Steady Accumulation Research Articles

Evaluation of Length and Fiber Count Determinations for Natural and Synthetic Microfibers Using the OpTest Fiber Quality Analyzer

Microfibers are small fiber particles that range from 1 µm to 5 mm in length, generated through the home laundering and daily wear of textile garments. Microfibers stemming from synthetic textiles are a global pollution problem marked by their slow biodegradation and steady environmental accumulation. Thus, the quantification and study of factors controlling their generation is of interest. The aim of the current study included exploring the use of a Fiber Quality Analyzer-360 (FQA) for examining fiber counts and lengths of microfibers derived from cotton, flax, ramie, hemp, acrylic, polyester, viscose, and polyamide, and to explore if additional preparation steps, such as sonication, would improve microfiber detection by the system. While probe sonication led to higher fiber counts for most microfiber types, average microfiber lengths were statistically similar for most samples, with only the hemp and ramie samples showing statistically shorter microfibers following sonication. FQA detection estimates for cotton, viscose, and ramie microfibers were high, at 99, 101, and 116% for viscose, flax, and cotton, respectively. In contrast, synthetic microfibers of acrylic, polyamide and polyester showed 77, 43, and 14% detection rates, respectively. The high detection rate for the cotton sample is partly due to the higher fineness value obtained from the gravimetric determination. A similar calculation using AFIS fineness showed 86% detection. These observations confirm the significance of properly suspending the samples to accurately quantify microfibers while using the FQA system. Furthermore, the reduced detection of the examined synthetic microfibers suggests the limitations of the FQA as a technique for the direct comparison of natural and synthetic microfiber counts.

Abstract A032: Performance evaluation of a new protein stabilizing blood collection tube with a novel whole blood separation device for clinical plasma proteomics

Abstract Introduction: We have developed a novel blood separation device (BCD) which separates plasma from cellular components by lateral flow and stabilizes the sample for transport to a testing laboratory. Patient blood is drawn into an anticoagulant blood collection tube (BCT) and then applied to the separation device. There is outstanding interest in the field of clinical proteomics regarding the formulation in BCTs and whether they would also additionally the plasma proteome. This is especially critical where hemoglobin may provide interference to the analyte being measured. We evaluated the performance of a newly available plasma protein stabilizing BCT in combination with the BCD and other currently available K2EDTA BCT (no stabilization). Methods: Whole blood from normal healthy donors was drawn into protein stabilizing BCT and a comparator anticoagulant BCT. At baseline, 24-, 48-, 72- and 120-hour time points, a 250 μL aliquot of whole blood from each tube was spotted on to the BCD to allow separation of the cellular components and plasma. All of the test specimens on the spotted devices were allowed to dry overnight to replicate time in transit. After drying, proteins were subjected to MALDI-TOF MS (mass spectrometry) after extraction with water and co- crystallization with sinapinic acid. Spectra were acquired in triplicate and m/z feature intensities for hemoglobin were assessed in R. Results: Visual inspection of the new protein stabilizing and K2EDTA BCTs showed the steady accumulation of hemoglobin over time in the plasma layer in the latter tubes. After spotting on the BCD and MALDI-TOF analysis, plasma from the protein- stabilizing BCT showed no significant increases in either the hemoglobin α or β subunits over the five (5) day period. This was consistent across all donors (heme α p = 0.7933, heme β p = 0.6425) and at all timepoints assessed. In the K2EDTA BCT, both the α and β hemoglobin subunits increased significantly over time and across all donors (heme α p < 0.0001, heme β p = 0.0232). The hemoglobin α subunit accumulated in the plasma component to a greater degree than did the β subunit (heme α slope = 4.863E-5, heme β slope = 1.398E-5). These data suggest that the formulation in the protein stabilizing BCT may attenuate red blood cell hemolysis to a greater degree as compared to conventional K2EDTA blood collection tubes. Additionally, the mean reproducibility for both hemoglobin subunits was lower when the protein stabilizing BCT was used than when the anticoagulant BCT was used across all donors at all time points (protein stabilizing BCT x ̅ CV = 8.5%, anticoagulant BCT x ̅ CV = 8.9%). Conclusions: The use of the newly available protein stabilizing BCT with the BCD reduces the accumulation of hemoglobin in the plasma component while improving reproducibility when compared to the currently used anticoagulant BCT. Interference by heme was significantly attenuated as measured by a sensitive MALDI-ToF assay. Citation Format: Colin McDowell, Nylev Vargas, Gary A Pestano. Performance evaluation of a new protein stabilizing blood collection tube with a novel whole blood separation device for clinical plasma proteomics [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A032.

Mechanistic Insights into the Potentiodynamic Electrosynthesis of PEDOT Thin Films at a Polarizable Liquid|Liquid Interface.

Conducting polymer (CP) thin films find widespread use, for example in bioelectronic, energy harvesting and storage, and drug delivery technology. Electrosynthesis at a polarizable liquid|liquid interface using an aqueous oxidant and organic soluble monomer provides a route to free-standing and scalable CP thin films, such as poly(3,4-ethylenedioxythiophene) (PEDOT), in a single step at ambient conditions. Here, using the potentiodynamic technique of cyclic voltammetry, interfacial electrosynthesis involving ion exchange, electron transfer, and proton adsorption charge transfer processes is shown to be mechanistically distinct from CP electropolymerization at a solid electrode|electrolyte interface. During interfacial electrosynthesis, the applied interfacial Galvani potential difference controls the interfacial concentration of the oxidant, but not the CP redox state. Nevertheless, typical CP electropolymerization electrochemical behaviors, such as steady charge accumulation with each successive cycle and the appearance of a nucleation loop, were observed. By combining (spectro)electrochemical measurements and theoretical models, this work identifies the underlying mechanistic origin of each feature on the cyclic voltammograms (CVs) due to charge accumulated from Faradaic and capacitive processes as the PEDOT thin film grows. To prevent overoxidation during interfacial electrosynthesis with a powerful cerium aqueous oxidant, scan rates in excess 25 mV·s-1 were optimal. The experimental methodology and theoretical models outlined in this article provide a broadly generic framework to understand evolving CVs during interfacial electrosynthesis using any suitable oxidant/monomer combination.

Impact factor does not predict long-term article impact across 15 journals

Academic journals are ranked using a variety of methods with the most common metric being ‘journal impact factor’. Authors who publish in journals with higher impact factors are deemed to contribute more to their discipline. However, the impact factor of a journal does not indicate how long a specific article stays in the scientific discourse, and metrics that measure the length of time articles within a journal continue to be cited are not typically used. We examined citations of 443,732 research articles [786,064 total] between 1980 and 2020 across 15 journals. We explored the range of longevity values found across different journals as well as the relationship between impact factor and longevity. We found no relationship between impact factor and longevity, indicating that immediate attention to an article is not correlated with longer-term impact. In the set of journals that we examined, articles published in some journals (e.g., Ecology, Genetics) continued to be cited at a steady rate long beyond their initial publication date. This slow but steady citation accumulation resulted in the total citations in these journals approaching those of higher impact journals (e.g., Science, Nature) within the length of a typical academic career (30–40 years).

Periodic Catatonia: A Tangled Spectra within Neuropsychiatry

Catatonia was first described by Kahlbaum in 1874. Subsequently, in 1908, Kraepelin delineated a cyclical pattern of catatonia in a group of patients with Schizophrenia. Further ahead, in 1938, Gjessing demonstrated the role of nitrogen phasic change in synchronous syntonic cases of periodic catatonia. However, Stokes et al., in 1941, demonstrated it to be a result of steady accumulation rather than a phasic change in nitrogen balance. There are no reliable prevalence figures for periodic catatonia. Prominent diagnostic manuals have not given this diagnostic entity a separate nosological status, despite evidence of a discrete metabolic profile. This case series elucidates periodic catatonia in different psychiatric disorders and how a separate diagnostic criterion could help in early detection and management. We narrate three case reports of catatonic manifestations in two young adolescents and one young adult male, with no underlying medical condition. The first case report highlights intermittent brief periods of catatonic excitement beginning with acute anxiety and followed by fainting spells. The second case report narrates an acute onset manic episode which alternates with the catatonic episode. The third case report shows seasonal advents of catatonia. The pharmacological intervention itself was adequate enough to resolve the catatonic symptoms. The three cases give a purview of catatonic manifestations with differential phenomenology. The treatment of catatonia bears challenges owing to a lack of awareness and differential response to available pharmacotherapy.

Not-so-mutually beneficial coral symbiosis

The partnership between corals and their intracellular algal symbionts has long been a textbook example of a mutually beneficial association. Here I argue that this view has been made obsolete by a steady accumulation of evidence over the past three decades. The coral-algal relationship is perhaps better viewed as one of domestication - think of it like a cattle farm, in which the coral is the farmer and the algae are the cows. I synthesize old and new evidence in support of this updated view and highlight remaining knowledge gaps, the largest of which continues to be the natural history of algal symbionts.

Unlocking mitochondrial dysfunction-associated senescence (MiDAS) with NAD+ – A Boolean model of mitochondrial dynamics and cell cycle control

The steady accumulation of senescent cells with aging creates tissue environments that aid cancer evolution. Aging cell states are highly heterogeneous. 'Deep senescent' cells rely on healthy mitochondria to fuel a strong proinflammatory secretome, including cytokines, growth and transforming signals. Yet, the physiological triggers of senescence such as reactive oxygen species (ROS) can also trigger mitochondrial dysfunction, and sufficient energy deficit to alter their secretome and cause chronic oxidative stress – a state termed Mitochondrial Dysfunction-Associated Senescence (MiDAS). Here, we offer a mechanistic hypothesis for the molecular processes leading to MiDAS, along with testable predictions. To do this we have built a Boolean regulatory network model that qualitatively captures key aspects of mitochondrial dynamics during cell cycle progression (hyper-fusion at the G1/S boundary, fission in mitosis), apoptosis (fission and dysfunction) and glucose starvation (reversible hyper-fusion), as well as MiDAS in response to SIRT3 knockdown or oxidative stress. Our model reaffirms the protective role of NAD+ and external pyruvate. We offer testable predictions about the growth factor- and glucose-dependence of MiDAS and its reversibility at different stages of reactive oxygen species (ROS)-induced senescence. Our model provides mechanistic insights into the distinct stages of DNA-damage induced senescence, the relationship between senescence and epithelial-to-mesenchymal transition in cancer and offers a foundation for building multiscale models of tissue aging.

Mountain Peatlands and Drought: Carbon Cycling in the Pyrenees Amidst Global Climate Change

AbstractThis study provides a multi‐year (2017–2022) Net Ecosystem Carbon Balance (NECB) of a Pyrenean mountainous peatland through the integration of field data, satellite imagery, and statistical modeling. Fluvial organic carbon export was measured at 30 min frequency, while gaseous (CO2 and CH4) exchanges were measured monthly using closed chambers. These measurements were combined with Sentinel‐2 derived chlorophyll index and in situ high frequency (1 hr) measurements of key environmental variables such as air temperature, photosynthetically active radiation, and water table level, to develop hourly gaseous carbon flux models (R2 = 0.69 for GPP, R2 = 0.84 for ER, R2 = 0.59 for CH4). Over the 2017–2022 period, modeled average GPP (610 ± 39 gC.m−2.year−1) and ER (641 ± 59 gC.m−2.year−1) showed that the peatland acted as a weak source of CO2 to the atmosphere, releasing 31 ± 73 gC.m−2.year−1. Considering fluvial carbon export and CH4 exchanges, the loss of carbon from the peatland increased to 55 ± 73 gC.m−2.year−1. Dissolved organic carbon constituted 8%–106% of the NECB. The estimated long‐term organic accumulation rate indicated a steady carbon accumulation rate of 16.4 gC.m−2.year−1, contrasting with the contemporary NECB, suggesting a recent shift in ecosystem functioning from a carbon sink to a source. The study underscores the role of water availability and air temperature through a drought index (DI), in shaping the NECB. The DI correlated significantly with annual carbon gaseous fluxes, except for 2022, marked by an intense drought. During this year the peatland became a large source of carbon (189 gC.m−2.year−1) to the atmosphere.

Philippine Psycholinguistics

Over the last decade, there has been a slow but steady accumulation of psycholinguistic research focusing on typologically diverse languages. In this review, we provide an overview of the psycholinguistic research on Philippine languages at the sentence level. We first discuss the grammatical features of these languages that figure prominently in existing research. We identify four linguistic domains that have received attention from language researchers and summarize the empirical terrain. We advance two claims that emerge across these different domains: ( a) The agent-first pressure plays a central role in many of the findings, and ( b) the generalization that the patient argument is the syntactically privileged argument cannot be reduced to frequency, but instead is an emergent phenomenon caused by the alignment of competing pressures toward an optimal candidate. We connect these language-specific claims to language-general theories of sentence processing.

The Cretaceous–Paleogene transition in spiny-rayed fishes: surveying “Patterson’s Gap” in the acanthomorph skeletal record

In contrast to the rich collections of articulated spiny-rayed fishes from early Late Cretaceous and Eocene Lagerstätten, similar skeletal remains are sparse in Maastrichtian–Paleocene strata. Here we coin this poorly understood span “Patterson’s Gap” and review known articulated skeletons from it, summarizing available information on their phylogenetic affinities, age, and environmental context. Roughly fifty percent of taxa in both the Maastrichtian and Paleocene come from Europe and North America, with percomorphs representing around 60% of the skeletal acanthomorph taxa in each interval. This is higher than the only pre-Maastrichtian assemblage with a reasonable sample of percomorphs, but lower than most Eocene and younger sites. Fossils from Patterson’s Gap show a steady accumulation of the principal lineages of spiny-rayed fishes. Material from Paleocene or older strata provides evidence for most of the roughly 20 major acanthomorph divisions recovered by molecular studies. Many fossils from Patterson’s Gap remain undescribed and unnamed, and almost none have been included within formal phylogenetic analyses. Revision of existing material, combined with additional fieldwork, should be a priority for future efforts seeking to clarify this murky but significant interval in the evolutionary history of a major vertebrate radiation.

CSF - injected contrast medium enhances post-traumatic spinal cord cysts. An experimental study in rats.

Spinal cord injury (SCI) is still one of the most challenging problems in neurosurgical practice. One of the major obstacles to neural regeneration following trauma is the formation of glial scarring and post-traumatic cysts which acts against proper growth of axons through the site of injury. Cerebrospinal fluid (CSF) delivery of bioactive agents into cystic cavities could represent a promising therapeutic strategy. In the present study, we investigated specifically the dynamics of intradural delivery of contrast medium and its relocation into post-traumatic cysts in an experimental model of spinal cord cryoinjury in rats. 32 male Sprague Dawley SPF rats were submitted to injury as previously described. Omnipaque-240 was injected either into the cisterna magna or at the level of the cauda equina. Subsequently, cerebral CT scan examinations were performed in order to check the CSF dynamics of the contrast medium. There was a steady accumulation of contrast medium into post-traumatic cysts as early as five minutes after injection. A dosage of 65 mg of iodine per kilogram ensured an adequate feeling of the cysts at an average of 30 minutes. Our data indicate that intraspinal injection of bioactive agents can easily reach the site of injury and fill post-traumatic cysts. This could represent an interesting potential therapeutic protocol for SCI.

Knowledge Landscape and Trend Analysis of Chinese Rural Education Research in the Perspective of Rural Revitalization

Abstract Chinese rural education research has gone through three stages of development: the period of slow exploration, the period of steady accumulation, and the period of broad development. This paper aims to clarify the knowledge landscape and trends of Chinese rural education research in the context of rural revitalization. To this end, based on the co-word analysis method, this paper collects terms, co-occurrence frequency statistics, and cluster analysis of academic literature on rural education research to give the current situation of literature based on spatial and temporal distribution and hotspot analysis of high-frequency keywords. The number of articles published in rural education research increased year by year from 2017 to 2021 with an average annual growth rate of 16.45%, and the total number of articles reached 465. Among the authors of the published articles, there are 25 core authors with three or more articles, accounting for 5.46% of the total number of all authors. From the distribution of hotspots of high-frequency keywords, the frequency of rural revitalization and rural education as the upper concept was 146 and 87 times, respectively, and the research on rural education showed a trend of diversification. Under the perspective of rural revitalization, academic literature research based on co-word analysis can clarify the policy orientation and research hotspot dynamics in the field of rural education and rural revitalization, examine the intrinsic correlation between rural revitalization and rural education, and explore the path options for promoting the development of rural education and realizing rural revitalization.

Looking similar but all different: Phylogenetic signature of Brazilian rocky outcrops and the influence of temperature variability on their phylogenetic structure

Abstract Old, climatically buffered, infertile landscapes (OCBILs) have a disjunct yet wide distribution worldwide. Old lineages, rare and geographically restricted species, generally characterise these landscapes. Although the last decade provided evidence supporting the OCBIL theory, many studies are biased towards local scales, woody plants and specific OCBILs. Therefore, broad‐scale investigations across different types of OCBILs are needed. We used 5186 flowering plant species (woody and herbaceous) distributed across 129 rocky outcrop sites in Brazil to investigate (1) the relative influence of climate on the phylogenetic diversity and structure of OCBILs; (2) their phylogenetic signature; (3) whether vegetation type influences phylogenetic diversity and structure of OCBILs after controlling for climate; and (4) the OCBILs' evolutionary median community age. We found that rocky outcrops exhibit lower than expected phylogenetic diversity and are home to plant communities composed of closely related species (i.e. phylogenetic clustering) relative to the reference species pool, primarily due to temperature seasonality. Each rocky outcrop shows a distinct phylogenetic signature, indicated by plant families with more descendant species than expected by chance. Even after controlling for climate, phylogenetic diversity and structure remain low and clustered in most rocky outcrops. The median community age estimated at the species level is lower in campos de altitude than in other rocky outcrops. Synthesis. We show that the influence of climate seasonality is pervasive in the phylogenetic diversity and structure of Brazilian rocky outcrops at different taxonomic levels. We also show that the phylogenetic signature of rocky outcrops comprises a mix of relatively old and young overrepresented plant families whose descendants contribute to their low phylogenetic diversity and phylogenetic clustering. Overall, the combination of low phylogenetic diversity, phylogenetic clustering and comparably low median community age across Brazilian rocky outcrops indicates that, on average, these OCBILs are subjected to strong environmental constraints and serve as arenas of recent diversification rather than a steady accumulation of taxa. Therefore, these findings indicate different OCBILs as hotspots for various plant lineages and species.

Impact of COVID-19 Vaccination on Women During Pregnancy and Breastfeeding.

Rapid development of anti-SARS-CoV-2 vaccinations in the late 2020s has significantly altered the trajectory in which the virus affects various patient demographics, especially the most susceptible ones. In light of ethical and conceptual safety considerations, pregnant women were initially barred from participating in clinical studies for the coronavirus disease 2019 (COVID-19) vaccination programs. However, the steady accumulation of reliable observational data from cohorts of pregnant women who received vaccinations enabled the research establishmentsto quickly address a number of open questions. Still, more than a year after vaccines were widely available, the safety concerns of expectant or nursing mothers are cited as the primary justification for refusing COVID-19 vaccination, and notably, the rate ofvaccination in the said populations isknown to beconsistently lower than those of the general populace. In light of such a scenario, we have made an attempt to garner relevant studies that evaluated the effect of COVID-19 vaccination on pregnant and lactating mothers which may prove to be supporting evidence for its wide usage among the said population.

Kin selection, kin recognition and kin discrimination in plants revisited: A claim for considering environmental and genetic variability.

Considering kin selection in the study of interacting conspecific plants broadens our vision of plant behaviour and brings arguments to explain plant-plant positive interactions. These interactions are the subject of abundant research in community ecology and the role of relatedness in interactions between individuals has become a hot topic. Indeed, the past decade has seen a steady accumulation of exciting but also controversial results regarding the behaviour of plants in the presence of genetically related neighbours, i.e., kin discrimination. In addition to the existence of some methodological and semantic aspects that should be strengthened to accurately reveal the occurrence of kin recognition or selection, we claim here that some key aspects must be considered to increase our ability to detect kin recognition and selection in plants. These aspects include intraspecific variability, the fact that plant-plant interactions are context-dependent, and the lifespan of species (particularly long-lived ones). Additionally, we note that the study of the population spatial genetic structure (SGS) could be a useful tool to identify candidate settings for the study of kin recognition and selection in plants. This article is protected by copyright. All rights reserved.

Ganymede's Radiation Cavity and Radiation Belts

AbstractWhile planetary radiation belts are all embedded within the low energy solar wind, Ganymede is in the unique situation of being surrounded by the energetic particles of Jupiter's magnetosphere. Here we study Ganymede's environment based the recent flyby of Juno, as well as through reanalysis of past measurements from the Galileo spacecraft. We find that Ganymede is surrounded by a radiation cavity with intensities that are lower compared to Jupiter. Particles are lost in the cavity due to absorption by Ganymede that is likely enhanced by scattering. In the core of the cavity we find radiation belts. Their intensities are comparable to Jupiter for ions but lower for electrons. The radiation belts form peaks in phase space density, which indicates that they cannot be produced through steady inward influx and accumulation of Jupiter particles. Other processes are needed such as local acceleration, or time dependent transport and loss processes.

Experimental and Numerical Investigation of Energy Evolution Characteristic of Granite considering the Loading Rate Effect

In order to investigate the loading rate effect of energy evolution in granite, the indoor physical simulation test of single face fast unloading-three directions and five faces stress-vertical continuous loading under different loading rates was conducted using a new true triaxial rockbursttest system. The energy accumulation-dissipation-release characteristics in the process of rock deformation and failure were revealed. Based on the three-dimensional discrete element theory and the polycrystalline modeling technique (randomly generated Voronoi mineral grains), the entire process of rockburst inoculation-occurrence-development, as well as the energy evolution characteristics under true triaxial single face unloading conditions, were studied. The test results indicate that the energy transport and conversion of rock samples under different loading rates exhibit distinct stage characteristics. It can be divided into the initial energy accumulation stage, steady energy accumulation stage, rapid energy dissipation stage, and rapid energy release stage. With a rise in loading rate, the specimen in the process of energy accumulation is accompanied by energy dissipation, more external input energy, and elastic strain energy release amount into the kinetic energy of fragments, resulting in the rockburst phenomenon. As the loading rate increases, the elastic strain energy conversion rate (Ue/U) falls, while the dissipative energy conversion rate (Ud/U) increases. The higher the elastic strain energy conversion rate and the lower the dissipative energy conversion rate, the more serious the rockburst occurs. Numerical simulation results show that the entire process of rockburst inoculation-occurrence-development is successfully simulated using the crystal scale fine model (CSFM) considering the grain mineral composition. The ejection failure process can be divided into four stages, including grains ejection, rock spalling into plates, rock shearing into fragments, and rock fragments ejection. The relationships between the peak strength, elastic strain energy of rock samples, and loading rates are obtained, which is consistent with the laboratory test results. The high rate linear growth of kinetic energy evolution between the two inflection points can provide precursor information for rockburst prediction.

Recommendations for weight management in osteoarthritis: A systematic review of clinical practice guidelines

ObjectiveWhile targeting obesity is central to osteoarthritis management, recent meta-analyses demonstrate only modest effects of weight loss on symptoms, and little on structure. The World Health Organisation recommends that effective management of obesity include prevention of weight gain, weight maintenance and weight loss. Therefore, we systematically reviewed the recommendations and approaches for management of obesity in clinical practice guidelines (CPGs) for osteoarthritis. DesignNine databases were searched (01.01.2010–15.03.2022) to identify guidelines informing the non-pharmacological management of osteoarthritis. Three reviewers appraised guidelines according to the AGREE II instrument, and independently extracted data on their characteristics. One author extracted and summarised guideline recommendations on weight management. This systematic review is registered on PROSPERO (CRD42021274195). ResultsOf the included fifteen CPGs (median AGREE II domain score 78.7%), weight loss was recommended for knee (12 of 13) and hip (10 of 11) but not hand (0 of 4) osteoarthritis. Combination approaches of diet and/or exercise were recommended for overweight or obese individuals in knee (8 of 12) and hip (4 of 10) osteoarthritis. Two guidelines specified ≥5% weight loss. One guideline specified strategies for maintenance of lost weight; none specifically recommended preventing weight gain. There was discordance between strength of recommendation for weight loss and level of evidence (3 of 15). ConclusionMost CPGs for knee and hip osteoarthritis recommend weight loss to manage obesity in osteoarthritis. As steady weight accumulation is common in adults, preventing weight gain should also be considered as it is a missed opportunity to improve outcomes in osteoarthritis.

Novel Self-Assembled Micelles With Increased Tumor Penetration and Anti-Tumor Efficiency Against Breast Cancer.

Recently, docetaxel (DTX) micelles based on retinoic acid derivative surfactants showed lower systemic toxicity and bioequivalence to polysorbate-solubilized docetaxel (Taxotere®) in a phase II clinical study. However, the poor stability of these surfactants in vitro and in vivo led to extremely harsh storage conditions with methanol, and the formed micelles were quickly disintegrated with rapid drug burst release in vivo. To further enhance the stability and accumulation in tumors of DTX micelles, a novel surfactant based on acitretin (ACMeNa) was synthesized and used to prepare DTX micelles to improve anti-tumor efficiency. Novel micelle-forming excipients were synthesized, and the micelles were prepared using the thin film hydration technique. The targeting effect in vitro, distribution in the tumor, and its mechanism were observed. Pharmacokinetics and anti-tumor effect were further investigated in rats and tumor-bearing female mice, respectively. The DTX-micelles prepared with ACMeNa (ACM-DTX) exhibited a small size (21.9 ± 0.3nm), 39% load efficiency, and excellent stability in vitro and in vivo. Long circulation time, sustained and steady accumulation, and strong penetration in the tumor were observed in vivo, contributing to a better anti-tumor effect and lower adverse effects. The micelles formed by ACMeNa showed a better balance between anti-tumor and adverse effects. It is a promising system for delivering hydrophobic molecules for cancer therapy.

Integrating Multiple Omics Identifies Phaeoacremonium rubrigenum Acting as Aquilaria sinensis Marker Fungus to Promote Agarwood Sesquiterpene Accumulation by Inducing Plant Host Phosphorylation.

ABSTRACTThe present study aimed to explore the factors that promote persistent agarwood accumulation. To this end, we first investigated the morphological changes and volatile compound distribution in five layers of “Guan Xiang” agarwood. The agarwood-normal transition layer (TL), an essential layer of persistent agarwood accumulation, showed clear metabolic differences by microscopy and GC-MS analysis. Microbiome analysis revealed that Phaeocremonium rubrigenum was the predominant biomarker fungus in the TL of “Guan Xiang” agarwood samples. Among the seven isolated fungi, P. rubrigenum exhibited a significantly heightened ability to induce the production in Aquilaria sinensis seedlings, especially for sesquiterpene. Tracing the proteome profile changes in P. rubrigenum-induced A. sinensis calli for 18 ds showed that the fungus-induced sesquiterpene biosynthesis increased mainly through the mevalonate (MVA) pathway. Specifically, the phosphorylation modification level, instead of the protein abundance of transcription factors (TFs), showed corresponding changes during sesquiterpene biosynthesis, thus indicating that induced phosphorylation is the key reason for enhanced sesquiterpene production.IMPORTANCE Agarwood is an expensive resinous portion derived from Aquilaria plants and has been widely used as medicine, incense, and perfume. The factors involved in steady agarwood accumulation remain elusive. Our current study suggests that as a TL marker fungus, P. rubrigenum could persistently promote agarwood sesquiterpene accumulation by inducing phosphorylation of the TFs-MVA network in A. sinensis. Moreover, our work provides strategies to improve agarwood industry management and sheds light on the potential molecular mechanisms of plant adaptation to native microbial conditions.