Extracellular bioreduction is the main Cr(VI) detoxification strategy of Bacillus sp. HL1.

Bacterium with high Cr(VI) detoxification capability belonged to the genus Bacillus have been largely explored, yet their reduction strategies are still in debate. Cr(VI) removal performance and mechanism of Bacillus sp. HL1 isolated from tailings a site was comprehensively investigated in this study. Approximately 88.31% of 100 mg/L Cr(VI) was continuously removed within 72 h, while it could resist up to 300 mg/L Cr(VI). Metal ions Mn2+ and Cu2+ could effectively improve the Cr(VI) removal performance to 14.41% and 3.41% under the optimal conditions, respectively. Cr(VI) removal performances by subcellular extracts showed that nearly 45.28% of 100 mg/L extracellular Cr(VI) was efficaciously reduced to Cr(III), while only 14.27%, 6.40%, and 2.73% of the cell-free extract, resting cells, and cell debris were reduced, respectively. This suggested that extracellular bioreduction was the primary Cr(VI) detoxification strategy despite a small part of Cr(VI) reduction took place intracellularly. In particular, the reduction products of the intracellular and extracellular compounds significantly differed, with organo-Cr(III) complex outside the cell and crystalline Cr(III) precipitate inside. Such observation was also evidenced by the intracellular black precipitate observed in the TEM image. XRD, XPS, and EPR analysis showed different Cr(III) compositions of intracellular and extracellular products. This study deepens our insights into the different fates of microorganisms that reduce Cr(VI) intracellularly and extracellularly.

Effects of three plant growth-promoting bacterial symbiosis with ryegrass for remediation of Cd, Pb, and Zn soil in a mining area.

The quality of soil containing heavy metals (HMs) around nonferrous metal mining areas is often not favorable for plant growth. Three types of plant growth promoting rhizobacteria (PGPR)-assisted ryegrass were examined here to treat Cd, Pb, and Zn contaminated soil collected from a nonferrous metal smelting facility. The effects of PGPR-assisted plants on soil quality, plant growth, and the migration and transformation of HMs were evaluated. Results showed that inter-root inoculation of PGPR to ryegrass increased soil redox potential, urease, sucrase and acid phosphatase activities, microbial calorimetry, and bioavailable P, Si, and K content. Inoculation with PGPR also increased aboveground parts and root length, P, Si, and K contents, and antioxidant enzyme activities. The most significant effect was that the simultaneous inoculation of all three PGPRs increased the ryegrass extraction (%) of Cd (59.04-79.02), Pb (105.56-157.13), and Zn (27.71-40.79), compared to CK control (without fungi). Correspondingly, the inter-root soil contents (%) of total Cd (39.94-57.52), Pb (37.59-42.17), and Zn (34.05-37.28) were decreased compared to the CK1 control (without fungi and plants), whereas their bioavailability was increased. Results suggest that PGPR can improve soil quality in mining areas, promote plant growth, transform the fraction of HMs in soil, and increase the extraction of Cd, Pb, and Zn by ryegrass. PGPR is a promising microbe-assisted phytoremediation strategy that can promote the re-greening of vegetation in the mining area while remediating HMs pollution.

BTNL2 promotes colitis-associated tumorigenesis in mice by regulating IL-22 production.

Interleukin 22 (IL-22) has an important role in colorectal tumorigenesis and many colorectal diseases such as inflammatory bowel disease and certain infections. However, the regulation of IL-22 production in the intestinal system is still unclear. Here, we present evidence that butyrophilin-like protein 2 (BTNL2) is required for colorectal IL-22 production, and BTNL2 knockout mice show decreased colonic tumorigenesis and more severe colitis phenotypes than control mice due to defective production of IL-22. Mechanistically, BTNL2 acts on group 3 innate lymphoid cells (ILC3s), CD4+ T cells, and γδ T cells to promote the production of IL-22. Importantly, we find that a monoclonal antibody against BTNL2 attenuates colorectal tumorigenesis in mice and that the mBTNL2-Fc recombinant protein has a therapeutic effect in a dextran sulfate sodium (DSS)-induced colitis model. This study not only identifies a regulatory mechanism of IL-22 production in the colorectal system but also provides a potential therapeutic target for the treatment of human colorectal cancer and inflammatory bowel diseases.

Tumor-Derived Small Extracellular Vesicles Involved in Breast Cancer Progression and Drug Resistance.

Breast cancer is one of the most serious and terrifying threats to the health of women. Recent studies have demonstrated that interaction among cancer cells themselves and those with other cells, including immune cells, in a tumor microenvironment potentially and intrinsically regulate and determine cancer progression and metastasis. Small extracellular vesicles (sEVs), a type of lipid-bilayer particles derived from cells, with a size of less than 200 nm, are recognized as one form of important mediators in cell-to-cell communication. sEVs can transport a variety of bioactive substances, including proteins, RNAs, and lipids. Accumulating evidence has revealed that sEVs play a crucial role in cancer development and progression, with a significant impact on proliferation, invasion, and metastasis. In addition, sEVs systematically coordinate physiological and pathological processes, such as coagulation, vascular leakage, and stromal cell reprogramming, to bring about premetastatic niche formation and to determine metastatic organ tropism. There are a variety of oncogenic factors in tumor-derived sEVs that mediate cellular communication between local stromal cells and distal microenvironment, both of which are important in cancer progression and metastasis. Tumor-derived sEVs contain substances that are similar to parental tumor cells, and as such, sEVs could be biomarkers in cancer progression and potential therapeutic targets, particularly for predicting and preventing future metastatic development. Here, we review the mechanisms underlying the regulation by tumor-derived sEVs on cancer development and progression, including proliferation, metastasis, drug resistance, and immunosuppression, which coordinately shape the pro-metastatic microenvironment. In addition, we describe the application of sEVs to the development of cancer biomarkers and potential therapeutic modalities and discuss how they can be engineered and translated into clinical practice.

SIPA1 Regulates LINC01615 to Promote Metastasis in Triple-Negative Breast Cancer.

Long non-coding RNAs (lncRNAs) are reported to play an important regulatory effect in carcinogenesis and malignancy. We found by high-throughput sequencing that LINC01615 is upregulated in breast cancer patients and reduces patients' overall survival. In vivo and in vitro experiments, we clarified that overexpression of LINC01615 can promote breast cancer cell metastasis ability. The expression of LINC01615 is regulated by the transcriptional activator SIPA1, thereby promoting carcinogenesis in breast cancer cells. Our research clarified that LINC01615 can act as an oncogenic factor in promoting the development of breast cancer.

Stress-strain and acoustic emission characteristics of cement-based materials used to simulate soft rock with fractures.

Instability failure in rock mass engineering is closely related to expansion of joint fissures. In this study, uniaxial compression tests and acoustic emission (AE) measurements were carried out simultaneously on specimens of soft rock-like material with different fracture angles and connectivity values to better understand their influence on the deformation and failure of the material. The stress-strain curve and AE signal of fractured soft rock-like material are similar to those of intact soft rock-like; specifically, they exhibit a compaction, elastic deformation, stable fracture development, and unstable fracture development. The main differences between fractured and intact material occur during post-peak failure stage. Under the combined influence of fracture angle and connectivity, the uniaxial compressive strength of fractured soft rock-like material ([Formula: see text]) is lower than that of the intact soft rock-like material (fcu), and can be described by the relationship [Formula: see text], where [Formula: see text] is the strength reduction coefficient, fitted as [Formula: see text]. In this equation, x is the fracture angle ([Formula: see text]) and y is the fracture connectivity (%). Under uniaxial compression, the main types of secondary cracks were wing cracks and secondary coplanar cracks. The specimen with a fracture angle of 30° mainly underwent tensile failure under loading, whereas those with fracture angles of 45° and 60°mainly experienced shear failure under high-connectivity conditions (45%).

Extracellular Vesicles Derived from SIPA1high Breast Cancer Cells Enhance Macrophage Infiltration and Cancer Metastasis through Myosin-9.

Tumour cell metastasis can be genetically regulated by proteins contained in cancer cell-derived extracellular vesicles (EVs) released to the tumour microenvironment. Here, we found that the number of infiltrated macrophages was positively correlated with the expression of signal-induced proliferation-associated 1 (SIPA1) in invasive breast ductal carcinoma tissues and MDA-MB-231 xenograft tumours. EVs derived from MDA-MB-231 cells (231-EVs) significantly enhanced macrophage migration, compared with that from SIPA1-knockdown MDA-MB-231 cells (231/si-EVs) both in vitro and in vivo. We revealed that SIPA1 promoted the transcription of MYH9, which encodes myosin-9, and up-regulated the expression level of myosin-9 in breast cancer cells and their EVs. We also found that blocking myosin-9 by either down-regulating SIPA1 expression or blebbistatin treatment led to the suppression of macrophage infiltration. Survival analysis showed that breast cancer patients with high expression of SIPA1 and MYH9 molecules had worse relapse-free survival (p = 0.028). In summary, SIPA1high breast cancer can enhance macrophage infiltration through EVs enriched with myosin-9, which might aggravate the malignancy of breast cancer.

T-cell activation Rho GTPase-activating protein maintains intestinal homeostasis by regulating intestinal T helper cells differentiation through the gut microbiota.

Common variants of the T-cell activation Rho GTPase-activating protein (TAGAP) are associated with the susceptibility to human inflammatory bowel diseases (IBDs); however, the underlying mechanisms are still unknown. Here, we show that TAGAP deficiency or TAGAP expression downregulation caused by TAGAP gene polymorphism leads to decreased production of antimicrobial peptides (AMPs), such as reg3g, which subsequently causes dysregulation of the gut microbiota, which includes Akkermansia muciniphila and Bacteroides acidifaciens strains. These two strains can polarize T helper cell differentiation in the gut, and aggravate systemic disease associated with the dextran sodium sulfate-induced (DSS) disease's phenotype in mice. More importantly, we demonstrated that recombinant reg3g protein or anti-p40 monoclonal antibody exerted therapeutic effects for the treatment of DSS-induced colitis in wild-type and TAGAP-deficient mice, suggesting that they are potential medicines for human IBD treatment, and they may also have a therapeutic effect for the patients who carry the common variant of TAGAP rs212388.

Microbial community profiles in soils adjacent to mining and smelting areas: Contrasting potentially toxic metals and co-occurrence patterns.

Mining and smelting activities have introduced severe potentially toxic metals (PTMs) contamination into surrounding soil settings. Influences of PTMs on microbial diversity have been widely studied. However, variations of microbial communities, network structures and community functions in different levels of PTMs contaminated soils adjacent to mining and smelting aera are still poorly investigated. In this study, microbial communities of soils around different levels of PTMs contamination were comprehensively studied by 16S rRNA gene amplicons high-throughput sequencing. Microbial interactions and module functions were also exploited to ascertain the discrepancies of PTMs concentration levels on microbial ecological functions. Results indicated that the microbial community composition was significantly distinct attributed to the phylum Protebacteria (p = 0.002) dominating in soil with high level PTMs contents but Actinobacteria (p = 0.002) in low level of PTMs-contaminated soil. Microbial α diversity was not significantly influenced by different levels of PTMs contaminations. Microorganisms proactively responded to PTMs content levels by means of strengthening network complexities and modularities among microbe-microbe interactions. The functions of main network modules were predicted associating membrane transport, amino acid metabolism, energy metabolism and carbohydrate metabolism. The PTMs detoxification and anti-oxidation were significantly strengthened at the high level of PTMs contamination. The present study demonstrated that modification of microbial community by the adaptive adjustment of microbial compositions and strengthening their network complexity and modularity.

SIPA1 Enhances Aerobic Glycolysis Through HIF-2α Pathway to Promote Breast Cancer Metastasis.

Increased dependence on aerobic glycolysis is characteristic of most cancer cells, whereas the mechanism underlying the promotion of aerobic glycolysis in metastatic breast cancer cells under ambient oxygen has not been well understood. Here, we demonstrated that aberrant expression of signal-induced proliferation-associated 1 (SIPA1) enhanced aerobic glycolysis and altered the main source of ATP production from oxidative phosphorylation to glycolysis in breast cancer cells. We revealed that SIPA1 promoted the transcription of EPAS1, which is known as the gene encoding hypoxia-inducible factor-2α (HIF-2α) and up-regulated the expression of multiple glycolysis-related genes to increase aerobic glycolysis. We also found that blocking aerobic glycolysis by either knocking down SIPA1 expression or oxamate treatment led to the suppression of tumor metastasis of breast cancer cells both in vitro and in vivo. Taken together, aberrant expression of SIPA1 resulted in the alteration of glucose metabolism from oxidative phosphorylation to aerobic glycolysis even at ambient oxygen levels, which might aggravate the malignancy of breast cancer cells. The present findings indicate a potential target for the development of therapeutics against breast cancers with dysregulated SIPA1 expression.

Exosomal Thrombospondin-1 Disrupts the Integrity of Endothelial Intercellular Junctions to Facilitate Breast Cancer Cell Metastasis.

Transendothelial migration of malignant cells plays an essential role in tumor progression and metastasis. The present study revealed that treating human umbilical vein endothelial cells (HUVECs) with exosomes derived from metastatic breast cancer cells increased the number of cancer cells migrating through the endothelial cell layer and impaired the tube formation of HUVECs. Furthermore, the expression of intercellular junction proteins, including vascular endothelial cadherin (VE-cadherin) and zona occluden-1 (ZO-1), was reduced significantly in HUVECs treated with carcinoma-derived exosomes. Proteomic analyses revealed that thrombospondin-1 (TSP1) was highly expressed in breast cancer cell MDA-MB-231-derived exosomes. Treating HUVECs with TSP1-enriched exosomes similarly promoted the transendothelial migration of malignant cells and decreased the expression of intercellular junction proteins. TSP1-down regulation abolished the effects of exosomes on HUVECs. The migration of breast cancer cells was markedly increased in a zebrafish in vivo model injected with TSP1-overexpressing breast cancer cells. Taken together, these results suggest that carcinoma-derived exosomal TSP1 facilitated the transendothelial migration of breast cancer cells via disrupting the intercellular integrity of endothelial cells.

PVP-templated highly luminescent copper nanoclusters for sensing trinitrophenol and living cell imaging.

Copper nanoclusters (CuNCs) exhibit susceptibility to oxidation in the subnanometer size range. In this work, a facile and green protocol is reported for the successful synthesis of water soluble CuNCs, with poly(vinylpyrrolidone) as a template and ascorbic acid as a mild reducing agent. The as-prepared CuNCs exhibit a green fluorescence and high quantum yield (QY = 44.67%) in water, which is the highest among the reported water soluble CuNCs. The origin of their highly luminescent nature was also investigated. In addition, the obtained CuNCs show good tolerability to high ionic strength, superior antioxidation properties, good photostability, time-stability, a large Stokes shift and ultralow cytotoxicity, laying the foundation for living cell imaging in THP-1 macrophages. A bright green fluorescence can be observed from the cells, indicating the potential practicality of CuNCs as a fluorescence marker in bioapplications. Interestingly, the as-prepared CuNCs exhibit a good selective fluorescence quenching response towards trinitrophenol over other nitro compounds. Furthermore, CuNCs were employed for sensing trinitrophenol based on the inner filter effect. A good linear relationship was obtained in the low concentration range of trinitrophenol, with a limit of detection of 3.91 × 10-7 M in aqueous medium. This result suggests the potential application of CuNCs as a probe in sensing and monitoring toxic trinitrophenol in the field of environmental security.

Soluble Hyperbranched Porous Organic Polymers.

Soluble porous organic polymers (SPOPs) are currently the subject of extensive investigation due to the enhanced processability compared to insoluble counterparts. Here, a new concept for the construction of SPOPs is presented, which combines the unique topological structure of hyperbranched polymers with rigid building blocks. By using this facile, one-step strategy, a class of novel SPOPs which possess surface areas up to 646 m2 g-1 have been synthesized. The extended π-conjugated backbone affords the polymers bright fluorescence under UV irradiation. Interestingly, after dissolution in a suitable solvent that was slowly evaporated, the polymers retain a large extent of porosity. The SPOPs are potential candidates for gas storage and separation, photovoltaic, and biological applications. In particular, due to the presence of an internal porous structure and open conformations, they show high drug loading efficiency (1.91 g of ibuprofen per gram), which is considerably higher than conventional porous organic polymers.

[Studies on nano-particle sols of hydroxyaptite and titanium dioxide for haemo-compatibility].

A biological evaluation is conducted for two types of nano-particle sols, hydroxyaptite(HAP) and titanium dioxide(TiO2). The results show that HAP sol significnatly prolongs the bleeding time and coagulation time of mice as well as the prothrombin time(PT) and partial thromboplastin time(PTT) of rats while TiO2 sol exhibits no such effects. Neither HAP sol nor TiO2 sol instigated in-vitro hemolysis of rabbit erythrocyte. However, both of the materials caused in-vitro aggregation of rabbit erythrocytes. The reason underlying the different results as to the two types of material is their specific stabilizer, heparin for HAP sol and PVC for TiO2 sol. We came to the conclusion that a biologically inert stablizer has no less significance than the nano-particle's very own nature in a nano-material's application prospect.