Arsenic (As) tends to mobilize in flooded paddy soil due to the reductive dissolution of the iron (oxyhydr)oxides to which As sorbs, resulting in elevated As accumulation in rice that poses a ...potential risk to the food safety and human health. Microbial sulfate reduction is an important biogeochemical process in paddy soils, but its impact on As mobilization remains poorly understood. In this study, we incubated eight As-contaminated paddy soils under flooded conditions to investigate the effect of sulfate addition on As mobility. Porewater Fe and As concentrations and As species were determined. Among the eight soils, an addition of 50 mg S kg−1 as sodium sulfate decreased porewater arsenite only in two soils, which also showed a high mobilization of Fe2+. Further experiments showed that the addition of sulfate to these two soils stimulated microbial sulfate reduction but decreased porewater concentrations of both arsenite and Fe2+. Additionally, the supply of sulfate increased the fractions of As associated with acid volatile sulfides in the solid phase and decreased As uptake by rice in pot experiments under similar conditions. The effect of sulfate addition on porewater As was diminished by the addition of molybdate, an inhibitor of sulfate reducing bacteria. These results suggest the formation of secondary FeS minerals which co-precipitate or sorb arsenite as a likely mechanism of As immobilization, which was also supported by thermodynamic modeling of the pore water. Thus, sulfate additions can immobilize As and reduce its availability to rice plants in paddy soils containing a high potential for microbial Fe reduction, providing an efficient way to mitigate the As transfer to the food chain.
Display omitted
•Sulfate addition decreased soluble As(III) in paddy soils with high soluble Fe2+.•Inhibition of sulfate reduction diminished the decrease in soluble As(III).•The decrease in soluble As(III) was due to the adsorption to secondary FeS.•Sulfate addition to paddy soils with high reducible Fe reduced rice grain As.
Sulfate addition can reduce As mobility in paddy soils containing a high potential of microbial Fe reduction, offering a potential strategy to mitigate grain As accumulation in these soils.
•Menstrual blood-derived MSC transplantation lower mortality of H7N9-induced ARDS.•Prospective and systematic study of H7N9-induced pneumonia to assess health status.•MSC transplantation has not ...harmful effect in human body with long-term follow-up.•MSC-based therapy is an alternative way to treat COVID-19 in severe ARDS patient.
H7N9 viruses quickly spread between mammalian hosts and carry the risk of human-to-human transmission, as shown by the 2013 outbreak. Acute respiratory distress syndrome (ARDS), lung failure, and acute pneumonia are major lung diseases in H7N9 patients. Transplantation of mesenchymal stem cells (MSCs) is a promising choice for treating virus-induced pneumonia, and was used to treat H7N9-induced ARDS in 2013. The transplant of MSCs into patients with H7N9-induced ARDS was conducted at a single center through an open-label clinical trial. Based on the principles of voluntariness and informed consent, 44 patients with H7N9-induced ARDS were included as a control group, while 17 patients with H7N9-induced ARDS acted as an experimental group with allogeneic menstrual-blood-derived MSCs. It was notable that MSC transplantation significantly lowered the mortality of the experimental group, compared with the control group (17.6% died in the experimental group while 54.5% died in the control group). Furthermore, MSC transplantation did not result in harmful effects in the bodies of four of the patients who were part of the five-year follow-up period. Collectively, these results suggest that MSCs significantly improve the survival rate of H7N9-induced ARDS and provide a theoretical basis for the treatment of H7N9-induced ARDS in both preclinical research and clinical studies. Because H7N9 and the coronavirus disease 2019 (COVID-19) share similar complications (e.g., ARDS and lung failure) and corresponding multi-organ dysfunction, MSC-based therapy could be a possible alternative for treating COVID-19.
Melanomas that result from mutations in the gene encoding BRAF often become resistant to BRAF inhibition (BRAFi), with multiple mechanisms contributing to resistance. While therapy-induced autophagy ...promotes resistance to a number of therapies, especially those that target PI3K/mTOR signaling, its role as an adaptive resistance mechanism to BRAFi is not well characterized. Using tumor biopsies from BRAF(V600E) melanoma patients treated either with BRAFi or with combined BRAF and MEK inhibition, we found that BRAFi-resistant tumors had increased levels of autophagy compared with baseline. Patients with higher levels of therapy-induced autophagy had drastically lower response rates to BRAFi and a shorter duration of progression-free survival. In BRAF(V600E) melanoma cell lines, BRAFi or BRAF/MEK inhibition induced cytoprotective autophagy, and autophagy inhibition enhanced BRAFi-induced cell death. Shortly after BRAF inhibitor treatment in melanoma cell lines, mutant BRAF bound the ER stress gatekeeper GRP78, which rapidly expanded the ER. Disassociation of GRP78 from the PKR-like ER-kinase (PERK) promoted a PERK-dependent ER stress response that subsequently activated cytoprotective autophagy. Combined BRAF and autophagy inhibition promoted tumor regression in BRAFi-resistant xenografts. These data identify a molecular pathway for drug resistance connecting BRAFi, the ER stress response, and autophagy and provide a rationale for combination approaches targeting this resistance pathway.
Recruitment of monocytic myeloid-derived suppressor cells (MDSCs) and differentiation of tumor-associated macrophages (TAMs) are the major factors contributing to tumor progression and metastasis. We ...demonstrated that differentiation of TAMs in tumor site from monocytic precursors was controlled by downregulation of the activity of the transcription factor STAT3. Decreased STAT3 activity was caused by hypoxia and affected all myeloid cells but was not observed in tumor cells. Upregulation of CD45 tyrosine phosphatase activity in MDSCs exposed to hypoxia in tumor site was responsible for downregulation of STAT3. This effect was mediated by the disruption of CD45 protein dimerization regulated by sialic acid. Thus, STAT3 has a unique function in the tumor environment in controlling the differentiation of MDSC into TAM, and its regulatory pathway could be a potential target for therapy.
Display omitted
•MDSC differentiation to TAM in hypoxic environment is regulated by STAT3 activity•STAT3 inhibition in MDSC was caused by upregulation of CD45 phosphatase activity•Activation of CD45 phosphatase was mediated by sialic acid•Degradation of sialic acid sensitized tumor myeloid cells to STAT3 inhibitor
Gabrilovich and colleagues demonstrate that tumor monocytic cells rapidly differentiate to macrophages due to hypoxia inducible decrease of STAT3 activity. Inhibition of CD45 phosphatase mediated by sialic acid was responsible for this effect. Degradation of sialic acid sensitized tumor myeloid cells to STAT3 inhibitor, resulting in potent antitumor effect.
The emerging photoluminescent carbon-based nanomaterials are promising in various fields besides cell imaging and carrier transport. Carbon nanomaterials with specific biological functions, however, ...are rarely investigated. Aspirin is a very common anti-inflammatory medication to relieve aches and pains. In this study, we have tried to create a carbon nanoparticle with aspirin, and we expect that this new carbon nanoparticle will have both anti-inflammatory and fluorescent biomarker functions. Fluorescent aspirin-based carbon dots (FACDs) were synthesized by condensing aspirin and hydrazine through a one-step microwave-assisted method. Imaging data demonstrated that FACDs efficiently entered into human cervical carcinoma and mouse monocyte macrophage cells in vitro with low cell toxicity. Results from quantitative polymerase chain reaction and histological analysis indicated that FACDs possessed effective anti-inflammatory effects in vitro and in vivo compared to aspirin only. Hematology, serum biochemistry, and histology results suggested that FACDs also had no significant toxicity in vivo. Our results clearly demonstrate that FACDs have dual functions, cellular imaging/bioimaging and anti-inflammation, and suggest that FACDs have great potential in future clinical applications.
In the context of innovative enterprises in China, the significance of sleep quality for employees' physical and mental well-being cannot be understated. This study explores the complex relationship ...between Mindfulness and sleep quality and examines the potential interaction between Social Interaction Anxiety and prolonged sleep behavior. To this end, a thorough evaluation involving the administration of the Mindfulness scale, Social Interaction Anxiety scale, sleep delay scale, and the Pittsburgh Sleep Quality Index (PSQI) was conducted among a significant sample of innovative enterprise employees (N = 1648). The findings reveal that a notable proportion of these employees, 31.1% to be precise (as per PSQI 8), grapple with compromised sleep quality. Subsequent analyses shed light on compelling patterns, underscoring a robust negative correlation between Mindfulness and factors like Social Interaction Anxiety, sleep delay, and sleep quality (β = -0.71, -0.37, -0.35; P < 0.01). Conversely, a significant positive correlation emerges connecting Social Interaction Anxiety, sleep delay, and sleep quality (β = 0.23, 0.37, 0.32; P < 0.01). Interestingly, mediation analysis demonstrates that Mindfulness significantly negatively influences sleep quality, independent of demographic factors such as sex and age. This impact is mediated by sleep delay, which also interacts with Social Interaction Anxiety. In summary, the research emphasizes the predictive function of Mindfulness in improving sleep quality among employees in innovative enterprises, achieved through its reduction of Social Interaction Anxiety and bedtime procrastination tendencies.
Immunologically-cold tumors including glioblastoma (GBM) are refractory to checkpoint blockade therapy, largely due to extensive infiltration of immunosuppressive macrophages (Mϕs). Consistent with a ...pro-tumor role of IL-6 in alternative Mϕs polarization, we here show that targeting IL-6 by genetic ablation or pharmacological inhibition moderately improves T-cell infiltration into GBM and enhances mouse survival; however, IL-6 inhibition does not synergize PD-1 and CTLA-4 checkpoint blockade. Interestingly, anti-IL-6 therapy reduces CD40 expression in GBM-associated Mϕs. We identify a Stat3/HIF-1α-mediated axis, through which IL-6 executes an anti-tumor role to induce CD40 expression in Mϕs. Combination of IL-6 inhibition with CD40 stimulation reverses Mϕ-mediated tumor immunosuppression, sensitizes tumors to checkpoint blockade, and extends animal survival in two syngeneic GBM models, particularly inducing complete regression of GL261 tumors after checkpoint blockade. Thus, antibody cocktail-based immunotherapy that combines checkpoint blockade with dual-targeting of IL-6 and CD40 may offer exciting opportunities for GBM and other solid tumors.
Abstract
Establishment and subsequent maintenance of distinct chromatin domains during embryonic stem cell (ESC) differentiation are crucial for lineage specification and cell fate determination. ...Here we show that the histone chaperone Chromatin Assembly Factor 1 (CAF-1), which is recruited to DNA replication forks through its interaction with proliferating cell nuclear antigen (PCNA) for nucleosome assembly, participates in the establishment of H3K27me3-mediated silencing during differentiation. Deletion of CAF-1 p150 subunit impairs the silencing of many genes including Oct4, Sox2 and Nanog as well as the establishment of H3K27me3 at these gene promoters during ESC differentiation. Mutations of PCNA residues involved in recruiting CAF-1 to the chromatin also result in defects in differentiation in vitro and impair early embryonic development as p150 deletion. Together, these results reveal that the CAF-1-PCNA nucleosome assembly pathway plays an important role in the establishment of H3K27me3-mediated silencing during cell fate determination.
Recent years, the power conversion efficiency (PCE) of normal configuration organic solar cells (OSCs) has obtained rapid progress to reach more than 6% under standard illumination, which is ...reasonable value for the commercial criterion. More and more research attention has been paid on the stability and lifetime of OSCs. A novel structural OSCs with high work function metal or metal oxide as the top electrode and low work function metal as the bottom anode is proposed and named as inverted configuration OSCs. The inverted configuration OSCs with high work function metal as top cathode could improve OSCs's lifetime, i.e., protecting cells from the damage by oxygen and moisture in air. Furthermore, the inverted configuration OSCs is the appealing alternative to the conventional regular structure due to the inherent vertical phase separation in the polymer active layers and high stability or long device lifetime. The inverted configuration OSCs have not only achieved an impressive PCE of 4.4%, but also exhibited an exceptional device lifetime without encapsulation. In this review article, the recent developments and vital researches on the inverted configuration OSCs are summarized.
A novel structural organic solar cells (OSCs) with high work function metal as the top electrode and low work function metal or metal oxide as the bottom anode was proposed and named as inverted configuration OSCs. In this review article, the recent developments and vital researches on the inverted configuration OSCs are summarized.
Display omitted
is a significant source of natural fungal medicines and has been used for the treatment of various diseases for many years. However, the use of
in cancer immunotherapy is poorly elucidated. In this ...study, we have analyzed 2,398 English-language papers and 6,968 Chinese-language papers published between 1987 and 2017 by using bibliometrics. A steady growth in the number of publications was observed before 2004, followed by an exponential increase between 2004 and 2017. The most common category for publications about
was "Pharmacology & Pharmacy," in which immunomodulation (25.60%) and cancer treatment (21.40%) were the most popular subcategories. Moreover, we have provided an overview of the bioactive components and combinatorial immunomodulatory effects for the use of
in the treatment of cancer, including the major pathways of immune cells. Immunomodulatory protein and polysaccharides are the key bioactive factors responsible for cancer immunotherapy, and the NF-κB and MAPK pathways are the most comprehensively investigated major pathways. Our results indicate that
has a broad-spectrum application for the treatment of cancer through the regulation of the immune system. This review provides guidance for future research into the role of
in cancer immunotherapy.
PDF
