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Abstract Acute lung injury (ALI) is the result of damage to the capillary endothelia and the alveolar epithelial cell caused by various direct and indirect factors, leading to significant pulmonary interstitial and alveolar edema and acute hypoxic respiratory insufficiency. A subset of ALI cases progresses to irreversible pulmonary fibrosis, a condition with fatal implications. Zafirlukast is a leukotriene receptor antagonist licensed for asthma prevention and long-term treatment. This study demonstrated a significant improvement in lung tissue pathology and a reduction in inflammatory cell infiltration in models of lipopolysaccharide (LPS)-induced ALI and bleomycin (BLM)-induced lung inflammation following zafirlukast administration, both in vivo and in vitro. Moreover, zafirlukast was found to suppress the inflammatory response of alveolar epithelial cells in vitro and lung inflammation in vivo by reducing the activation of the TLR4/NF-κB/NLRP3 inflammasome pathway. In conclusion, zafirlukast relieved lung injury and the infiltration of inflammatory cells in the lung by regulating the TLR4/NF-κB/NLRP3 pathway.

In this paper, five dangerous rockfall collapses at K1515 of the Shanghai-Chengdu expressway are taken as the research object. Through investigation, statistics, and analysis, the engineering geological conditions and developmental deformation characteristics of the dangerous rockfall collapse area are clarified. The research results show that: (1) the failure modes of dangerous rock masses W1 and W2 are misbreaking and cracking, the destruction mode of W3-1 dangerous rock mass is dumping, the destruction mode of W3-2 dangerous rock mass is sliding, and the destruction mode of W4 and W5 is bulging; (2) the stability coefficient of W1 and W2 is 1.12 and 1.61 respectively, which are in basically stable ~ stable state; the stability coefficient of dumping failure of W3-1 is 0.41 and in unstable state; the stability coefficient of sliding failure of W3-2 in W 3-2 is greater than 1.35 and in stable state; under rainstorm condition; the stability coefficient of bulging deformation of W4 and W5 is 1.25 and 1.15 respectively, which are in basically stable state; (3) The authors summarize the governance strategy of “reduce risk, minimize disturbance, ensure safe stability and feasible technology”, and adopt comprehensive remidiation measures of “embedding concrete retaining wall at the toe of slope + local active SNS network protection + prestressed anchor protection”, and the treatment effect was good. It can provide reliable reference basis for the treatment measures of dangerous rock collapse.

Carbon fiber (CF) is one of the conductive fillers with the best electrical conductivity, but it is expensive and difficult to disperse in cement matrix, which limits the application and development of CF conductive cement-based composites. Therefore, this paper took the conductive cement slurry with CF content of 1.0 % as the control group, and proposed to use low-cost graphite (G) and nano-carbon black (NCB) instead of some CFs to prepare conductive cement-based composites. The synergistic enhancement effect between different conductive fillers was explored to reduce the cost of materials while maintaining electrical conductivity. The results showed that the resistivity decreased first, then increased, then decreased and then increased with the increase of the proportion of particle conductive filler instead of CF. The resistivity of conductive cement slurry was 125.65 Ω·cm when G replaced 20 % CF, the resistivity of conductive cement slurry was 140.66 Ω·cm when NCB replaced 30 % CF, and the resistivity of conductive cement slurry was 122.05 Ω·cm when G and NCB replaced 30 % CF, which were close to the resistivity of the control group (122.35 Ω·cm). The purpose of reducing the cost of materials without affecting the conductivity of conductive cement slurry was achieved.

Abstract BAZ2A, an epigenetic regulatory factor that affects ribosomal RNA transcription, has been shown to be highly expressed in several cancers and promotes tumor cell migration. This study explored the expression and mechanism of BAZ2A in tumorigenesis at the pan-cancer level. The Cancer Genome Atlas, Gene Expression Omnibus databases and TIMER2.0, cBioPortal and other tools were used to analyze the level of expression of BAZ2A in various tumor tissues and to examine the relationship between BAZ2A and survival, prognosis, mutation and immune invasion. In vitro experiments were performed to assess the function of BAZ2A in cancer cells. Using combined transcriptome and proteome analysis, we examined the possible mechanism of BAZ2A in tumors. BAZ2A exhibited high expression levels in multiple tumor tissues and displayed a significant association with cancer patient prognosis. The main type of BAZ2A genetic variation in cancer is gene mutation. Downregulation of BAZ2A inhibited proliferation, migration, and invasion and promoted apoptosis in LM6 liver cancer cell. The mechanism of BAZ2A in cancer development may involve lipid metabolism. These results help expand our understanding of BAZ2A in tumorigenesis and development and suggest BAZ2A may serve as a prognostic and diagnostic factor in several cancers.

BackgroundCardiovascular diseases persist as the primary cause of mortality in the global population. Hypertension (HTN) is widely recognized as one of the most crucial risk factors contributing to severe cardiovascular conditions. In recent years, a growing body of research has highlighted the therapeutic potential of gut microbiota (GM) in addressing cardiovascular diseases, particularly HTN. Consequently, unraveling and synthesizing the connections between GM and HTN, key research domains, and the underlying interaction mechanisms have grown increasingly vital.MethodsWe retrieved articles related to GM and HTN from 2014 to 2023 using Web of Science. Bibliometric tools employed in this analysis include CiteSpace and VOSviewer.ResultFrom 2014 to 2023, we identified 1,730 related articles. These articles involved 88 countries (regions) and 9,573 authors. The articles were published in 593 journals, with 1000 references exhibiting co-occurrence more than 10 times. The number of studies in this field has been increasing, indicating that it remains a research hotspot. We expect this field to continue gaining attention in the future. China leads in the number of published articles, while the United States boasts the most extensive international collaborations, signifying its continued prominence as a research hub in this domain. Tain You-Lin, Hsu Chien-Ning, Raizada Mohan K, and Yang Tao are among the authors with the highest publication volume. Publications in this field are frequently found in nutrition, cardiovascular, and molecular biology journals. The most frequently occurring keywords include metabolic syndrome, cardiovascular disease, inflammation, short-chain fatty acids, trimethylamine N-oxide, chronic kidney disease, heart failure, and high-salt diet.ConclusionThe relationship between GM and HTN is presently one of the most active research areas. By employing bibliometric tools, we analyzed critical and innovative articles in this field to provide an objective summary of the primary research directions, such as the relationship between GM and HTN, GM metabolites, high-salt diet, the developmental origins of health and disease, obstructive sleep apnea-Induced hypertension and antihypertensive peptide. Our analysis aims to offer researchers insights into hotspots and emerging trends in the field of GM and HTN for future research reference.

China, the largest country in Asia, has a land area of approximately 9.6 million square kilometres. There are 1481 bird species (following the taxonomy of IOC World Bird List version 12.1) recorded in two zoogeographical realms, seven regions and 19 subregions in the country. From 1955 to 2017, six authoritative monographs were published, which recorded the distribution area for all bird species in China and were widely quoted by research papers and field guides. This massive amount of data could be used to address many hot topics in ornithology, biogeography and ecology. However, rapid changes in the taxonomic status and different schemes of zoogeographical regionalisation in these six monographs provided limits to the utilisation of these valuable data.By integrating the data from the six monographs, we presented an open-access dataset on the occurrences and residence types of all Chinese bird species in zoogeographical regions over the past 60 years. The taxonomic statuses for these species were determined following the IOC World Bird List version 12.1 and the zoogeographical regions were based on the updated scheme. These data provide valuable information for the research in bird ecology and conservation biology.

The fast development of brain-inspired neuromorphic computing systems has stimulated urgent requirements for artificial synapses with low-power consumption. In this work, a photonic synaptic device based on (Al,Ga)N nanowire/graphene heterojunction has been proposed and demonstrated successfully. In the artificial synaptic device, the incident light, the nanowire/graphene heterojunction, and the light-generated carriers play the roles of action potential, pre-synaptic/post-synaptic membrane, and neurotransmitter in a biological synapse, respectively. As a key synaptic function, the paired pulse facilitation index of the photonic synapse can reach 202%, which can be modulated by the interval time between two adjacent light pulses. It is found that the graphene defects, the surface band bending, and the Al vacancies on the surface of (Al,Ga)N nanowires can be the key reasons contributing to the synaptic characteristics of artificial photonic devices. Hence, the dynamic “learning–forgetting” performance of the artificial synaptic device can resemble the “learning–forgetting” behavior of the human brain. Furthermore, the hand-written digits are set up to mimic a typical characteristic of human perceptual learning. After only three training epochs, the simulated network can achieve a high recognition rate of over 90% based on the experimental conductance for long-term potentiation and long-term depression. In supervised learning processes, such few training times are beneficial to reduce energy consumption significantly. Therefore, in the area of neuromorphic computing technology and artificial intelligence systems requiring low-power consumption, this work paves a potential way to develop the optoelectronic synapse based on semiconductor nanowires.

Abstract Non‐invasive light‐based antibacterial therapy has a good prospect in non‐surgical treatment of peri‐implant infections. However, its applications are severely limited by poor penetration of light into human tissues, leading to unsatisfying outcomes. Moreover, as an essential prerequisite for traditional light therapy, lasers can no longer meet the patients’ needs for convenient treatment at any time. To break through the spatial and temporal limitations of traditional light therapy, a wireless‐powered blue‐light zirconia implant for readily available treatment of peri‐implant infection is proposed. In space, complete irradiation to complex peri‐implant structure is realized by the built‐in wireless‐powered light source, thus improving the efficacy. In time, wireless‐powering allows timely and controllable anti‐infection treatment. Blue micro‐light emitting diodes are used as therapeutic light sources, which effectively kill peri‐implant infection‐related bacteria without exogenous photosensitive agents. Porphyromonas gingivalis biofilm on implant surface can be completely killed after 20 min irradiation in vitro. The bactericidal rate of peri‐implant methicillin‐resistant Staphylococcus aureus infection reaches 99.96 ± 0.03% under 30 min per day blue light exposure in vivo. Within the scope of this study, the treatment of peri‐implant infection with blue‐light implant has preliminary feasibility, giving a new approach to non‐invasive treatment of deep oral infections, including peri‐implant infections.

In order to study the synergistic effect of polymer and conductive functional materials on the properties of cement-based materials, polymer conductive cement-based materials were prepared by mixing four polymer lotions of silicon–acrylate emulsion (SG), phenylacrylic emulsion (SR), waterborne epoxy resin emulsion (SH), and acrylic emulsion (SX) with carbon fiber (CF) and carbon black (CB), two conductive functional materials, in a certain proportion. The effects of the different polymer–cement ratios (P/C) of the four polymers on the physical, mechanical, and electrical properties of conductive cement-based materials were studied. The results illustrated that SH improved the fluidity of cement paste, and the four polymers all had a delaying effect, which led to the hardening of the specimens and the extension of the demoulding specimens to varying degrees. SH and SR can increase the ratio of flexural strength to compressive strength (F/C) in cement paste and improve the toughness of materials, and the maximum value is reached when the P/C is 0.15. Except for SX, the other three polymer lotions can reduce the resistivity of cement paste, which is beneficial to the improvement of conductivity. The improvement sequence is SH > SR > SG. Among them, both SH group and SR group achieved the lowest electrical resistivity at the P/C of 0.15. The four kinds of polymer lotion can significantly reduce the water absorption of the specimen and promote the waterproof performance. The improvement effect: SH > SR > SG > SX. Among them, both the SH group and SR group achieved the minimum water absorption at the P/C of 0.15.

Northward expansions of bird distributions have been commonly observed in the Northern Hemisphere, likely as a result of climate change. The causes and ecological impacts of such range shifts have received extensive attention, but studies on the process of range shifts are still relatively scarce. The Brownish-flanked Bush Warbler (Horornis fortipes) has expanded northward from 35° N to 40° N during the past decade. In this study, we collated 77 records of the species beyond its traditional distribution during the past ten years from citizen science data. Most of the new records were from northeast of its traditional distribution, including the North China Plain, Taihang Mountains, and Taishan Mountain, and a few records from the northern margin of the Qinling Mountains and Qinghai–Tibet Plateau. We concluded that the Brownish-flanked Bush Warbler has bred in this new area in at least six sites. The newly established populations are assumed to belong to the subspecies H. f. davidianus, which can be divided into eastern and western dialect groups based on differences in songs. Song recordings from 10 males from Beijing and its adjacent areas were collected. Bayesian analysis based on the acoustic traits indicated that these males were most likely from the western dialect area, with a posterior probability of 99.975%. Combining topographical data with the habitat preference of the species, we inferred that these individuals spread northeastward from the Qinling Mountains to Taihang Mountains, and further along the Yanshan Mountains. This study is a case study of the distribution expansion of a bird species, which reflects the dynamics of a species in the early stage of its northward expansion.

Dendrobium officinale polysaccharides (DOPs) are important active polysaccharides found in Dendrobium officinale, which is commonly used as a conventional food or herbal medicine and is well known in China. DOPs can influence the composition of the gut microbiota and the degradation capacity of these symbiotic bacteria, which in turn may determine the efficacy of dietary interventions. However, the necessary analysis of the relationship between DOPs and the gut microbiota is lacking. In this review, we summarize the extraction, structure, health benefits, and related mechanisms of DOPs, construct the DOPs-host axis, and propose that DOPs are potential prebiotics, mainly composed of 1,4-β-D-mannose, 1,4-β-D-glucose, and O-acetate groups, which induce an increase in the abundance of gut microbiota such as Lactobacillus, Bifidobacterium, Akkermansia, Bacteroides, and Prevotella. In addition, we found that when exposed to DOPs with different structural properties, the gut microbiota may exhibit different diversity and composition and provide health benefits, such as metabolism regulations, inflammation modulation, immunity moderation, and cancer intervention. This may contribute to facilitating the development of functional foods and health products to improve human health.

Abstract Antibody‐nanoparticle conjugates are promising candidates for precision medicine. However, developing a controllable method for conjugating antibodies to nanoparticles without compromising the antibody activity represents a critical challenge. Here, a facile and generalizable film‐coating method is presented using zeolitic imidazole framework‐8 (ZIF‐8) to immobilize antibodies on various nanoparticles in a favorable orientation for enhanced cell targeting. Different model and therapeutic antibodies (e.g., Herceptin) are assembled on nanoparticles via a biomineralized film‐coating method and exhibited high antibody loading and targeting efficiencies. Importantly, the antibodies selectively bind to ZIF‐8 via their Fc regions, which favorably exposes the functional Fab regions to the biological target, thus improving the cell targeting ability of antibody‐coated nanoparticles. In combination, molecular dynamics simulations and experimental studies on antibody immobilization, orientation efficiency, and biofunctionality collectively demonstrate that this versatile site‐specific antibody conjugation method provides effective control over antibody orientation and leads to improved cell targeting for a variety of nanoparticles.

Reliable precipitation data are essential for studying water cycle patterns and climate change. However, there are always temporal or spatial errors in precipitation data from various sources. Most precipitation fusion methods are influenced by high-dimensional input features and do not make good use of the spatial correlation between precipitation and environmental variables. Thus, this study proposed a novel multi-source precipitation spatiotemporal fusion method for improving the spatiotemporal accuracy of precipitation. Specifically, the attention mechanism was used to first select critical input information to dimensionalize the inputs, and the Convolutional long-short-term memory network (ConvLSTM) was used to merge precipitation products and environmental variables spatiotemporally. The Yalong River in the southeastern part of the Tibetan Plateau was used as the case study area. The results show that: (1) Compared with the original precipitation products (IMERG, ERA5 and CHIRPS), the proposed method has optimal accuracy and good robustness, and its correlation coefficient (CC) reaches 0.853, its root mean square coefficient (RMSE) decreases to 3.53 mm/d and its mean absolute error (MAE) decreases to 1.33 mm/d. (2) The proposed method can reduce errors under different precipitation intensities and greatly improve the detection capability for strong precipitation. (3) The merged precipitation generated by the proposed method can be used to describe the rainfall–runoff relationship and has good applicability. The proposed method may greatly improve the spatiotemporal accuracy of precipitation in complex terrain areas, which is important for scientific management and the allocation of water resources.

(1) Background: Heart failure (HF) is the final stage of multiple cardiac diseases, which have now become a severe public health problem worldwide. β-Adrenergic receptor (β-AR) overactivation is a major pathological factor associated with multiple cardiac diseases and mediates cardiac fibrosis and inflammation. Previous research has demonstrated that Bruton’s tyrosine kinase (BTK) mediated cardiac fibrosis by TGF-β related signal pathways, indicating that BTK was a potential drug target for cardiac fibrosis. Zanubrutinib, a second-generation BTK inhibitor, has shown anti-fibrosis effects in previous research. However, it is unclear whether Zanubrutinib can alleviate cardiac fibrosis induced by β-AR overactivation; (2) Methods: In vivo: Male C57BL/6J mice were treated with or without the β-AR agonist isoproterenol (ISO) to establish a cardiac fibrosis animal model; (3) Results: In vivo: Results showed that the BTK inhibitor Zanubrutinib (ZB) had a great effect on cardiac fibrosis and inflammation induced by β-AR. In vitro: Results showed that ZB alleviated β-AR-induced cardiac fibroblast activation and macrophage pro-inflammatory cytokine production. Further mechanism studies demonstrated that ZB inhibited β-AR-induced cardiac fibrosis and inflammation by the BTK, STAT3, NF-κB, and PI3K/Akt signal pathways both in vivo and in vitro; (4) Conclusions: our research provides evidence that ZB ameliorates β-AR-induced cardiac fibrosis and inflammation.

Abstract Operational factors and microbial interactions affect the ecology in anaerobic digestion systems. From 12 lab-scale reactors operated under distinct engineering conditions, bacterial communities were found driven by temperature, while archaeal communities by both temperature and substrate properties. Combining the bacterial and archaeal community clustering patterns led to five sample groups (ambient, mesophilic low-solid-substrate, mesophilic, mesophilic co-digestion and thermophilic) for co-occurrence network analysis. Network topological properties were associated with substrate characteristics and hydrolysis-methanogenesis balance. The hydrolysis efficiency correlated (p

Summary: Activating the macrophage NLRP3 inflammasome can promote excessive inflammation with severe cell and tissue damage and organ dysfunction. Here, we show that pharmacological or genetic inhibition of pyruvate dehydrogenase kinase (PDHK) significantly attenuates NLRP3 inflammasome activation in murine and human macrophages and septic mice by lowering caspase-1 cleavage and interleukin-1β (IL-1β) secretion. Inhibiting PDHK reverses NLRP3 inflammasome-induced metabolic reprogramming, enhances autophagy, promotes mitochondrial fusion over fission, preserves crista ultrastructure, and attenuates mitochondrial reactive oxygen species (ROS) production. The suppressive effect of PDHK inhibition on the NLRP3 inflammasome is independent of its canonical role as a pyruvate dehydrogenase regulator. Our study suggestsa non-canonical role of mitochondrial PDHK in promoting mitochondrial stress and supporting NLRP3 inflammasome activation during acute inflammation.

To obtain independent navigation results for autonomous underwater vehicles (AUVs) and construct high-resolution consistent seabed maps, a particle filter-based bathymetric simultaneous localization and mapping (BSLAM) method with the mean trajectory map representation is proposed. To reduce the computational consumption, particles only keep the current estimated position of the vehicle, while all historical states of the vehicle are stored in the mean trajectory map. Using this set-up, only the weights of the particles which closed to the mean trajectory map are calculated with newly collected bathymetric data. A hierarchical clustering procedure is also discussed to identify invalid loop closures. The performance of the proposed method is validated using both the simulated data and the field data collected from sea trails. The results demonstrate that the proposed method is 50% more accurate and 50% faster than a state-of-the-art particle filter-based BSLAM method, and it has similar accuracy but 30% faster compared with a graph-based BSLAM method.

A graph-based particle filter bathymetric simultaneous localization and mapping (BSLAM) method is proposed to solve the oscillation problem of the trajectories estimated by particles when using a low precise vehicle motion model and obtain accurate navigation results for autonomous underwater vehicles (AUVs). A graph-based trajectory update method is proposed to update the trajectories stored in particles before particle weighting to weaken the influence of the low precise odometer model on the particle trajectories. A particle weighting method based on submap matching is proposed to improve the robustness of the particle filter. Besides, a graph-based map generation method is proposed to solve the map selection problem of the particle filtering theory. The performance of the proposed method is demonstrated using a simulated dataset and a field dataset collected from a sea trial. The results show that the proposed method is more accurate and effective compared with a state-of-art particle filter BSLAM method.

H9N2 avian influenza viruses are widely prevalent in birds and pose an increasing threat to humans because of their enhanced virulence and transmissibility in mammals. Active surveillance on the prevalence and evolution of H9N2 viruses in different avian hosts will help develop eradication measures. We isolated 16 H9N2 viruses from chickens, green peafowls, and wild birds in eastern China from 2017 to 2019 and characterized their comparative genetic evolution, receptor-binding specificity, antigenic diversity, replication, and transmission in chickens and mice. The phylogenetic analysis indicated that the green peafowl viruses and swan reassortant shared the same ancestor with the poultry H9N2 viruses prevalent in eastern China, while the seven wild bird viruses belonged to wild bird lineage. The chicken, peafowl, and swan H9N2 viruses that belonged to the poultry lineage preferentially recognized α-2, 6-linked sialic acids (human-like receptor), but the wild bird lineage viruses can bind both α-2, 3 (avian-like receptor) and human-like receptor similarly. Interestingly, the H9N2 viruses of poultry lineage replicated well and transmitted efficiently, but the viruses of wild bird lineage replicated and transmitted with low efficiency. Importantly, the H9N2 viruses of poultry lineage replicated in higher titer in mammal cells and mice than the viruses of wild birds lineage. Altogether, our study indicates that co-circulation of the H9N2 viruses in poultry, wild birds, and ornamental birds increased their cross-transmission risk in different birds because of their widespread dissemination.

Abstract Background Asthma, a common respiratory disease, is harmful biological effect to our health. As a traditional Chinese medicine for asthma, Majie cataplasm could alleviate the symptoms of asthma and its compositions have immunomodulatory effects. Previous experiments showed that Majie cataplasm was an effective approach to mitigate asthma airway remodeling and had the potential to regulate Th2 cytokines of IL-5 and IL-13. Therefore, our further research focuses on the explanation about the regulatory effect of Majie cataplasm on reshaping Th1/Th2 through their related transcription factors. Methods In this experiment, the launch of asthma model was made by inducing with Ovalbumin (OVA) in C57 mice (n = 40), including 4 groups: the untreated control group (n = 10), the asthma model group (n = 10), the dexamethasone group (n = 10) and the Majie cataplasm group (n = 10). After the intervention, all groups of animals got detected for serum IgE levels, and HE staining of lung tissues was to observe and examine pathological changes. Meanwhile, we analyzed the secretion of IL-4+ T cells and IFN-γ+ T cells in spleen by flow cytometry. The expressions of transcription factor STAT6 mRNA, GATA-3 mRNA and T-bet mRNA in lung tissues was tested by PCR, and western blot had been used to detect levels of JAK2 and STAT3. Results We found that Majie cataplasm eased the content of serum IgE and lung inflammation. It could lower the increased number of IL-4+ T cells and IFN-γ+ T cells (P

Micro- and nanoscale photonic structures and devices play important roles in the development of advanced biophotonic systems, in particular, implantable light sources for optogenetic stimulations. In this paper, we numerically investigate silicon (Si) photonics based microprobes that can achieve multi-site, multi-spectral optical excitation in the deep animal brain. On Si substrates, silicon nitride (Si3N4) based planar waveguides can deliver visible light in the deep tissue with low losses, and couple to grating emitters diffracting light in targeted brain regions. In our model, we combine near-field wave optic and far-field ray tracing simulations, showing that the designed photonic structures spectrally split blue, green and red photons into different locations in the tissue. Furthermore, by introducing dual grating components, photons at different wavelengths can be spatially separated at different depths. Therefore, these photonic probes can be used to selectively activate or inhibit specific neurons and nuclei, when expressing various corresponding light sensitive opsins. We anticipate that such device strategies can find wide applications in the design of advanced implantable photonic systems for neuroscience and neuroengineering.

Inhaling silica dust in the environment can cause progressive pulmonary fibrosis, then silicosis. Silicosis is the most harmful occupational disease in the world, so the study of the mechanism is of great significance for the prevention and treatment of silicosis. Long non-coding RNAs (lncRNAs) are important players in the pathological process of fibrotic diseases. However, the function of specific lncRNA in regulating pulmonary fibrosis remains elusive. In this study, a mouse model of pulmonary fibrosis via intratracheal instillation of silica particles was established, and the differential expression of lnc-SNHG1 and miR-326 in lung tissues and TGF-β1-treated fibroblasts was detected by the qRT-PCR method. Short interfering RNA (siRNA) and plasmid were designed for knockdown or overexpression of lnc-SNHG1 in fibroblasts. MiRNA simulant was designed for overexpression of miR-326 in vivo and in vitro. Dual-luciferase reporter system, immunofluorescence, western blot, wound healing and transwell assay were performed to investigate the function and the underlying mechanisms of lnc-SNHG1. As a result, we found that lnc-SNHG1 was highly expressed in fibrotic lung tissues of mice and TGF-β1-treated fibroblasts. Moreover, the high expression of lnc-SNHG1 facilitated the migration and invasion of fibroblasts and the secretion of fibrotic molecules, while the low expression of lnc-SNHG1 exerted the opposite effects. Further mechanism studies showed that miR-326 was the potential target of lnc-SNHG1, and there is a negative correlation between the expression levels of lnc-SNHG1 and miR-326. Combined with mitigating fibrotic effects of miR-326 in a mouse model of silica particles exposure, we revealed that lnc-SNHG1 significantly sponged miR-326 and facilitated the expression of SP1, thus accelerating fibroblast-to-myofibroblast transition and synergistically promoting the development of pulmonary fibrosis. Our study uncovered a key mechanism by which lnc-SNHG1 regulated pulmonary fibrosis through miR-326/SP1 axis, and lnc-SNHG1 is a potential target for the prevention and treatment of silicosis.

Macrophages play a central role in the pathogenesis of atherosclerosis. Our previous study demonstrated that solute carrier family 37 member 2 (SLC37A2), an endoplasmic reticulum-anchored phosphate-linked glucose-6-phosphate transporter, negatively regulates macrophage Toll-like receptor activation by fine-tuning glycolytic reprogramming in vitro. Whether macrophage SLC37A2 impacts in vivo macrophage inflammation and atherosclerosis under hyperlipidemic conditions is unknown. We generated hematopoietic cell-specific SLC37A2 knockout and control mice in C57Bl/6 Ldlr−/− background by bone marrow transplantation. Hematopoietic cell-specific SLC37A2 deletion in Ldlr−/− mice increased plasma lipid concentrations after 12-16 wks of Western diet induction, attenuated macrophage anti-inflammatory responses, and resulted in more atherosclerosis compared to Ldlr−/− mice transplanted with wild type bone marrow. Aortic root intimal area was inversely correlated with plasma IL-10 levels, but not total cholesterol concentrations, suggesting inflammation but not plasma cholesterol was responsible for increased atherosclerosis in bone marrow SLC37A2-deficient mice. Our in vitro study demonstrated that SLC37A2 deficiency impaired IL-4-induced macrophage activation, independently of glycolysis or mitochondrial respiration. Importantly, SLC37A2 deficiency impaired apoptotic cell-induced glycolysis, subsequently attenuating IL-10 production. Our study suggests that SLC37A2 expression is required to support alternative macrophage activation in vitro and in vivo. In vivo disruption of hematopoietic SLC37A2 accelerates atherosclerosis under hyperlipidemic pro-atherogenic conditions.

Bovine parainfluenza virus 3 (BPIV3) is one of several viruses that contribute to bovine respiratory disease complex (BRDC). During this study, isolation of BPIV3 was attempted from 20 PCR-positive swabs by Madin-Darby Bovine Kidney (MDBK) cells. Nine samples showed obvious cytopathic lesions identified as BPIV3 by reverse-transcription polymerase chain reaction amplification and sequencing. The genomes of isolates XJ21032-1 and XJ20055-3 were sequenced using Illumina sequencing technology and determined to have lengths of 15,512 bp and 15,479 bp, respectively. Phylogenetic analysis revealed that isolate XJ21032-1 was genotype B, and isolate XJ20055-3 was genotype C. In addition, the two isolates had multiple amino acid changes in nucleocapsid protein, fusion protein, and hemagglutinin/neuraminidase, major antigenic proteins. This allows the further recognition of the presence of BPIV3 type B in Chinese cattle herds. We hope this will help trace the origin of BPIV3, improve the understanding of differences between genotypes, and provide data support for vaccine development.

Terrain aided navigation (TAN) technology can yield accurate navigation results in long-endurance underwater operation of autonomous underwater vehicles (AUVs). Most TAN research focus on the high-precision terrain matching algorithms. However, terrain matching algorithms estimate the position of the vehicle by observing a unique combination of features in the terrain, making it difficult to locate a vehicle with flat terrain. This paper presents a path planning method for AUV seabed TAN process to decrease positioning errors by avoiding flat areas. In this paper, a TAN path planning algorithm based on sector search is proposed. Parameters of the sector search algorithm are determined through theoretical analysis, which means the generated path can stably provide accurate TAN location results. Meanwhile, a control coefficient is proposed to maximize the terrain information contained in the sector searching area, bring out a high success rate of AUV positioning. The TAN performance of the paths generated using the proposed path planning method was verified in simulations, which show that the TAN can yield accurate positioning results stably on the path planned.

Satellite-retrieved and model-based reanalysis precipitation products with high resolution have received increasing attention in recent decades. Their hydrological performance has been widely evaluated. However, whether they can be applied in characterizing the novel category of extreme events, such as compound moist heat-flood (CMHF) events, has not been fully investigated to date. The CMHF refers to the rapid transition from moist heat stress to devastating floods and has occurred increasingly frequently under the current warming climate. This study focuses on the applicability of the Integrated Multi-satellite Retrievals for Global Precipitation Measurement (IMERG) and the fifth generation of European Reanalysis (ERA5-Land) in simulating CMHF events over 120 catchments in China. Firstly, the precipitation accuracy of IMERG and ERA5-Land products is appraised for each catchment, using the gridded in situ meteorological dataset (CN05.1) as a baseline. Then, the ability of IMERG and ERA5-Land datasets in simulating the fraction, magnitude, and decade change of floods and CMHFs is comprehensively evaluated by forcing the XAJ and GR4J hydrological models. The results show that: (a) the IMERG and ERA5-Land perform similarly in terms of precipitation occurrences and intensity; (b) the IMERG yields discernably better performance than the ERA5-Land in streamflow simulation, with 71.7% and 50.8% of catchments showing the Kling–Gupta efficiency (KGE) higher than 0.5, respectively; (c) both datasets can roughly capture the frequency, magnitude, and their changes of floods and CMHFs in recent decades, with the IMERG exhibiting more satisfactory accuracy. Our results indicate that satellite remote sensing and atmospheric reanalysis precipitation can not only simulate individual hydrological extremes in most regions, but monitor compound events such as CMHF episodes, and especially, the IMERG satellite can yield better performance than the ERA5-Land reanalysis.

TRPV4 (transient receptor potential vanilloid 4), a calcium permeable TRP ion channel, is known to play a key role in endocytosis. However, whether it contributes to exocytosis remains unclear. Here, we report that activation of TRPV4 induced massive exocytosis in both melanoma A375 cell and heterologous expression systems. We show here that, upon application of TRPV4-specific agonists, prominent vesicle priming from endoplasmic reticulum (ER) was observed, followed by morphological changes of mitochondrial crista may lead to cell ferroptosis. We further identified interactions between TRPV4 and folding/vesicle trafficking proteins, which were triggered by calcium entry through activated TRPV4. This interplay, in turn, enhanced TRPV4-mediated activation of folding and vesicle trafficking proteins to promote exocytosis. Our study revealed a signaling mechanism underlying stimulus-triggered exocytosis in melanoma and highlighted the role of cellular sensor TRPV4 ion channel in mediating ferroptosis.

[This corrects the article DOI: 10.1371/journal.ppat.1004508.].

In this paper, the microstructure and mechanical properties of FeCrMoVC high-speed steels fabricated using a rapid solidification technique were investigated. It was found that the alloy with free V content exhibited ultra-high fracture strength of 4900 MPa and large compression strain of 31.8%, but a lower yield strength of 1100 MPa. In contrast, with V content to 4 at%, the yield strength increased significantly to 3200 MPa. Micro-structure analysis revealed that the V addition plays an important role in promoting the formation of skeleton-like carbide (V6C5 phase), which can hinder the rapid propagation of shear bands, resulting in a good mechanical property. This special hard and finely ramified carbide network throughout the overall specimen can be regarded as a specific structure signal for the excellent mechanical properties of FeCrMoVC alloys. This result of the alloy with good mechanical property is expected to be used in industry as a high strength tool steel. Keywords: Microstructure, High-strength, Large compression strain, Carbide network

In practical applications, the rational operation rule derivation can lead to significant improvements in the middle and long-term joint operation of cascade hydropower stations. The key issue of actual optimal operation is to select effective attributions from the deterministic optimal operation results, however, there is still no general and mature method to solve this problem. Firstly, the joint optimal operation model of hydropower reservoirs considering backwater effects are established. Then, the dynamic programming and progressive optimality algorithm are applied to solve the joint optimal operation model and the deterministic optimization results are obtained. Finally, the grey relational analysis method is applied to select more effective factors from the obtained results as the input of a support vector machine for further operation rule derivation. The Xi Luo-du and Xiang Jia-ba cascade reservoirs in the upper Yangtze river of China are selected as a case study. The results show that the proposed method can obtain better input factors to improve the performance of SVM, and smallest value of root mean square error by the proposed method of Xi Luo-du and Xiang Jia-ba are 94.33 and 21.32, respectively. The absolute error of hydropower generation for Xi Luo-du and Xiang Jia-ba are 2.57 and 0.42, respectively. Generally, this study provides a well and promising alternative tool to guide the joint operation of hydropower reservoir systems.

Abstract Background Classical swine fever (CSF) is a highly contagious fatal infectious disease caused by classical swine fever virus (CSFV). A better understanding of CSFV replication is important for the study of pathogenic mechanism of CSF. With the development of novel RNA in situ Hybridization method, quantitatively localization and visualization of the virus RNA molecular in cultured cell or tissue section becomes very important tool to address these pivotal pathogenic questions. In this study, we established ViewRNA ISH method to reveal the dynamic distribution of CSFV RNA in PK15 cells. Methods We designed several specific probes of CSFV RNA and reference gene β-actin for host PK15 cells to monitor the relative location of CSFV RNA and house-keeping gene in the infected cells. After determining the titer of reference strain CSFV (HeBHH1/95) with the 50% tissue culture infective dose (TCID50), we optimized the protease K concentration and formalin fixation time to analyze the hybridization efficiency, fluorescence intensity and repeatability. In order to measure the sensitivity of this assay, we compared it with the fluorescent antibody test (FAT) and immunohistochemical(IHC) method. Specificity of the ViewRNA ISH was tested by detecting several sub genotypes of CSFV (sub genotype 1.1, 2.1, 2.2 and 2.3) which are present in China and other normal pig infectious virus (bovine viral diarrhea virus (BVDV), porcine parvovirus (PPV), porcine pseudorabies virus (PRV) and porcine circovirusII(PCV-2). Results The lowest detection threshold of the ViewRNA ISH method was 10−8, while the sensitivity of FAT and IHC were 10−5 and 10−4, respectively. The ViewRNA ISH was specific for CSFV RNA including 1.1, 2.1, 2.2 and 2.3 subtypes, meanwhile, there was no cross-reaction with negative control and other viruses including BVDV, PPV, PRV and PCV-2. Our results showed that after infection at 0.5 hpi (hours post inoculation, hpi), the CSFV RNA can be detected in nucleus and cytoplasm; during 3–9 hpi, RNA was mainly distributed in nucleus and reached a maximum at 12hpi, then RNA copy number was gradually increased around the cell nucleus during 24–48 hpi and reached the peak at 72hpi. Conclusions To our knowledge, this is the first to reveal the dynamic distribution of medium virulence CSFV RNA in PK15 cells using the ViewRNA ISH method. The sensitivity of the ViewRNA ISH was three to four orders of magnitude higher than that of FAT and IHC methods. The specificity experiment showed that the ViewRNA ISH was highly specific for CSFV and no cross-reaction occurred to negative control and other pig infectious virus. This assay is more suitable for studying the CSFV RNA life cycle in cell nucleus. The results proved that CSFV RNA enters into PK15 cells earlier than 0.5hpi, relative to the eclipse period of cytoplasm is 6–9 hpi and CSFV RNA has ever existed in nucleus.

Diabetic retinopathy (DR), one of the leading causes of blindness, is mainly diagnosed based on the vascular pathology of the disease. Current treatment options largely focus on this aspect with mostly insufficient therapeutic long-term efficacy. Mounting evidence implicates mitochondrial dysfunction and oxidative stress in the central etiology of DR. Consequently, drug candidates that aim at normalizing mitochondrial function could be an attractive therapeutic approach. This study compared the mitoprotective compounds, idebenone and elamipretide, side-by-side against two novel short-chain quinones (SCQs) in a rat model of DR. The model effectively mimicked type 2 diabetes over 21 weeks. During this period, visual acuity was monitored by measuring optokinetic response (OKR). Vision loss occurred 5–8 weeks after the onset of hyperglycemia. After 10 weeks of hyperglycemia, visual function was reduced by 65%. From this point, the right eyes of the animals were topically treated once daily with the test compounds. The left, untreated eye served as an internal control. Only three weeks of topical treatment significantly restored vision from 35% to 58–80%, while visual acuity of the non-treated eyes continued to deteriorate. Interestingly, the two novel SCQs restored visual acuity better than idebenone or elamipretide. This was also reflected by protection of retinal pathology against oxidative damage, retinal ganglion cell loss, reactive gliosis, vascular leakage, and retinal thinning. Overall, mitoprotective and, in particular, SCQ-based compounds have the potential to be developed into effective and fast-acting drug candidates against DR.

Dew is a significant water resource in arid desert areas. However, information regarding dew is scarce because it is difficult to measure due to the harsh environment of locations such as Gurbantunggut Desert, China. In this study, a non-destructive field experiment was conducted from 2015 to 2018 at a desert test station located in the western edge of the Gurbantunggut Desert, using a calibrated leaf wetness sensor (LWS) to measure dew yield. The results are as follows: (1) Dew formed after sunset with the atmospheric temperature gradually dropping and evaporated after sunrise with the temperature increasing in the second morning. (2) Dew was featured as ‘high frequency and low yield’. The average daily dew yield during dew days was 0.10 mm with a daily maximum of 0.62 mm, while dew days accounted for 44% of the total monitoring days, with a monthly maximum of 25 days. Compared with rainfall, dew days were two times as frequent as rainy days, while the average annual dewfall (12.21 mm) was about 1/11th of the average annual rainfall (134.6 mm), which indicates the dew contribution to regional water balance is about 9%. (3) March–April and October–November are the main periods of dew occurrence in this region because accumulated snow begins to melt slowly in March–April, providing sufficient vapor for dew formation, and the air temperature difference between day and night in October–November is the highest in the year, meaning that the temperature drops rapidly at night, making it easier to reach the dewpoint for vapor condensation. (4) Daily dew yield (D) was positively correlated to relative humidity (RH) and the difference between soil temperature at 10 cm below the ground and surface soil temperature (Tss), and negatively correlated to wind speed (V), air temperature (Ta), surface soil temperature (Ts), cloud cover (N), dewpoint temperature (Td) and the difference between air temperature and dewpoint temperature (Tad). It should be noted that the measured values of all factors above were the average value of the overnight period. The multivariate regression equation, D = −0.705 + 0.011 × RH − 0.006 × N − 0.01 × V, can estimate the daily dew yield with the thresholds of the parameters, i.e., RH > 70%, N < 7 (oktas) and V < 6 m/s.

Optical fibers and waveguides in general effectively control and modulate light propagation, and these tools have been extensively used in communication, lighting and sensing. Recently, they have received increasing attention in biomedical applications. By delivering light into deep tissue via these devices, novel applications including biological sensing, stimulation and therapy can be realized. Therefore, implantable fibers and waveguides in biocompatible formats with versatile functionalities are highly desirable. In this review, we provide an overview of recent progress in the exploration of advanced optical fibers and waveguides for biomedical applications. Specifically, we highlight novel materials design and fabrication strategies to form implantable fibers and waveguides. Furthermore, their applications in various biomedical fields such as light therapy, optogenetics, fluorescence sensing and imaging are discussed. We believe that these newly developed fiber and waveguide based devices play a crucial role in advanced optical biointerfaces.

Osteosarcoma is the most frequent type of malignant bone tumor in children and adolescents and is associated with a high propensity for lung metastasis. Recent experiments have indicated that PLA2G16 contributes to osteosarcoma progression and metastasis in both mouse and human osteosarcoma cell lines. The aim of this study was to compare the expression of PLA2G16 in non-metastatic and metastatic osteosarcomas to determine whether PLA2G16 expression can serve as a biomarker of osteosarcoma prognosis and metastasis.Quantitative real-time PCR was used to examine PLA2G16 mRNA in primary osteosarcoma patients (18 patients without metastases and 17 patients with metastases), and immunohistochemistry (IHC) staining of PLA2G16 was performed on tissue microarrays from 119 osteosarcoma patients. Tumor metastatic behavior and survival of the patients were followed up for a minimum of 36 months and a maximum of 171 months. The prognostic value of PLA2G16 expression was evaluated by the Kaplan-Meier method and a log-rank test. Multivariate Cox regression analysis was used to identify significant independent prognostic factors.Osteosarcoma patients with metastasis showed a higher expression of PLA2G16 at both the mRNA and protein levels (both at P values< 0.05) than did patients without metastasis. Osteosarcoma patients with positive IHC staining of PLA2G16 expression at primary sites had shorter overall survival and metastasis-free survival (both at P values

H9N2 subtype influenza viruses have been detected in different species of wild birds and domestic poultry in many countries for several decades. Because these viruses are of low pathogenicity in poultry, their eradication is not a priority for animal disease control in many countries, which has allowed them to continue to evolve and spread. Here, we characterized the genetic variation, receptor-binding specificity, replication capability, and transmission in mammals of a series of H9N2 influenza viruses that were detected in live poultry markets in southern China between 2009 and 2013. Thirty-five viruses represented 17 genotypes on the basis of genomic diversity, and one specific "internal-gene-combination" predominated among the H9N2 viruses. This gene combination was also present in the H7N9 and H10N8 viruses that have infected humans in China. All of the 35 viruses preferentially bound to the human-like receptor, although two also retained the ability to bind to the avian-like receptor. Six of nine viruses tested were transmissible in ferrets by respiratory droplet; two were highly transmissible. Some H9N2 viruses readily acquired the 627K or 701N mutation in their PB2 gene upon infection of ferrets, further enhancing their virulence and transmission in mammals. Our study indicates that the widespread dissemination of H9N2 viruses poses a threat to human health not only because of the potential of these viruses to cause an influenza pandemic, but also because they can function as "vehicles" to deliver different subtypes of influenza viruses from avian species to humans.