Exosomes are a subset of extracellular vesicles that carry specific combinations of proteins, nucleic acids, metabolites, and lipids. Mounting evidence suggests that exosomes participate in ...intercellular communication and act as important molecular vehicles in the regulation of numerous physiological and pathological processes, including cancer development. Exosomes are released by various cell types under both normal and pathological conditions, and they can be found in multiple bodily fluids. Moreover, exosomes carrying a wide variety of important macromolecules provide a window into altered cellular or tissue states. Their presence in biological fluids renders them an attractive, minimally invasive approach for liquid biopsies with potential biomarkers for cancer diagnosis, prediction, and surveillance. Due to their biocompatibility and low immunogenicity and cytotoxicity, exosomes have potential clinical applications in the development of innovative therapeutic approaches. Here, we summarize recent advances in various technologies for exosome isolation for cancer research. We outline the functions of exosomes in regulating tumor metastasis, drug resistance, and immune modulation in the context of cancer development. Finally, we discuss prospects and challenges for the clinical development of exosome-based liquid biopsies and therapeutics.
PD-L1 has been widely demonstrated to contribute to failed antitumor immunity. Blockade of PD-L1 with monoclonal antibody could modulate the tumor immune environment to augment immunotherapy. PD-L1 ...expression is also detected in several types of cancer and is associated with poor prognosis. However, the prognostic role of PD-L1 in oral squamous cell carcinoma (OSCC) is still controversial. Our aim was to determine the role of PD-L1 in the prognosis of OSCC patients to identify its potential therapeutic relevance. PD-L1 immunoreactivity was analyzed by immunohistochemistry in 305 cancer specimens from primary OSCC patients. The medium follow-up time after surgery was 3.8 years (range from 0.1 to 11.1 years). The prognostic value of PD-L1 on overall survival was determined by Kaplan-Meier analysis and Cox proportional hazard models. Higher PD-L1 expression is more likely in tumor tissues of female than male OSCC patients (P = 0.0062). Patients with distant metastasis also had high PD-L1 expression (P = 0.0103). Multivariate analysis identified high PD-L1 expression as an independent risk factor in males and smokers (males: hazard ratio = 1.556, P = 0.0077; smokers: hazard ratio = 2.058, P = 0.0004). We suggest that PD-L1 expression, determined by IHC staining, could be an independent prognostic marker for OSCC patients who are male or who have a smoking habit.
3D integration with through-silicon via (TSV) is a promising candidate to perform system-level integration with smaller package size, higher interconnection density, and better performance. TSV ...fabrication is the key technology to permit communications between various strata of the 3D integration system. TSV fabrication steps, such as etching, isolation, metallization processes, and related failure modes, as well as other characterizations are discussed in this invited review paper.
Agricultural food production is at the base of food and fodder, with fertilization having fundamentally and continuously increased crop yield over the last decades. The performance of crops is ...intimately tied to their microbiome as they together form holobionts. The importance of the microbiome for plant performance is, however, notoriously ignored in agricultural systems as fertilization disconnects the dependency of plants for often plant-beneficial microbial processes. Moreover, we lack a holistic understanding of how fertilization regimes affect the soil microbiome. Here, we examined the effect of a 2-year fertilization regime (no nitrogen fertilization control, nitrogen fertilization, and nitrogen fertilization plus straw amendment) on entire soil microbiomes (bacteria, fungi, and protist) in three common agricultural soil types cropped with maize in two seasons.
We found that the application of nitrogen fertilizers more strongly affected protist than bacterial and fungal communities. Nitrogen fertilization indirectly reduced protist diversity through changing abiotic properties and bacterial and fungal communities which differed between soil types and sampling seasons. Nitrogen fertilizer plus straw amendment had greater effects on soil physicochemical properties and microbiome diversity than nitrogen addition alone. Moreover, nitrogen fertilization, even more together with straw, increased soil microbiome network complexity, suggesting that the application of nitrogen fertilizers tightened soil microbiomes interactions.
Together, our results suggest that protists are the most susceptible microbiome component to the application of nitrogen fertilizers. As protist communities also exhibit the strongest seasonal dynamics, they serve as the most sensitive bioindicators of soil changes. Changes in protist communities might have long-term effects if some of the key protist hubs that govern microbiome complexities as top microbiome predators are altered. This study serves as the stepping stone to promote protists as promising agents in targeted microbiome engineering to help in reducing the dependency on exogenous unsustainably high fertilization and pesticide applications.
Increasing reports on epidemiological, diagnostic, and clinical studies suggest that dysfunction of the inflammatory reaction results in chronic illnesses such as cancer, arthritis, arteriosclerosis, ...neurological disorders, liver diseases, and renal disorders. Chronic inflammation might progress if injurious agent persists; however, more typically than not, the response is chronic from the start. Distinct to most changes in acute inflammation, chronic inflammation is characterized by the infiltration of damaged tissue by mononuclear cells like macrophages, lymphocytes, and plasma cells, in addition to tissue destruction and attempts to repair. Phagocytes are the key players in the chronic inflammatory response. However, the important drawback is the activation of pathological phagocytes, which might result from continued tissue damage and lead to harmful diseases. The longer the inflammation persists, the greater the chance for the establishment of human diseases. The aim of this review was to focus on advances in the understanding of chronic inflammation and to summarize the impact and involvement of inflammatory agents in certain human diseases.
Chronic inflammation is a greater the chance for the establishment of human diseases.
Clayey silt reservoirs bearing natural gas hydrates (NGH) are considered to be the hydrate-bearing reservoirs that boast the highest reserves but tend to be the most difficult to exploit. They are ...proved to be exploitable by the first NGH production test conducted in the South China Sea in 2017. Based on the understanding of the first production test, the China Geological Survey determined the optimal target NGH reservoirs for production test and conducted a detailed assessment, numerical and experimental simulation, and onshore testing of the reservoirs. After that, it conducted the second offshore NGH production test in 1225 m deep Shenhu Area, South China Sea (also referred to as the second production test) from October 2019 to April 2020. During the second production test, a series of technical challenges of drilling horizontal wells in shallow soft strata in deep sea were met, including wellhead stability, directional drilling of a horizontal well, reservoir stimulation and sand control, and accurate depressurization. As a result, 30 days of continuous gas production was achieved, with a cumulative gas production of 86.14 ×104 m3. Thus, the average daily gas production is 2.87 ×104 m3, which is 5.57 times as much as that obtained in the first production test. Therefore, both the cumulative gas production and the daily gas production were highly improved compared to the first production test. As indicated by the monitoring results of the second production test, there was no anomaly in methane content in the seafloor, seawater, and atmosphere throughout the whole production test. This successful production test further indicates that safe and effective NGH exploitation is feasible in clayey silt NGH reservoirs. The industrialization of hydrates consists of five stages in general, namely theoretical research and simulation experiments, exploratory production test, experimental production test, productive production test, and commercial production. The second production test serves as an important step from the exploratory production test to experimental production test.
Cancer-associated fibroblasts (CAFs), the most abundant cells in the tumor microenvironment, have prominent roles in the development of solid tumors as stromal targets. However, the underlying ...mechanism of CAFs' function in oral squamous cell carcinoma (OSCC) development remains unclear. Here, we investigated the role of lysyl oxidase (LOX) expression in CAFs in tumor stromal remodeling and the mechanism of its effect on OSCC progression.
Multiple immunohistochemistry (IHC) staining was performed to detect the correlation of CAFs and LOX in the stroma of OSCC specimens, as well as the correlation with clinicopathological parameters and prognosis. The expression of LOX in CAFs were detected by RT-qPCR and western blot. The effects of LOX in CAFs on the biological characteristics of OSCC cell line were investigated using CCK-8, wound-healing and transwell assay. CAFs were co-cultured with type I collagen in vitro, and collagen contraction test, microstructure observation and rheometer were used to detect the effect of CAFs on remodeling collagen matrix. Then, collagen with different stiffness were established to investigate the effect of matrix stiffness on the progression of OSCC. Moreover, we used focal adhesion kinase (FAK) phosphorylation inhibitors to explored whether the increase in matrix stiffness promote the progression of OSCC through activating FAK phosphorylation pathway.
LOX was colocalized with CAFs in the stroma of OSCC tissues, and its expression was significantly related to the degree of malignant differentiation and poor prognosis in OSCC. LOX was highly expressed in CAFs, and its knockdown impaired the proliferation, migration, invasion and EMT process of OSCC cells. The expression of LOX in CAFs can catalyze collagen crosslinking and increase matrix stiffness. Furthermore, CAFs-derived LOX-mediated increase in collagen stiffness induced morphological changes and promoted invasion and EMT process in OSCC cells by activating FAK phosphorylation pathway.
Our findings suggest that CAFs highly express LOX in the stroma of OSCC and can remodel the matrix collagen microenvironment, and the increase in matrix stiffness mediated by CAFs-derived LOX promotes OSCC development through FAK phosphorylation pathway. Thus, LOX may be a potential target for the early diagnosis and therapeutic treatment of OSCC.
Published emission factors (EFs) often vary significantly, leading to high uncertainties in emission estimations. There are few reliable EFs from field measurements of residential wood combustion in ...China. In this study, 17 wood fuels and one bamboo were combusted in a typical residential stove in rural China to measure realistic EFs of particulate matter (PM), organic carbon (OC), and elemental carbon (EC), as well as to investigate the influence of fuel properties and combustion conditions on the EFs. Measured EFs of PM, OC, and EC (EFPM, EFOC, and EFEC, respectively) were in the range of 0.38–6.4, 0.024–3.0, and 0.039–3.9 g/kg (dry basis), with means and standard derivation of 2.2 ± 1.2, 0.62 ± 0.64, and 0.83 ± 0.69 g/kg, respectively. Shrubby biomass combustion produced higher EFs than tree woods, and both species had lower EFs than those of indoor crop residue burning (p < 0.05). Significant correlations between EFPM, EFOC, and EFEC were expected. By using a nine-stage cascade impactor, it was shown that size distributions of PM emitted from tree biomass combustions were unimodal with peaks at a diameter less than 0.4 μm (PM0.4), much finer than the PM from indoor crop residue burning. Approximately 79.4% of the total PM from tree wood combustion was PM with a diameter less than 2.1 μm (PM2.1). PM size distributions for shrubby biomasses were slightly different from those for tree fuels. On the basis of the measured EFs, total emissions of PM, OC, and EC from residential wood combustion in rural China in 2007 were estimated at about 303, 75.7, and 92.0 Gg.
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•High-entropy transition metal disulfide (HES2) spheres were used for K+ storage.•The substantial configurational entropy of HES2 minimizes the shuttle effect.•HES2 anode exhibit a ...capacity of 348 mA h g−1 after 1800 cycles at 500 mA g−1.•HES2 anode in potassium-ion full battery exhibits a capacity of 258.6 mA h g−1.•HES2 potassium-ion hybrid capacitor delivers 63.7 Wh kg−1 after 6000 cycles.
High-entropy metal disulfide (HES2) colloid clusters were synthesized through a two-step templated solvothermal method for used as anode materials for potassium-ion storage devices. HES2’s large configuration entropy stabilizes its crystal structure and promotes chemical diversity by introducing multiple cations, thus reducing the impact of the shuttle effect, retaining active materials and extending cycling life up to 1800 cycles. During cycling, crystalline-amorphous grain boundaries formed in situ enhance electrochemical reaction activities and ensure the exposure of active sites. Elements with lower electronegativity allow S to bring more negative charges, improving the electrostatic force between S and K+ and enabling better anchoring of potassium polysulfide. Meanwhile, the retained close-packed cluster structure of HES2 provides a large contact area to accelerate the reduction reaction of the electrolyte in the sphere during the repeating K+ insertion/extraction. We further demonstrate the excellent performance of HES2 anodes on practical potassium-ion full battery and hybrid capacitor applications. The pioneering concept in atomic compositional engineering and structural design of transition metal sulfide electrodes presented in this work marks a significant step forward in the development of chalcogenide electrode systems for energy storage devices.
High‐glucose (HG) suppresses mesenchymal stem cell (MSC) functions, resulting in a decrease in cardiac regenerative capability for MSC in diabetes mellitus (DM). Resveratrol enhances MSC functions ...under stress. This study explores if cardiac regenerative capability can be enhanced in MSCs pretreated with resveratrol in DM rats receiving MSCs. In vitro evidence confirms that HG decreases MSCs capability through suppression of survival markers, AMP‐activated protein kinase (AMPK)/Sirtuin 1 (Sirt1) axis, and expression of apoptotic markers. All of these markers are improved when MSCs are cocultured with resveratrol. Wistar male rats were randomly divided into Sham, DM (DM rats), DM rats with autologous transplantation of adipose‐derived stem cells (DM + ADSC), and DM rats with resveratrol pretreated ADSC (DM + RSVL‐ADSC). Compared to the Sham, DM induces pathological pathways (including fibrosis, hypertrophy, and apoptosis) and suppresses survival as well as the AMPK/Sirt1 axis in the DM group. DM + ADSC slightly improves the above pathways whereas DM + RSVL‐ADSC significantly improves the above pathways when compared to the DM group. These results illustrate that resveratrol pretreated with MSCs may show clinical potential in the treatment of heart failure in patients with DM.
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High‐glucose (HG) environment can decrease survival signalings in stem cells and pretreatment of resveratrol can increase survival signalings in stem cells with an HG environment.
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Regeneration of heart functions (including suppression of apoptotic pathway, suppression of fibrotic pathway, suppression of hypertrophic pathway, an increase of longevity pathway, and increase of survival signalings) for resveratrol pretreated stem cells is significantly better than stem cells without resveratrol pretreatment.
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