l-2-Hydroxyglutarate contributes to tumor radioresistance through regulating the hypoxia-inducible factor-1α signaling pathway.

l-2-Hydroxyglutarate (l-2-HG) has been regarded as a tumor metabolite, and it plays a crucial role in adaptation of tumor cells to hypoxic conditions. However, the role of l-2-HG in tumor radioresistance and the underlying mechanism have not yet been revealed. Here, we found that l-2-HG exhibited to have radioresistance effect on U87 human glioblastoma cells, which could reduce DNA damage and apoptosis caused by irradiation, promote cell proliferation and migration, and impair G2/M phase arrest. Mechanistically, l-2-HG upregulated the protein level of hypoxia-inducible factor-1α (HIF-1α) and the expression levels of HIF-1α downstream target genes. The knockdown of l-2-hydroxyglutarate dehydrogenase (L2HGDH) gene promoted the tumor growth and proliferation of U87 cells in nude mice by increasing HIF-1α expression level in vivo. In addition, the low expression level of L2HGDH gene was correlated with the short survival of patients with glioma or kidney cancer. In conclusion, our study revealed the role and mechanism of l-2-HG in tumor radioresistance and may provide a new perspective for overcoming tumor radioresistance and broaden our comprehension of the role of metabolites in tumor microenvironment.

Efficient removal of p-nitrophenol from water by imidazolium ionic liquids functionalized cellulose microsphere.

Removing p-nitrophenol (PNP) from water resources is crucial due to its significant threat to the environment and human health. Herein, imidazolium ionic liquids with short/long alkyl chain ([C2VIm]Br and [C8VIm]Br) modified cellulose microspheres (MCC-[C2VIm]Br and MCC-[C8VIm]Br) were synthesized by radiation method. To examine the impact of adsorbent hydrophilicity on adsorption performance, batch and column experiments were conducted for PNP adsorption. The MCC-[C2VIm]Br and MCC-[C8VIm]Br, with an equivalent molar import amount of ionic liquids, exhibited maximum adsorption capacities of 190.84 mg/g and 191.20 mg/g for PNP, respectively, and the adsorption equilibrium was reached within 30 min. Both adsorbents displayed exceptional reusability. Integrating the findings from XPS and FTIR analyses, and AgNO3 identification, the suggested adsorption mechanism posited that the adsorbents engaged with PNP through ion exchange, hydrogen bonds and π-π stacking. Remarkably, the hydrophobic MCC-[C8VIm]Br exhibited superior selectivity for PNP than the hydrophilic MCC-[C2VIm]Br, while had little effect on adsorption capacity and rate. MCC-[C8VIm]Br-2 with high grafting yield increased the adsorption capacity to 327.87 mg/g. Moreover, MCC-[C8VIm]Br-2 demonstrated efficient PNP removal from various real water samples, and column experiments illustrated its selective capture of PNP from groundwater. The promising adsorption performance indicates that MCC-[C8VIm]Br-2 holds potential for PNP removal from wastewater.

Bioinspired Suspended Sensing Membrane Array with Modulable Wedged-Conductive Channels for Crosstalk-Free and High-Resolution Detection.

High spatial-resolution detection is essential for biomedical applications and human-machine interaction. However, as the sensor array density increases, the miniaturization will lead to interference between adjacent units and deterioration in sensing performance. Here, inspired by the cochlea's sensing structure, a high-density flexible pressure sensor array featuring with suspended sensing membrane with sensitivity-enhanced customized channels is presented for crosstalk-free and high-resolution detection. By imitating the basilar membrane attached to spiral ligaments, a sensing membrane is fixed onto a high-stiffness substrate with cavities, forming a stable braced isolation to provide an excellent crosstalk-free capability (crosstalk coefficient: 47.24 dB) with high-density integration (100 units within 1 cm2). Similar to the opening of ion channels in hair cells, the wedge-type expansion of the embedded cracks introduced by stress concentration structures enables a high sensitivity (0.19 kPa-1) and a large measuring range (400 kPa). Finally, it demonstrates promising applications in distributed displays and the condition monitoring of medical-surgical intubation.

Catalyzing sustainable development: Exploring the interplay between access to clean water, sanitation, renewable energy and electricity services in shaping China's energy, economic growth, and environmental landscape.

The Sustainable Development Goals (SDGs) reflect the shift in global economic conversation toward inclusive growth. The growth can promote inclusivity and widespread sharing of its advancements by concentrating on four key dimensions. (a) Equality of opportunity, (b) sharing prosperity, (3) environmental sustainability/climate adaptation, and (4) macroeconomic stability. We used the Kao cointegration test to study how certain variables are connected over a long period. The relationship between CO2 and GDP per capita, renewable energy and tourism, improved water and sanitation, and access to power all have a positive feedback effect on each other. Based on FMOLS's findings, a 1 % increase in Inclusive growth leads to a 0.342 % (Model 1) and 0.258 % (Model 3) increase in CO2 emissions. An increase of 1 percent in energy consumption per person resulted in a rise of 1.343 % in CO2 emissions in Case 1, 0.524 % in Case 2, and 0.618 % in Case 3. Increasing the tourism sector's proportion of total exports by just one percent will reduce CO2 emissions by 0.221 % (case 1) and 0.234 % (case 3). Based on CCR findings, a 1 % improvement in inclusive growth leads to a 0.403.

Development and Application of the Novel Plant Growth Regulator Guvermectin: A Perspective.

Plant growth regulators (PGRs) play an important role in alleviating the detrimental effects of biotic and abiotic stress and improving crop yield and quality. As a novel PGR from Streptomyces registered in 2021, guvermectin (GV) has the potential to improve plant yield and defense, making its application in agriculture a subject of interest. Here, we describe the discovery process, functional activities, agricultural applications, toxicity, environmental safety, and biosynthetic mechanism of GV. This Perspective provides a guide for the development of novel PGRs from microorganisms.

Deciphering the Performance Enhancement, Cell Failure Mechanism, and Amelioration Strategy of Sodium Storage in Metal Chalcogenides-Based Andes.

Transition metal chalcogenides (TMCs) emerge as promising anode materials for sodium-ion batteries (SIBs), heralding a new era of energy storage solutions. Despite their potential, the mechanisms underlying their performance enhancement and susceptibility to failure in ether-based electrolytes remain elusive. This study delves into these aspects, employing CoS2 electrodes as a case in point to elucidate the phenomena. The investigation reveals that CoS2 undergoes a unique irreversible and progressive solid-liquid-solid phase transition from its native state to sodium polysulfides (NaPSs), and ultimately to a Cu1.8S/Co composite, accompanied by a gradual morphological transformation from microspheres to a stable 3D porous architecture. This reconstructed 3D porous structure is pivotal for its exceptional Na+ diffusion kinetics and resilience to cycling-induced stress, being the main reason for ultrastable cycling and ultrahigh rate capability. Nonetheless, the CoS2 electrode suffers from an inevitable cycle life termination due to the microshort-circuit induced by Na metal corrosion and separator degradation. Through a comparative analysis of various TMCs, a predictive framework linking electrode longevity is established to electrode potential and Gibbs free energy. Finally, the cell failure issue is significantly mitigated at a material level (graphene encapsulation) and cell level (polypropylene membrane incorporation) by alleviating the NaPSs shuttling and microshort-circuit.

Hydroxylamine supplementation accelerated the rates of cell growth, aerobic denitrification and nitrous oxide emission of Pseudomonas taiwanensis EN-F2.

Hydroxylamine can disrupt the protein translation process of most reported nitrogen-converting bacteria, and thus hinder the reproduction of bacteria and nitrogen conversion capacity. However, the effect of hydroxylamine on the denitrification ability of strain EN-F2 is unclear. In this study, the cell growth, aerobic denitrification ability, and nitrous oxide (N2O) emission by Pseudomonas taiwanensis were carefully investigated by addition of hydroxylamine at different concentrations. The results demonstrated that the rates of nitrate and nitrite reduction were enhanced by 2.51 and 2.78 mg/L/h after the addition of 8.0 and 12.0 mg/L hydroxylamine, respectively. The N2O production from nitrate and nitrite reaction systems were strongly promoted by 4.39 and 8.62 mg/L, respectively, through the simultaneous acceleration of cell growth and both of nitrite and nitrate reduction. Additionally, the enzymatic activities of nitrate reductase and nitrite reductase climbed from 0.13 and 0.01 to 0.22 and 0.04 U/mg protein when hydroxylamine concentration increased from 0 to 6.0 and 12.0 mg/L. This may be the main mechanism for controlling the observed higher denitrification rate and N2O release. Overall, hydroxylamine supplementation supported the EN-F2 strain cell growth, denitrification and N2O emission rates.

The A subunit of vacuolar H+-ATPase gene (CmVHA-A) plays opposite roles in plant growth and drought tolerance of chrysanthemum under different growing conditions.

As the most prominent proton pumps in plants, vacuolar H+-ATPases (VHAs) comprise multiple subunits that are important for physiological processes and stress tolerance in plants. However, few studies on the roles of subunit genes of VHAs in chrysanthemum have been reported to date. In this study, the gene of A subunit of V-ATPase in chrysanthemum (CmVHA-A) was cloned and identified. CmVHA-A was conserved with VHA-A proteins from other plants. Expression analysis showed that CmVHA-A was highly expressed in most tissues of chrysanthemum except for the flower bud, and was readily induced by polyethylene glycol (PEG) treatment. Functional analysis demonstrated that CmVHA-A exerted a negative influence on the growth and development of shoot and root of chrysanthemum under normal conditions. RNA-sequencing (RNA-seq) analysis revealed the possible explanations for phenotypic differences between transgenic and wild-type (WT) plants. Under drought conditions, CmVHA-A positively affected the drought tolerance of chrysanthemum by enhancing antioxidase activity and alleviating photosynthetic disruption. Overall, CmVHA-A plays opposite roles in plant growth and drought tolerance of chrysanthemums under different growing conditions.

Natural product guvermectin inhibits guanosine 5'-monophosphate synthetase and confers broad-spectrum antibacterial activity.

Bacterial diseases caused substantial yield losses worldwide, with the rise of antibiotic resistance, there is a critical need for alternative antibacterial compounds. Natural products (NPs) from microorganisms have emerged as promising candidates due to their potential as cost-effective and environmentally friendly bactericides. However, the precise mechanisms underlying the antibacterial activity of many NPs, including Guvermectin (GV), remain poorly understood. Here, we sought to explore how GV interacts with Guanosine 5'-monophosphate synthetase (GMPs), an enzyme crucial in bacterial guanine synthesis. We employed a combination of biochemical and genetic approaches, enzyme activity assays, site-directed mutagenesis, bio-layer interferometry, and molecular docking assays to assess GV's antibacterial activity and its mechanism targeting GMPs. The results showed that GV effectively inhibits GMPs, disrupting bacterial guanine synthesis. This was confirmed through drug-resistant assays and direct enzyme inhibition studies. Bio-layer interferometry assays demonstrated specific binding of GV to GMPs, with dependency on Xanthosine 5'-monophosphate. Site-directed mutagenesis identified key residues crucial for the GV-GMP interaction. This study elucidates the antibacterial mechanism of GV, highlighting its potential as a biocontrol agent in agriculture. These findings contribute to the development of novel antibacterial agents and underscore the importance of exploring natural products for agricultural disease management.

High intensity interval training vs. moderate intensity continuous training on aerobic capacity and functional capacity in patients with heart failure: a systematic review and meta-analysis.

Background: Exercise training is commonly employed as a efficacious supplementary treatment for individuals suffering from heart failure, but the optimal exercise regimen is still controversial. The objective of the review was to compare the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on the exercise capacity, cardiac function, quality of life (QoL) and heart rate among patients with heart failure with reduced ejection fraction. Methods: A systematic search was performed using the following eight databases from their inception to July 5, 2023: PubMed, Web of Science, Embase, Cochrane Library, Clinical Trials, China Knowledge Network, Wan fang Data, and the China Biology Medicine databases. The meta-analysis results were presented as mean difference (MD) and 95% confidence interval (CI). The Cochrane Risk of Bias tool was used for the included studies. The Grading of Recommendations Assessment, Development, and Evaluations was used to assess the certainty of evidence. Results: Thirteen randomized controlled trials were included in the study. The results showed that HIIT had a significant positive effect on peak oxygen uptake (MD = 1.78, 95% CI for 0.80-2.76), left ventricular ejection fraction (MD = 3.13, 95% CI for 1.25-5.02), six-minute walk test (MD = 28.13, 95% CI for 14.56-41.70), and Minnesota Living with Heart Failure Questionnaire (MD = -4.45, 95% CI for -6.25 to -2.64) compared to MICT. However, there were no statistically significant differences observed in resting heart rate and peak heart rate. Conclusions: HIIT significantly improves peak oxygen uptake, left ventricular ejection fraction, six-minute walk test, and Minnesota Living with Heart Failure Questionnaire in patients with heart failure with reduced ejection fraction. Additionally, HIIT exhibits greater effectiveness in improving peak oxygen uptake among patients with lower body mass index. Systematic Review Registration: https://www.doi.org/10.37766/inplasy2023.7.0100, identifier (INPLASY2023.7.0100).

Exploring the Role of Inulin in Targeting the Gut Microbiota: An Innovative Strategy for Alleviating Colonic Fibrosis Induced By Irradiation.

The use of radiation therapy to treat pelvic and abdominal cancers can lead to the development of either acute or chronic radiation enteropathy. Radiation-induced chronic colonic fibrosis is a common gastrointestinal disorder resulting from the above radiation therapy. In this study, we establish the efficacy of inulin supplements in safeguarding against colonic fibrosis caused by irradiation therapy. Studies have demonstrated that inulin supplements enhance the proliferation of bacteria responsible to produce short-chain fatty acids (SCFAs) and elevate the levels of SCFAs in feces. In a mouse model of chronic radiation enteropathy, the transplantation of gut microbiota and its metabolites from feces of inulin-treated mice were found to reduce colonic fibrosis in validation experiments. Administering inulin-derived metabolites from gut microbiota led to a notable decrease in the expression of genes linked to fibrosis and collagen production in mouse embryonic fibroblast cell line NIH/3T3. In the cell line, inulin-derived metabolites also suppressed the expression of genes linked to the extracellular matrix synthesis pathway. The results indicate a novel and practical approach to safeguarding against chronic radiation-induced colonic fibrosis.

Silicon eccentric shell nanoparticles fabricated by template-assisted deposition for Mie magnetic resonances enhanced light confinement.

We report a structure of silicon eccentric shell particles array, fabricated by the SiO2particles monolayer array assisted deposition of amorphous Si, for high-efficiency light confinement. The SiO2particles monolayer array is tailored to regulate its interparticle distance, followed by silicon film deposition to obtain silicon eccentric shell arrays with positive and negative off-center distancee. We studied the Mie resonances of silicon solid sphere, concentric shell, eccentric shell and observed that the eccentric shell with positive off-centeresupports superior light confinement because of the enhanced Mie magnetic resonances. Spectroscopic measurements and finite difference time domain simulations were conducted to examine the optical performance of the eccentric shell particles array. Results show that the Mie magnetic resonance wavelength can be easily regulated by the size of the inner void of the silicon shell to realize tunable enhanced light confinement. It was found silicon shell withD= 460/520 nm offered high enhanced light absorption efficiency at wavelength ofλ= 830 nm, almost beyond the bandgap of the amorphous silicon.

Review of the mechanisms involved in dissimilatory nitrate reduction to ammonium and the efficacies of these mechanisms in the environment.

Dissimilatory nitrate reduction to ammonium (DNRA) is currently of great interest because it is an important method for recovering nitrogen from wastewater and offers many advantages, over other methods. A full understanding of DNRA requires the mechanisms, pathways, and functional microorganisms involved to be identified. The roles these pathways play and the effectiveness of DNRA in the environment are not well understood. The objectives of this review are to describe our current understanding of the molecular mechanisms and pathways involved in DNRA from the substrate transfer perspective and to summarize the effects of DNRA in the environment. First, the mechanisms and pathways involved in DNRA are described in detail. Second, our understanding of DNRA by actinomycetes is reviewed and gaps in our understanding are identified. Finally, the effects of DNRA in the environment are assessed. This review will help in the development of future research into DNRA to promote the use of DNRA to treat wastewater and recover nitrogen.

Multiscale Interface Engineering of Sulfur-Doped TiO2 Anode for Ultrafast and Robust Sodium Storage.

Sodium-ion batteries (SIBs) are a promising electrochemical energy storage system; however, their practical application is hindered by the sluggish kinetics and interfacial instability of anode-active materials. Here, to circumvent these issues, we proposed the multiscale interface engineering of S-doped TiO2 electrodes with minor sulfur/carbon inlaying (S/C@sTiO2), where the electrode-electrolyte interface (SEI) and electrode-current collector interface (ECI) are tuned to improve the Na-storage performance. It is found that the S dopant greatly promotes the Na+ diffusion kinetics. Moreover, the ether electrolyte generates much less NaF in the cycled electrode, but relatively richer NaF in the SEI in comparison to fluoroethylene carbonate-contained ester electrolyte, leading to a thin (9 nm), stable, and kinetically favorable SEI film. More importantly, the minor sodium polysulfide intermediates chemically interact with the Cu current collector to form a Cu2S interface between the electrode and the Cu foil. The conductive tree root-like Cu2S ECI serves not only as active sites to boost the specific capacity but also as a 3D "second current collector" to reinforce the electrode and improve the Na+ reaction kinetics. The synergy of S-doping and optimized SEI and ECI realizes large specific capacity (464.4 mAh g-1 at 0.1 A g-1), ultrahigh rate capability (305.8 mAh g-1 at 50 A g-1), and ultrastable cycling performance (91.5% capacity retention after 3000 cycles at 5 A g-1). To the best of our knowledge, the overall SIB performances of S/C@sTiO2 are the best among all of the TiO2-based electrodes.

Glutathione Depletion-Induced Versatile Nanomedicine for Potentiating the Ferroptosis to Overcome Solid Tumor Radioresistance and Enhance Immunotherapy.

A high level of reduced glutathione is a major factor contributing to the radioresistance observed in solid tumors. To address this radioresistance associated with glutathione, a cinnamaldehyde (CA) polymer prodrug, referred to as PDPCA, is fabricated. This prodrug is created by synthesizing a pendent CA prodrug with acetal linkages in a hydrophobic block, forming a self-assembled into a core-shell nanoparticle in aqueous media. Additionally, it encapsulates all-trans retinoic acid (ATRA) for synchronous delivery, resulting in PDPCA@ATRA. The PDPCA@ATRA nanoparticles accumulate reactive oxygen species through both endogenous and exogenous pathways, enhancing ferroptosis by depleting glutathione. This approach demonstrates efficacy in overcoming tumor radioresistance in vivo and in vitro, promoting the ferroptosis, and enhancing the cytotoxic T lymphocyte (CTL) response for lung tumors to anti-PD-1 (αPD-1) immunotherapy. Furthermore, this study reveals that PDPCA@ATRA nanoparticles promote ferroptosis through the NRF2-GPX4 signaling pathway, suggesting the potential for further investigation into the combination of radiotherapy and αPD-1 immune checkpoint inhibitors in cancer treatment.

Predictive Value of Nutritional Risk for All-Cause Death and Functional Outcomes in Chinese Elderly Patients with Acute Stroke: A 3-Year Follow-Up Study.

Purpose: To explore the predictive value of nutritional risk for all-cause death and functional outcomes among elderly acute stroke patients. Patients and Methods: A total of 479 elderly acute stroke patients were enrolled in this study. The nutritional risk of patients was screened by the GNRI and NRS-2002. The primary outcome was all-cause death, and the secondary outcome was poor prognosis defined as a modified Rankin Scale (mRS) score ≥3. Results: Based on the NRS-2002, patients with nutritional risk had a higher risk of all-cause death at 3 months (adjusted OR: 3.642, 95% CI 1.046~12.689) and at 3 years (adjusted OR: 2.266, 95% CI 1.259~4.076) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 2.748, 95% CI 1.518~4.972. Based on the GNRI, compared to those without nutritional risk, patients with mild malnutrition also had a higher risk of all-cause death at 3 months (adjusted OR: 7.186, 95% CI 1.550~33.315) and at 3 years (adjusted OR: 2.255, 95% CI 1.211~4.199) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 1.947, 95% CI 1.030~3.680), so patients with moderate and severe malnutrition had a higher risk of all-cause death at 3 months (adjusted OR: 6.535, 95% CI 1.380~30.945) and at 3 years (adjusted OR: 2.498, 95% CI 1.301~4.799) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 2.213, 95% CI 1.144~4.279). Conclusion: Nutritional risk increases the risk of poor short-term and long-term outcomes in elderly patients with acute stroke. For elderly stroke patients, we should pay attention to early nutritional risk screening, and effective intervention should be provided to improve the prognosis of such patients.

NRF2 promotes radiation resistance by cooperating with TOPBP1 to activate the ATR-CHK1 signaling pathway.

Background: Radiation resistance is the main limitation of the application of radiotherapy. Ionizing radiation (IR) kills cancer cells mainly by causing DNA damage, particularly double-strand breaks (DSBs). Radioresistant cancer cells have developed the robust capability of DNA damage repair to survive IR. Nuclear factor erythroid 2-related factor 2 (NRF2) has been correlated with radiation resistance. We previously reported a novel function of NRF2 as an ATR activator in response to DSBs. However, little is known about the mechanism that how NRF2 regulates DNA damage repair and radiation resistance. Methods: The TCGA database and tissue microarray were used to analyze the correlation between NRF2 and the prognosis of lung cancer patients. The radioresistant lung cancer cells were constructed, and the role of NRF2 in radiation resistance was explored by in vivo and in vitro experiments. Immunoprecipitation, immunofluorescence and extraction of chromatin fractions were used to explore the underlying mechanisms. Results: In this study, the TCGA database and clinical lung cancer samples showed that high expression of NRF2 was associated with poor prognosis in lung cancer patients. We established radioresistant lung cancer cells expressing NRF2 at high levels, which showed increased antioxidant and DNA repair abilities. In addition, we found that NRF2 can be involved in the DNA damage response independently of its antioxidant function. Mechanistically, we demonstrated that NRF2 promoted the phosphorylation of replication protein A 32 (RPA32), and DNA topoisomerase 2-binding protein 1 (TOPBP1) was recruited to DSB sites in an NRF2-dependent manner. Conclusion: This study explored the novel role of NRF2 in promoting radiation resistance by cooperating with RPA32 and TOPBP1 to activate the ATR-CHK1 signaling pathway. In addition, the findings of this study not only provide novel insights into the molecular mechanisms underlying the radiation resistance of lung cancer cells but also validate NRF2 as a potential target for radiotherapy.

Trichoderma-derived emodin competes with ExpR and ExpI of Pectobacterium carotovorum subsp. carotovorum to biocontrol bacterial soft rot.

BACKGROUND: Quorum sensing inhibitors (QSIs) are an emerging control tool that inhibits the quorum sensing (QS) system of pathogenic bacteria. We aimed to screen for potential QSIs in the metabolites of Trichoderma and to explore their inhibitory mechanisms. RESULTS: We screened a strain of Trichoderma asperellum LN004, which demonstrated the ability to inhibit the color development of Chromobacterium subtsugae CV026, primarily attributed to the presence of emodin as its key QSI component. The quantitative polymerase chain reaction with reverse transcription results showed that after emodin treatment of Pectobacterium carotovorum subsp. carotovorum (Pcc), plant cell wall degrading enzyme-related synthetic genes were significantly downregulated, and the exogenous enzyme synthesis gene negative regulator (rsmA) was upregulated 3.5-fold. Docking simulations indicated that emodin could be a potential ligand for ExpI and ExpR proteins because it exhibited stronger competition than the natural ligands in Pcc. In addition, western blotting showed that emodin attenuated the degradation of n-acylhomoserine lactone on the ExpR protein and protected it. Different concentrations of emodin reduced the activity of pectinase, cellulase, and protease in Pcc by 20.81%-72.21%, 8.38%-52.73%, and 3.57%-47.50%. Lesion size in Chinese cabbages, carrots and cherry tomatoes following Pcc infestation was reduced by 10.02%-68.57%, 40.17%-88.56% and 11.36%-86.17%. CONCLUSION: Emodin from T. asperellum LN004 as a QSI can compete to bind both ExpI and ExpR proteins, interfering with the QS of Pcc and reducing the production of virulence factors. The first molecular mechanism reveals the ability of emodin as a QSI to competitively inhibit two QS proteins simultaneously. © 2023 Society of Chemical Industry.

Small extracellular vesicles from irradiated lung epithelial cells promote the activation of fibroblasts in pulmonary fibrosis.

BACKGROUND: Alveolar epithelial injury and dysfunction are the risk factors for radiation-induced pulmonary fibrosis (RIPF). However, it is not clear about the relationship between RIPF and the small extracellular vesicles (sEV) secreted by irradiated alveolar epithelial cells. Based on the activation of fibroblasts, this study explored the role of sEV derived from alveolar epithelial cells in RIPF and the potential mechanisms. METHODS: Transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting were used to characterize sEV. Western blotting was used to detect fibrosis-associated proteins. Cell counts and transwell assays were used to evaluate the proliferation and migration ability of fibroblasts. RT-PCR was used to observe the extracellular matrix (ECM) synthesized by fibroblasts, miRNA changes in the sEV were determined by second-generation sequencing. RESULTS: TEM, NTA, and western blotting showed the extracellular vesicles with a double-layer membrane structure of approximately 100 nm in diameter. The sEV derived from irradiated A549, HBEC3-KT, and MLE12 cells upregulated FN1 and alpha-SMA proteins expression in fibroblasts and drove the fibroblast to myofibroblast transition, and the sEV from irradiated mouse bronchoalveolar lavage fluid (BALF) affirmed the same results. In addition, the sEV derived from irradiated alveolar epithelial cells significantly increased the migration ability of fibroblasts and the expression of extracellular matrix proteins such as FN1. The results of miRNA sequencing of sEV in BALF of rats with RIPF showed that the metabolic pathway may be important for miRNA to regulate the activation of fibroblasts. CONCLUSION: The sEV derived from radiated pulmonary epithelial cells promote the activation, migration and extracellular matrix proteins expression of lung fibroblasts; miRNA in sEV may be an important molecular that affects the activation of lung fibroblasts.

Genetic diversity, population structure, and DNA fingerprinting of Ailanthus altissima var. erythrocarpa based on EST-SSR markers.

Ailanthus altissima var. erythrocarpa is an A. altissima variety with high economic, ecological and ornamental value, but there have been no reports on the development of SSR primers for it. According to the SSR primer information provided by the transcriptome of A. altissima var. erythrocarpa, 120 individuals with different redness levels were used to screen polymorphic primers. Transcriptomic analysis revealed 10,681 SSR loci, of which mononucleotide repeats were dominant (58.3%), followed by dinucleotide and trinucleotide repeats (16.6%, 15.1%) and pentanucleotide repeats (0.2%). Among 140 pairs of randomly selected primers, nineteen pairs of core primers with high polymorphism were obtained. The average number of alleles (Na), average number of effective alleles (Ne), average Shannon's diversity index (I), average observed heterozygosity (Ho), average expected heterozygosity (He), fixation index (F) and polymorphic information content (PIC) were 11.623, 4.098, 1.626, 0.516, 0.696, 0.232 and 0.671, respectively. Nineteen EST-SSR markers were used to study the genetic diversity and population structure of A. altissima var. erythrocarpa. The phylogenetic tree, PCoA, and structure analysis all divided the tested resources into two categories, clearly showing the genetic variation between individuals. The population showed high genetic diversity, mainly derived from intraspecific variation. Among nineteen pairs of primers, 4 pairs (p33, p15, p46, p92) could effectively distinguish and be used for fingerprinting of the tested materials. This study is of great significance for genetic diversity analysis and molecular-assisted breeding of A. altissima var. erythrocarpa.