Search

Abstract Background Our previous study demonstrated that β2-microglobulin (β2M) promoted ER+/HER2– breast cancer survival via the SGK1/Bcl-2 signaling pathway. However, the role of β2M has not been investigated in ER–/HER2+ breast cancer. Here, we aimed to determine the role of β2M in ER–/HER2+ breast cancer. Methods The interaction between β2M and HFE was confirmed by co-immunoprecipitation, mass spectrometry, yeast two-hybrid screening, and His pull-down. The knockdown and overexpression of β2M or HFE were performed in MDA-MB-453 cells, and ERK signaling pathway was subsequently analyzed via western blotting. Apoptotic cells were detected using flow cytometer. β2M, HFE, and p-ERK1/2 were examined in tumor and paired adjacent tissues via immunohistochemistry. Results HFE was found to be an interacting protein of β2M in ER–/HER2+ breast cancer cells MDA-MB-453 by co-immunoprecipitation and mass spectrometry. A yeast two-hybrid system and His-pull down experiments verified that β2M directly interacted with HFE. β2M and HFE as a complex were mainly located in the cytoplasm, with some on the cytomembrane of MDA-MB-453 cells. In addition to breast cancer cells BT474, endogenous β2M directly interacted with HFE in breast cancer cells MDA-MB-453, MDA-MB-231, and MCF-7. β2M activated the ERK signaling pathway by interacting with HFE and induced apoptosis of MDA-MB-453 cells. The expression of HFE and p-ERK1/2 showed significantly high levels in HER2-overexpressing breast cancer tumor tissue compared with adjacent normal tissue, consistent with the results obtained from the cell experiments. Conclusions β2M induced apoptosis of tumor cells via activation of the ERK signal pathway by directly interacting with HFE in HER2-overexpressing breast cancer.

The accumulation of the active pharmaceutical chemical in the environment usually results in environmental pollution to increase the risk to human health. Indomethacin is a non-steroidal anti-inflammatory drug that potentially causes systemic and developmental toxicity in various tissues. However, there have been few studies for its potential effects on cardiac development. In this study, we systematically determined the cardiotoxicity of acute indomethacin exposure in zebrafish at different concentrations with morphological, histological, and molecular levels. Specifically, the malformation and dysfunction of cardiac development, including pericardial oedema, abnormal heart rate, the larger distance between the venous sinus and bulbus arteriosus (SV-BA), enlargement of the pericardial area, and aberrant motor capability, were determined after indomethacin exposure. In addition, further investigation indicated that indomethacin exposure results in myocardial apoptosis in a dose-dependent manner in zebrafish at early developmental stage. Mechanistically, our results revealed that indomethacin exposure mainly regulates key cardiac development-related genes, especially genes related to the cardiac muscle contraction-related signaling pathway, in zebrafish embryos. Thus, our findings suggested that acute indomethacin exposure might cause cardiotoxicity by disturbing the cardiac muscle contraction-related signaling pathway and inducing myocardial apoptosis in zebrafish embryos.

Abstract Entering the era of AI 2.0, bio‐inspired target recognition facilitates life. However, target recognition may suffer from some risks when the target is hijacked. Therefore, it is significantly important to provide an encryption process prior to neuromorphic computing. In this work, enlightened from time‐varied synaptic rule, an in‐memory asymmetric encryption as pre‐authentication is utilized with subsequent convolutional neural network (ConvNet) for target recognition, achieving in‐memory two‐factor authentication (IM‐2FA). The unipolar self‐oscillated synaptic behavior is adopted to function as in‐memory asymmetric encryption, which can greatly decrease the complexity of the peripheral circuit compared to bipolar stimulation. Results show that without passing the encryption process with suitable weights at the correct time, the ConvNet for target recognition will not work properly with an extremely low accuracy lower than 0.86%, thus effectively blocking out the potential risks of involuntary access. When a set of correct weights is evolved at a suitable time, a recognition rate as high as 99.82% can be implemented for target recognition, which verifies the effectiveness of the IM‐2FA strategy.

Triphenyl phosphate (TPhP) serves as a major organophosphorus flame retardant, and its induced neurodevelopmental toxicity has attracted widespread attention, but the mechanism remains unclear. In this study, we involved zebrafish to explore the new mechanism of TPhP inducing oxidative stress and ferroptosis to promote neurodevelopmental toxicity. The results suggested that TPhP affected the embryonic development, reduced the number of new neurons, and led to abnormal neural behavior in zebrafish larvae. TPhP also induced ROS accumulation, activated the antioxidant defense signal Nrf2 and Keap1, and significantly changed the activities of Acetylcholinesterase (AChE), Adenosine triphosphatase (ATPase) and glutathione S-transferase (GST). In addition, TPhP induced ferroptosis in zebrafish, which was reflected in the increase of Fe2+ content, the abnormal expression of GPX4 protein and genes related to iron metabolism (gpx4a, slc7a11, acsl4b, tfa, slc40a1, fth1b, tfr2, tfr1a, tfr1b and ncoa4). Astaxanthin intervention specifically inhibited ROS levels, and reversed SLC7A11 and GPX4 expression levels and Fe2+ metabolism thus alleviating ferroptosis induced by TPhP. Astaxanthin also partially reversed the activity of AChE, GST and the expression of neurodevelopmental-related genes (gap43, gfap, neurog1 and syn2a), so as to partially rescue the embryonic developmental abnormalities and motor behavior disorders induced by TPhP. More interestingly, the expression of mitochondrial apoptosis-related protein BAX, anti-apoptotic protein BCL-2, Caspase3 and Caspase9 was significantly altered in the TPhP exposed group, which could be also reversed by Astaxanthin intervention. In summary, our results suggested that TPhP exposure can induce oxidative stress and ferroptosis, thereby causing neurodevelopment toxicity to zebrafish, while Astaxanthin can partially reverse oxidative stress and reduce the neurodevelopmental toxicity of zebrafish larvae by activating Nrf2/Keap1/HO-1 signaling pathway.

The inactivation kinetic of peroxidase in Capsella bursa-pastoris during blanching was evaluated using first-order, Weibull, and Logistic models. The goodness-of-fit of the three tested models was assessed using the coefficient of determination (R2), chi-square (x2), root mean square error (RMSE), accuracy factor (Af), bias factor (Bf). Moreover, the best goodness-of-fit model was used to predict the blanching process according to the content of vitamin C. The results indicated that the Logistic model was most suitable than other models for predicting POD inactivation. The performance of the Logistic model indicated a strong fit by the high coefficient of determination (R2=0.9980) and low prediction error (x2=0.96×10−4, RMSE=0.0097, Af=1.1304, Bf=1.0070). While the blanching inactivated 95% peroxidase activity in Capsella bursa-pastoris, the relative enzyme activity of POD was 0.050±0.001 after blanching at 100 ℃ for 20 s and 80 ℃ for 287 s according to Logistic model. There was a significant difference in vitamin C content after blanching, high-temperature-short-time blanching could reduce the loss of vitamin C. The inactivation kinetic model of POD can predict the blanching process conditions, which can reduce the loss of heat-sensitive nutrients such as vitamin C.

Polybrominated diphenyl ether flame retardants are known to have adverse effects on the development of organisms. We investigated the molecular mechanisms associated with the developmental hazards of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) in zebrafish, as well as the behavioral and morphological alterations involved, focusing on endoplasmic reticulum stress (ERS), oxidative stress, and apoptosis. Our study revealed behavioral alterations in zebrafish exposed to BDE-47, including impaired motor activity, reduced exploration, and abnormal swimming patterns. In addition, we observed malformations in craniofacial regions and other developmental abnormalities that may be associated with ERS-induced cellular dysfunction. BDE-47 exposure showed apparent changes in ERS, oxidative stress, and apoptosis biomarkers at different developmental stages in zebrafish through gene expression analysis and enzyme activity assays. The study indicated that exposure to BDE-47 results in ERS, as supported by the upregulation of ERS-related genes and increased activity of ERS markers. In addition, oxidative stress-related genes showed different expression patterns, suggesting that oxidative stress is involved in the BDE-47 toxic effects. Moreover, an assessment of apoptotic biomarkers revealed an imbalance in the expression levels of pro- and anti-apoptotic genes, suggesting that BDE-47 exposure activated the apoptotic pathway. These results highlight the complex interactions between ERS, oxidative stress, apoptosis, behavioral alterations, and morphological malformations following BDE-47 exposure in zebrafish. Understanding the mechanisms of toxicity of developmental hazards is essential to elucidate the toxicological effects of environmental contaminants. The knowledge can help develop strategies to mitigate their adverse effects on the health of ecosystems and humans.

Rapid and accurate detection of the pathogens, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for COVID-19, is critical for mitigating the COVID-19 pandemic. Current state-of-the-art pathogen tests for COVID-19 diagnosis are done in a liquid medium and take 10–30 min for rapid antigen tests and hours to days for polymerase chain reaction (PCR) tests. Herein we report novel accurate pathogen sensors, a new test method, and machine-learning algorithms for a breathalyzer platform for fast detection of SARS-CoV-2 virion particles in the aerosol in 30 s. The pathogen sensors are based on a functionalized molecularly-imprinted polymer, with the template molecules being the receptor binding domain spike proteins for different variants of SARS-CoV-2. Sensors are tested in the air and exposed for 10 s to the aerosols of various types of pathogens, including wild-type, D614G, alpha, delta, and omicron variant SARS-CoV-2, BSA (Bovine serum albumin), Middle East respiratory syndrome–related coronavirus (MERS-CoV), influenza, and wastewater samples from local sewage. Our low-cost, fast-responsive pathogen sensors yield accuracy above 99% with a limit-of-detection (LOD) better than 1 copy/μL for detecting the SARS-CoV-2 virus from the aerosol. The machine-learning algorithm supporting these sensors can accurately detect the pathogens, thereby enabling a new and unique breathalyzer platform for rapid COVID-19 tests with unprecedented speeds.

Laser cladding is a new technology for fabricating coatings with good properties, such as wear resistance, lubrication, and corrosion resistance. Usually, parts of 45 steel are used as a shaft under conditions of high-speed rotation or friction and wear, and they have a short service life and sometimes cause accidents. In order to avoid serious accidents, a cladding coating made from a Ni-based alloy with ceramic particles was fabricated via laser technology on a substrate of 45 steel in this research. The microstructure and properties were investigated via SEM, EDS, XRD, and a wear and friction tester. The results show that there was an obvious boundary between the cladding coating and the substrate. The main phases were γ(Fe, Ni), WC, TiC, Cr2Ti, and Cr23C6. In the middle of cladding coating, the microstructure was composed of dendrite and cellular crystals, while the microstructure was composed of equiaxial crystals in the bonding region. Inside the cellular crystal, the main phase was γ~(Fe, Ni), which occasionally also showed the appearance of some white particles inside the cellular crystal. Compared with the cellular crystal, the boundary had less of the Fe and Ni elements and more of the Cr and W elements. The amount of C element around the dendrite crystal was more than that around the boundary of cellular crystal due to the long formation time of dendrite. The white particles around the boundary were carbides, such as WC and Cr23C6 phases. Meanwhile, the segregation of the Si element also appeared around the boundaries of the crystal. The maximum microhardness was 772.4 HV0.5, which was about 3.9 times as much as the substrate’s microhardness. The friction coefficients of the 45 steel substrate and Ni-based alloy coating were usually around 0.3 and 0.1, respectively. The Ni-based coating had a smaller coefficient and more stable fluctuations. The wear volume of the cladding coating (0.16 mm3) was less than that of the substrate (1.1 mm3), which was about 14.5% of the wear volume of 45 steel substrate. The main reason was the existence of reinforced phases, such as γ~(Fe, Ni), Cr23C6, and Cr2Ti. The added small WC and TiC particles also enhanced the wear resistance further. The main wear mechanism of the cladding coating was changed to be adhesive wear due to the ceramic particles, which was helpful in improving the service life of 45 steel.

As a substitute for polybrominated diphenyl ethers (PBDEs), organophosphate flame retardant triphenyl phosphate (TPhP) is widely used in our daily products and diffusely exists in our living surroundings, but there is a paucity of information concerning its neurodevelopmental toxicity. Herein, we investigated the effects of TPhP exposure on developmental parameters, locomotor behavior, oxidative stress, apoptosis and transcriptional levels in zebrafish at different developmental stages, so as to explore the effects of TPhP exposure on zebrafish neural development and the underlying molecular mechanisms. TPhP concentration gradient exposure reduced the survival rate, hatchability, heart rate, body length and eye distance of zebrafish embryos/larvae, and caused malformations of zebrafish larvae. TPhP also leads to abnormal locomotor behaviors, such as reduced swimming distance and swimming speed, and impaired panic avoidance reflex to high light stimulation. TPhP caused ROS accumulation in 96 hpf larvae and induced Nrf2-antioxidant response in zebrafish. In addition, TPhP further activated mitochondrial signaling pathways, which affected apoptosis in the zebrafish eye region, resulting in visual impairment. Neurodevelopmental (mbpa, syn2a, foxo3a and pax6a), Retinoid acid metabolism (cyp26a1, raraa, rbp5, rdh1, crabp1a and rbp2a) and apoptosis-related genes (bcl2a, baxa and casp9) revealed the molecular mechanism of abnormal behavior and phenotypic symptoms, and also indicated that 96 hpf larvae are more sensitive than 7 dpf larvae. Thus, in the present study, we revealed the neurotoxic effects of TPhP at different early life stages in zebrafish, and zebrafish locomotor behavior impairments induced by TPhP exposure are attributed to co-regulation of visuomotor dysfunction and neuro-related genes. These results suggest that the safety of TPhP in organisms and even in humans needs to be further studied.

Background: Polybrominated diphenyl ethers (PBDEs), a group of brominated flame retardants (BFRs), were reported exist extensively in various ecological environmental. Studies have indicated that PBDEs induce reproductive toxic effects on human health, but the mechanisms remain poorly understood. In this study, the adult female zebrafish were used to investigate the effects of 2, 2′, 4, 4′-tetrabromodiphenyl ether (BDE-47) on the reproductive endocrine system and its mechanism. Methods: Female zebrafish (AB strains) were continuously exposed to BDE-47 at the concentrations of 0, 10, 50, 100 and 500 µg/L till 21 days. The morphology of ovary were stained and evaluated with hematoxylin-eosin (H&E), and levels of sex hormones including follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T) and 17β-estradiol (E2) and the biomarkers of oxidative stress such as superoxide dismutase (SOD) and malondialdehyde (MDA), were measured via ELISA. Subsequently, the expression of genes along the hypothalamic pituitary-gonad (HPG) and oxidative stress were determined using quantitative real-time PCR (qRT-PCR). Result: The results showed that exposure to high level of BDE-47 reduced the index of condition factor (CF) and gonadosomatic index (GSI). Treatment with BDE-47 impaired the normal development and structure of oocytes in zebrafish ovary. Moreover, the steroid hormone of FSH, LH, T and E2 were significantly decreased in BDE-47 exposure group. A dose-dependent elevation in SOD activity and MDA levels were recorded. Meanwhile, the transcription level of cyp19a, cyp19b, fshβ, lhβ were up-regulated while the transcription of fshr, lhr, cyp17a, 17βhsd were down-regulated in the gonad of female adult zebrafish. Conclusion: Exposure to BDE-47 have detrimental impact on the development of ovary, decreasing sex hormone levels, inducing oxidative damage as well as altering HPG axis-related genes.

Polybrominated biphenyl ethers (PBDEs) are new persistent pollutants that are widely exist in the environment and have many toxic effects. However, their toxicity mechanisms on neurodevelopment are still unclear. In this study, zebrafish embryos were exposed to 2, 2′, 4, 4′-tetrabromodiphenyl ether (BDE-47) (control, 10, 50 and 100 μg/L) at 2 h postfertilization (hpf) – 7 dpf. Locomotion analysis indicated that BDE-47 increased spontaneous coiling activity in zebrafish embryos under high-intensity light stimuli and decreased locomotor in zebrafish larvae. RNA-Seq analysis revealed that most of the up-regulated pathways were related to the metabolism of cells and tissues, while the down-regulated pathways were related to neurodevelopment. Consistent with the locomotion and KEGG results, BDE-47 affected the expression of genes for central nervous system (gfap, mbpa, bdnf & pomcb), early neurogenesis (neurog1 & elavl3), and axonal development (tuba1a, tuba1b, tuba1c, syn2a, gap43 & shha). Furthermore, BDE-47 interfered with gene expression of the Wnt signaling pathway, especially during embryonic stages, suggesting that the mechanisms of BDE-47 toxicity to zebrafish at various stages of neurodevelopment may be different. In summary, early neurodevelopment effects and metabolic disturbances may have contributed to the abnormal neurobehavioral changes induced by BDE-47 in zebrafish embryos/larvae, suggesting the neurodevelopmental toxicity of BDE-47.

Cervical cancer (CC) is reported as the second-most common female cancer worldwide, of which 99% is caused by persistent human papillomavirus (HPV) infection. HPV vaccine protects against HPV infection and most cases of CC, which has only been introduced for a short time in mainland China. This study aimed to evaluate the attitude and practice related to HPV infection and vaccination among students at secondary occupational health school (SOHS) in China. We conducted a cross-sectional study in Southern China where data of 2248 participants were collected through questionnaires to estimate attitude and practice of students. Only 4.1% believed they were easily infected by HPV, 38.2% were willing to receive HPV vaccine and 30.8% intended to do regular screening of HPV infection in the future. Students in the second grade (OR = 1.51, 95%CI [1.25, 1.81]) and third grade (OR = 3.99, 95%CI [2.53, 6.27]) were more willing to take HPV vaccine compared to students in the first grade. Among the non-vaccinated participants, the most frequent reason for not receiving HPV vaccine was insufficient knowledge about HPV (91.1%). Characteristics of higher grade, personal education before enrollment and academic performance, medical specialty, history of sex experience and HPV vaccine and family history of other cancers were associated with higher attitude scores (p

Flowering is the most studied ornamental trait in orchids where long vegetative phase may span up to three years. Cymbidium orchids produce beautiful flowers with astonishing shapes and pleasant scent. However, an unusually long vegetative phase is a major drawback to their ornamental value. We observed that under certain culture conditions, three cymbidium species (Cymbidium ensifolium, C. goeringii and C. sinense) skipped vegetative growth phase and directly flowered within six months, that could be a breakthrough for future orchids with limited vegetative growth. Hormonal and floral regulators could be the key factors arresting vegetative phase. Therefore, transcriptomic analyses were performed for leafless flowers and normal vegetative leaves to ascertain differentially expressed genes (DEGs) related to hormones (auxin, cytokinin, gibberellin, abscisic acid and ethylene), floral integrators and MADS-box genes. A significant difference of cytokinin and floral regulators was observed among three species as compared to other hormones. The MADS-box genes were significantly expressed in the leafless flowers of C. sinense as compared to other species. Among the key floral regulators, CONSTANS and AGAMOUS-like genes showed the most differential expression in the leafless flowers as compared to leaves where the expression was negligible. However, CONSTANS also showed downregulation. Auxin efflux carriers were mainly downregulated in the leafless flowers of C. ensifolium and C. sinense, while they were upregulated in C. goeringii. Moreover, gibberellin and cytokinin genes were also downregulated in C. ensifolium and C. sinense flowers, while they were upregulated in C. goeringii, suggesting that species may vary in their responses. The data mining thus, outsources the valuable information to direct future research on orchids at industrial levels.

During orchid seed culture, seeds germinate as protocorms, and protocorms normally develop into plant with leaves and roots. Orchids require many years of vegetative development for flowering. However, under a certain combination of growth cultures, we observed that protocorms can directly flower without leaves and roots. Therefore, we performed comparative transcriptome analysis to identify the different transcriptional regulators of two types of protocorms of Cymbidium ensifolium, Cymbidium sinense, and Cymbidium goeringii. Zinc finger, MYB, AP2, and bHLH were the most abundant transcription factor (TF) families in the transcriptome. Weighted gene coexpression network analysis (WGCNA) was performed to identify hub genes related to leaf and flower development. The key hubs included SPL6, SVP, SEP2, KNOX1, AP2, OFP1, COL12, MYB13, MYB36, MYB59, bHLH086, and ARF7. The hub genes were further validated through statistical tools to propose the roles of key TFs. Therefore, this study initiates to answer that why there is no leaf initiation and root development and how can protocorm bypass the vegetative phase to flower? The outcomes can direct future research on short-span flowering in orchids through protocorms.

Controlling an underactuated robot is an attractive research issue as some of the robot joints cannot be controlled directly. Besides, facing the unknown time-varying disturbance, the nature of the plant makes the stability of such uncertain nonlinear system more challenging. This work presents a robust finite-time control scheme that combines Hölder condition based extended state observer and sliding mode control approach to cope with the mentioned issues. The unknown time-varying disturbance and other uncertainties can be well recognized and actively compensated under the proposed scheme. Besides, this control scheme is easy to be implemented due to the small amount of information required. Simulation results demonstrate the performance of the proposed scheme and validate its better robustness and convergent speed compared with other schemes.

Micromelalopha troglodyta (Graeser) (Lepidoptera: Notodontidae) is a notorious pest of poplar. Coevolution with poplars rich in plant secondary metabolites prompts M. troglodyta to expand effective detoxification mechanisms against toxic plant secondary metabolites. Although glutathione S-transferases (GSTs) play an important role in xenobiotic detoxification in M. troglodyta, it is unclear how GSTs act in response to toxic secondary metabolites in poplar. In this study, five GST gene core promoters were accurately identified by a 5’ loss luciferase reporter assay, and the core promoters were significantly induced by two plant secondary metabolites in vitro. Two transcription factors, cap ‘n’ collar C (CncC) and aryl hydrocarbon receptor nuclear translocator (ARNT), were cloned in M. troglodyta. MtCncC and MtARNT clustered well with other insect CncCs and ARNTs, respectively. In addition, MtCncC and MtARNT could bind the MtGSTt1 promoter and strongly improve transcriptional activity, respectively. However, MtCncC and MtARNT had no regulatory function on the MtGSTz1 promoter. Our findings revealed the molecular mechanisms of the transcription factors MtCncC and MtARNT in regulating the GST genes of M. troglodyta. These results provide useful information for the control of M. troglodyta.

Twenty-one ionic ferrocenyl ammonium (1–17) and 1,2,4-triazolium (18–21) compounds derived from 5,5′-bis(1-hydroxytetrazole) were synthesized and characterized by NMR, FT-IR, UV − Vis and elemental analysis, aiming at improving anti-migration ability of neutral ferrocene-based burning rate catalysts and reducing sensitivity of the ionic ferrocenyl compounds containing picrate anions. Six new compounds were additionally characterized by single-crystal X-ray diffraction. The characterization results showed that, by ion-exchange reactions, 1–10, 12, 15 and 17 are the anticipated compounds in their molecular structures, compounds 11, 13 and 16 were formed by C-N bond cleavage of the dinuclear ferrocenyl cation units and 18–21 were obtained by protonation of the divalent 5,5′-bis(1-hydroxytetrazolate) anion at one oxygen atom. Thermal gravimetry and anti-migration test indicated that the new compounds are highly thermally stable and show low volatility and low migration tendency. Cyclic voltammetry studies suggested that most of the novel salts are irreversible redox systems. The sensitivity tests towards impact revealed that compounds 1–17 are insensitive compounds. The catalytic tests implied that all compounds exhibit great effects on the thermal degradation of ammonium perchlorate and 1,3,5-trinitro-1,3,5-triazacyclohexane. Compounds 13–15 can be used as potential alternatives to catocene in the composite solid propellants.

Integrated inductor is one of the fundamental components and has been widely used in radio frequency integrated circuits (RFICs). It has been challenging to achieve simultaneously high inductance and quality factor, particularly at GHz frequencies. In this work, we reported a novel integrated solenoid inductor with a magnetic NiZn ferrite as the core material, which was deposited by a low-cost spin spray technique. These integrated inductors showed a significant improvement in both inductance and quality factor at GHz frequencies over their air core counterparts. A stable inductance was observed within a wide frequency ranged from 700 MHz to 6 GHz. The peak value of quality factor reached 23, a relatively higher value not reported for solenoid inductors up to date. Our results indicate that the integrated inductor are promising for applications in RFICs.