather than nurse-centered, but included assistance for tasks like medication delivery, vital monitoring, and social interaction. Most applications emerged from India, with limited evidence from the United States despite commercial availability of nurse-assistive cobots. Robots ranged from proof-of-concept to commercially deployed systems.

Discussion: This review highlights the need for further published studies on cobotic development and evaluation. A larger body of evidence is needed to recognize current limitations and pragmatic opportunities to assist nurses and patients using state-of-the-art robotics. Human-centered design can assist in discovering the right opportunities for cobotic assistance. Committed research-practice partnerships and human-centered design are needed to guide the technical development of nurse-centered cobotic solutions.
Precision sketching with de-aging networks in forensics
Authors: Martis Jason Elroy , Sannidhan M. S. , Pratheeksha Hegde N. , Sadananda L.
Published: June 2024

Addressing the intricacies of facial aging in forensic facial recognition, traditional sketch portraits often fall short in precision. This study introduces a pioneering system that seamlessly integrates a de-aging module and a sketch generator module to overcome the limitations inherent in existing methodologies. The de-aging module utilizes a deepfake-based neural network to rejuvenate facial features, while the sketch generator module leverages a pix2pix-based Generative Adversarial Network (GAN) for the generation of lifelike sketches. Comprehensive evaluations on the CUHK and AR datasets underscore the system’s superior efficiency. Significantly, comprehensive testing reveals marked enhancements in realism during the training process, demonstrated by notable reductions in Frechet Inception Distance (FID) scores (41.7 for CUHK, 60.2 for AR), augmented Structural Similarity Index (SSIM) values (0.789 for CUHK, 0.692 for AR), and improved Peak Signal-to-Noise Ratio (PSNR) metrics (20.26 for CUHK, 19.42 for AR). These findings underscore substantial advancements in the accuracy and reliability of facial recognition applications. Importantly, the system, proficient in handling diverse facial characteristics across gender, race, and culture, produces both composite and hand-drawn sketches, surpassing the capabilities of current state-of-the-art methods. This research emphasizes the transformative potential arising from the integration of de-aging networks with sketch generation, particularly for age-invariant forensic applications, and highlights the ongoing necessity for innovative developments in de-aging technology with broader societal and technological implications.
Ecological and human health risk of heavy metals in Nubui River: a case of rural remote communities
Authors: Norvivor Forgive Awo , Azizi Shohreh , Fuku Xolile , Atibu Emmanuel K. , Idris Azeez Olayiwola , Sibali Linda , Maaza Malik , Kamika Ilunga
Published: June 2024

Introduction

The Nubui River is a primary source of water for drinking purposes and other domestic activities in the rural communities dotted along its riparian zone, with agriculture being the major activity occurring in this important ecotone. The river has become a potential sink for agrochemical residue, including heavy metals, and has apparent aesthetic water quality issues, with associated health consequences. This study, therefore, assessed the health risks of heavy metals within the rural populations in the catchment areas, who have limited sources of improved water supply.

Methods

The concentration of iron (Fe), lead (Pb), cadmium (Cd), mercury (Hg), and zinc (Zn) was assessed on cumulatively 275 water samples, using a Perkin Elmer PINAAcle 900 T atomic absorption spectrophotometer for 11 months. A cross-sectional survey was conducted amongst 338 community members, following field observations on utilisation types, aesthetic appeal, and perceived quality of water from the Nubui River. To determine the potential human and ecological risks of heavy metals, the hazard quotient, chronic daily intake, contamination factor, and health pollution indices of heavy metals were computed. STATA version 16 was used to analyse the survey results.

Results

Descriptive statistics of average concentrations of heavy metals in surface water at all sampling stations showed the pattern Hg < Pb < Cd < Zn < Fe, with relatively low concentrations, between 0.001 and 0.004 mg/L for Hg, 0.0011 and 0.0019 mg/L for Pb, 0.0461 and 0.0739 mg/L for Zn, and 0.2409 and 0.377 mg/L for Fe. The findings, however, showed relatively high cadmium levels between 0.0215 mg/L and 0.0383 mg/L in two of five sampling stations in comparison with the World Health Organisation (WHO) drinking water guideline values in some months. Hazard quotient values indicate that the population is safe from the non-carcinogenic health risks of exposure to heavy metals through oral routes. The contamination factor and heavy metal pollution indices for cadmium exceed recommended guideline values of 1 and 100, respectively. Meanwhile, 73.1% of community members evidently preferred the Nubui River for various domestic activities with 86.1% of them utilising it for drinking purposes. This occurrence results in exposure to associated health risks.
Grass-livestock interaction: a critical review of current research progress
Authors: Zhu Xiaoyu , Tan Dongfei , Li Yutong , Shao Changliang , Yan Ruirui , Zhou Wenneng , Xin Xiaoping
Published: June 2024

Introduction

Grass-livestock interaction is of great value in maintaining ecological balance, regional economic development, and the sustainability of grassland husbandry, which has gained attention in recent years in both academia and practice, however, study on grass-livestock interaction possesses cognitive bias and gaps.

Methods

This study clarified the latest research progress and development trend in the grass-livestock interaction field by illuminating publication trend, cooperative network, keyword co-occurrence relationship, keyword clustering during 2000 to 2022 based on the Web of Science core database.

Results

The results indicated that the annual number of publications in the grass-livestock interaction field showed a globally increasing with interdisciplinary and international collaboration, and the United States of America ranked firstly, followed by Brazil, England, Australia, China. Agricultural Research Service, the U.S. Department of Agricultures was the organization with the highest number of publications, and Rangeland Ecology & Management, Agriculture, Ecosystems & Environment, Grass and Forage Science were the top three journals. Furthermore, in terms of the temporal evolution, the research targeting the grass-livestock interaction mainly went through three stages: initial exploration period (2000–2011), to the period of rapid development (2012–2016) to transitional development period (2017–2022), and the notable existing keywords was Management, Livestock, Cattle, Vegetation, Growth, Soil. In terms of the structural composition, four broad divisions including mechanism of human activities, grassland resource monitoring and management, grassland livestock competition/adaptability, grassland land/soil research were identified. The results provide positive and objective insights into that grassland sustainability and grazing control through strengthening cross-disciplinary and cross-regional cooperation, and applying of standard methods based on evaluation system in the grass-livestock interaction field.

Discussion

The overall contribution of the work is provision of novel insight into the intellectual structure and temporal progression of grass-livestock interaction research at a macroscopic scale and the directions in which the field is headed currently.
Usability Testing of Novel IoT-Infused Digital Services on Farm Equipment Reveals Farmer’s Requirements towards Future Human–Machine Interface Design Guidelines
Authors: Sebald Christina , Treiber Maximilian , Eryilmaz Esmahan , Bernhardt Heinz
Published: June 2024

The application of digital technologies in the agricultural sector is increasing. One of the new key technologies is the Internet of Things (IoT), which can facilitate the everyday work of farmers. For the successful adoption of IoT-enabled digital products and to ensure improved workflows, the usability of human–machine interfaces is highly important. Various design approaches of human–machine interfaces (HMIs) can currently be found in the monitoring of agricultural machinery. In this work, the most well-known HMIs are considered. Based on a usability test (participants n = 9), the user interface (UI) of a novel mobile application (NEVONEX Cockpit App) was chosen as an example of a design approach of an IoT ecosystem that is oriented towards the UI design of mobile applications. This work aims to identify the weak points of this UI. Conclusions about the needs, and thus an improvement of the user experience, are based on the suggestions for improvement and the information about the general requirements of farmers for a UI for agricultural machinery. Here, it was found that most farmers are satisfied with the UI design of their familiar tractor monitors. According to the survey, the three most important points to be considered in the UI design are intuitive operation and menu navigation, easy access to the essential functions and buttons, and sufficiently large control panels. The conducted usability tests can be considered a basis for developing HMIs for agriculture machinery. Through repeated execution of comparable usability tests, there is the possibility of developing future HMI guidelines for agriculture to improve the user experience (UX). For the NEVONEX ecosystem, feedback from the user interface testing was incorporated in a major revision of the Cockpit App’s design, where a lot more display space was given to the agronomic digital services by smartly arranging infrastructure functions in tiles.
Investigations into the Charge Times of Lead–Acid Cells under Different Partial-State-of-Charge Regimes
Authors: Parker Max , McMahon Richard
Published: June 2024

Partial state of charge (PSOC) is an important use case for lead–acid batteries. Charging times in lead–acid cells and batteries can be variable, and when used in PSOC operation, the manufacturer’s recommended charge times for single-cycle use are not necessarily applicable. Knowing how long charging will take and what the variability in time required is allows for better planning of operations and algorithm creation for battery energy storage system (BESS) manufacturers. This paper details and demonstrates a procedure for identifying the charging time of cells when different charge throughputs occur prior to reaching full charge. The results showed that the charging time in PSOC operations was highly variable when a charge-factor-controlled full-charge procedure was used. Also noted were that higher voltages for the same state of charge were reached as the number of cycles following reaching full charge increased. None of the regimes tested in this paper caused any significant capacity degradation, which demonstrates that PSOC operations can be performed even on cells not specifically designed for them, provided the correct regime is chosen.