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Various phthalic acid esters (PAEs) such as dibutyl phthalate (DBP) and butyl benzyl phthalate (BBP) co-exist with nanopollutants in aquatic environment. In this study, Daphnia magna was exposed to nano-CuO and DBP or BBP at environmental relevant concentrations for 21-days to investigate these combined toxic effects. Acute EC50 values (48 h) of nano-CuO, DBP, and BBP were 12.572 mg/L, 8.978 mg/L, and 4.785 mg/L, respectively. Results showed that co-exposure with nano-CuO (500 μg/L) for 21 days significantly enhanced the toxicity of DBP (100 μg/L) and BBP (100 μg/L) to Daphnia magna by 18.37% and 18.11%, respectively. The activities of superoxide dismutase, catalase, and glutathione S-transferase were enhanced by 10.95% and 14.07%, 25.63% and 25.91%, and 39.93% and 35.01% in nano-CuO+DBP and nano-CuO+BBP treatments as compared to the individual exposure groups, verifying that antioxidative defense responses were activated. Furthermore, the co-exposure of nano-CuO and PAEs decreased the population richness and diversity microbiota, and changed the microbial community composition in Daphnia magna. Metabolomic analysis elucidated that nano-CuO + PAEs exposure induced stronger disturbance on metabolic network and molecular function, including amino acid, nucleotides, and lipid metabolism-related metabolic pathways, as comparison to PAEs single exposure treatments. In summary, the integration of physiological, microflora, and untargeted metabolomics analysis offers a fresh perspective into the potential ecological risk associated with nanopollutants and phthalate pollution in aquatic ecosystems.

Interleukin (IL)-17A, a pro-inflammatory cytokine, is a fundamental function in the onset and advancement of multiple immune diseases. To uncover the primary compounds with IL-17A inhibitory activity, a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions. Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus, Myrothecium gramineum, showed remarkable IL-17A inhibitory activity. Nine new aureane-type sesquiterpene tetraketides, myrogramins A–I (1, 4–11), and two known ones (2 and 3) were isolated and identified from the strain. Compounds 1, 3, 4, 10, and 11 exhibited significant IL-17A inhibitory activity. Among them, compound 3, with a high fermentation yield dose-dependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions. Strikingly, compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension. Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity, and hold great promise applications in treating IL-17A-mediated immune diseases.

Theanine, polyphenols, and caffeine not only affect the flavor of tea, but also play an important role in human health benefits. However, the specific regulatory mechanism of Se NMs on fat-reducing components is still unclear. In this study, the synthesis of fat-reducing components in Fuding Dabai (FDDB) tea was investigated. The results indicated that the 100-bud weight, theanine, EGCG, total catechin, and caffeine contents of tea buds were optimally promoted by 10 mg·L−1 Se NMs in the range of 24.3%, 36.2%, 53.9%, 67.1%, and 30.9%, respectively. Mechanically, Se NMs promoted photosynthesis in tea plants, increased the soluble sugar content in tea leaves (30.3%), and provided energy for the metabolic processes, including the TCA cycle, pyruvate metabolism, amino acid metabolism, and the glutamine/glutamic acid cycle, ultimately increasing the content of amino acids and antioxidant substances (catechins) in tea buds; the relative expressions of key genes for catechin synthesis, CsPAL, CsC4H, CsCHI, CsDFR, CsANS, CsANR, CsLAR, and UGGT, were significantly upregulated by 45.1–619.1%. The expressions of theanine synthesis genes CsTs, CsGs, and CsGOGAT were upregulated by 138.8–693.7%. Moreover, Se NMs promoted more sucrose transfer to the roots, with the upregulations of CsSUT1, CsSUT2, CsSUT3, and CsSWEET1a by 125.8–560.5%. Correspondingly, Se NMs enriched the beneficial rhizosphere microbiota (Roseiarcus, Acidothermus, Acidibacter, Conexicter, and Pedosphaeraceae), enhancing the absorption and utilization of ammonium nitrogen by tea plants, contributing to the accumulation of theanine. This study provides compelling evidence supporting the application of Se NMs in promoting the lipid-reducing components of tea by enhancing its nitrogen metabolism.

To understand the occurrence state of fracturing fluid in shale gas matrix-fracture system, an experimental method for evaluating fracturing fluid flow characteristics in matrix-fracture system was established. By using Nuclear Magnetic Resonance method, the flow characteristics of fracturing fluid were investigated from three processes of filtration, well shut-in and flowback. The T2 spectrum of fracturing fluid flow process and fracturing fluid saturation in matrix-fracture core model were clarified. The results demonstrate that the peak area of T2 spectra increases gradually during the filtration process, and the fracturing fluid quickly fills the fractures and matrix pores. During the well shut-in process, the fracturing fluid gradually flows from the fracture space to the matrix pores, and the signal of the matrix pores increases by 50.5%. During the flowback process, fracturing fluid flows out of the matrix and fracture. And when it reaches a stable state, the peak signal in the fracture decreases by 64.5% and the matrix signal reduces by 18.8%. The better the porosity and permeability characteristics of the core, the more likely the fracturing fluid is to stay in the formation and cannot be discharged. This paper would contribute to basic parameters for shale gas fracturing design and production strategy optimization.

Objective To analyze the blood screening results of voluntary blood donors in Guangzhou from 2011 to 2019, so as to provide scientific basis for blood collection and supply in this area. Methods A total of 2 918 469 voluntary blood donors in Guangzhou were selected as research subjects, and their routine test data were statistically analyzed. Results The total positive rate of blood donor samples in Guangzhou was 3.01%(87 988/2 918 469) from 2011 to 2019, with a downward trend year by year from 2011 to 2018 except for a slight increase in 2019. The difference of total positive rate in each year was statistically significant (P

Abstract Bubbles in subsurface porous media spontaneously coarsen to reduce free energy. Bubble coarsening dramatically changes surface area and pore occupancy, which affect the hydraulic conductivity, mass and heat transfer coefficients, and chemical reactions. Coarsening kinetics in porous media is thus critical in modeling geologic CO2 sequestration, hydrogen subsurface storage, hydrate reservoir recovery, and other relevant geophysical problems. We show that bubble coarsening kinetics in porous media fundamentally deviates from classical Lifshitz‐Slyozov‐Wagner theory, because porous structure quantizes the space and rescales the mass transfer coefficient. We develop a new coarsening theory that agrees well with numerical simulations. We identify a pseudo‐equilibrium time proportional to the cubic of pore size. In a typical CO2 sequestration scenario, local equilibrium can be achieved in 1s for media consisting of sub‐micron pores, while in decades for media consisting of 1 mm pores. This work provides new insights in modeling complex fluid behaviors in subsurface environment.

Given the rapid development of nanotechnology, it is crucial to understand the effects of nanoparticles on living organisms. However, it is laborious to perform toxicological tests on a case-by-case basis. Quantitative structure–activity relationship (QSAR) is an effective computational technique because it saves time, costs, and animal sacrifice. Therefore, this review presents general procedures for the construction and application of nano-QSAR models of metal-based and metal-oxide nanoparticles (MBNPs and MONPs). We also provide an overview of available databases and common algorithms. The molecular descriptors and their roles in the toxicological interpretation of MBNPs and MONPs are systematically reviewed and the future of nano-QSAR is discussed. Finally, we address the growing demand for novel nano-specific descriptors, new computational strategies to address the data shortage, in situ data for regulatory concerns, a better understanding of the physicochemical properties of NPs with bioactivity, and, most importantly, the design of nano-QSAR for real-life environmental predictions rather than laboratory simulations.

Abstract Background Intercostal artery pseudoaneurysm is rare and at the risk of rupture. The aetiology is always reported to be iatrogenic and traumatic injury. Embolisation is the most common therapeutic method. Here, we report a case of spontaneous intercostal artery pseudoaneurysm and cured by combining covered stent grafting and surgical management. Case presentation A 60-year-old man complained of acute right back pain for 5 h. Computed tomography showed right massive hemothorax and a giant mass with distinct feeding vessel originated from the thoracic aorta within the right hemithorax. Thoracocentesis was performed, and then a covered stent was positioned across the origin of the feeding vessel. The patient was diagnosed with intercostal artery pseudoaneurysm. Finally, we successfully resected the pseudoaneurysm and ligated the proximal part of the artery. Histologic examination have proved the diagnosis. The postoperative course was uneventful, and the patient was discharged on postoperative day 10. There is no recurrence reported during follow-up. Conclusions Spontaneous intercostal artery pseudoaneurysm is extremly rare. Delayed hemothorax due to rupture of the pseudoaneurysm may occur years after the formation. Early diagnosis is important and a combined treatment of endovascular intervention and surgical management is feasible, especially for the case of ruptured large tumour-like mass presentation of the pseudoaneurysm.

Strategies to reduce the risk of drought damage are urgently needed as intensified climate change threatens agricultural production. One potential strategy was using nanomaterials (NMs) to enhance plant resistance by regulating various physiological and biochemical processes. In the present study, 10 mg kg−1 manganese ferrite (MnFe2O4) NMs had the optimal enhancement to elevate the levels of biomass, photosynthesis, nutrient elements, and polysaccharide in rice by 10.9–525.0%, respectively, under drought stress. The MnFe2O4 NMs were internalized by rice plants, which provided the possibility for rice to better cope with drought. Furthermore, as compared with drought control and equivalent ion control, the introduction of MnFe2O4 NMs into the roots significantly upregulated the drought-sensing gene CLE25 (29.4%) and the receptor gene NCED3 (59.9%). This activation stimulated downstream abscisic acid, proline, malondialdehyde, and wax biosynthesis by 23.3%, 38.9%, 7.2%, and 26.2%, respectively. In addition, 10 mg·kg−1 MnFe2O4 NMs significantly upregulated the relative expressions of OR1, AUX2, AUX3, PIN1a, and PIN2, and increased IAA content significantly, resulting in an enlarged root angle and a deeper and denser root to help the plant withstand drought stresses. The nutritional quality of rice grains was also improved. Our study provides crucial insight for developing nano-enabled strategies to improve crop productivity and resilience to climate change.

The direct uptake of extracellular DNA (eDNA) via transformation facilitates the dissemination of antibiotic resistance genes (ARGs) in the environment. CeO2 nanoparticles (NPs) have potential in the regulation of conjugation-dominated ARGs propagation, whereas their effects on ARGs transformation remain largely unknown. Here, CeO2 NPs at concentrations lower than 50 mg L−1 have been applied to regulate the transformation of plasmid-borne ARGs to competent Escherichia coli (E. coli) cells. Three types of exposure systems were established to optimize the regulation efficiency. Pre-incubation of competent E. coli cells with CeO2 NPs at 0.5 mg L−1 inhibited the transformation (35.4%) by reducing the ROS content (0.9-fold) and cell membrane permeability (0.9-fold), thereby down-regulating the expression of genes related to DNA uptake and processing (bhsA, ybaV, and nfsB, 0.7–0.8 folds). Importantly, CeO2 NPs exhibited an excellent binding capacity with the plasmids, decreasing the amounts of plasmids available for cellular uptake and down-regulating the gene expression of DNA uptake (bhsA, ybaV, and recJ, 0.6–0.7 folds). Altogether, pre-exposure of plasmids with CeO2 NPs (10 and 25 mg L−1) suppressed the transformation with an efficiency of 44.5–51.6%. This study provides a nano-strategy for controlling the transformation of ARGs, improving our understanding on the mechanisms of nanomaterial-mediated ARGs propagation.

Organic carbonates (OCs) are a class of compounds featured by a carbonyl flanked by two alkoxy/aryloxy groups. They exist in either linear or cyclic forms, of which the majority encountered in nature adopt a pentacyclic structure. However, the enzymatic basis for pentacyclic carbonate ring formation remains elusive. Here, we reported that a four-protein metabolon (AlmUII–UV) assembled by a small peptide protein (AlmUV) appends a reactive N-hydroxylcarbamoyl moiety to the decarboxylated aldgamycins followed by a non-enzymatic condensation to give the pentacyclic carbonate ring. Our results have documented an unprecedent mechanism for carbonate formation.

Objective: To investigate the role of the periotic mesenchyme (POM) in the development of sensory cells of developing auditory epithelium. Methods: Developing auditory epithelium with or without periotic mesenchyme was isolated from mice at embryonic days 11.5 (E11.5), E12.5 and E13.5, respectively, and cultured in vitro to an equivalent of E18.5’s epithelium in vivo. Then, the explants were co-stained with antibodies targeting myosin VIIA, Sox2 and BrdU. Results: More hair cells in E11.5 + 7 DIV, E12.5 + 6 DIV and E13.5 + 5 DIV auditory epithelia were found upon culture with POM (225.90 ± 62.44, 476.94 ± 100.81, and 1386.60 ± 202.38, respectively) compared with the non-POM group (68.17 ± 23.74, 205.00 ± 44.23, and 1266.80 ± 38.84, respectively). Moreover, regardless of developmental stage, the mesenchymal tissue increased the amount of cochlear sensory cells as well as the ratio of differentiated hair cells to total sensory cells. Conclusions: The periotic mesenchyme promotes the development of cochlear sensory cells, and its effect depends on the developmental stage of the auditory epithelium.

Cingulin, a cytoplasmic element of tight junctions (TJs), is involved in maintenance of the integrity of epithelial and endothelial cells. However, the role of cingulin in the development of auditory organs remains unclear. Zebrafish is popular as a model organism for hearing research. Using the whole mount in situ hybridization (WISH) experiment, we detected the expression of cingulin b in the posterior lateral line system (PLLs) of zebrafish. We traced the early development progress of zebrafish PLLs from 36 hpf to 72 hpf, and found that inhibition of cingulin b by target morpholinos resulted in severe developmental obstruction, including decreased number of neuromasts, reduced proliferative cells in the primordium, and repressed hair cell differentiation in the neuromasts. To examine the potential mechanism of cingulin b in the development of zebrafish PLL neuromasts, we performed RNA-seq analysis to compare the differently expressed genes (DEGs) between cingulin b knockdown samples and the controls. The KEGG enrichment analysis revealed that MAPK signaling pathway and cellular senescence were the key pathways with most DEGs in cingulin b-MO morphants compared to the Control-MO embryos. Furthermore, quantitative RT-PCR analysis confirmed the findings by RNA-seq that the transcript levels of cell cycle negative regulators such as tp53 and cdkn1a, were remarkably upregulated after inhibition of cingulin b. Our results therefore indicated an important role of cingulin b in the development of auditory organs, and MAPK signaling pathway was inhibited while cellular senescence pathway was activated after downregulation of cingulin b. We bring forward new insights of cingulin by exploring its function in auditory system.

Kif15, a kinesin family member, is powerful in the formation of bipolar spindles. There is emerging evidence indicating that Kif15 plays vital roles in influencing the growth of axons and interference with the progression of the tumor. However, the function of Kif15 in the auditory organs remains unknown. The Western blotting test was used to examine the effect of Kif15 downregulation by specific morpholino targeting Kif15 (Kif15-MO). The development of the inner ear and posterior lateral line (PLL) system in zebrafish was under continuous observation from spawns to 96 h postfertilization (hpf) to investigate the potential role of Kif15 in the auditory and vestibular system. We uncovered that Kif15 inhibition induced otic organ deformities in zebrafish, including malformed semicircular canals, abnormal number and location of otoliths, and reduced number of hair cells (HCs) both in utricle and saccule. Furthermore, a remarkable reduction in the number of PLL neuromasts was also explored in Kif15-MO morphants compared to the normal larvae. We also detected notably reduced activity in locomotion after Kif15 was knocked down. Additionally, we performed rescue experiments with co-injection of Kif15 mRNA and found that the Kif15 splicing MO-induced deformities in otic vesicle and PLL of zebrafish were successfully rescued, and the severely reduced locomotor activity caused by Kif15-MO was partially rescued compared to the control-MO (Con-MO) embryos. Our findings uncover that Kif15 is essential in the early development of auditory and vestibular organs using zebrafish as models.

Various long non-coding RNAs (lncRNAs) are closely associated with lung adenocarcinoma (LUAD), playing oncogenic or anti-oncogenic roles in tumorigenesis and progression. Herein, we report a novel lncRNA—long intergenic non-protein coding RNA 1426 (LINC01426)—that has not yet been characterized in LUAD. We note that LINC01426 expression was markedly upregulated in LUAD tissues, and that functional assays verified that LINC01426 knockdown markedly inhibited cell proliferation, migration, and invasion in vitro. Xenografts derived from A549 cells knocked down of LINC01426 had evidently lower tumor weights and smaller tumor volumes. Our study also found that LINC01426 bound to hsa-miR-30b-3p as a competitive endogenous RNA in LUAD. Moreover, LINC01426 affected LUAD wound healing by interacting and combining with AZGP1, and LINC01426 expression was significantly associated with tumor-node-metastasis (TNM) staging and prognosis in patients with LUAD. To summarize, our study elucidates the oncogenic roles of LINC01426 in LUAD tumorigenesis and progression. We think that LINC01426 can serve as a potential diagnostic biomarker and therapeutic target in patients with LUAD.

This work reported a facile route for fabricating super-hydrophobic concrete via sizing sand grains. It was found that mixing the sands with a size ranging from 150–180 μ m into cement enabled the formation of a lotus-like surface with a papillary structure at micro-scale. SEM showed that the size of bumper was about 3 μ m. When spraying a fluorocarbon solution onto this surface, the porous nature of the cement matrix showed the advantage of taking the fluorocarbon into the internal structure of the concrete via capillary force. As a result, the sub surface up to a depth of ∼1.5 mm were transformed into a thick superhydrophobic layer directly. The contact angle (CA) of water droplets could reach 157° on this surface, and which could remain more than 150° after abrasion 100 cycles under a weight of 300 g at 360 grit sandpaper. This thick hydrophobic layer significantly reduced the corrosion rate of the steel the concrete at the Cl ^- environment by 620 times. The measurement of British pendulum number and compression strength revealed that this superhydrophobic layer was beneficial for maintaining the friction coefficient of the concrete surface in wet condition without altering the mechanical integrity of the concrete.

Objectives: This study aimed to assess the effect of hearing and speech rehabilitation in patients with Nurotron® cochlear implants. Design: Ninety-eight paediatric patients with bilateral severe-to-profound sensorineural deafness who received cochlear implantation were divided into three groups according to age: group A (≤3 years), group B (4–7 years), and group C (8–16 years). All patients were followed up for one year for hearing and speech performance after the surgery. The comprehensive Auditory Perception Assessment, MAIS, CAP and SIR hearing and speech assessments and rating materials were used for assessment before the surgery and at 3, 6, and 12 months after implant activation. Results: The scores of patients in the open-set speech assessment, Chinese Auditory Perception Assessment, MAIS, CAP and SIR significantly improved after cochlear implantation in all age groups. The younger the age at implantation, the better the results. Moreover, the hearing and speech performance of cochlear implant recipients gradually improved with the extension of rehabilitation time. Conclusions: Nurotron® Venus™ cochlear implantation can improve the hearing and speech performance of patients with bilateral severe-to-profound sensorineural deafness. Keywords: Hearing loss, Sensorineural, Cochlear implant, Rehabilitation, Speech perception, Assessment

Flavonoids contribute to fruit sensorial and nutritional quality. They are also highly beneficial for human health and can effectively prevent several chronic diseases. There is increasing interest in developing alternative food sources rich in flavonoids, and nano-enabled agriculture provides the prospect for solving this action. In this study, triiron tetrairon phosphate (Fe7(PO4)6) nanomaterials (NMs) were synthesized and amended in soils to enhance flavonoids accumulation in tomato fruits. 50 mg kg−1 of Fe7(PO4)6 NMs was the optimal dose based on its outstanding performance on promoting tomato fruit flavonoids accumulation. After entering tomato roots, Fe7(PO4)6 NMs promoted auxin (IAA) level by 70.75 and 164.21% over Fe-EDTA and control, and then up-regulated the expression of genes related to PM H+ ATPase, leading to root proton ef-flux at 5.87 pmol cm−2 s−1 and rhizosphere acidification. More Mg, Fe, and Mn were thus taken up into plants. Subsequently, photosynthate was synthesized, and transported into fruits more rapidly to increase flavonoid synthesis potential. The metabolomic and transcriptomic profile in fruits further revealed that Fe7(PO4)6 NMs regulated sucrose metabolism, shi-kimic acid pathway, phenylalanine synthesis, and finally enhanced flavonoid biosynthesis. This study implies the potential of NMs to improve fruit quality by enhancing flavonoids synthesis and accumulation.

Acetylation tubulin is one of the major post-translational modifications of microtubules. Stable microtubules are well known to contain acetylated tubulin. Here, we examined the spatiotemporal expression of acetylated tubulin in the mouse cochlea during postnatal development. At postnatal day 1 (P1), acetylated tubulin was localized primarily to the auditory nerve inside the cochlea and their synaptic contacts with the inner and outer hair cells (IHCs and OHCs). In the organ of Corti, acetylated tubulin occurred first at the apex of pillar cells. At P5, acetylated tubulin first appeared in the phalangeal processes of Deiters’ cells. At P8, staining was maintained in the phalangeal processes of Deiters’ cells. At P10, labeling in Deiters’ cells extended from the apices of OHCs to the basilar membrane. Labeling was expressed throughout the cytoplasm of pillar cells. At P12, acetylated tubulin displayed prominent and homogeneous labeling along the full length of the pillar cells. Linear labeling was present mainly in the Deiters’ cell bodies underlying OHCs. Between P14 and P17, acetylated tubulin was strongly expressed in inner and outer pillar cells and Deiters’ cells in a similar pattern as observed in the adult, and labeling in these cells were arranged in bundles. In addition, acetylated tubulin was intensely expressed in stria vascularis, root cell bodies, and a small number of fibrocytes of the spiral ligament until the adult. In the adult mouse cochlea, immunostaining continued to predominate in Deiters’ cells and pillar cells. Immunolabeling formed cups securing OHCs basal portions, and continued presence of acetylated tubulin-labeled nerve terminals below IHCs was shown. Our results presented here underscored the essential role played by acetylated tubulin in postnatal cochlear development, auditory neurotransmission and cochlear mechanics.

Dihydrochalcomycin (1) and chalcomycin, (2), two known chalcomycins, and chalcomycin E (3), a new compound, were isolated from marine-derived Streptomyces sp. HK-2006-1. Their structures were elucidated by detailed spectroscopic and X-ray crystallographic analysis. The antimicrobial activities against Staphylococcus aureus, Escherichia coli, Candida albicans, and Aspergillus niger of 1–3 were evaluated. Compounds 1–2 exhibited activities against S. aureus with minimal inhibitory concentrations (MICs) of 32 µg/mL and 4 µg/mL, respectively. The fact that 1–2 showed stronger activity against S. aureus 209P than 3 indicated that the epoxy unit was important for antimicrobial activity. This structure–activity tendency of chalcomycins against S. aureus is different from that of aldgamycins reported in our previous research, which provide a valuable example for the phenomenon that 16-membered macrolides with different sugars do not have parallel structure–activity relationships.