Study on the causes of changes in colour during Hibiscus syriacus flowering based on transcriptome and metabolome analyses.

BACKGROUND: The flower colour of H. syriacus 'Qiansiban' transitions from fuchsia to pink-purple and finally to pale purple, thereby enhancing the ornamental value of the cultivars. However, the molecular mechanism underlying this change in flower colour in H. syriacus has not been elucidated. In this study, the transcriptomic data of H. syriacus 'Qiansiban' at five developmental stages were analysed to investigate the impact of flavonoid components on flower colour variation. Additionally, five cDNA libraries were constructed from H. syriacus 'Qiansiban' during critical blooming stages, and the transcriptomes were sequenced to investigate the molecular mechanisms underlying changes in flower colouration. RESULTS: High-performance liquid chromatography‒mass spectrometry detected five anthocyanins in H. syriacus 'Qiansiban', with malvaccin-3-O-glucoside being the predominant compound in the flowers of H. syriacus at different stages, followed by petunigenin-3-O-glucoside. The levels of these five anthocyanins exhibited gradual declines throughout the flowering process. In terms of the composition and profile of flavonoids and flavonols, a total of seven flavonoids were identified: quercetin-3-glucoside, luteolin-7-O-glucoside, Santianol-7-O-glucoside, kaempferol-O-hexosyl-C-hexarbonoside, apigenin-C-diglucoside, luteolin-3,7-diglucoside, and apigenin-7-O-rutinoside. A total of 2,702 DEGs were identified based on the selected reference genome. Based on the enrichment analysis of differentially expressed genes, we identified 9 structural genes (PAL, CHS, FLS, DRF, ANS, CHI, F3H, F3'5'H, and UFGT) and 7 transcription factors (3 MYB, 4 bHLH) associated with flavonoid biosynthesis. The qRT‒PCR results were in good agreement with the high-throughput sequencing data. CONCLUSION: This study will establish a fundamental basis for elucidating the mechanisms underlying alterations in the flower pigmentation of H. syriacus.

Effect of incubation temperature on identification of key odorants of sewage sludge using headspace GC analysis.

Currently, headspace gas chromatography-mass spectrometry is a widely used method to identify the key odorants of sludge. However, the effect of incubation temperature on the generation and emission of key odorants from sludge was still uncertain. Thus, in this paper, headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) and headspace gas chromatography-coupled ion mobility spectrometry (HS-GC-IMS) were carried out to analyze the volatiles emitted from the sludge incubated at different temperatures (30 °C, 50 °C, 60 °C, and 80 °C). The results indicated that the total volatile concentration of the sludge increased with temperatures, which affected the identified proportion of sludge key odorants to a certain extent. Differently from the aqueous solutions, the variation of volatile emission from the sludge was inconsistent with temperature changes, suggesting a multifactorial influence of incubation temperature on the identification of sludge odorants. The microbial community structure and adenosine triphosphate (ATP) metabolic activity of the sludge samples were analyzed at the initial state, 30 °C, and 80 °C. Although no significant effect of incubation temperature on the microbial community structure of the sludge, the incubation at 80 °C led to a noticeable decrease in microbial ATP metabolic activity, accompanied by a significant change in the proportion of odor-related microorganisms with low relative abundances. Changes in the composition and activity of these communities jointly contributed to the differences in odor emission from sludge at different temperatures. In summary, the incubation temperature affects the production and emission of volatiles from sludge through physicochemical and biochemical mechanisms, by which the microbial metabolism playing a crucial role. Therefore, when analyzing the key odorants of sludge, these factors should be considered.

Solid-liquid redistribution and degradation of antibiotics during hydrothermal treatment of sewage sludge: Interaction between biopolymers and antibiotics.

Waste activated sludge serves an important reservoir for antibiotics within wastewater treatment plants, and understanding the occurrence and evolution of antibiotics during sludge treatment is crucial to mitigate the potential risks of subsequent resource utilization of sludge. This study explores the degradation and transformation mechanisms of three typical antibiotics, oxytetracycline (OTC), ofloxacin (OFL), and azithromycin (AZI) during sludge hydrothermal treatment (HT), and investigates the influence of biopolymers transformation on the fate of these antibiotics. The findings indicate that HT induces a shift of antibiotics from solid-phase adsorption to liquid-phase dissolution in the initial temperature range of 25-90 °C, underscoring this phase's critical role in preparing antibiotics for subsequent degradation phases. Proteins (PN) and humic acids emerge as crucial for antibiotic binding, facilitating their redistribution within sludge. Specifically, the binding capacity sequence of biopolymers to antibiotics is as follows: OFL>OTC>AZI, highlighting that OFL-biopolymers display stronger electrostatic attraction, more available adsorption sites, and more stable binding strength. Furthermore, antibiotic degradation mainly occurs above 90 °C, with AZI being the most temperature-sensitive, degrading 92.97% at 180 °C, followed by OTC (91.26%) and OFL (52.51%). Concurrently, the degradation products of biopolymers compete for active sites to form novel amino acid-antibiotic conjugates, which inhibits the further degradation of antibiotics. These findings illuminate the effects of biopolymers evolution on intricate dynamics of antibiotics fate in sludge HT and are helpful to optimize the sludge HT process for effective antibiotics abatement.

Microstructure and Texture Evolution in Cold-Rolled and Annealed Oxygen-Free Copper Sheets.

Commercial oxygen-free copper sheets were cold-rolled with reduction rates ranging from 20% to 87% and annealed at 400, 500 and 600 °C. The microstructure and texture evolution during the cold-rolling and annealing processes were studied using optical microscopy (OM), scanning electron microscopy (SEM) and electron back-scattered diffraction (EBSD). The results show that the deformation textures of {123}<634> (S), {112}<111> (Copper) and {110}<112> (Brass) were continuously enhanced with the increase in cold-rolling reduction. The orientations along the α-oriented fiber converged towards Brass, and the orientation density of ß fiber obviously increased when the rolling reduction exceeded 60%. The recrystallization texture was significantly affected by the cold-rolling reduction. After 60% cold-rolling reduction, Copper and S texture components gradually decreased, and the {011}<511> recrystallization texture component formed with the increase in annealing temperature. After 87% cold-rolling reduction, a strong Cube texture formed, and other textures were inhibited with the increase in annealing temperature. The strong Brass and S deformation texture was conducive to the formation of a strong Cube annealing texture. The density of the annealing twin boundary decreased with the increase in annealing temperature, and more annealing twin boundaries formed in the oxygen-free copper sheets with the increase in cold-rolling reduction.

Molecular insights into effects of chemical conditioning on dissolved organic phosphorus transformation and bioavailability during sludge composting.

Phosphorus is enriched in waste activated sludge (WAS) during wastewater treatment, and organic phosphorus (OP) is a potential slow-release P fertilizer. The chemical coagulants used in sludge dewatering leave numerous residues in WAS that affect sludge composting. In this study, the effects of polyaluminum chloride (PAC) and polyferric sulfate (PFS) on the bioconversion of dissolved OP (DOP) during sludge composting were investigated. The results revealed that PFS conditioning promoted the transformation and bioavailability of DOP, whereas PAC conditioning inhibited. Results indicated that PFS conditioning enhanced the transformation of OP molecules in the thermophilic phase. Through oxidation and dehydrogenation reactions, 1-hydroxy-pentane-3,4-diol-5-phosphate and D-ribofuranose 5-phosphate with high bioactivity were generated in the PFS-conditioned compost. Enzymatic hydrolysis experiments further verified that PFS conditioning enhanced the DOP bioavailability in the compost, whereas PAC conditioning inhibited it. The study has provided molecular insights into the effects of chemical conditioning on DOP conversion during sludge composting.

Effect of surface functional groups of polystyrene micro/nano plastics on the release of NOM from flocs during the aging process.

Currently, the hidden risk of microplastics in the coagulation process has attracted much attention. However, previous studies aimed at improving the removal efficiency of microplastics and ignored the importance of interactions between microplastics and natural organic matter (NOM). This study investigated how polystyrene micro/nano particles impact the release of NOM during the aging of flocs formed by aluminum-based coagulants Al13 and AlCl3. The results elucidated that nano-particles with small particle sizes and agglomerative states are more likely to interact with coagulants. After 7 years of floc aging, the DOC content of the nano system decreased by more than 40%, while the micron system did not change significantly. During coagulation, the benzene rings in polystyrene particles form complexes with electrophilic aluminum ions through π-bonding, creating new Al-O bonds. NOM tends to adsorb at micro/nano plastic interfaces due to hydrophobic interactions and conformational entropy. In the aging process, the structure of PS-Al13 or PS-AlCl3 flocs and the functional groups on the surface of micro/nano plastics control the absorption and release of organic matter through hydrophobic, van der Waals forces, hydration, and polymer bridging. In the system with the addition of nano plastics, several DBPs such as TCAA, DCAA, TBM, DBCM and nitrosamines were reduced by more than 50%. The reaction order of different morphological structures and surface functional groups of microplastics to Al13 and AlCl3 systems is aromatic C-H > C-OH > C-O > NH2 > aromatic CC > aliphatic C-H and C-O>H-CO> NH2 >C-OH> aliphatic C-H. The results provided a new sight to explore the effect of micro/nano plastics on the release of NOM during flocs aging.

Leaching hazards of tire wear particles in hydrothermal treatment of sludge: Exploring molecular composition, transformation mechanism, and ecological effects of tire wear particle-derived compounds.

Tire wear particles (TWPs) are considered a significant contributor of microplastics (MPs) in the sludge during heavy rainfall events. Numerous studies have shown that hydrothermal treatment (HT) of sludge can accelerate the leaching of MP-derived compound into hydrothermal liquid, thus impairing the performance of subsequent anaerobic digestion and the quality of the hydrothermal liquid fertilizer. However, the leaching behavior of TWPs in the HT of sludge remains inadequately explored. This study examined the molecular composition of TWP-derived compounds and transformation pathways of representative tire-related additives under different hydrothermal temperatures using liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with mass difference analysis. The acute toxicity and phytotoxicity of TWP leachates were assessed using Vibrio qinghaiensis Q67 and rice hydroponics experiments. The results indicated that elevating the hydrothermal temperature not only amplified the leaching behavior of TWPs but also enhanced the chemical complexity of the TWP leachate. Utilizing both suspect and non-target screenings, a total of 144 compounds were identified as additives, including N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6-PDD), hexa(methoxymethyl)melamine (HMMM), dibutyl phthalate (DBP). These additives underwent various reactions, such as desaturation, acetylation, and other reactions, leading to the formation of different transformation products (TPs). Moreover, certain additives, including caprolactam and 2,2,6,6-tetramethyl-4-piperidinol, demonstrated the potential to form conjugate products with amino acids or Maillard products. Meanwhile, TWP-derived compounds showed significant acute toxicity and detrimental effects on plant growth. This study systematically investigated the environmental fate of TWPs and their derived compounds during the HT of sludge, offering novel insights into the intricate interactions between the micropollutants and dissolved organic matter (DOM) in sludge.

Atom-Modified gDNA Enhances Cleavage Activity of TtAgo Enabling Ultra-Sensitive Nucleic Acid Testing.

The DNA-guided (gDNA) Argonaute from Thermus thermophilus (TtAgo) has little potential for nucleic acid detection and gene editing due to its poor dsDNA cleavage activity at relatively low temperature. Herein, the dsDNA cleavage activity of TtAgo is enhanced by using 2'-fluorine (2'F)-modified gDNA and developes a novel nucleic acid testing strategy. This study finds that the gDNA with 2'F-nucleotides at the 3'-end (2'F-gDNA) can promote the assembly of the TtAgo-guide-target ternary complex significantly by increasing its intermolecular force to target DNA and TtAgo, thereby providing ≈40-fold activity enhancement and decreasing minimum reaction temperature from 65 to 60°C. Based on this outstanding advance, a novel nucleic acid testing strategy is proposed, termed FAST, which is performed by using the 2'F-gDNA/TtAgo for target recognition and combining it with Bst DNA polymerase for nucleic acid amplification. By integrating G-quadruplex and Thioflavin T, the FAST assay achieves one-pot real-time fluorescence analysis with ultra-sensitivity, providing a limit of detection up to 5 copies (20 µL reaction mixture) for miR-21 detection. In summary, an atom-modification-based strategy has been developed for enhancing the cleavage activity of TtAgo efficiently, thereby improving its practicability and establishing a TtAgo-based nucleic acid testing technology with ultra-sensitivity and high-specificity.

Nicotine inhalant via E-cigarette facilitates sensorimotor function recovery by upregulating neuronal BDNF-TrkB signalling in traumatic brain injury.

BACKGROUND AND PURPOSE: Traumatic brain injury (TBI) causes lifelong physical and psychological dysfunction in affected individuals. The current study investigated the effects of chronic nicotine exposure via E-cigarettes (E-cig) (vaping) on TBI-associated behavioural and biochemical changes. EXPERIMENTAL APPROACH: Adult C57/BL6J male mice were subjected to controlled cortical impact (CCI) followed by daily exposure to E-cig vapour for 6 weeks. Sensorimotor functions, locomotion, and sociability were subsequently evaluated by nesting, open field, and social approach tests, respectively. Immunoblots were conducted to examine the expression of mature brain-derived neurotrophic factor (mBDNF) and associated downstream proteins (p-Erk, p-Akt). Histological analyses were performed to evaluate neuronal survival and neuroinflammation. KEY RESULTS: Post-injury chronic nicotine exposure significantly improved nesting performance in CCI mice. Histological analysis revealed increased survival of cortical neurons in the perilesion cortex with chronic nicotine exposure. Immunoblots revealed that chronic nicotine exposure significantly up-regulated mBDNF, p-Erk and p-Akt expression in the perilesion cortex of CCI mice. Immunofluorescence microscopy indicated that elevated mBDNF and p-Akt expression were mainly localized within cortical neurons. Immunolabelling of Iba1 demonstrated that chronic nicotine exposure attenuated microglia-mediated neuroinflammation. CONCLUSIONS AND IMPLICATIONS: Post-injury chronic nicotine exposure via vaping facilitates recovery of sensorimotor function by upregulating neuroprotective mBDNF/TrkB/Akt/Erk signalling. These findings suggest potential neuroprotective properties of nicotine despite its highly addictive nature. Thus, understanding the multifaceted effects of chronic nicotine exposure on TBI-associated symptoms is crucial for paving the way for informed and properly managed therapeutic interventions.

c-Jun targets miR-451a to regulate HQ-induced inhibition of erythroid differentiation via the BATF/SETD5/ARHGEF3 axis.

Benzene, a widely used industrial chemical, has been clarified to cause hematotoxicity. Our previous study suggested that miR-451a may play a role in benzene-induced impairment of erythroid differentiation. However, the mechanism underlying remains unclear. In this study, we explored the role of miR-451a and its underlying mechanisms in hydroquinone (HQ)-induced suppression of erythroid differentiation in K562 cells. 0, 1.0, 2.5, 5.0, 10.0, and 50µM HQ treatment of K562 cells resulted in a dose-dependent inhibition of erythroid differentiation, as well as the expression of miR-451a. Bioinformatics analysis was conducted to predict potential target genes of miR-451a and dual-luciferase reporter assays confirmed that miR-451a can directly bind to the 3'-UTR regions of BATF, SETD5, and ARHGEF3 mRNAs. We further demonstrated that over-expression or down-regulation of miR-451a altered the expression of BATF, SETD5, and ARHGEF3, and also modified erythroid differentiation. In addition, BATF, SETD5, and ARHGEF3 were verified to play a role in HQ-induced inhibition of erythroid differentiation in this study. Knockdown of SETD5 and ARHGEF3 reversed HQ-induced suppression of erythroid differentiation while knockdown of BATF had the opposite effect. On the other hand, we also identified c-Jun as a potential transcriptional regulator of miR-451a. Forced expression of c-Jun increased miR-451a expression and reversed the inhibition of erythroid differentiation induced by HQ, whereas knockdown of c-Jun had the opposite effect. And the binding site of c-Jun and miR-451a was verified by dual-luciferase reporter assay. Collectively, our findings indicate that miR-451a and its downstream targets BATF, SETD5, and ARHGEF3 are involved in HQ-induced erythroid differentiation disorder, and c-Jun regulates miR-451a as a transcriptional regulator in this process.

Aspartate Transaminase-to-Albumin Ratio (ATAR), a Novel Prognostic Index, Predicts Outcomes in Patients with Small-Cell Lung Cancer.

BACKGROUND: Small cell lung cancer (SCLC) is characterized by high invasion rates, rapid progression, and poor prognoses. Thus, identifying SCLC patients at high risk of progression and death is critical to improve long-term survival. In this study, the aspartate transaminase-to-albumin ratio (ATAR) was examined as a prognostic factor for SCLC patients. METHODS: We screened 196 SCLC patients from December 2013 to September 2022 at the Sichuan Cancer Hospital. The data was collected from patients' medical information as well as from their blood results during diagnosis. Using the Youden index as a cutoff value, patients were divided into high-risk（> 0.54) and low-risk (≤ 0.54) ATAR groups. We analyzed the prognostic factors for overall survival (OS) using the Kaplan-Meier method, univariate and multivariate analyses, Cox regression, and the C-index. RESULTS: There were 109 (55.6%) smokers among the patients, and the median OS was 17.55 months. The Kaplan-Meier analysis indicated that patients with high-risk ATAR had significantly lower OS (p < 0.0001). A multivariate analysis demonstrated that elevated ATAR is an independent adverse predictor of OS (p < 0.001, HR = 1.907). Our study found that ATAR is an independent predictor of survival outcomes in SCLC, which was superior to ALB, PNI, and SII in predicting outcomes in low-risk and high-risk groups (all p < 0.05). Models combining ATAR with ALB, PNI, and SII showed more powerful prognostic value than their corresponding original models. Moreover, the prognostic indicator ATAR can significantly stratify stage I - II and III - IV SCLC patients (p ＜ 0.05). CONCLUSIONS: Peripheral blood ATAR prognostic index can be used as an independent predictor of SCLC patients before treatment.

Prognostic value of creatine kinase (CK)-MB to total-CK ratio in colorectal cancer patients after curative resection.

OBJECTIVES: This study aimed to evaluate the prognostic significance of postoperative Creatine Kinase type M and B (CK-MB) to total Creatine Kinase (CK) ratio (CK-MB/CK) in colorectal cancer (CRC) patients after radical resection. METHODS: This was a single-center retrospective cohort analysis. Subjects were stage I-III CRC patients hospitalized in Sichuan Cancer Hospital from January 2017 to May 2021. Patients were divided into abnormal group and normal group according to whether the CK-MB/CK ratio was abnormal after surgery. Through a comparative analysis of clinical data, laboratory test results, and prognosis differences between the two groups, we aimed to uncover the potential relationship between abnormal CK-MB > CK results and CRC patients. To gauge the impact of CK-MB/CK on overall survival (OS) and disease-free survival (DFS), we employed the multivariable COX regression and LASSO regression analysis. Additionally, Spearman correlation analysis, logistic regression, and receiver-operating characteristic (ROC) curve analysis were conducted to assess the predictive value of the CK-MB/CK ratio for postoperative liver metastasis. RESULTS: Cox regression analysis revealed that the CK-MB/CK ratio was a stable risk factors for OS (HR = 3.82, p < 0.001) and DFS (HR = 2.31, p < 0.001). To distinguish hepatic metastases after surgery, the ROC area under the curve of CK-MB/CK was 0.697 (p < 0.001), and the optimal cut-off value determined by the Youden index was 0.347. CONCLUSIONS: Postoperative abnormal CK-MB/CK ratio predicts worse prognosis in CRC patients after radical resection and serves as a useful biomarker for detecting postoperative liver metastasis.

Structure-function relationship and biological activity of polysaccharides from mulberry leaves: A review.

Mulberry (Latin name "Morus alba L.") is a perennial deciduous tree in the family of Moraceae, widely distributed around the world. In China, mulberry is mainly distributed in the south and the Yangtze River basin. Its leaves can be harvested 3-6 times a year, which has a great resource advantage. Mulberry leaves are regarded as the homology of medicine and food traditional Chinese medicine (TCM). Polysaccharides, as its main active ingredients, have various effects, such as antioxidant, hypoglycemic, hepatoprotective, and immunomodulatory. This review summarizes the research progress in the extraction, purification, structural characterization, and structure-function relationship of polysaccharides from mulberry leaves in the last decade, hoping to provide a reference for the subsequent development and market application of polysaccharides from mulberry leaves.

Bacillus velezensis SQR9 promotes plant growth through colonization and rhizosphere-phyllosphere bacteria interaction.

The rhizosphere and phyllosphere of plants are home to a diverse range of microorganisms that play pivotal roles in ecosystem services. Consequently, plant growth-promoting bacteria (PGPB) are extensively utilized as inoculants to enhance plant growth and boost productivity. Despite this, the interactions between the rhizosphere and phyllosphere, which are influenced by PGPB inoculation, have not been thoroughly studied to date. In this study, we inoculated Bacillus velezensis SQR9, a PGPB, into the bulk soil, rhizosphere or phyllosphere, and subsequently examined the bacterial communities in the rhizosphere and phyllosphere using amplicon sequencing. Our results revealed that PGPB inoculation increased its abundance in the corresponding compartment, and all treatments demonstrated plant growth promotion effects. Further analysis of the sequencing data indicated that the presence of PGPB exerted a more significant impact on bacterial communities in both the rhizosphere and phyllosphere than in the inoculation compartment. Notably, the PGPB stimulated similar rhizosphere-beneficial microbes regardless of the inoculation site. We, therefore, conclude that PGPB can promote plant growth both directly and indirectly through the interaction between the rhizosphere and phyllosphere, leading to the enrichment of beneficial microorganisms.

Evaluation of electromagnetic scattering characteristics of construction solid waste-A theoretical study of solid waste identification.

The surge in urban development has resulted in a substantial accumulation of construction solid waste (CSW). However, prevailing identification methods of CSW remain predominantly two-dimensional in scope and need to be more efficient. This study employs an approach, combining simulation and experimental analyses, to delve into the factors influencing the electromagnetic scattering characteristics of CSW, investigating the feasibility of employing Synthetic Aperture Radar (SAR) to recognize CSW. The findings show that the computational time of MLFMM and PO is only 3.28 % and 0.029 % of MM among different simulation methods. The results underscore the collective impact of material types, surface structures, and curvature on the scattering characteristics of CSW. The difference in average intensity between different materials can reach up to 13 dB. Exploiting these distinctions in scattering enables the precise identification of high-value waste components, such as intact bricks and steel bars, within the intricate landscape of CSW.

Asymmetrically Coordinated Mn-S1 N3 Configuration Induces Localized Electric Field-Driven Peroxymonosulfate Activation for Remarkably Efficient Generation of 1 O2.

Singlet oxygen (1 O2 ) species generated in peroxymonosulfate (PMS)-based advanced oxidation processes offer opportunities to overcome the low efficiency and secondary pollution limitations of existing AOPs, but efficient production of 1 O2 via tuning the coordination environment of metal active sites remains challenging due to insufficient understanding of their catalytic mechanisms. Herein, an asymmetrical configuration characterized by a manganese single atom coordinated is established with one S atom and three N atoms (denoted as Mn-S1 N3 ), which offer a strong local electric field to promote the cleavage of O─H and S─O bonds, serving as the crucial driver of its high 1 O2 production. Strikingly, an enhanced the local electric field caused by the dynamic inter-transformation of the Mn coordination structure (Mn-S1 N3 ↔ Mn-N3 ) can further downshift the 1 O2 production energy barrier. Mn-S1 N3 demonstrates 100% selective product 1 O2 by activation of PMS at unprecedented utilization efficiency, and efficiently oxidize electron-rich pollutants. This work provides an atomic-level understanding of the catalytic selectivity and is expected to guide the design of smart 1 O2 -AOPs catalysts for more selective and efficient decontamination applications.

Enhancing Inclusive Teaching in China: Examining the Effects of Principal Transformational Leadership, Teachers' Inclusive Role Identity, and Efficacy.

This research examined the effects of principal transformational leadership on teachers' inclusive teaching behaviour, with a particular inquiry into the mediating effects of teachers' inclusive role identity and efficacy for inclusive practice, as informed by identity theory and social cognitive theory. Structural equation modelling with bootstrapping estimation was conducted using data from 712 teachers delivering inclusive teaching in primary or secondary schools in China. The results revealed the sequentially mediating mechanisms of teachers' inclusive role identity and efficacy underlying the principal transformational leadership effects on teachers' inclusive teaching behaviour. Research implications are also discussed.

Adaptive strategies and ecological roles of phages in habitats under physicochemical stress.

Bacteriophages (phages) play a vital role in ecosystem functions by influencing the composition, genetic exchange, metabolism, and environmental adaptation of microbial communities. With recent advances in sequencing technologies and bioinformatics, our understanding of the ecology and evolution of phages in stressful environments has substantially expanded. Here, we review the impact of physicochemical environmental stress on the physiological state and community dynamics of phages, the adaptive strategies that phages employ to cope with environmental stress, and the ecological effects of phage-host interactions in stressful environments. Specifically, we highlight the contributions of phages to the adaptive evolution and functioning of microbiomes and suggest that phages and their hosts can maintain a mutualistic relationship in response to environmental stress. In addition, we discuss the ecological consequences caused by phages in stressful environments, encompassing biogeochemical cycling. Overall, this review advances an understanding of phage ecology in stressful environments, which could inform phage-based strategies to improve microbiome performance and ecosystem resilience and resistance in natural and engineering systems.

OxLDL enhances procoagulant activity of endothelial cells by TMEM16F-mediated phosphatidylserine exposure.

Oxidized low-density lipoprotein (oxLDL), a key component in atherosclerosis and hyperlipidemia, is a risk factor for atherothrombosis in dyslipidemia, yet its mechanism is poorly understood. In this study, we used oxLDL-induced human aortic endothelial cells (HAECs) and high-fat diet (HFD)-fed mice as a hyperlipidemia model. Phosphatidylserine (PS) exposure, cytosolic Ca2+, reactive oxygen species (ROS), and lipid peroxidation were measured by flow cytometer. TMEM16F expression was detected by immunofluorescence, western blot, and reverse transcription polymerase chain reaction. Procoagulant activity (PCA) was measured by coagulation time, intrinsic/extrinsic factor Xase, and thrombin generation. We found that oxLDL-induced PS exposure and the corresponding PCA of HAECs were increased significantly compared with control, which could be inhibited over 90% by lactadherin. Importantly, TMEM16F expression in oxLDL-induced HAECs was upregulated by enhanced intracellular Ca2+ concentration, ROS, and lipid peroxidation, which led to PS exposure. Meanwhile, the knockdown of TMEM16F by short hairpin RNA significantly inhibited PS exposure in oxLDL-induced HAECs. Moreover, we observed that HFD-fed mice dramatically increased the progress of thrombus formation and accompanied upregulated TMEM16F expression by thromboelastography analysis, FeCl3-induced carotid artery thrombosis model, and western blot. Collectively, these results demonstrate that TMEM16F-mediated PS exposure may contribute to prothrombotic status under hyperlipidemic conditions, which may serve as a novel therapeutic target for the prevention of thrombosis in hyperlipidemia.

DNA topoisomerase II inhibition potentiates osimertinib's therapeutic efficacy in EGFR-mutant non-small cell lung cancer models.

Development of effective strategies to manage the inevitable acquired resistance to osimertinib, a third-generation EGFR inhibitor for the treatment of EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC), is urgently needed. This study reports that DNA topoisomerase II (Topo II) inhibitors, doxorubicin and etoposide, synergistically decreased cell survival, with enhanced induction of DNA damage and apoptosis in osimertinib-resistant cells; suppressed the growth of osimertinib-resistant tumors; and delayed the emergence of osimertinib-acquired resistance. Mechanistically, osimertinib decreased Topo IIα levels in EGFRm NSCLC cells by facilitating FBXW7-mediated proteasomal degradation, resulting in induction of DNA damage; these effects were lost in osimertinib-resistant cell lines that possess elevated levels of Topo IIα. Increased Topo IIα levels were also detected in the majority of tissue samples from patients with NSCLC after relapse from EGFR tyrosine kinase inhibitor treatment. Enforced expression of an ectopic TOP2A gene in sensitive EGFRm NSCLC cells conferred resistance to osimertinib, whereas knockdown of TOP2A in osimertinib-resistant cell lines restored their susceptibility to osimertinib-induced DNA damage and apoptosis. Together, these results reveal an essential role of Topo IIα inhibition in mediating the therapeutic efficacy of osimertinib against EGFRm NSCLC, providing scientific rationale for targeting Topo II to manage acquired resistance to osimertinib.