Thrombospondin-1-mediated crosstalk between autophagy and oxidative stress orchestrates repair of blast lung injury.

Coal mining carries inherent risks of catastrophic gas explosions capable of inflicting severe lung injury. Using complementary in vivo and in vitro models, we explored mechanisms underlying alveolar epithelial damage and repair following a gas explosion in this study. In a rat model, the gas explosion was demonstrated to trigger inflammation and injury within the alveolar epithelium. The following scRNA-sequencing revealed that alveolar epithelial cells exhibited the most profound transcriptomic changes after gas explosion compared to other pulmonary cell types. In the L2 alveolar epithelial cells, the blast was found to cause autophagic flux by inducing autophagosome formation, LC3 lipidation, and p62 degradation. Transcriptomic profiling of the L2 cells identified PI3K-Akt and p53 pathways as critical modulators governing autophagic and oxidative stress responses to blast damage. Notably, Thrombospondin-1 (Thbs1) was determined for the first time as a pivotal node interconnecting these two pathways. The findings of this study illuminate intricate mechanisms of alveolar epithelial injury and recovery after blast trauma, highlighting autophagic and oxidative stress responses mediated by Thbs1-associated PI3K-Akt and p53 pathways as high-value therapeutic targets, and strategic modulation of these pathways in future studies may mitigate lung damage by reducing oxidative stress while engaging endogenous tissue repair processes like autophagy.

Activation of AMPK signalling by Metformin: Implication an important molecular mechanism for protecting against mice silicosis via inhibited endothelial cell-to-mesenchymal transition by regulating oxidative stress and apoptosis.

Inhalation of silica particles (SiO2) causes oxidative stress-induced inflammation and cell apoptosis, ultimately resulting in irreversible pulmonary fibrosis, Unfortunately, effective treatment or preventative measures have yet to be fully established. Metformin (Met), a relatively safe and effective medication for treating diabetes, may hold promise as protective agent against early-stage pulmonary fibrosis in mice through the activation of autophagy and inhibition of endothelial cell to mesenchymal transition (EndoMT). Here, we investigated whether Met could reduce silicosis in mice by regulating inflammation, oxidative stress, and apoptosis, and to identify the underlying protective effect on endothelial cells. First, through pathological observation, we found that 21 consecutive days of Met (100 mg/kg) administration is optimal against silicosis. Next, using haematoxylin-eosin and Masson's trichrome staining and immunoblotting, we found that Met effectively blunted the inflammatory response and collagen deposition at 56 days after exposure to SiO2. We also demonstrated that Met effectively activates AMPK signalling and markedly relieves oxidative stress, the mitochondrial apoptotic pathway and EndoMT induced by SiO2 exposure both in vivo and in vitro. Overall, Met can alleviate SiO2-induced pulmonary fibrosis by regulating oxidative stress and the mitochondrial apoptotic pathway. The current study provides a rationale for the clinical treatment of SiO2-induced pulmonary fibrosis.

Association between prenatal exposure to ambient ozone, birth weight, and macrosomia in healthy women.

Studies have shown that prenatal ozone exposure is associated with an increased risk of adverse pregnancy outcomes, among which abnormal birth weight is a detrimental factor for diseases in adulthood, but the association between birth weight and ozone is inconclusive. Herein, we conducted this study by enrolling 407 couples of pregnant women and collected their demographical materials, their exposure to ambient ozone was assessed according to the place of their residence. The hourly monitored ozone was first averaged to the daily level, then monthly and whole-gestationally levels. After adjusting confounders, we processed a multivariate generalized addictive analysis to predict the association between prenatal ozone exposure and birth weight. We also divided the cohort into two categories according to whether the infant met the standard of macrosomia, and the occurrence of macrosomia was studied via univariate and multivariate logistic regression analyses as extreme conditions of the effects of ozone exposure on birth weight. We found that the ground-level ozone in Jinan changed with temperature periodically, higher in summer and lower in winter. Over the past 8 years from 2014, the ambient ozone increased by 1.74 µg/m3 per year. Of the 407 singleton-pregnant women, 21 infants were diagnosed with macrosomia. After adjusting confounders, we found that each unit increase in prenatal ozone exposure caused 8.80% [ORozone90%CI: 0.912 (0.850, 0.978)] decreased risk of macrosomia, but the splined ambient ozone exposure data was not statistically associated with birth weight, which is probably due to the limited sample size. In conclusion, prenatal ozone exposure is associated with decreased risk of macrosomia but is weakly linked to birth weight.

Characterization of Cathepsin B in Mediating Silica Nanoparticle-Induced Macrophage Pyroptosis via an NLRP3-Dependent Manner.

Introduction: Silica nanoparticles (SiNPs) are one of the most widely used inorganic nanomaterials, and exposure to SiNP has been demonstrated to induce pulmonary inflammation, primarily promoted by the NLRP3-mediated macrophage pyroptosis. However, mechanisms underlying the activation of NLRP3 signaling are complex, and whether cathepsin B (CTSB), an enzyme released by the ruptured lysosome, could trigger NLRP3 assembly is controversial. Methods: To further characterize the role of CTSB in silica-induced pyroptosis, we conducted this study by establishing SiNP exposure models in vitro. The morphological features of SiNPs were exhibited by the SEM and TEM, and the effects of SiNPs' internalization on macrophages were examined by the TEM and immunofluorescent staining. Moreover, Western blot was performed to detect the expression of proteins related to pyroptosis and CTSB after blocking the expression of NLRP3 and CTSB. Results: We found that SiNPs internalization caused the rupture of macrophage membrane and promoted the aging of cells with increased intracellular vacuoles. Also, the expression of NLRP3, ASC, Caspase-1, GSDMD, Pro-IL-1ß, IL-1ß, and CTSB increased under the stimulation of SiNP, which could be suppressed by additional treatment with MCC950, an NLRP3-specific inhibitor. Besides, we found SiNP joint treatment with leupeptin, a CTSB inhibitor, could inhibit the expression of CTSB, but it had no effect on the expression of NLRP3, ASC, and Caspase-1, and the process of macrophage pyroptosis was also not affected. Conclusion: SiNP exposure induces rupture of macrophages and the release of lysosomal CTSB, but CTSB fails to specifically act on the NLRP3 inflammasome to induce pyroptosis which is causally linked to lung inflammation and fibrosis.

Metformin mitigates gas explosion-induced blast lung injuries through AMPK-mediated energy metabolism and NOX2-related oxidation pathway in rats.

Gas explosions are a recurrent event in coal mining that cause severe pulmonary damage due to shock waves, and there is currently no effective targeted treatment. To illustrate the mechanism of gas explosion-induced lung injury and to explore strategies for blast lung injury (BLI) treatment, the present study used a BLI rat model and supplementation with metformin (MET), an AMP-activated protein kinase (AMPK) activator, at a dose of 10 mg/kg body weight by intraperitoneal injection. Protein expression levels were detected by western blotting. Significantly decreased expression of phosphorylated (p)-AMPK, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) and metabolic activity were observed in the BLI group compared with those in the control group. However, the mitochondrial stability, metabolic activity and expression of p-AMPK and PGC1α were elevated following MET treatment. These results suggested that MET could attenuate gas explosion-induced BLI by improving mitochondrial homeostasis. Meanwhile, high expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX2) and low expression of catalase (CAT) were observed in the BLI group. The expression levels of NOX2 and CAT were restored in the BLI + MET group relative to changes in the BLI group, and the accumulation of oxidative stress was successfully reversed following MET treatment. Overall, these findings revealed that MET could alleviate BLI by activating the AMPK/PGC1α pathway and inhibiting oxidative stress caused by NOX2 activation.

Establishment and evaluation of an in vitro blast lung injury model using alveolar epithelial cells.

Background: Gas explosion is a fatal disaster commonly occurred in coal mining and often causes systematic physical injuries, of which blast lung injury is the primary one and has not yet been fully investigated due to the absence of disease models. To facilitate studies of this field, we constructed an in vitro blast lung injury model using alveolar epithelial cells. Methods: We randomly divided the alveolar epithelial cells into the control group and blast wave group, cells in the blast wave group were stimulated with different strengths of blast wave, and cells in the control group received sham intervention. Based on the standards we set up for a successful blast injury model, the optimal modeling conditions were studied on different frequencies of blast wave, modeling volume, cell incubation duration, and cell density. The changes of cell viability, apoptosis, intracellular oxidative stress, and inflammation were measured. Results: We found that cell viability decreased by approximately 50% at 6 h after exposing to 8 bar energy of blast wave, then increased with the extension of culture time and reached to (74.33 ± 9.44) % at 12 h. By applying 1000 ~ 2500 times of shock wave to 1 ~ 5 × 105 cells /ml, the changes of cell viability could well meet the modeling criteria. In parallel, the content of reactive oxide species (ROS), malonaldehyde (MDA), interleukin 18 (IL-18), tumor necrosis factor alpha (TNF-α), and transforming growth factor beta (TGF-ß) increased in the blast wave group, while superoxide dismutase (SOD) and Glutathione -S- transferase (GST) decreased, which were highly consistent with that of human beings with gas explosion-induced pulmonary injury. Conclusion: An in vitro blast lung injury model is set up using a blast wave physiotherapy under 8 bar, 10 Hz blast wave on (1 ~ 5) ×105 alveolar epithelial cells for 1 000 times. This model is flexible, safe, and stable, and can be used for studies of lung injury caused by gas explosion and blast-associated other external forces.

[Comparative study on anti-depressant effect of Zhizichi Decoction and its solid fermentation product on CUMS rats].

Chronic unpredicted mild stress(CUMS) combined with isolated feeding was used to induce depressed rat model. The anti-depressant effects of Zhizichi Decoction(ZZCD) and its solid fermented product(ZZC) were analyzed by behavioral test and comparison of pathological tissues of hippocampus and liver, metabolic characteristics of intestinal flora, and relative abundance of species. The results showed that ZZC could increase sucrose preference, shorten the immobility time in the forced swim test and tail suspension test(P<0.05), and repair damaged hippocampus and liver tissues, and the effect was superior to that of ZZCD. The results of Biolog ECO plates showed that the average well color development(AWCD) of intestinal flora in the model group significantly decreased and the metabolic levels of sugar and amino acids were reduced, while the AWCD of the treatment groups increased. The metabolic levels of the two carbon sources were improved in the ZZC group, while only sugar metabolic level was elevated in the ZZCD group. Metagenomic analysis of intestinal flora showed that the ratio of Firmicutes/Bacteroidetes was 3.87 in the control group, 21.77 in the model group, 5.91 in the ZZC group, and 18.48 in the ZZCD group. Lactobacillus increased by 3.28 times, and Prevotella and Bacteroidetes decreased by 75.59% and 76.39%, respectively in the model group as compared with that in the control group. Lactobacillus decreased by 31.13%, and Prevotella and Bacteroidetes increased by more than three times in the ZZC group as compared with that in the model group, while the corresponding changes in the ZZCD group were not significant. ZZC could improve depression-like beha-viors by regulating the structure of intestinal flora and metabolic functions and repairing damaged hippocampus and liver tissues in depressed rats, showing an anti-depressant effect superior to that of ZZCD. This study is expected to provide a basis for the development of new anti-depressant food products.

Toward High-Performance Self-Driven Photodetectors via Multistacking Van der Waals Heterostructures.

The unique optoelectronic properties of layered van der Waals (vdW) heterostructures open up exciting opportunities for high-performance photodetectors. Self-driven photodetectors are desirable for reducing power consumption and minimizing the device size. Here, a semiconductor-insulator-semiconductor-type multistacking WSe2/graphene/h-BN/MoS2 vdW heterostructure is demonstrated to realize an enhanced self-powered photodetector with a high on-off current ratio of about 1.2 × 105 and a high photoresponsivity of 3.6 A/W without applying bias, which is the highest photoresponsivity ever reported for self-powered photodetectors. Because of the difference in the Fermi level, a built-in electrical field is formed at the WSe2/graphene junction, where the photoexcited electrons and holes can be efficiently separated and the carriers can easily tunnel through the MoS2/h-BN junction driven by the enhanced potential. Therefore, the enhanced self-powered photodetection is attributable to highly efficient carrier tunneling through large h-BN electron barriers. By comparison, when the stacking sequence is changed to make WSe2/MoS2 p-n heterojunctions lay on graphene/h-BN, the self-powered photocurrent is still generated because of the type-II band alignment, which exhibits lower but still relevant values with a light on/off ratio of ∼8 × 103 and a photoresponsivity of ∼2.39 A/W. The efficient enhancement demonstrates that multistacking heterostructures significantly elevate the performance of self-powered photodetectors, providing a feasible route to develop high-performance self-powered optoelectronic devices and extend their applications in integrated optoelectronic systems.

New Type of Thermoelectric CdSSe Nanowire Chip.

Facing the increasingly serious problem of environmental pollution and energy waste, the thermoelectric generator has been attracting more and more attention owing to its advantages including low cost, no pollution, and good stability. The family of thermoelectric material is constantly extended with enhanced performance. Note that nanostructuring can enhance thermoelectric performance. However, the most recent excellent material with effective thermoelectric transformation reported from bulk materials has definite benefits to the practical application compared to nanomaterials. In this work, a nanostructure integrated macroscale thermoelectric chip, that is an alloyed band gap gradient macroscale chip (1.0 cm × 2.0 cm) composed of CdSSe nanowires, has been proven as an excellent thermoelectric generator for the first time. A high Seebeck coefficient of -152.4 µV/K and the average output voltage of 10.8 mV are obtained after optimizing the electrode patterns and distance between electrodes. More interestingly, upon illumination by white light from a xenon lamp, a photo-thermoelectric output voltage is greatly elevated to 45 mV due to the high concentration of photogenerated carriers. The CdSSe thermoelectric chip also shows good repeatability and high stability with a relative error of <6%. No study on the thermoelectric performance of such an alloyed band gap gradient macroscale chip is mentioned before. The results illustrate a bright avenue to realize a type of light-modulated macroscale thermoelectric chips by nanostructure, allowing such kinds of CdSSe chips to be used to generate electric energy in the near future.

On-chip programmable optical switch based on CdS multibranched nanowire arrays.

Micro/nano optoelectronic devices are widely studied as basic building blocks for on-chip integrated microsystem and multichannel logic units with excellent optoelectronic properties that are especially important part for interconnection route construction. Here, based on anisotropic waveguides, an optical switch with an on/off ratio of 2.14 is built up in a 2D CdS branched nanowire array. Because the branches are obliquely distributed at the same side of the trunk in a highly ordered form, the guided photoluminescence (PL) intensity from the trunk into the branch tightly relates to its angle. Based on the different intensity of the guided PL emitted from the end of each branch, the position of the incident spot in the backbone area can be identified accurately, making a feasible construction of an on-chip position-sensitive detector to realize an all-optical information process.

Comparative Studies on Two-Dimensional (2D) Rectangular and Hexagonal Molybdenum Dioxide Nanosheets with Different Thickness.

Molybdenum dioxide (MoO2) a kind of semi-metal material shows many unique properties, such as high melting point, good thermal stability, large surface area-to-volume ratio, high-density surface unsaturated atoms, and excellent conductivity. There is a strong connection between structural type and optoelectronic properties of 2D nanosheet. Herein, the rectangular and hexagonal types of thin and thick MoO2 2D nanosheets were successfully prepared from MoO3 powder using two-zone chemical vapor deposition (CVD) with changing the experimental parameters, and these fabricated nanosheets displayed different colors under bright-field microscope, possess margins and smooth surface. The thickness of the blue hexagonal and rectangular MoO2 nanosheets are ~ 25 nm and ~ 30 nm, respectively, while typical thickness of orange-colored nanosheet is around ~ 100 nm. Comparative analysis and investigations were carried out, and mix-crystal phases were indentified in thick MoO2 as main matrix through Raman spectroscopy. For the first time, the emission bands obtained in thick MoO2 nanosheets via a Cathodoluminescence (CL) system exhibiting special properties of semi-metallic and semi-conductors; however, no CL emission detected in case of thin nanosheets. The electrical properties of thin MoO2 nanosheets with different morphologies were compared, and both of them demonstrated varying metallic properties. The resistance of thin rectangular nanosheet was ~ 25 Ω at ± 0.05 V while 64 Ω at ± 0.05 V was reported for hexagonal nanosheet, and observed lesser resistance by rectangular nanosheet than hexagonal nanosheet.

Polarization-Sensitive Self-Powered Type-II GeSe/MoS2 van der Waals Heterojunction Photodetector.

Polarization-sensitive photodetectors are highly desirable for high-performance optical signal capture and stray light shielding in order to enhance the capability for detection and identification of targets in dark, haze, and other complex environments. Usually, filters and polarizers are utilized for conventional devices to achieve polarization-sensitive detection. Herein, to simplify the optical system, a two-dimensional self-powered polarization-sensitive photodetector is fabricated based on a stacked GeSe/MoS2 van der Waals (vdW) heterojunction which facilitates efficient separation and transportation of the photogenerated carriers because of type-II band alignment. Accordingly, a high-performance self-powered photodetector is achieved with merits of a very large on-off ratio photocurrent at zero bias of currently 104 and a high responsivity (Rλ) of 105 mA/W with an external quantum efficiency of 24.2%. Furthermore, a broad spectral photoresponse is extended from 380 to 1064 nm owing to the high absorption coefficient in a wide spectral region. One of the key benefits from these highly anisotropic orthorhombic structures of layered GeSe is self-powered polarization-sensitive detection with a peak/valley ratio of up to 2.95. This is realized irradiating with a 532 nm wavelength laser with which a maximum photoresponsivity of up to 590 mA/W is reached when the input polarization is parallel to the armchair direction. This work provides a facile route to fabricate self-powered polarization-sensitive photodetectors from GeSe/MoS2 vdW heterojunctions for integrated optoelectronic devices.

Overexpression of amyA and glaA substantially increases glucoamylase activity in Aspergillus niger.

The purpose of this study was to obtain an engineered Aspergillus niger strain with high glucoamylase activity by overexpressing the glucoamylase gene glaA and α-amylase gene amyA in A. niger CICC2462. Three recombinant strains containing a single copy of amyA (1A), containing two copies of amyA (2A), and coexpressing amyA and glaA (AG), respectively, were constructed. The transcript levels of amyA in 1A and 2A were increased by 2.95 folds and 3.09 folds, respectively. The levels of amyA and glaA in AG were increased by 1.21 folds and 2.86 folds, but the maximum extracellular glucoamylase activities did not differ significantly. In addition, after 1% casein phosphopeptides (CPPs) was added to the fermentation medium, the maximum extracellular glucoamylase activities for strains 1A, 2A, and AG were 35,200, 37,300, and 40,710 U/ml, respectively, which were significantly higher than that of the parental strain CICC2462 (28,250 U/ml), while CPPs alone had no effect on the parental strain CICC2462. We demonstrate that overexpression of amyA and glaA substantially increases the expression and secretion of glucoamylase in A. niger, and CPPs effectively improves the yield of glucoamylase in recombinant A. niger strains overexpressing amyA and glaA. The newly developed strains and culture methods may have extensive industrial applications.

CdSSe nanowire-chip based wearable sweat sensor.

BACKGROUND: Sweat, as an easily accessible bodily fluid, is enriched with a lot of physiological and health information. A portable and wearable sweat sensor is an important device for an on-body health monitoring. However, there are only few such devices to monitor sweat. Based on the fact that sweat is mainly composed of moisture and salt which is much more abundant than other trace ions in sweat, a new route is proposed to realize wearable sweat sensors using CdSSe nanowire-chips coated with a polyimide (PI) membrane. RESULTS: Firstly, the composition-graded CdS1-xSex (x = 0-1) nanowire-chip based sensor shows good photo-sensitivity and stress sensitivity which induces linear humidity dependent conductivity. This indicates good moisture response with a maximum responsivity (dI/I) 244% at 80% relative humidity (RH) even in the dark. Furthermore, the linear current decrease with salt increase illustrates the chip sensor has a good salt-sensing ability with the best salt dependent responsivity of 80%, which guarantees the high prediction accuracy in sweat sensing. The sensor current is further proven to nonlinearly correlate to the amount of sweat with excellent stability, reproducibility and recoverability. The wearable sweat sensor is finally applied on-body real-time sweat analysis, showing good consistence with the body status during indoor exercise. CONCLUSIONS: These results suggest that this CdSSe nanowire-chip based PI-coated integrated sensor, combined with inorganic and organic functional layers, provides a simple and reliable method to build up diverse portable and wearable devices for the applications on healthcare and athletic status.

Lithium ion detection in liquid with low detection limit by laser-induced breakdown spectroscopy.

Lithium (Li), as the lightest metal and the most important powerful material in battery fabrication, is widely used in many fields. The fast detection of Li is necessary for industrial application. The slow-speed detection methods, including atomic absorption spectroscopy and inductively coupled plasma mass spectroscopy with high accuracy and low limit of detection, are hard to utilize in in situ industrial control due to complex prepreparation of samples. Here, through the analysis of the typical spectrum line at Li I 670.79 nm, Li ions in water were detected quantitatively in 1 min, including sample preparation by laser-induced breakdown spectroscopy (LIBS) with filter paper as the adsorption substrate. The calibration curve by polynomial function fitting is used to predict the Li+ concentration. The limit of detection (LOD) as low as 18.4 ppb is obtained, which is much lower than the results ever reported by using filter paper. The related factor R2 reaches 99%, and the prediction error is lower than 2%, proving the fast and online monitor for Li+ by LIBS is feasible. Furthermore, by comparison with the results with filter paper enrichment, the Li+ detection from water directly shows higher LOD to 10.5 ppm. Moreover, the plasma images, by gate-controlled intensified charge-coupled device, illustrate a different morphology and evolution between that on water surface and filter paper surface through visual observation. This study provides experimental and theoretical experience in a fast way for the quantitative detection of the lightest metal ion (Li+) in liquid.