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Mesenchymal stem cell (MSC)-based therapies have emerged as promising methods for regenerative medicine; however, how to precisely enhance their tissue repair effects is still a major question in the field. Circulating extracellular vesicles (EVs) from diseased states carry diverse pathological information and affect the functions of recipient cells. Based on this unique property, we report that disease-derived circulating EV (disease-EV) preconditioning is a potent strategy for precisely enhancing the tissue repair potency of MSCs in diverse disease models. Briefly, plasma EVs from lung or kidney tissue injuries were shown to contain distinctly enriched molecules and were shown to induce tissue injury-specific gene expression responses in cultured MSCs. Disease-EV preconditioning improved the performance (including proliferation, migration, and growth factor production) of MSCs through metabolic reprogramming (such as via enhanced oxidative phosphorylation and lipid metabolism) without inducing an adverse immune response. Consequently, compared with normal MSCs, disease-EV-preconditioned MSCs exhibited superior tissue repair effects (including anti-inflammatory and antiapoptotic effects) in diverse types of tissue injury (such as acute lung or kidney injury). Disease-derived EVs may serve as a type of “off-the-shelf” product due to multiple advantages, such as flexibility, stability, long-term storage, and ease of shipment and use. This study highlights the idea that disease-EV preconditioning is a robust strategy for precisely enhancing the regenerative capacity of MSC-based therapies.

Abstract Bovine mastitis is an infectious disease that causes substantial economic losses to the dairy industry worldwide. Current antibiotic therapy faces issues of antibiotic misuse and antimicrobial resistance, which has aroused concerns for both veterinary and human medicine. Thus, this study explored the potential of Colo EVs (bovine colostrum-derived extracellular vesicles) to address mastitis. Using LPS-induced murine mammary epithelial cells (HC11), mouse monocyte macrophages (RAW 264.7), and a murine mastitis model with BALB/C mice, we evaluated the safety and efficacy of Colo EVs, in vivo and in vitro. Colo EVs had favorable biosafety profiles, promoting cell proliferation and migration without inducing pathological changes after injection into murine mammary glands. In LPS-induced murine mastitis, Colo EVs significantly reduced inflammation, improved inflammatory scores, and preserved tight junction proteins while protecting milk production. Additionally, in vitro experiments demonstrated that Colo EVs downregulated inflammatory cytokine expression, reduced inflammatory markers, and attenuated NF-κB pathway activation. In summary, we inferred that Colo EVs have promise as a therapeutic approach for mastitis treatment, owing to their anti-inflammatory properties, potentially mediated through the NF-κB signaling pathway modulation. Graphical Abstract

Abstract Macrophages (Mφ) autophagy is a pivotal contributor to inflammation-related diseases. However, the mechanistic details of its direct role in acute kidney injury (AKI) were unclear. Here, we show that Mφ promote AKI progression via crosstalk with tubular epithelial cells (TECs), and autophagy of Mφ was activated and then inhibited in cisplatin-induced AKI mice. Mφ-specific depletion of ATG7 (Atg7Δmye) aggravated kidney injury in AKI mice, which was associated with tubulointerstitial inflammation. Moreover, Mφ-derived exosomes from Atg7Δmye mice impaired TEC mitochondria in vitro, which may be attributable to miR-195a-5p enrichment in exosomes and its interaction with SIRT3 in TECs. Consistently, either miR-195a-5p inhibition or SIRT3 overexpression improved mitochondrial bioenergetics and renal function in vivo. Finally, adoptive transfer of Mφ from AKI mice to Mφ-depleted mice promotes the kidney injury response to cisplatin, which is alleviated when Mφ autophagy is activated with trehalose. We conclude that exosomal miR-195a-5p mediate the communication between autophagy-deficient Mφ and TECs, leading to impaired mitochondrial biogenetic in TECs and subsequent exacerbation of kidney injury in AKI mice via miR-195a-5p-SIRT3 axis.

The ionic liquid, as a new treatment agent, has been increasingly applied in oil fields due to its strong temperature resistance, good solubility and high surface activity. In this paper, we systematically discuss the action mechanism and application effect of ionic liquids in oilfield chemistry. Ionic liquids can inhibit shale hydration expansion and reduce fluid loss through adsorption and intercalation, inhibit the formation of natural gas hydrate through imidazole five-membered ring structure as a space barrier, reduce viscosity of heavy oil by breaking chemical bonds of heavy oil macromolecules and charge transfer, improve oil displacement efficiency by forming ions pairs with carboxyl groups in crude oil, demulsify by forming channels between dispersed water droplets, acidify the formation by reacting with water to produce acid, interacts with organic material through weak hydrogen bonds and extracts it from oilfield wastewater, desulphurize by inserting sulfide molecules into the “stack” structure and form liquid inclusion complex, inhibit corrosion by forming a protective film on the metal surface. Based on the above aspects, the development direction of ionic liquids is proposed. The application of ionic liquids in oilfield chemistry is still in its infancy. It is urgent to fully explore the application performance of ionic liquids in oilfield chemistry, which also provides theoretical and technical supports for efficient reservoir development.

Abstract In this study, much work has been performed to accurately and efficiently develop representative actual driving cycles. Electric vehicle road tests were conducted and the associated data were gathered based on the manual driving method, and the Changsha Driving Cycle Construction (CS-DCC) method was proposed to achieve systematical construction of a representative driving cycle from the original data. The results show that the refined data exhibit greater stability and a smoother pattern in contrast to the original data after noise reduction by five-scale wavelet analysis. The Gaussian Kernel Principal Component Analysis (KPCA) algorithm is chosen to reduce the dimensionality of the characteristic matrix, and the number of principal components is selected as 5 with a cumulative contribution rate of 85.99%. The average error of the characteristic parameters between the optimized drive cycle and the total data is further reduced from 13.6 to 6.1%, with a reduction ratio of 55.1%. Meanwhile, the constructed driving cycle has prominent local characteristics compared with four standard driving cycles, demonstrating the necessity of constructing an actual driving cycle that reflects localized driving patterns. The findings present a powerful application of artificial intelligence in advancing engineering technologies.

Osteoporosis (OP) is a systemic skeletal disease that primarily affects the elderly population, which greatly increases the risk of fractures. Here we report that Kindlin-2 expression in adipose tissue increases during aging and high-fat diet fed and is accompanied by decreased bone mass. Kindlin-2 specific deletion (K2KO) controlled by Adipoq-Cre mice or adipose tissue-targeting AAV (AAV-Rec2-CasRx-sgK2) significantly increases bone mass. Mechanistically, Kindlin-2 promotes peroxisome proliferator-activated receptor gamma (PPARγ) activation and downstream fatty acid binding protein 4 (FABP4) expression through stabilizing fatty acid synthase (FAS), and increased FABP4 inhibits insulin expression and decreases bone mass. Kindlin-2 inhibition results in accelerated FAS degradation, decreased PPARγ activation and FABP4 expression, and therefore increased insulin expression and bone mass. Interestingly, we find that FABP4 is increased while insulin is decreased in serum of OP patients. Increased FABP4 expression through PPARγ activation by rosiglitazone reverses the high bone mass phenotype of K2KO mice. Inhibition of FAS by C75 phenocopies the high bone mass phenotype of K2KO mice. Collectively, our study establishes a novel Kindlin-2/FAS/PPARγ/FABP4/insulin axis in adipose tissue modulating bone mass and strongly indicates that FAS and Kindlin-2 are new potential targets and C75 or AAV-Rec2-CasRx-sgK2 treatment are potential strategies for OP treatment.

Abstract Objective While existing literature has provided insights into involvement of circEPHB4, SOX2 in glioma, their precise molecular mechanisms and synergistic implications in glioma pathogenesis still dim. This study aims to investigate significance and underlying mechanism of m6A‐modified circEPHB4 in regulating SOX2/PHLDB2 axis in gliomas. Methods The mRNA and protein expression were tested by qRT‐PCR and Western blot, respectively. ChIP assay was performed to detect SOX2 enrichment on the PHLDB2 promoter. Cell sphere‐forming assay to detect self‐renewal ability, flow cytometry to determine positivity of CD133 expressions, Malignant behavior of glioma cells were detected by CCK‐8, plate colony formation, scratch, and transwell assays. Glioma xenograft models were constructed to investigate effects of CircEPHB4 in tumor development in vivo. Results Methyltransferase MELLT3 upregulated m6A modification of CircEPHB4, and YTHDC1 promoted cytoplasmic localization of m6A‐modified CircEPHB4. Overexpression of wild‐type CircEPHB4 enhanced glioma cells' stemness, metastasis, and proliferation. Cytoplasmic CircEPHB4 increased SOX2 mRNA stability by binding to IGF2BP2, and the effects observed by SOX2 knockdown were reversed by CircEPHB4 in glioma cells. SOX2 promoted transcriptional expression of PHLDB2 by enriching the PHLDB2 promoter region. SOX2 reversed the inhibition of PHLDB2 knockdown on stemness of glioma, cell proliferation, and metastasis. In vivo experiments also revealed that CircEPHB4 upregulated PHLDB2 expression by stabilizing SOX2 mRNA, which promoted in vivo tumor growth and accelerated stemness of glioma cells and metastasis. Conclusion This study reveals functional interaction and molecular mechanisms of m6A‐modified circEPHB4 in regulating SOX2/PHLDB2 axis, highlighting their importance in glioma pathogenesis and potential as therapeutic targets.

To investigate the effect of the chemical composition of a metal–organic crosslinker on the performances of fracturing fluid in high-temperature conditions, four zirconium (Zr) crosslinkers and one aluminum–zirconium (Al-Zr) crosslinker with a polyacrylamide were used. The crosslinkers possessed the same Zr concentration, but they differed in component amounts and the order of the addition of the crosslinker components, leading to different chemical compositions in the crosslinkers. The fracturing fluids prepared by different tested crosslinkers were compared in terms of properties of rheological behavior, sand-carrying ability, microstructure, and gel breaking characteristics. The results showed that the fracturing fluids prepared by zirconium lactic acid, ethanediamine, and sorbitol crosslinkers offered the slowest viscosity development and highest final viscosity compared to the zirconium lactic acid crosslinker and the zirconium lactic acid and ethanediamine crosslinker. The zirconium sorbitol, lactic acid, and ethanediamine crosslinker exhibited a faster crosslinking rate and a higher final viscosity than the zirconium lactic acid, ethanediamine, and sorbitol crosslinker; the crosslinker showed crosslinking density and crosslinking reactivity, resulting in more crosslinking sites and a higher strength in the fracturing fluid. The Al-Zr-based crosslinker possessed better properties in temperature and shear resistance, viscoelasticity, shear recovery, and sand-carrying ability than the Zr-based crosslinker due to the synergistic crosslinking effect of aluminum and zirconium ions. The tertiary release gelation mechanism of the Al-Zr-based fracturing fluid achieved a temperature resistance performance in the form of continuous crosslinking, avoiding the excessive crosslinking dehydration and reducing viscosity loss caused by early shear damage. These results indicated that the chemical compositions of metal–organic crosslinkers were important factors in determining the properties of fracturing fluids. Therefore, the appropriate type of crosslinker could save costs without adding the additional components required for high-temperature reservoirs.

Extracellular vesicles are nanoscale vesicles that transport signals between cells, mediating both physiological and pathological processes. EVs facilitate conserved intercellular communication. By transferring bioactive molecules between cells, EVs coordinate systemic responses, regulating homeostasis, immunity, and disease progression. Given their biological importance and involvement in pathogenesis, EVs show promise as biomarkers for veterinary diagnosis, and candidates for vaccine production, and treatment agents. Additionally, different treatment or engineering methods could be used to boost the capability of extracellular vesicles. Despite the emerging veterinary interest, EV research has been predominantly human-based. Critical knowledge gaps remain regarding isolation protocols, cargo loading mechanisms, in vivo biodistribution, and species-specific functions. Standardized methods for veterinary EV characterization and validation are lacking. Regulatory uncertainties impede veterinary clinical translation. Advances in fundamental EV biology and technology are needed to propel the veterinary field forward. This review introduces EVs from a veterinary perspective by introducing the latest studies, highlighting their potential while analyzing challenges to motivate expanded veterinary investigation and translation.

During the drilling process for oil and gas production, a larger number of drilling fluids invade the formation, causing severe formation damage and wellbore collapsing, which seriously hinders the efficient production of deep oil and gas. Although several plugging agents have been developed for efficient fracture sealing in recent years, the development of high-performance plugging agents with self-adaptive ability and high-temperature resistance remain a challenge. Herein, we report the synthesis of an internal rigid and external flexible plugging agent PANS by reversed-phase emulsion polymerization with nano-silica as the rigid core and poly (acrylamide-co-N-vinylpyrrolidone) as a flexible shell. The plugging agent has a median particle size of 10.5 μm and can self-adapt to seal the microfractures and fractures in the formation, leading to an effective reduction in the filtration loss of bentonite water-based drilling fluid under both low temperature and low pressure (LTLP) and high temperature and high pressure (HTHP) conditions. In addition, compared with the neat nano-silica (500 nm), the sealing efficiency of PANS toward 100–120 mesh sand bed was increased by 71.4% after hot rolling at 180°C.

In this paper, we conduct a comprehensive investigation into PVA fiber modified with SiO2 to improve the mechanical properties of oil-well cements. Specifically, SiO2 was coated onto the surface of polyvinyl alcohol fiber (PVAF) as its silicon source via a sol-gel process by using tetraethyl orthosilicate (TEOS), while hydrochloric acid and ammonia were respectively used as the catalyst in the sol (hydrolysis) and the gel (condensation) processes. The PVAF microstructure was then characterized with the scanning electron microscope (SEM), while the effects of the modified PVAF on both mechanical and rheological properties of oil-well cements were examined. Due to the fact that SiO2 can be uniformly coated onto the PVAF surface, such modified PVAF can slightly improve the rheology of the cement slurry, while the raw PVAF exhibits poor dispersion at a high dosage. Compared with those of cement stone without PVAF after curing for 28 days at 60 °C, the flexural strength, compressive strength, and elastic modulus of the cement stone incorporated with the modified PVAFs were enhanced by 37.7%, 66.1%, and 50.0%, respectively. The SEM test (EDX) test, XRD test, and thermogravimetric test prove that the SiO2 coating on the PVAF surface can promote the hydration of cement clinker and can react with Ca(OH)2 to generate CSH gel. The SiO2 grafted onto the surface of PVAFs can improve the bond strength at the fiber/cement matrix interface, thus improving the mechanical properties of cement stone.

This research aims to investigate thermal characteristics and assess thermal hazards of hydroxylamine nitrate (HAN)-based liquid propellant using a combination of accelerating rate calorimeter and high-pressure differential scanning calorimetry. Adiabatic experiments revealed that the exothermic reaction initiated at 115.7 °C and a rise sharply was at 128.4 °C with a maximum self-heating rate of 164.3 °C/min and the exothermic event was accompanied by a pressure rise of 3.7 bar in 0.03s. The corrected values of adiabatic temperature rise and time to maximum rate were 605.6 °C and 1.46 min, which confirms the vulnerability of the propellant to undergo a catastrophic explosion. To prevent thermal loss prevention accidents, time to maximum rate was obtained as 24 h under 111.3 °C. The apparent activation energy calculated decreased greatly with the increase of storage temperature from 25 °C to 45 °C, and so did the thermal explosion temperature (Tb) and self-accelerating decomposition temperature (TSADT). Additionally, the linear relationship between Ea and T was E = 991.7–2.7904T. The reliability of TSADT prediction was validated through slow cook-off test. Furthermore, the propellant exhibited more violent thermal decomposition under high pressure, resulting in a higher peak power. The thermokinetic parameters related to this phenomenon were identified, specifically at pressure of 4.0 MPa.

A model coupling Reynolds-averaged Navier-Stokes (RANS) method and linearized Navier-Stokes equations (LNSEs) was established in order to investigate the acoustic excitation and attenuation effect from a coupling perspective of time–space–frequency under various flow velocities and mass fractions of methane. Results show that the energy distribution of acoustic modes under high-frequency acoustic excitation is more uniform. The amplitude of the acoustic oscillation at a multiple coupling physical field is 10,000 times higher than that at simple flow field. The case when w C H 4 = 0.8 owns the largest percentage of energy conversion from fundamental to high-frequency signals, the largest percentage of transmitted waves from the combustion chamber system to outside and the strongest non-linear effect. When w C H 4 rises, the amplitude of oscillations at points and the attenuation effect of high-frequency signals along the axial are enhanced. At the case of U in = 15 m/s, the amplitude of harmonics is reduced by 18% compared with other cases, while the proportion of the high-frequency harmonic increases, proving the non-linearity cannot be neglected in this case. As velocity rises, the energy conversion from fundamental to high-frequency signals enhances; while closer to the outlet position, the more complex the oscillation signal is. Model-shapes analysis shows that a case of w C H 4 = 0.8 owns the largest amplitude of the second harmonic at downstream of the burner, while the amplitude of the harmonics rapidly increases at U in = 15 m/s at the end of the burner, which further indicates that the energy conversion of low-frequency signals to high-frequency signals occurs mainly in the middle and downstream regions.

In underwater wireless sensor network (UWSN), the AoA/TDoA-based ranging localization problem for nodes was formulated from a time-variant perspective, and a zeroing neural dynamics model was proposed to solve it.Then, the convergence of the proposed model was theoretically analyzed.Furthermore, computer simulations on UWSN localization were carried out to demonstrate the effectiveness of the proposed models in terms of accuracy and robustness to the mobile localization.Additionally, through tests performed in Qinghai lake, the coordinates of nodes of UWSN test-bed were leverage to illustrate the potential applicability of the proposed model in the true underwater environment.

Severe acute pancreatitis-associated acute lung injury (SAP-ALI) is a serious disease associated with high mortality. Emodin has been applied to alleviate SAP-ALI; however, the mechanism remains unclear. We report that the therapeutic role of emodin in attenuating SAP-ALI is partly dependent on an exosomal mechanism. SAP rats had increased levels of plasma exosomes with altered protein contents compared to the sham rats. These infused plasma exosomes tended to accumulate in the lungs and promoted the hyper-activation of alveolar macrophages and inflammatory damage. Conversely, emodin treatment decreased the plasma/pancreatic exosome levels in the SAP rats. Emodin-primed exosomes showed less pro-inflammatory effects in alveolar macrophages and lung tissues than SAP exosomes. In detail, emodin-primed exosomes suppressed the NF-κB pathway to reduce the activation of alveolar macrophage and ameliorate lung inflammation by regulating PPARγ pathway, while these effects were amplified/abolished by PPARγ agonist/antagonist. Blockage of pancreatic acinar cell exosome biogenesis also exhibited suppression of alveolar macrophage activation and reduction of lung inflammation. This study suggests a vital role of exosomes in participating inflammation-associated organ-injury, and indicates emodin can attenuate SAP-ALI by reducing the pancreatic exosome-mediated alveolar macrophage activation.

By combing the characteristics of drilling in Antarctic region, performance requirements on drilling fluid for Antarctic low temperature conditions, and research progress of low temperature drilling fluid, current problems of the drilling fluid have been sorted out, and the development direction of the drilling fluid has been pointed out. Drilling in the Antarctic region mainly includes drilling in snow, ice and subglacial rock formations, and drilling in Antarctic low temperature conditions will face problems in four aspects: (1) low temperature and large temperature changes in the drilling area; (2) likely well leakage and drillstring-sticking in the snow layer, creep in the ice layer, ice chip gathering jamming in the warm ice layer, well wall collapse in the subglacial rock formations; (3) lack of infrastructure and difficulty in logistical support; (4) fragile environment and low carrying capacity. After years of development, progresses have been made on low-temperature drilling fluids for the Antarctic region. Low-temperature petroleum-based drilling fluid, ethanol/ethylene glycol-based drilling fluid, ester-based drilling fluid and silicone oil-based drilling fluid have been developed. However, these drilling fluids have problems such as insufficient low-temperature tolerance, low environmental performance and weak wellbore stability, etc. In order to meet the performance requirements of drilling fluid under low-temperature conditions in Antarctic region, the working mechanisms of low-temperature drilling fluid must be examined in depth; environment-friendly low-temperature base fluid of drilling fluid and related additives must be developed to prepare environmentally friendly low temperature drilling fluid systems; multi-functional integrated adjustment method for drilling fluid must be worked out to ensure well wall stability and improve cutting-carry capacity when drilling ice formations and ice-rock interlayers; and on-site support operation codes must be established to provide technical support for Antarctic drilling.

Senescence of bone marrow mesenchymal stem cells (BMSCs) is one of the leading causes of osteoporosis. SIRT3, an essential NAD-dependent histone deacetylase, is highly correlated with BMSC senescence-mediated bone degradation and mitochondrial/heterochromatic disturbance. S-sulfhydration of cysteine residues favorably enhances SIRT3 activity by forming persulfides. Nevertheless, the underlying molecular mechanism of SIRT3 S-sulfhydration on mitochondrial/heterochromatic homeostasis involved in BMSC senescence remains unknown. Here, we demonstrated that CBS and CSE, endogenous hydrogen sulfide synthases, are downregulated with BMSC senescence. Exogenous H2S donor NaHS-mediated SIRT3 augmentation rescued the senescent phenotypes of BMSCs. Conversely, SIRT3 deletion accelerated oxidative stress-induced BMSC senescence through mitochondrial dysfunction and the detachment of the heterochromatic protein H3K9me3 from the nuclear envelope protein Lamin B1. H2S-mediated SIRT3 S-sulfhydration modification rescued the disorganized heterochromatin and fragmented mitochondria induced by the S-sulfhydration inhibitor dithiothreitol, thus leading to elevated osteogenic capacity and preventing BMSC senescence. The antisenescence effect of S-sulfhydration modification on BMSCs was abolished when the CXXC sites of the SIRT3 zinc finger motif were mutated. In vivo, aged mice-derived BMSCs pretreated with NaHS were orthotopically transplanted to the ovariectomy-induced osteoporotic mice, and we proved that SIRT3 ameliorates bone loss by inhibiting BMSC senescence. Overall, our study for the first time indicates a novel role of SIRT3 S-sulfhydration in stabilizing heterochromatin and mitochondrial homeostasis in counteracting BMSC senescence, providing a potential target for the treatment of degenerative bone diseases.

An inhibitor that can effectively inhibit shale hydration is necessary for the safe and efficient development of shale gas. In this study, a novel ionic liquid copolymer shale inhibitor (PIL) was prepared by polymerizing the ionic liquid monomers 1-vinyl-3-aminopropylimidazolium bromide, acrylamide, and methacryloyloxyethyl trimethyl ammonium chloride. The chemical structure was characterized using fourier transform infrared spectroscopy (FT-IR) and hydrogen-nuclear magnetic resonance (H-NMR), and the inhibition performance was evaluated using the inhibition of slurrying test, bentonite flocculation test, linear expansion test, and rolling recovery test. The experimental results showed that bentonite had a linear expansion of 27.9% in 1 wt% PIL solution, 18% lower than that in the polyether amine inhibitor. The recovery rate of shale in 1 wt% PIL was 87.4%. The ionic liquid copolymer could work synergistically with the filtrate reducer, reducing filtration loss to 7.2 mL with the addition of 1%. Mechanism analysis showed that PIL adsorbed negatively charged clay particles through cationic groups, which reduced the electrostatic repulsion between particles. Thus, the stability of the bentonite gel systems was destroyed, and the hydration dispersion and expansion of bentonite were inhibited. PIL formed a hydrophobic film on the surface of clay and prevented water from entering into the interlayer of clay. In addition, PIL lowered the surface tension of water, which prevented the water from intruding into the rock under the action of capillary force. These are also the reasons for the superior suppression performance of PIL.

Drilling fluids play an essential role in shale gas development. It is not possible to scale up the use of water-based drilling fluid in shale gas drilling in Yunnan, China, because conventional inhibitors cannot effectively inhibit the hydration of the illite-rich shale formed. In this study, the inhibition performance of modified asphalt was evaluated using the plugging test, expansion test, shale recovery experiment, and rock compressive strength test. The experimental results show that in a 3% modified asphalt solution, the expansion of shale is reduced by 56.3%, the recovery is as high as 97.8%, water absorption is reduced by 24.3%, and the compression resistance is doubled compared with those in water. Moreover, the modified asphalt can effectively reduce the fluid loss of the drilling fluid. Modified asphalt can form a hydrophobic membrane through a large amount of adsorption on the shale surface, consequently inhibiting shale hydration. Simultaneously, modified asphalt can reduce the entrance of water into the shale through blocking pores, micro-cracks, and cracks and further inhibit the hydration expansion of shale. This demonstrates that modified asphalt will be an ideal choice for drilling shale gas formations in Yunnan through water-based drilling fluids.

Abstract Mitochondrial damage plays vital roles in the pathology of many diseases, such as cancers, neurodegenerative diseases, aging, metabolic diseases and many types of organ injury. However, the regulatory mechanism of mitochondrial functions among different cells or organs in vivo is still unclear, and efficient therapies for attenuating mitochondrial damage are urgently needed. Extracellular vesicles (EVs) are cell‐derived nanovesicles that can deliver bioactive cargoes among cells or organs. Interestingly, recent evidence shows that diverse mitochondrial contents are enriched in certain EV subpopulations, and such mitoEVs can deliver mitochondrial components to affect the functions of recipient cells under different conditions, which has emerged as a hot topic in this field. However, the overview and many essential questions with respect to this event remain elusive. In this review, we provide a global view of mitoEVs biology and mainly focus on the detailed sorting mechanisms, functional mitochondrial contents, and diverse biological effects of mitoEVs. We also discuss the pathogenic or therapeutic roles of mitoEVs in different diseases and highlight their potential as disease biomarkers or therapies in clinical translation. This review will provide insights into the pathology and drug development for various mitochondrial injury‐related diseases.

Ensuring wellbore stability is of utmost importance for safety when drilling in deep formations. However, high temperatures severely disrupt the drilling fluid gel system, leading to severe stability issues within ultra-deep formations containing micropores. This study focused on the development of a polymer-based plugging material capable of withstanding high temperatures up to 200 °C. A kind of microsphere, referred to as SST (styrene–sodium styrene sulfonate copolymer), was synthesized with a particle size of 322 nm. Compared to polystyrene, the thermal stability of SST is greatly improved, with a thermal decomposition temperature of 362 °C. Even after subjecting SST to hot rolling at 200 °C for 16 h, the particle size, elemental composition, and zeta potential remained stable within an aqueous dispersion system. The results of core displacement and NMR tests demonstrate that SST considerably reduces the pore diameter with a remarkable plugging efficiency of 78.9%. Additionally, when drilling fluids reach 200 °C, SST still enhances drilling fluid suspension and dispersion, and reduces fluid loss by over 36% by facilitating the dispersion of clay particles, improving the gel structure of the drilling fluid, resisting clay dehydration, and promoting plugging. The development of SST provides valuable insights into the preparation of high-temperature-resistant microspheres and the formulation of effective plugging agents for deep-well drilling fluids.

With the gradual depletion of shallow oil and gas, deep oil and gas has become the focus of development. However, deep formations generally face the challenge of high-temperature and high-salinity, and drilling fluid agents are prone to failure, leading to drilling fluid intrusion into the formation that can cause serious drilling accidents such as well bore collapse. For this, a styrene-based nano-microsphere (SSD) modified with amphoteric ions was developed, with a particle size of 228 nm which could resist temperatures up to 200 °C and sodium chloride (NaCl) up to saturation. SSD has significant salt-responsive properties and its aqueous dispersion becomes transparent with increasing salinity. The SSD provided superior plugging performance in solutions containing NaCl, with a core plugging efficiency of 95.2%, and it was significantly better than the anion-modified microspheres. In addition, in drilling fluids under high temperature and high-salinity conditions, the SSD promotes particle gradation of drilling fluids and improves the zeta potential through its own plugging and synergistic effect with clay, which significantly improves the comprehensive performance of drilling fluids, such as stability, rheological performance, and filtration reduction performance. The development of SSD provides a new idea for research of high-temperature and high-salinity-resistant drilling fluid agents.

Ultra-wideband (UWB) antennas have recently gained prominence in communication, radar technology, and electronic warfare domains. The quick development of these antennas is due to the wide bandwidth requirements of pulse radar, ground penetrating radar, electromagnetic compatibility, spaceborne communication systems, stealth target detection, and more. Aiming to address the defects of existing UWB antennas, which often have narrow bandwidth and low gain, a planar ultra-wideband microstrip array antenna was designed to achieve good ultra-wideband characteristics and effectively improve the gain of the antenna. The initial bandwidth of the rectangular monopole antenna was 10 GHz–20 GHz. After loading multiple steps on the monopole patch, the bandwidth was increased to between 10 and 38 GHz. Using the new ultra-wideband array method that combines series feed and angle feed and the defective ground structure (DGS), the array maintains the ultrawide bandwidth span of 10–38 GHz of the array element, and the maximum gain of the antenna in the bandwidth was increased from 5.18 dBi to 9.55 dBi. The challenge of impedance matching of antenna units in ultra-wideband is resolved by the novel array technique, which also increases the antenna’s gain within the bandwidth. The antenna simulation is consistent with the measurement results. With its extensive operating frequency band, high gain, compactness, and favorable radiation attributes, this newly designed antenna holds significant promise for application in UWB radar systems.

Aim. The present study aimed at investigating associations of the platelet-to-monocyte ratio (PMR), a novel hematological indicator of inflammatory responses with 30-day outcomes in patients with HBV-associated decompensated cirrhosis (HBV-DeCi). Methods. We recruited 329 patients with HBV-DeCi for this retrospective study and extracted baseline clinical data and laboratory characteristics from medical records. Univariate and multivariate analyses were performed to determine major factors influencing 30-day mortality. Receiver operating characteristic curve analysis was performed to compare the predictive values of prognostic markers. Results. During the 30-day follow-up period, 21 (6.4%) patients died. The PMR was significantly different between nonsurvivors and survivors. Lower PMR was found to be associated with an increased risk of 30-day mortality, and PMR (odds ratio: 1.011; 95% CI: 1.003–1.019; P=0.005) was found to be an independent predictor of 30-day mortality in patients with HBV-DeCi with a significant predictive value (AUC = 0.826, 95% CI: 0.781–0.865). The combination of PMR and MELD score could improve prognostic accuracy in these patients (AUC = 0.911, 95% CI: 0.876–0.940). Conclusions. Our results demonstrate that low PMR may be an independent predictor of 30-day mortality in patients with HBV-DeCi, and combined with the MELD score, it may be useful to complement other conventional measures to enable effective management of these patients.

ObjectiveThe aim of this study is to evaluate the long-term efficacy and safety of ultrasound-guided percutaneous laser ablation (PLA) for the treatment of elderly patients with papillary thyroid microcarcinoma (PTMC).MethodsFrom September 2015 to April 2017, 38 elderly patients with PTMC confirmed through fine-needle aspiration biopsy (FNAB) were treated with PLA. Before the treatment, the location and volume of the nodule together with the patients’ symptoms were evaluated. Twenty-four hours after the treatment, contrast-enhanced ultrasound (CEUS) was performed to evaluate the completeness of the ablation. To evaluate the volume of the ablation area and recurrence or metastasis, ultrasound examination was performed at 1, 3, 6, and 12 months after the treatment and every 6 months thereafter. FNAB was performed for any suspicious recurrence or metastasis lesions.ResultThe ablation of all the 38 patients was all achieved completely as confirmed by CEUS. No obvious complications were found. The success rate of single ablation was 100%. The average follow-up time was 64.58 ± 5.29 months (60–78 months). By the time of the last follow-up, 31 (81.58%) ablation lesions disappeared completely and seven (18.42%) ablation lesions showed scar-like changes. The volume of nodules was 40.69 ± 16.45 mm3 before operation, which decreased to 0.22 ± 0.76 mm3 by the end of 42 months, and all nodules disappeared 4 years after ablation (P < 0.01). At 6, 12, 18, 24, 30, 36, and 42 months after ablation, the average volume reduction rates (VRRs) were 12.09%, 31.21%, 50.9%, 72.06%, 84.79%, 95.65%, and 100%, respectively. Of all the patients enrolled, one patient (2.6%) had local recurrence and was treated with PLA again. No regrowth of treated nodule or lymph node metastasis and distant metastases was detected.ConclusionUltrasound-guided PLA is effective and safe for the treatment of elderly patients with PTMC who are ineligible for surgery.

Organ fibrosis is a serious health challenge worldwide, and its global incidence and medical burden are increasing dramatically each year. Fibrosis can occur in nearly all major organs and ultimately lead to organ dysfunction. However, current clinical treatments cannot slow or reverse the progression of fibrosis to end-stage organ failure, and thus advanced anti-fibrotic therapeutics are urgently needed. As a type of naturally derived nanovesicle, native extracellular vesicles (EVs) from multiple cell types (e.g., stem cells, immune cells, and tissue cells) have been shown to alleviate organ fibrosis in many preclinical models through multiple effective mechanisms, such as anti-inflammation, pro-angiogenesis, inactivation of myofibroblasts, and fibrinolysis of ECM components. Moreover, the therapeutic potency of native EVs can be further enhanced by multiple engineering strategies, such as genetic modifications, preconditionings, therapeutic reagent-loadings, and combination with functional biomaterials. In this review, we briefly introduce the pathology and current clinical treatments of organ fibrosis, discuss EV biology and production strategies, and particularly focus on important studies using native or engineered EVs as interventions to attenuate tissue fibrosis. This review provides insights into the development and translation of EV-based nanotherapies into clinical applications in the future.

Choroid plexus epithelial cells can secrete cerebrospinal fluid into the ventricles, serving as the major structural basis of the selective barrier between the neurological system and blood in the brain. In fact, choroid plexus epithelial cells release the majority of cerebrospinal fluid, which is connected with particular ion channels in choroid plexus epithelial cells. Choroid plexus epithelial cells also produce and secrete a number of essential growth factors and peptides that help the injured cerebrovascular system heal. The pathophysiology of major neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, as well as minor brain damage diseases like hydrocephalus and stroke is still unknown. Few studies have previously connected choroid plexus epithelial cells to the etiology of these serious brain disorders. Therefore, in the hopes of discovering novel treatment options for linked conditions, this review extensively analyzes the association between choroid plexus epithelial cells and the etiology of neurological diseases such as Alzheimer's disease and hydrocephalus. Finally, we review CPE based immunotherapy, choroid plexus cauterization, choroid plexus transplantation, and gene therapy.

Hydrocephalus is mainly characterized by excessive production or impaired absorption of cerebrospinal fluid that causes ventricular dilation and intracranial hypertension. Astrocytes are the key response cells to inflammation in the central nervous system. In hydrocephalus, astrocytes are activated and show dual characteristics depending on the period of development of the disease. They can suppress the disease in the early stage and may aggravate it in the late stage. More evidence suggests that therapeutics targeting astrocytes may be promising for hydrocephalus. In this review, based on previous studies, we summarize different forms of hydrocephalus-induced astrocyte reactivity and the corresponding function of these responses in hydrocephalus. We also discuss the therapeutic effects of astrocyte regulation on hydrocephalus in experimental studies.

In this paper, the performance and emission characteristics of a diesel engine were investigated with varying ratios of tung oil-based biodiesel blends (B10, B20, and B50) and neat diesel under different operating conditions. The experimental results showed that the addition of biodiesel blends had different effects on engine power and torque depending on the blend ratio. B10 displayed a slight increase in power and torque, which increased by 1.9% and 6.6%. At the same time, B20 and B50 showed declines slightly. The fuel consumption rate increased slightly with an increasing percentage of biodiesel added. In general, all the blends exhibited significantly lower emissions of CO, NOX, HC, and smoke compared to neat diesel. B10 displayed the most notable reduction of CO emissions, with a 42.86% decrease at medium to high loads. NOX emissions of tung oil-based biodiesel blends were reduced at all load conditions except for B50. In addition, HC emissions were all reduced, especially for B20, which led to a 27.54% reduction at 50% load. Among all the tested blends, B50 showed the greatest decrease in smoke emissions of 38.05% compared to neat diesel at 2000 rpm. The research concluded that using biodiesel fuels from renewable resources, such as tung oil, presents a promising environmentally friendly alternative fuel option.

To develop high-salinity, high-temperature reservoirs, two hydrophobically associating polymers as fracturing fluid thickener were respectively synthesized through aqueous solution polymerization with acrylamide (AM), acrylic acid (AA), 2-acrylamido-2-methylpropanesulfonic acid (AMPS), nonionic polymerizable surfactant (NPS) and double-tail hydrophobic monomer (DHM). The thickener ASDM (AM/AA/AMPS/NPS/DHM) and thickener ASD (AM/AA/AMPS/DHM) were compared in terms of properties of water dissolution, thickening ability, rheological behavior and sand-carrying. The results showed that ASDM could be quickly diluted in water within 6 min, 66.7% less than that of ASD. ASDM exhibited salt-thickening performance, and the apparent viscosity of 0.5 wt% ASDM reached 175.9 mPa·s in 100,000 mg/L brine, 100.6% higher than that of ASD. The viscosity of 0.5 wt% ASDM was 85.9 mPa·s after shearing for 120 min at 120 °C and at 170 s−1, 46.6% higher than that of ASD. ASDM exhibited better performance in thickening ability, viscoelasticity, shear recovery, thixotropy and sand-carrying than ASD. The synergistic effect of hydrophobic association and linear entanglement greatly enhancing the performance of ASDM and the compactness of the spatial network structure of the ASDM was enhanced. In general, ASDM exhibited great potential for application in extreme environmental conditions with high salt and high temperatures.

At partial load, traditional automotive gasoline engines have high pumping losses due to the throttling of the intake charge for load control. Variable Valve Timing (VVT) and the introduction of externally cooled EGR could reduce the pumping losses but only with a very limited effect. On the other hand, in the medium to full load range, the engine cannot utilize a high compression ratio due to limitations in knocking. A variable displacement, variable compression ratio device which utilizes an asymmetric camshaft to realize the different closure times of the two intake valves is discussed in this paper. The large-scale change in the intake valve timing leads to the large-scale change in the effective cylinder volume at the intake valve closure, which realizes a variable cylinder volume and a variable effective compression ratio. The device is utilized to reduce the pumping losses and to increase the in-cylinder thermal efficiency at the same time. Engine dyno test results indicate that, in the low to medium load range, a later closure of the intake valve could reduce the effective cylinder volume, and the intake pressure could be significantly increased, and therefore pumping losses reduced. However, the reduced effective cylinder volume due to a later intake valve closure would lead to reduction in the effective compression ratio (ECR) and a drop in in-cylinder thermal efficiency. Therefore, there is a balance point between the pumping loss reduction and the drop in in-cylinder thermal efficiency. On the other side, in the medium to full load range, when avoiding knocking becomes the major controlling factor of the combustion phasing (degree of constant-volume combustion) and the effective expansion ratio (EER), too high of an effective compression ratio would lead to significant drop in the effective expansion ratio EER and also the in-cylinder thermal efficiency. Therefore, there exists a best compromise between the ECR and EER, and the best system would be one with a moderate ECR but an EER as high as possible. The quantitative equations which include both ECR and EER in the thermal efficiency calculations captured the above observations pretty well and can be utilized to optimize for the best compromise of IVC, EVO, ECR, EER and engine performances during the concept stage and/or the calibration stage of an engine.

The extent of damage that is developed during the production, transportation, storage, and handling of propellants after a low-velocity impact is an important factor in evaluating a dangerous threat such as deflagration-to-detonation transition. In this paper, a friability test was performed to evaluate the critical impact ignition velocity (CIIV), fragmentation degree, and potential reaction violence of four 3, 3-Bis(azidomethyl)oxetane (BAMO) and tetrahydrofuran (THF) copolymer-propellants (PBT-propellants) with various 3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) contents under impact at different velocities. The results showed that as the HMX contents increased, the CIIV decreased and changes of that also decreased. Simultaneously, the fragmentation degree increased with the increase in impact velocity, as it was judged by the initial dynamic activity ratio. Then, we calculated the maximum value of the initial dynamic activity ratio by fitting the data using Boltzmann, which were 27 (HMX = 0), 39 (HMX = 5%), 48 (HMX = 10%), and 56 (HMX = 15%). The ratios of the maximum value of the initial dynamic activity ratio between PBT-propellants containing HMX and those without HMX were 1.44, 1.78, and 2.07. The addition of HMX increased the maximum fragmentation degree of PBT-propellants under impact. The potential reaction violence increased as the impact velocity increased due to the increase in the fragmentation degree of PBT-propellants after impact. Similarly, we also obtained the maximum values of potential reaction violence, which were 62.39, 50.17, 41.89, and 34.65. The maximum value of potential reaction violence decreased with the increase in HMX contents, and the addition of HMX improved the safety of PBT-propellants burning after impact.

Autophagy is a highly conserved cellular progress for the degradation of cytoplasmic contents including micromolecules, misfolded proteins, and damaged organelles that has recently captured attention in kidney diseases. Basal autophagy plays a pivotal role in maintaining cell survival and kidney homeostasis. Accordingly, dysregulation of autophagy has implicated in the pathologies of kidney diseases. In this review, we summarize the multifaceted role of autophagy in kidney aging, maladaptive repair, tubulointerstitial fibrosis and discuss autophagy-related drugs in kidney diseases. However, uncertainty still remains as to the precise mechanisms of autophagy in kidney diseases. Further research is needed to clarify the accurate molecular mechanism of autophagy in kidney diseases, which will facilitate the discovery of a promising strategy for the prevention and treatment of kidney diseases.

Background Previously, we developed a monoclonal antibody (mAb) NJ001 that binds to the antigen SP70 in human non‐small cell lung cancer (NSCLC) cells and showed it could inhibit lung adenocarcinoma (AD) growth. Here, we investigated the effect and mechanisms of NJ001 in lung AD metastasis. Methods Human lung AD cells (SPC‐A1 and A549) were treated with different concentrations of mAb NJ001, and the effects of NJ001 on cell migration and invasive activity were investigated using wound‐healing and Matrigel assays, respectively. The molecular mechanism of this inhibition was explored by microarrays, qRT‐PCR, western blot, luciferase assays and electrophoretic mobility shift assays (EMSA). Results MAb NJ001 markedly suppressed lung AD cell migration; and the invasiveness of SPC‐A1 and A549 cells treated with mAb NJ001 was diminished by 65%. Tissue inhibitor of matrix metalloproteinase‐3 (TIMP‐3) was highly expressed in SPC‐A1 cells treated with mAb NJ001, whereas knockdown of TIMP‐3 by shRNA significantly increased SPC‐A1 and A549 invasiveness. MAb NJ001 affects lung AD by inhibiting TIMP‐3 through direct transcriptional regulation of FOXP1 binding sites in the TIMP‐3 promoter region, as shown in luciferase assays and EMSA. Conclusions MAb NJ001 inhibits invasiveness and metastasis in lung AD through the FOXP1 binding sites in the TIMP‐3 promoter region. It may have clinical applications in preventing and treating metastatic lung AD.

Abstract Background Pyroptosis is a novel programmed cell death. It is identified as caspase-1 dependent and characterized by plasma-membrane rupture and release of proinflammatory intracellular contents inculuding IL-1 beta and IL-18. Pyroptosis is distinct from other forms of cell death, especially apoptosis that is characterized by nuclear and cytoplasmic condensation and is elicited via activation of a caspase cascade. In pyroptosis, gasdermin D (GSDMD) acts as a major executor, while NLRP3 related inflammasome is closely linked to caspase-1 activation. Given that pyroptosis has played a critical role in the progression of non-alcoholic steatohepatitis (NASH), here, we investigated whether the regulation of pyroptosis activation is responsible for the protective role of monounsaturated oleic acids in the context of hepatocellular lipotoxicity. Methods Human hepatoma cell line HepG2 cells were exposed to palmitic acid (PA) with or without oleic acids (OA) or/and endoplasmic reticulum (ER) stress inhibitor tauroursodeoxycholic acid (TUDCA) for 24 h. Besides, the cells were treated with the chemical ER stressor tunicamycin (TM) with or without OA for 24 h as well. The expressions of pyroptosis and ER stress related genes or proteins were determined by real-time PCR, Western blot or immunofluorescence. The morphology of pyroptosis was detected by acridine orange and ethidium bromide (AO/EB) staining. The release of IL-1 beta and tumor necrosis factor alpha (TNF-α) was determined by ELISA. Sprague–Dawley (SD) rats were fed with high fat diet (HFD) for 16 w, then, HFD was half replaced by olive oil to observe the protective effects of olive oil. The blood chemistry were analyzed, and the liver histology and the expressions of related genes and proteins were determined in the liver tissues. Results We demonstrated that PA impaired the cell viability and disturbed the lipid metabolism of HepG2 cells (P

Allergic airway inflammation is a universal airway disease that is driven by hyperresponsiveness to inhaled allergens. Group 2 innate lymphoid cells (ILC2s) produce copious amounts of type 2 cytokines, which lead to allergic airway inflammation. Here, we discovered that both peripheral blood of human and mouse lung ILC2s express the endothelin-A receptor (ETAR), and the expression level of ETAR was dramatically induced upon interleukin-33 (IL-33) treatment. Subsequently, both preventive and therapeutic effects of BQ123, an ETAR antagonist, on allergic airway inflammation were observed, which were associated with decreased proliferation and type 2 cytokine productions by ILC2s. Furthermore, ILC2s from BQ123 treatment were found to be functionally impaired in response to an interleukin IL-33 challenged. And BQ123 treatment also affected the phosphorylation level of the extracellular signal-regulated kinase (ERK), as well as the level of GATA binding protein 3 (GATA3) in activated ILC2s. Interestingly, after BQ123 treatment, both mouse and human ILC2s in vitro exhibited decreased function and downregulation of ERK signaling and GATA3 stability. These observations imply that ETAR is an important regulator of ILC2 function and may be involved in ILC2-driven pulmonary inflammation. Therefore, blocking ETAR may be a promising therapeutic strategy for allergic airway inflammation.

Drilling fluid is the blood of drilling engineering. In the polar drilling process, the ultra-low temperature environment puts high demands on the rheological performance of drilling fluids. In this paper, the effects of temperature, ice debris concentration and weighting agent on the rheological properties of drilling fluids were studied. It was found that the lower the temperature and the higher the ice debris concentration, the higher the drilling fluid viscosity, but when the ice debris concentration was below 2%, the drilling fluid rheology hardly changed. Secondly, the low temperature rheological properties of drilling fluid were adjusted by three different methods: base fluid ratio, organoclay, and polymers (dimer acid, polymethacrylate, ethylene propylene copolymer, and vinyl resin). The results showed that the base fluid rheological performance was optimal when the base fluid ratio was 7:3. Compared with polymers, organoclay has the most significant improvement on the low temperature rheological performance of drilling fluid. The main reason is that organoclay can transform the drilling fluid from Newtonian to non-Newtonian fluid, which exhibits excellent shear dilution of drilling fluid. The organoclay is also more uniformly dispersed in the oil, forming a denser weak gel mesh structure, so it is more effective in improving the cuttings carrying and suspension properties of drilling fluids. However, the drilling fluid containing polymer additives is still a Newtonian fluid, which cannot form a strong mesh structure at ultra-low temperatures, and thus cannot effectively improve the low-temperature rheological performance of drilling fluid. In addition, when the amount of organoclay is 2%, the improvement rate of the yield point reaches 250% at −55 °C, which can effectively improve the cuttings carrying and suspension performance of drilling fluid at ultra-low temperature.

Antenna beam deflection, along with miniaturization and wideband of the antenna is in demand for practical applications. In this paper, a cylindrical conformal array antenna with a small-tilt forward beam was designed. The microstrip antenna unit was loaded with the artificial electromagnetic structure, which reduced the size of the antenna unit. As a result, the center spacing of the array elements can be shortened with the same array element spacing. The beam deflection angle can be increased in this way without increasing the coupling effect between the parts. Changing the number of line array elements and the number of line arrays can regulate the beam width of E-field and H-field, respectively. The bandwidth of the antenna can be significantly extended by slotting the ground plane. This work implemented a cylindrical conformal array of the antenna’s forward beam with a small dip angle using a cylindrical carrier as an example. The measurement results showed that the angle between the main beam and the carrier axis of the conformal antenna was less than 30°, the bandwidth was more than 30%, and the antenna volume decreased by 40.4%.

Ammonia, as an alternative fuel for internal combustion engines, can achieve nearly zero carbon emissions. Although the development of the pure ammonia engine is limited by its poor combustion characteristics, ammonia–hydrocarbon mixed combustion can effectively improve the combustion of ammonia fuel. With the increase in the ammonia fuel proportion in the fuel mixture, a large number of nitrogen oxides (NOX) and unburned ammonia may be discharged, which have a poor impact on the environment. In this study, the performance of selective catalytic reduction (SCR) aftertreatment technology in reducing NOX and ammonia emissions from ammonia–diesel dual-fuel engines was investigated using simulation. A good cross-dimensional model was established under the coupling effect, though the effect of a single-dimensional model could not be presented. The results show that when the exhaust gas in the engine cylinder is directly introduced into the SCR without additional reducing agents such as urea, unburned ammonia flowing into SCR model is in excess, and there will be only ammonia at the outlet; however, if the unburned ammonia fed into the SCR model is insufficient to reduce NO, the ammonia concentration at the outlet will be 0. NOX can be 100% effectively reduced to N2 under most engine conditions; thus, unburned ammonia in exhaust plays a role in reducing NOX emissions from ammonia–diesel dual-fuel engines. However, when the concentration of unburned ammonia in the exhaust gas of an ammonia–diesel dual-fuel engine is large, its ammonia emissions are still high even after the SCR. In addition, the concentrations of N2O after SCR do not decrease, but increase by 50.64 in some conditions, the main reason for which is that by the action of the SCR catalyst, NO2 is partially converted into N2O, resulting in an increase in its concentration at the SCR outlet. Adding excessive air or oxygen into the SCR aftertreatment model can not only significantly reduce the ammonia concentration at the outlet of the model without affecting the NOX conversion efficiency of SCR, but inhibit N2O production to some extent at the outlet, thus reducing the unburned ammonia and NOX emissions in the tail gas of ammonia–diesel dual-fuel engines at the same time without the urea injection. Therefore, this study can provide theoretical guidance for the design of ammonia and its mixed-fuel engine aftertreatment device, and provide technical support for reducing NOX emissions of ammonia and its mixed fuel engines.

Abstract Background Diabetic nephropathy (DN) is one of the most severe chronic diabetic complications and the main cause of end-stage renal disease. Chronic inflammation plays a key role in the development of DN. However, few treatment strategies are available; therefore, new and effective strategies to ameliorate DN at the early stage must be identified. Methods Mesenchymal stem cells (MSCs) are characterized by anti-inflammatory and immune regulatory abilities. We developed a rhesus macaque model of DN and administered MSCs four times over 2 months. We measured blood glucose level, HbA1c, and levels of renal function parameters in the blood and urine, and cytokine levels in the kidney and blood circulatory system of rhesus macaques. Also, we analyzed the renal pathological changes of rhesus macaques. In vitro, we treated tubular epithelial cells (HK2) with 30 mmol/L glucose and 10 ng/mL human recombinant TNF-alpha (rhTNF-α) and explored the effects of MSCs on inflammation and Na+-glucose cotransporter 2 (SGLT2) expression in HK2. Results We found that MSCs decreased the blood glucose level and daily insulin requirement of DN rhesus macaques. Furthermore, MSCs had a dominant function in improving renal function and decreasing SGLT2 expression on renal tubular epithelial cells. Also, renal pathological changes were ameliorated after MSC treatment. Moreover, MSCs powerfully reduced inflammation, especially decreased the level of pro-inflammatory cytokine interleukin-16 (IL-16), in the kidney and blood circulatory system. Conclusions Our study is an important step to explore the mechanism of MSCs in ameliorating the early stage of DN, potentially through influencing SGLT2 expression and resulting in improved glycemic control and anti-inflammation. We hope these findings would provide insights for the clinical application of MSCs in DN.

To overcome the problems of long dissolution time and high investment in surface facilities of powder thickeners in hydraulic fracturing, a novel suspension of a thickener as a fracturing fluid was prepared using powder polyacrylamide, nano-silica, and polyethylene glycol by high-speed mixing. The suspension and powder were compared in terms of properties of solubility, rheological behavior, sand carrying, drag reduction, and gel breaking. The results showed that the suspension could be quickly diluted in brine within 5 min, whereas the dissolution time of powder was 120 min. The suspension exhibited better performance in salt resistance, temperature resistance, shear resistance, viscoelasticity, sand carrying, and drag reduction than powder. The powder solution was broken more easily and had a lower viscosity than suspension diluent. These improvements in properties of the suspension were due to the dispersion of nano-silica in the polymer matrix; the mobility of thickener chains was inhibited by the steric hindrance of the nano-silica. Nano-silica particles acted as crosslinkers by attaching thickener chains, which strengthened the network structure of the thickener solution. The presence of hydrogen bonds between the thickener matrix and the nano-silica restricted the local movement of thickener chains, leading to a stronger spatial network. Therefore, this novel suspension showed good potential for fracturing applications.

Senescence of bone marrow-derived mesenchymal stem cells (BMSCs) has been widely reported to be closely correlated with aging-related diseases, including osteoporosis (OP). Moreover, the beneficial functions of BMSCs decline with age, limiting their therapeutic efficacy in OP. In the present study, using RNA sequencing (RNA-Seq), we found that leucine-rich repeat containing 17 (LRRc17) expression in BMSCs was highly positively correlated with age. Therefore, we investigated whether LRRc17 knockdown could rejuvenate aged MSCs and increase their therapeutic efficacy in OP. Consistent with the RNA-Seq results, the protein expression of LRRc17 in senescent BMSCs was significantly increased, whereas LRRc17 knockdown inhibited cell apoptosis and reduced the expression of age-related proteins and G2 and S phase quiescence. Furthermore, LRRc17 knockdown shifted BMSCs from adipogenic to osteogenic differentiation, indicating the critical role of LRRc17 in BMSC senescence and differentiation. Additionally, similar to rapamycin (RAPA) treatment, LRRc17 knockdown activated mitophagy via inhibition of the mTOR/PI3K pathway, which consequently reduced mitochondrial dysfunction and inhibited BMSC senescence. However, the effects of LRRc17 knockdown were significantly blocked by the autophagy inhibitor hydroxychloroquine (HCQ), demonstrating that LRRc17 knockdown prevented BMSC senescence by activating mitophagy. In vivo, compared with untransfected aged mouse-derived BMSCs (O-BMSCs), O-BMSCs transfected with sh-LRRc17 showed effective amelioration of ovariectomy (OVX)-induced bone loss. Collectively, these results indicated that LRRc17 knockdown rejuvenated senescent BMSCs and thus enhanced their therapeutic efficacy in OP by activating autophagy.

Ischemic diseases refer to a wide range of diseases caused by reduced blood flow and a subsequently deficient oxygen and nutrient supply. The pathogenesis of ischemia is multifaceted and primarily involves inflammation, oxidative stress and an apoptotic response. Over the last decade, mesenchymal stem cells (MSCs) have been widely studied as potential cell therapy agents for ischemic diseases due to their multiple favourable functions. However, the low homing and survival rates of transplanted cells have been concerns limiting for their clinical application. Recently, increasing studies have attempted to enhance the efficacy of MSCs by various strategies including genetic modification, pretreatment, combined application and biomaterial application. The purpose of this review is to summarize these creative strategies and the progress in basic and preclinical studies.

With the continuous exploration and development of oil and gas resources to deep formations, the key treatment agents of water-based drilling fluids face severe challenges from high temperatures and salinity, and the development of high temperature and salt resistance filtration reducers has always been the focus of research in the field of oilfield chemistry. In this study, a nano-silica-modified co-polymer (NS-ANAD) gel was synthesized by using acrylamide, isopropylacrylamide, 2-acrylamide-2-methyl propane sulfonic acid, diallyl dimethyl ammonium chloride, and double-bond-modified inorganic silica particles (KH570-SiO2) through free radical co-polymerization. The introduction of nanotechnology enhances the polymer’s resistance to high temperature degradation, making it useful as a high-temperature-resistant fluid loss reducer. Moreover, the anions (sulfonates) and cations (quaternary ammonium) enhance the extension of the polymer and the adsorption on the surface of bentonite particles in a saline environment, which in turn improves the salt resistance of the polymer. The drilling fluids containing 2.0 wt% NS-ANAD co-polymer gels still show excellent rheological and filtration performance, even after aging in high temperature (200 °C) and high salinity (saturated salt) environments, showing great potential for application in deep and ultra-deep drilling engineering.

The endothelin-A receptor antagonist BQ123 is an effective treatment agent for hypertension and obese cardiomyopathy. However, the role of BQ123 in controlling acute inflammatory diseases and its underlying mechanisms are not well understood. Here, we showed that BQ123 activated polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in mice and that the IL13/STAT6/Arg1 signaling pathway is involved in this process. Importantly, both treatment with BQ123 and the transfer of BQ123-induced PMN-MDSCs (BQ123-MDSCs) were effective in relieving inflammation, including dextran sulfate sodium (DSS)-induced colitis, papain-induced pneumonia, and concanavalin A (ConA)-induced hepatitis, in mice. The treatment effects were mediated by the attenuation of the inflammation associated with the accumulation of PMN-MDSCs in the colon, lung, and liver. However, concurrent injection of Gr1 agonistic antibody with BQ123 induced PMN-MDSC aggravated the observed acute inflammation. Interestingly, no remission of inflammation was observed in Rag2 knockout mice administered BQ123-MDSCs, but co-injection with CD3+ T cells significantly relieved acute inflammation. In summary, BQ123-induced PMN-MDSCs attenuated acute inflammation in a T cell-dependent manner, providing a novel potential strategy to prevent the occurrence of acute inflammation.

Aim: Low grade glioma (LGG) is a lethal brain cancer with relatively poor prognosis in young adults. Thus, this study was performed to develop novel molecular biomarkers to effectively predict the prognosis of LGG patients and finally guide treatment decisions. Methods: survival-related genes were determined by Kaplan-Meier survival analysis and multivariate Cox regression analysis using the expression and clinical data of 506 LGG patients from The Cancer Genome Atlas (TCGA) database and independently validated in a Chinese Glioma Genome Atlas (CGGA) dataset. A prognostic risk score was established based on a linear combination of 10 gene expression levels using the regression coefficients of the multivariate Cox regression models. GSEA was performed to analyze the altered signaling pathways between the high and low risk groups stratified by median risk score. Results: We identified a total of 1489 genes significantly correlated with patients’ prognosis in LGG. The top 5 protective genes were DISP2, CKMT1B, AQP7, GPR162 and CHGB , the top 5 risk genes were SP1, EYA3, ZSCAN20, ITPRIPL1 and ZNF217 in LGG. The risk score was predictive of poor overall survival and relapse-free survival in LGG patients. Pathways of small cell lung cancer, pathways in cancer, chronic myeloid leukemia, colorectal cancer were the top 4 most enriched pathways in the high risk group. SP1, EYA3, ZSCAN20, ITPRIPL1, ZNF217 and GPR162 were significantly up-regulated, while DISP2, CKMT1B, AQP7 were down-regulated in 523 LGG tissues as compared to 1141 normal brain controls. Conclusions: The 10-gene signature may become novel prognostic and diagnostic biomarkers to considerably improve the prognostic prediction in LGG.

With increasing global energy consumption, oil/gas drilling has gradually expanded from conventional shallow reservoirs to deep and ultra-deep reservoirs. However, the harsh geological features including high temperature and high salinity in ultra-deep reservoirs have become a critical challenge faced by water-based drilling fluids (WDFs), which seriously deteriorate the rheology and fluid loss properties, causing drilling accidents, such as wellbore instability and formation collapse. In this study, a novel temperature- and salt-resistant micro-crosslinked polyampholyte gel was synthesized using N,N-dimethylacrylamide, diallyldimethyl ammonium chloride, 2-acrylamido-2-methylpropanesulfonic acid, maleic anhydride and chemical crosslinking agent triallylamine through free radical copolymerization. Due to the synergistic effect of covalent micro-crosslinking and the reverse polyelectrolyte effect of amphoteric polymers, the copolymer-based drilling fluids exhibit outstanding rheological and filtration properties even after aging at high temperatures (up to 200 °C) and high salinity (saturated salt) environments. In addition, the zeta potential and particle size distribution of copolymer-based drilling fluids further confirmed that the copolymer can greatly improve the stability of the base fluid suspension, which is important for reducing the fluid-loss volume of WDFs. Therefore, this work will point out a new direction for the development of temperature- and salt-resistant drilling fluid treatment agents.

BackgroundMoyamoya disease (MMD) is an important cause of stroke in children and young adults in Asia. To date, diagnosis remains challenging due to varying clinical manifestations and unknown pathogenesis. The study aims to identify cerebrospinal fluid (CSF) exosomal microRNAs (exomiRs) that can serve as a novel diagnostic biomarker for diagnosis and assess its clinical applications.MethodsCSF samples were taken from 31 MMD patients and 31 healthy controls. Initial screening of miRNA expression was performed on samples pooled from MMD patients and controls using microarray and validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The diagnostic accuracy of the potential exosomal miRNAs was evaluated using receiver operating characteristic curve analyses in an independent patient cohort. The potential pathways regulated by the miRNAs was also determined using bioinformatics analysis.ResultsThe microarray results demonstrated that six exomiRs were dysregulated in the MMD patients compared to the controls. Using qRT-PCR, we validated four of the miRNAs (miR-3679-5p, miR-6165, miR-6760-5p, and miR-574-5p) as a biomarker for MMD diagnosis. The four exomiRs showed enhanced sensitivity (75%) and specificity (93.75%) in terms of differentiating MMD patients from healthy subjects [area under the curve (AUC) = 0.9453]. Pathway enrichment analysis for potential targets of six exomiRs identified proteins involved in cell adhesion and junction formation in the brain.ConclusionsWe identified a novel and highly sensitive exomiRs signature for MMD detection and explored its potential targets using bioinformatics analysis.