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38096590 | VSCode-Antimony: A Source Editor for Building, Analyzing, and Translating Antimony Models. | Developing biochemical models in systems biology is a complex, knowledge-intensive activity. Some modelers (especially novices) benefit from model development tools with a graphical user interface (GUI). However, as with the development of complex software, text-based representations of models provide many benefits for advanced model development. At present, the tools for text-based model development are limited, typically just a textual editor that provides features such as copy, paste, find, and replace. Since these tools are not "model aware", they do not provide features for: (i) model building such as autocompletion of species names; (ii) model analysis such as hover messages that provide information about chemical species; and (iii) model translation to convert between model representations. We refer to these as BAT features. |
38096591 | Oxygen self-supplied nanoparticle for enhanced chemiexcited photodynamic therapy. | Photodynamic therapy (PDT) is one of the most promising strategies for efficiently curing cancer. However, it still faces severe challenges including poor laser penetration and the insufficient oxygen (O2) in solid tumors. Here, we constructed an intelligent O2 self-supplied nanoparticles (NPs) for tumor hypoxia relief as well as effective chemiexcited photodynamic therapy. The NPs were obtained via self-assembly of bovine serum albumin (BSA), bis[3,4,6-trichloro2-(pentyloxycarbonyl)phenyl]oxalate (TCPO), perfluorohexane (PFH), and chlorin e6 (Ce6) (denoted as BTPC). In the H2O2-overexpressed tumor cells, the TCPO in the NPs could react with H2O2, thus releasing energy to activate photosensitizer Ce6 to generate cytotoxic singlet oxygen (1O2) to kill tumor cells in a laser irradiation-independent manner. Moreover, the O2 carried by PFH could not only reduce therapeutic resistance by alleviating tumor hypoxia but also increase 1O2 generation for enhanced chemiexcited photodynamic therapy. The remarkable cytotoxicity to various cancer cell lines and A549 tumor manifested the advantage of BTPC in alleviating hypoxic status and inhibiting tumor growth. Our results proved that BTPC appeared to be a promising therapeutic nanoplatform for cancer therapy. |
38096592 | Structural, electronic and magnetic properties of greigite Fe3S4 by GGA and GGA+U versus SCAN meta-GGA density functionals. | The performance of exchange-correlation functional of density functional theory (DFT) represented in generalized gradient approximation (GGA) and in the strongly constrained and appropriately normed (SCAN) meta-GGA scheme to study structural, electronic, and magnetic properties of greigite (Fe3S4) was investigated. The effects of inclusion of strong electron correlations represented by on-site Hubbard correction U, and nonlocality of the long-range van der Waals (vdW) interactions were also considered. Geometry optimization yielded the inverse spinel structure and lattice parameter of greigite in good agreement with experimental data. Calculated electronic structure revealed a half-metallic nature of the greigite bands for the applied functionals except for GGA, which predicts metallic behavior. Antiferromagnetic coupling of iron ions in tetrahedral and octahedral coordinations makes the overall crystal structure ferrimagnetic. In general the GGA+U and SCAN show comparable performance in prediction physical properties of greigite. Inclusion of the vdW correction does not change the character of the bands.
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38096594 | Pain catastrophizing and risk of progression to widespread pain among patients with chronic low back pain: A retrospective cohort study. | Chronic low back pain often progresses to widespread pain. Although many factors are associated with progression, their roles in contributing to chronic widespread pain (CWP) are often unclear. |
38096593 | Increased S. aureus colonization and reduced antimicrobial peptide expression in erythrodermic psoriasis. | Erythrodermic psoriasis (EP) is a severe and rare condition characterized by prominent erythema and scaling over 75 % of the body surface area. Unlike psoriasis vulgaris (PV), EP carries high risk of systemic involvement, including superficial skin infections and sepsis, particularly those caused by Staphylococcus aureus. |
38096595 | Toxicological effects induced by two carbamates on earthworms (Eisenia fetida): Acute toxicity, arrested regeneration and underlying mechanisms. | Eisenia fetida is recognised as advantageous model species in ecotoxicological and regeneration investigations. The intensive utilization of carbamate pesticides (CARs) imposes heavy residue burdens and grave hazards on edaphic environments as well as soil fauna therein. However, precise mechanisms whereby the specific CAR exerted toxic effects on earthworms remain largely elusive, notably from regenerative perspective. Herein, acute responses and regenerative toxicity of two carbamates (metolcarb, MEB and fenoxycarb, FEB) against E. fetida were dissected using biochemical, histological as well as molecular approaches following OECD guidelines at the cellular, tissue and organismal level. The acute toxicity data implied that MEB/FEB were very toxic/medium to extremely toxic, respectively in filter paper contact test and low to medium toxic/low toxic, respectively in artificial soil test. Chronic exposure to MEB and FEB at sublethal concentrations significantly mitigated the soluble protein content, protein abundance while enhanced the protein carbonylation level. Moreover, severely retarded posterior renewal of amputated earthworms was noticed in MEB and FEB treatments relative to the control group, with pronouncedly compromised morphology, dwindling segments and elevated cell apoptosis of blastema tissues, which were mediated by the rising Sox2 and decreasing TCTP levels. Taken together, these findings not only presented baseline toxicity cues for MEB and FEB exposure against earthworms, but also yielded mechanistic insights into regenerative toxicity upon CAR exposure, further contributing to the environmental risk assessment and benchmark formulation of agrochemical pollution in terrestrial ecosystem. |
38096596 | Characteristics of non-sleep related apneas in children with alternating hemiplegia of childhood. | Non-sleep related apnea (NSA) has been observed in alternating hemiplegia of childhood (AHC) but has yet to be characterized. |
38096597 | Fat embolism syndrome in Duchenne muscular dystrophy: Report on a novel case and systematic literature review. | We report a non-ambulatory 13-year-old boy with Duchenne muscular dystrophy who experienced severe acute respiratory distress syndrome and cerebral fat embolism following elective soft tissue surgery. Post-surgery radiological examination revealed bilateral femoral fractures and marked osteopenia that were believed to have caused disseminated pulmonary and cerebral fat embolism. The patient had never been on glucocorticoid treatment. Five months post-surgery, he remained in a state of minimal consciousness. A literature review was performed and eleven publications included, providing case reports of a total number of 23 patients with Duchenne muscular dystrophy with fat embolism syndrome. The most common causes were falls from the wheelchair that predominantly resulted in femoral fractures. Median age at the event was around 14 years. Seven patients succumbed to complications of fat embolism. No event was described in the context of surgery. We want to raise awareness that spontaneous unnoticed fractures may occur especially in adolescents with DMD from traumatic injury of large bones and also during elective surgery with a high risk of causing fat embolism with severe sequelae. |
38096598 | A critical analysis of newspaper accounts of violence against doctors in India. | This paper presents a critical analysis of newspaper articles (N = 60) published in a leading vernacular newspaper about violence against doctors in India. Adopting a theoretical perspective that considers 'news as a cultural practice,' a qualitative content analysis was conducted to examine how the phenomenon is framed and presented in the news, i.e., what is problematized, what causal links are drawn or hinted at, what moral stance is taken or alluded to, and what solutions are proffered and why, to arrive at a nuanced understanding of various aspects of this social phenomenon. Three overlapping key themes emerged from the analysis, namely the narrative of victimization, the changing doctor-patient relationship, and the crisis facing the 'noble profession' of medicine. It reveals how the media shapes public opinion and attitudes towards the state of the medical profession while in turn, reflecting existing opinions, attitudes, and cultural values; the analysis also reveals missing perspectives such as the voices of the patients and the public. We highlight how the findings are not merely the dominant ways in which the rise in incidents of violence against doctors is reported and is understood in society, but how media might have shaped the popular discourse around the issue and why. We reflect on what the reportage says about the state of the medical profession and its standing in society in India. |
38096599 | The stigma of smoking among women: A systematic review. | Smoking stigma has been well documented, but little is known regarding its specific features and effects on women. Notably, women face unique social, cultural, and economic challenges that may interact with smoking stigma and impact health outcomes. This review investigates the extent to which smoking women encounter and internalise stigma, while examining the various coping mechanisms they employ to manage these negative experiences. |
38096601 | Autoinhibition and activation of kinesin-1 and their involvement in amyotrophic lateral sclerosis. | Kinesin-1, composed of kinesin heavy chain and kinesin light chain, is a founding member of kinesin superfamily and transports various neuronal cargos. Kinesin-1 is one of the most abundant ATPases in the cell and thus need to be tightly regulated to avoid wastage of energy. It has been well established that kinesin-1 is regulated by the autoinhibition mechanism. This review focuses on the recent researches that have contributed to the understanding of mechanisms for the autoinhibition of kinesin-1 and its unlocking. Recent electron microscopic studies have shown an unanticipated structure of autoinhibited kinesin-1. Biochemical reconstitution have revealed detailed molecular mechanisms how the autoinhibition is unlocked. Importantly, misregulation of kinesin-1 is emerging as one of the major causes of amyotrophic lateral sclerosis. |
38096600 | The "spillover effect" of long-term care insurance in China on spouses' health and well-being. | This study examined the spillover effect of long-term care insurance (LTCI) on the health outcomes and well-being of spouses for Chinese middle and old-aged adults with expected LTC demand or actual care burdens. Using panel data from the China Health and Retirement Longitudinal Study between 2011 and 2018, we investigated the impact of the introduction of LTCI pilots across several cities on old individuals by using the difference-in-differences (DID) approach. We found a spillover effect of LTCI on the health and well-being outcomes of spouses of middle and old-aged individuals with functional limitations. It might due to the fact that LTCI could relieve economic burden by reducing out-of-pocket medical expenditures, which further affects health and well-being of spouses. The spillover effect on health and well-being was found to be stronger for male spouses and low-educated spouses. Spouses of the individuals aged below 80 years old and those live without adult children were more likely to benefit from the introduction of LTCI. Moreover, providing combination benefits seems to make spouses better off than offering direct services. Therefore, the results implied that the expansion of LTCI not only helped the care recipients themselves but could also improve the health and well-being of the spouses of functionally impaired older adults. |
38096602 | Organelle morphology and positioning orchestrate physiological and disease-associated processes. | In cells, organelles are distributed nonrandomly to regulate cells' physiological and disease-associated processes. Based on their morphology, position within the cell, and contacts with other organelles, they exert different biological functions. Endo-lysosomes are critical cell metabolism and nutrient-sensing regulators modulating cell growth and cellular adaptation in response to nutrient availability. Their spatial distribution is intimately linked to their function. In this review, we will discuss the role of endolysosomes under physiological conditions and in the context of cancer progression, with a special focus on their morphology, the molecular mechanisms determining their subcellular position, and the contacts they form with other organelles. We aim to highlight the relationship between cell architecture and cell function and its impact on maintaining organismal homeostasis. |
38096604 | Effect of low visceral fat area on long-term survival of stage I-III colorectal cancer. | The prognostic significance of a low visceral fat area (VFA) in colorectal cancer (CRC) remains unclear. The aim of this study was to evaluate the prognostic effects of a low VFA on the long-term outcomes of patients with CRC after laparoscopic surgery. |
38096603 | Oral glutamine supplementation relieves muscle loss in immobilized rats, altering p38MAPK and FOXO3a signaling pathways. | Skeletal muscle synthesizes, stores, and releases body L-glutamine (GLN). Muscle atrophy due to disabling diseases triggers the activation of proteolytic and pro-apoptotic cell signaling, thus impairing the body's capacity to manage GLN content. This situation has a poor therapeutic prognosis. |
38096605 | Psychological factors and barriers to donating and receiving milk from human milk banks: A review. | Human milk banks (HMBs), established in the early 20th century, aimed to provide safe breast milk for infants with challenges obtaining it. The spread of infections since the 1980s resulted in strict regulations and screening in HMBs, to ensure the safety of donated milk. Several social and personal factors discourage mothers from practicing breastfeeding, making donated milk a viable alternative because of its protective and immunity-enhancing properties. However, psychological barriers can affect the decision to donate or receive donated milk. To identify psychological factors related to donating and receiving human milk from HMBs, we searched PubMed to identify studies reporting psychological factors in donating and receiving milk and excluding studies not reporting psychological factors. The search identified 28 articles meeting the inclusion criteria. Eligible studies from various countries spanned from 1995 to 2023 and focused on psychological factors influencing milk donation and receiving. Most studies were descriptive-qualitative. Factors facilitating or hindering milk donation and reception included perceptions, psychological aspects, and previous experiences. Positive factors for donors included the desire to help other mothers, support from health care professionals, and personal well-being. Negative factors included breast milk exclusivity and discomfort caused by health checks. For recipients, awareness of donated milk benefits was a positive factor, whereas fear regarding safety was negative. The altruistic motivation to help other mothers drove many women to donate. Proper awareness and support from health care professionals and families can help women understand the value of milk donation and support their personal and identity reintegration, especially in cases of the loss of a child. |
38096607 | Formulation and in vitro characterization of nanoemulsions containing remdesivir or licorice extract: A potential subcutaneous injection for coronavirus treatment. | The management of coronavirus necessitates that medicines are available, reasonably priced, and easy to administer. The work aimed at formulating and characterizing remdesivir and licorice extract nanoemulsions and comparing their efficacy against coronavirus for further subcutaneous injection. First, the solubility of remdesivir was determined in different oils, surfactants, and co-surfactants to choose the optimal nanoemulsion components. Nanoemulsions were optimized concerning surfactant: co-surfactant ratio (5:1, 4:1, 3:1, 2:1, and 1:1) and oil to surfactant: co-surfactant ratio (1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, and 1:1). The formulations were evaluated concerning % transmittance, emulsification time, pH, viscosity, droplet size, polydispersity index, zeta potential, drug content, transmission electron microscopy, in-vitro drug release, stability (of the optimal formulas), and antiviral effect against coronavirus. The optimal nanoemulsion formula was F7, exhibiting an acceptable pH level, a rapid emulsification rate, a viscosity of 20 cP, and 100% drug content. The formulation droplet size was 16 and 17 nm, the polydispersity index was 0.18 and 0.26, and the zeta potential was - 6.29 and - 10.34 mV for licorice extract and remdesivir nanoemulsions, respectively. However, licorice extract nanoemulsion exhibited better release and physical stability. Licorice extract nanoemulsion may be a potential subcutaneous injection for combating mild to moderate coronavirus. |
38096606 | Corrigendum to "Long-term exposure to phenanthrene at environmental-level induces intestinal dysbiosis and disrupted hepatic lipid metabolism in mice" [Environ. Pollut. 268 (2021) 115738]. | |
38096608 | Tailoring the properties of composite scaffolds with a 3D-Printed lattice core and a bioactive hydrogel shell for tissue engineering. | The optimal performance of scaffolds for tissue engineering relies on a proper combination of their constituent biomaterials and on the design of their structure. In this work, composite scaffolds with a core-shell architecture are realized by grafting a gelatin-chitosan hydrogel onto a 3D-printed polylactic acid (PLA) core, aiming in particular at bone regeneration. This hydrogel was recently found to sustain osteogenic differentiation of mesenchymal stromal cells, leading to new bone tissue formation. Here, the integration with rigid PLA lattice structures provides improved mechanical support and finer control of strength and stiffness. The core is prepared by fused deposition modeling with the specific aim to study several lattice structures and thereby better tune the scaffold mechanical properties. In fact, the core architecture dictates the scaffold strength and stiffness, which are seen to match those of different types of bone tissue. For all lattice types, the hydrogel is found to penetrate throughout the entire core and to present highly interconnected pores for cell colonization. By varying the void volume fraction in the core it is possible to significantly change the bioactive shell content, as well as the mechanical properties, over a wide range of values. Looking for design guidelines, relationships between stiffness/strength and density are here outlined for scaffolds featuring different lattice parameters. Moreover, by acting on the core strut arrangement, scaffolds are reinforced along specific directions, as evaluated under compressive and bending loading conditions. |
38096610 | Physiochemical effects of acid exposure on bone composition and function. | Bone is primarily composed of collagen and apatite, two materials which exhibit a high sensitivity to pH dysregulation. As a result, acid exposure of bone, both clinically and in the laboratory is expected to cause compositional and mechanical changes to the tissue. Clinically, Metabolic acidosis (MA), a condition characterized by a reduced physiological pH, has been shown to have negative implications on bone health, including a decrease in bone mineral density and volume as well as increased fracture risk. The addition of bone-like apatite to ionic solutions such as phosphate buffered saline (PBS) and media has been shown to acidify the solution leading to bone acid exposure. Therefore, is it essential to understand how reduced pH physiochemically affects bone composition and in turn its mechanical properties. This study investigates the specific changes in bone due to physiochemical dissolution in acid. Excised murine bones were placed in PBS solutions at different pHs: a homeostatic pH level (pH 7.4), an acidosis equivalent (pH 7.0), and an extreme acidic solution (pH 5.5). After 5 days, the bones were removed from the solutions and characterized to determine compositional and material changes. We found that bones, without cells, were able to regulate pH via buffering, leading to a decrease in bone mineral content and an increase in collagen denaturation. Both of these compositional changes contributed to an increase in bone toughness by creating a more ductile bone surface and preventing crack propagation. Therefore, we conclude that the skeletal systems' physiochemical response to acid exposure includes multifaceted and spatially variable compositional changes that affect bone mechanics. |
38096609 | Multiscale analysis of Klf10's impact on the passive mechanical properties of murine skeletal muscle. | Skeletal muscle is a hierarchical structure composed of multiple organizational scales. A major challenge in the biomechanical evaluation of muscle relates to the difficulty in evaluating the experimental mechanical properties at the different organizational levels of the same tissue. Indeed, the ability to integrate mechanical properties evaluated at various levels will allow for improved assessment of the entire tissue, leading to a better understanding of how changes at each level evolve over time and/or impact tissue function, especially in the case of muscle diseases. Therefore, the purpose of this study was to analyze a genetically engineered mouse model (Klf10 KO: Krüppel-Like Factor 10 knockout) with known skeletal muscle defects to compare the mechanical properties with wild-type (WT) controls at the three main muscle scales: the macroscopic (whole muscle), microscopic (fiber) and submicron (myofibril) levels. Passive mechanical tests (ramp, relaxation) were performed on two types of skeletal muscle (soleus and extensor digitorum longus (EDL)). Results of the present study revealed muscle-type specific behaviors in both genotypes only at the microscopic scale. Interestingly, loss of Klf10 expression resulted in increased passive properties in the soleus but decreased passive properties in the EDL compared to WT controls. At the submicron scale, no changes were observed between WT and Klf10 KO myofibrils for either muscle; these results demonstrate that the passive property differences observed at the microscopic scale (fiber) are not caused by sarcomere intrinsic alterations but instead must originate outside the sarcomeres, likely in the collagen-based extracellular matrix. The macroscopic scale revealed similar passive mechanical properties between WT and Klf10 KO hindlimb muscles. The present study has allowed for a better understanding of the role of Klf10 on the passive mechanical properties of skeletal muscle and has provided reference data to the literature which could be used by the community for muscle multiscale modeling. |
38096611 | Influence of surface pre-reacted glass-ionomer (S-PRG) filler eluate on collagen morphology, remineralization, and ultimate tensile strength of demineralized dentin. | To evaluate the effect of ions released from surface pre-reacted glass-ionomer (S-PRG) filler on collagen morphology, remineralization, and ultimate tensile strength (UTS) of demineralized dentin. |
38096613 | Predictors of executive function among 2 years old from a Thai birth cohort. | Executive function (EF) is a critical skill for academic achievement. Research on the psychosocial and environmental predictors of EF, particularly among Southeast Asian, agricultural, and low income/rural populations, is limited. Our longitudinal study explored the influence of agricultural environmental, psychosocial, and temperamental factors on children's emerging EF. Three-hundred and nine farm worker women were recruited during the first trimester of pregnancy. We evaluated the effects of prenatal insecticide exposure and psychosocial factors on "cool" (i.e., cognitive: A-not-B task, looking version) and "hot" EF (i.e., affective, response inhibition) measures of emerging EF. Maternal urine samples were collected monthly during pregnancy, composited, and analyzed for dialkylphosphate (DAP) metabolites of organophosphate insecticides. Psychosocial factors included socioeconomic status, maternal psychological factors, and quality of mother-child behavioral interactions. Backward stepwise regressions evaluated predictors of children's EF at 12 (N = 288), 18 (N = 277) and 24 (N = 280) months of age. We observed different predictive models for cool EF, as measured by A-not-B task, vs. hot EF, as measured by response inhibition tasks. Report of housing quality as a surrogate for income was a significant predictor of emerging EF. However, these variables had opposite effects for cool vs. hot EF. More financial resources predicted better cool EF performance but poorer hot EF performance. Qualitative findings indicate that homes with fewer resources were in tribal areas where children must remain close to an adult for safety reasons. This finding suggests that challenging physical environments (e.g., an elevated bamboo home with no electricity or running water), may contribute to development of higher levels of response inhibition through parental socialization methods that emphasize compliance. Children who tended to show more arousal and excitability, and joy reactivity as young infants in the laboratory setting had better cognitive performance. In contrast, maternal emotional availability was a significant predictor of hot EF. As expected, increased maternal exposure to pesticides during pregnancy was associated with worse cognitive performance but was not associated with inhibitory control. Identifying risk factors contributing to the differential developmental pathways of cool and hot EF will inform prevention strategies to promote healthy development in this and other unstudied rural, low income Southeast Asian farming communities. |
38096612 | A comparison of fracture response in female and male lumbar spine in simulated under body blast component tests. | Underbody blasts (UBB) from mines and improvised explosive devices in military combat can cause debilitating spine injuries to vehicle mounted soldiers. Due to the exclusion of females in combat roles in prior US Department of Defense policy, UBB exposure and injury have predominantly affected male soldiers. Recent policy changes have opened many combat roles to women serving in the US Military (Carter, 2015) and have increased the need to understand the injury potential for female Warfighters. The goal of this study was to investigate the fracture response of adult female lumbar spines compared to adult male spines in UBB relevant loading to identify potential differences in either fracture mechanism or force. Results are presented for 15 simulated UBB spine compression tests using three small female (SF), five large female (LF), and seven mid-sized male (MM) post-mortem human subjects (PMHS). These PMHS groups align to 5th- and 75th-percentile female and 50th-percentile males, based on height and weight from the 2012 Anthropometric Survey of U.S. Army Personnel (Gordon et al., 2014). Both small females and large females (similar in size to the males) were included to assess the role of size and/or sex in the response. Tests were conducted at Virginia Tech on a cam-driven linear compression rig, which included a 6-axis load cell and ram accelerometer to evaluate the fracture. Fracture was visualized through high-speed x-ray video. All female and male spines exhibited similar fracture initiation at the end plates and progression through the vertebral body. The resulting severe compression and burst fractures were representative of reported theatre injuries (Freedman et al., 2014). Mean axial fracture forces were -4182 ± 940 N (SF), -6225 ± 1180 N (LF), -5459 ± 1472 N (All Females) and -7993 ± 2445 N (MM). The SF group was found to have statistically significant differences in mean fracture force compared to both LF and MM groups, while no significant difference was found between LF and MM groups, although the mean force at initial fracture was lower for the LF group. The All-Females group Fz mean was significantly different from the MM group. These data suggest that the significant difference in weight between the SF and LF groups, did have an influence on the Fz outcome, when controlling for sex. Conversely, controlling for size in the LF and MM comparison, sex did influence the mean Fz, but was not statistically significant. Groups with combined sex and size differences, however, did show significant differences in mean Fz. Further study is warranted to understand whether sex or size has a larger effect on fracture force. Mean ram displacement (spine compression) values at fracture initiation were -6.0 ± 5.3 mm (SF), -4.4 ± 0.8 mm (LF), -5.0 ± 3.0 mm (All Females), -6.2 ± 4.5 mm (MM). Spine compression did not seem to be largely influenced by either sex or size, and none of the groups was found to have significant differences in mean displacement values. |
38096614 | Effects of lakeshore landcover types and environmental factors on microplastic distribution in lakes on the Inner Mongolia Plateau, China. | Microplastic pollution in freshwater environments has received increasing attention. However, limited research on the occurrence and distribution of microplastics in plateau lakes. This study investigated the microplastic characteristics and influencing factors in lakes with different land cover types on the Inner Mongolia Plateau. Results showed that microplastic abundance ranged from 0.5 to 12.6 items/L in water and 50-325 items/kg in sediments. Microplastics in water were predominantly polypropylene (50.5%), fragments (40.5%), and 50-200 µm (66.7%). High-density (27.9%), fibrous (69.3%), and large-sized microplastics (47.7%) were retained primarily in lake sediments. The highest microplastic abundance in water was found in cropland lakes and grassland lakes, while that in sediments was in descending order of desert lakes > cropland lakes > grassland lakes > forest-grassland lakes. Differences among lake types suggest that agriculture, tourism, and atmospheric transport may be critical microplastic sources. Microplastic distribution was positively correlated with farmland and artificial surface coverage, showing that land cover types related to human activities could exacerbate microplastic pollution in lakes. Redundancy analysis showed that ammonia nitrogen and pH were the key physicochemical factors affecting microplastic distribution in lakes, indicating the potential sources of microplastics in lakes and the uniqueness of microplastic occurrence characteristics in desert saline-alkaline lakes, respectively. |
38096615 | Does muscle-type myosin have ADPase activity? | Adenosine diphosphate (ADP) is a nucleotide that is structurally very similar to ATP but lacks one of the two high-energy bonds due to hydrolysis. In muscle studies, ADP is usually considered exclusively as a product formed during myosin cross-bridge cycling and is not otherwise involved in this process. In our study, we question the widely held view of ADP as a final product formed during muscle contraction. Using biophysical and biochemical methods, we managed to show that ADP can act as a substrate for myosins in at least three types of muscles: smooth and striated adductor muscles of bivalves (Mytilidae and Pectinidae), and also vertebrate skeletal muscles. According to our data, the differences in the effect of ATP and ADP on the optical, biochemical, and structural properties of actomyosins are exclusively quantitative. We explain the previous ideas about ADP as a compound capable of inhibiting the ATPase activity of actomyosin by the ability of ATP and ADP to depolymerize the polymeric myosin when the concentration in the medium reaches more than 0.3 mM. |
38096616 | NDUFA8 is transcriptionally regulated by EP300/H3K27ac and promotes mitochondrial respiration to support proliferation and inhibit apoptosis in cervical cancer. | Cervical cancer, a common malignancy in women, poses a significant health burden worldwide. In this study, we aimed to investigate the expression, function, and potential mechanisms of NADH: ubiquinone oxidoreductase subunit A8 (NDUFA8) in cervical cancer. The Gene Expression Profiling Interactive Analysis (GEPIA) database and immunohistochemical scoring were used to analyze NDUFA8 expression in cervical cancer tissues and normal tissues. Quantitative real-time PCR and Western blot analyses were performed to assess the expression level of NDUFA8 in cervical cancer cell lines. NDUFA8 knockdown or overexpression experiments were conducted to evaluate its impact on cell proliferation and apoptosis. The mitochondrial respiratory status was analyzed by measuring cellular oxygen consumption, adenosine triphosphate (ATP) levels, and the expression levels of Mitochondrial Complex I activity, and Mitochondrial Complex IV-associated proteins Cytochrome C Oxidase Subunit 5B (COX5B) and COX6C. NDUFA8 exhibited high expression levels in cervical cancer tissues, and these levels were correlated with reduced survival rates. A significant upregulation of NDUFA8 expression was observed in cervical cancer cell lines compared to normal cells. Silencing NDUFA8 hindered cell proliferation, promoted apoptosis, and concurrently suppressed cellular mitochondrial respiration, resulting in decreased levels of available ATP. Conversely, NDUFA8 overexpression induced the opposite effects. Herein, we also found that E1A Binding Protein P300 (EP300) overexpression facilitated Histone H3 Lysine 27 (H3K27) acetylation enrichment, enhancing the activity of the NDUFA8 promoter region. NDUFA8, which is highly expressed in cervical cancer, is regulated by transcriptional control via EP300/H3K27 acetylation. By promoting mitochondrial respiration, NDUFA8 contributes to cervical cancer cell proliferation and apoptosis. These findings provide novel insights into NDUFA8 as a therapeutic target in cervical cancer. |
38096617 | Nardilysin determines hematopoietic stem cell fitness by regulating protein synthesis. | Nardilysin (NRDC) is a multifunctional protein required for maintaining homeostasis in various cellular and tissue contexts. However, its role in hematopoietic stem cells (HSCs) remains unclear. Here, through the conditional deletion of NRDC in hematopoietic cells, we demonstrate that NRDC is required for HSCs expansion in vitro and the reconstitution of hematopoiesis in vivo after transplantation. We found NRDC-deficient HSCs lose their self-renewal ability and display a preferential bias to myeloid differentiation in response to replication stress. Transcriptome data analysis revealed the upregulation of heat shock response-related genes in NRDC-deficient HSCs. Additionally, we observed increased protein synthesis in cultured NRDC-deficient HSCs. Thus, loss of NRDC may cause the inability to control protein synthesis in response to replication induced protein stress, leading to the impaired HSC self-renewal ability. This highlights a novel model of action of NRDC specifically in HSCs. |
38096618 | The role of integrin αvβ3 in biphasic calcium phosphate ceramics mediated M2 Macrophage polarization and the resultant osteoinduction. | Calcium phosphate ceramics-based biomaterials were reported to have good biocompatibility and osteoinductivity and have been widely applied for bone defect repair and regeneration. However, the mechanism of their osteoinductivity is still unclear. In our study, we established an ectopic bone formation in vivo model and an in vitro macrophage cell co-culture system with calcium phosphate ceramics to investigate the effect of biphasic calcium phosphate on osteogenesis via regulating macrophage M1/M2 polarization. Our micro-CT data suggested that biphasic calcium phosphate had significant osteoinductivity, and the fluorescence co-localization detection found increased F4/80+/integrin αvβ3+ macrophages surrounding the biphasic calcium phosphate scaffolds. Besides, our study also revealed that biphasic calcium phosphate promoted M2 polarization of macrophages via upregulating integrin αvβ3 expression compared to tricalcium phosphate, and the increased M2 macrophages could subsequently augment the osteogenic differentiation of MSCs in a TGFβ mediated manner. In conclusion, we demonstrated that macrophages subjected to biphasic calcium phosphate could polarize toward M2 phenotype via triggering integrin αvβ3 and secrete TGFβ to increase the osteogenesis of MSCs, which subsequently enhances bone regeneration. |
38096619 | Risk prediction models for postoperative delirium in elderly patients with fragility hip fracture: A systematic review and critical appraisal. | Elderly patients with fragility hip fracture continue to experience a high rate of postoperative delirium (POD), which has a significant negative impact on prognosis and imposes a huge economic burden. A number of risk prediction models have been developed to detect POD early. However, the risk of bias and clinical applicability of the models remain unclear. The aim of this study was to systematically evaluate risk prediction models for POD. |