Targeting HSP47 for cancer treatment.

Heat shock protein 47 (HSP47) serves as an endoplasmic reticulum residing collagen-specific chaperone and plays an important role in collagen biosynthesis and structural assembly. HSP47 is encoded by the SERPINH1 gene, which is located on chromosome 11q13.5, one of the most frequently amplified regions in human cancers. The expression of HSP47 is regulated by multiple cellular factors, including cytokines, transcription factors, microRNAs, and circular RNAs. HSP47 is frequently upregulated in a variety of cancers and plays an important role in tumor progression. HSP47 promotes tumor stemness, angiogenesis, growth, epithelial-mesenchymal transition, and metastatic capacity. HSP47 also regulates the efficacy of tumor therapies, such as chemotherapy, radiotherapy, and immunotherapy. Inhibition of HSP47 expression has antitumor effects, suggesting that targeting HSP47 is a feasible strategy for cancer treatment. In this review, we highlight the function and expression of regulatory mechanisms of HSP47 in cancer progression and point out the potential development of therapeutic strategies in targeting HSP47 in the future.

When transition-metal catalysis meets electrosynthesis: a recent update.

While aiming at sustainable synthesis, organic electrosynthesis has attracted increasing attention in the past few years. In parallel, with a deeper understanding of catalyst and ligand design, 3d transition-metal catalysis allows the conception of more straightforward synthetic routes in a cost-effective fashion. Owing to their intrinsic advantages, the merger of organic electrosynthesis with 3d transition-metal catalysis has offered huge opportunities for conceptually novel transformations while limiting ecological footprint. This review summarizes the key advancements in this direction published in the recent two years, with specific focus placed on strategy design and mechanistic aspects.

Exposure Order to Photoaging and Humic Acids Significantly Modifies the Aggregation and Transformation of Nanoplastics in Aqueous Solutions.

The colloidal stability of nanoplastics in aqueous solutions is greatly regulated by photoaging and dissolved organic matter (DOM). However, how the exposure order to sunlight and DOM modifies the environmental behavior of nanoplastics is seldomly determined. Here, with two different exposure orders, we investigated the impact of molecular-weight (MW)-fractionated humic acids (HAs) derived from biochar and the Suwannee River, respectively, on the aggregation of poly(ethylene terephthalate) nanoplastics (PET-NPs) in mono- and divalent electrolyte solutions. For exposure pattern (i) (photoaging followed by HA coating), photoaged PET-NPs had more oxidized surfaces and exhibited 22-320% higher binding affinity to HAs (especially the higher MW fractions) than the pristine counterparts, which greatly improved the dispersion of PET-NPs. For exposure pattern (ii) (HA coating followed by photoaging), HA-PET assemblies were formed, the dispersion of which increased with increasing irradiation time and was significantly higher than that of the samples in the exposure pattern (i) at the end of the experiment. This high dispersion of photoaged HA-PET assemblies was ascribed to the extra oxidation of PET by reactive oxygen species generated in the PET-HA interfaces during photoaging. These findings highlight the "active nature" of HA-PET assemblies, which provide new insight into the reaction of HA with nanoplastics beyond adsorption in the natural environment.

PAI-1 induction during kidney injury promotes fibrotic epithelial dysfunction via deregulation of klotho, p53, and TGF-ß1-receptor signaling.

Renal fibrosis leads to chronic kidney disease, which affects over 15% of the U.S. population. PAI-1 is highly upregulated in the tubulointerstitial compartment in several common nephropathies and PAI-1 global ablation affords protection from fibrogenesis in mice. The precise contribution of renal tubular PAI-1 induction to disease progression, however, is unknown and surprisingly, appears to be independent of uPA inhibition. Human renal epithelial (HK-2) cells engineered to stably overexpress PAI-1 underwent dedifferentiation (E-cadherin loss, gain of vimentin), G2/M growth arrest (increased p-Histone3, p21), and robust induction of fibronectin, collagen-1, and CCN2. These cells are also susceptible to apoptosis (elevated cleaved caspase-3, annexin-V positivity) compared to vector controls, demonstrating a previously unknown role for PAI-1 in tubular dysfunction. Persistent PAI-1 expression results in a loss of klotho expression, p53 upregulation, and increases in TGF-ßRI/II levels and SMAD3 phosphorylation. Ectopic restoration of klotho in PAI-1-transductants attenuated fibrogenesis and reversed the proliferative defects, implicating PAI-1 in klotho loss in renal disease. Genetic suppression of p53 reversed the PA1-1-driven maladaptive repair, moreover, confirming a pathogenic role for p53 upregulation in this context and uncovering a novel role for PAI-1 in promoting renal p53 signaling. TGF-ßRI inhibition also attenuated PAI-1-initiated epithelial dysfunction, independent of TGF-ß1 ligand synthesis. Thus, PAI-1 promotes tubular dysfunction via klotho reduction, p53 upregulation, and activation of the TGF-ßRI-SMAD3 axis. Since klotho is an upstream regulator of both PAI-1-mediated p53 induction and SMAD3 signaling, targeting tubular PAI-1 expression may provide a novel, multi-level approach to the therapy of CKD.

Novel Insights into the Impact of Nano-Biochar on Composition and Structural Transformation of Mineral/Nano-Biochar Heteroaggregates in the Presence of Root Exudates.

Multiple lines of existing evidence indicate that natural organic matter (NOM) could protect poorly crystalline Fe(III) (oxyhydr)oxides from Fe(II)-catalyzed mineral transformation. Conversely, we find that nano-sized biochar (nano-BC), a pyrogenic form of NOM, promotes the phase transformation of ferrihydrite (Fh) in nano-BC/Fh heteroaggregates in the presence of aqueous Fe(II) and rice root exudates. The nano-BC/Fh heteroaggregates are composed of a core-shell like structure where the inner-layered nano-BC is more compacted and plays the dominant role in accelerating the phase transformation of Fh relative to that in the outer sphere. The extent of phase transformation is more regulated by the reversible redox reactions between quinone and hydroquinone in nano-BC than the electron transfer via its condensed aromatic structures. Furthermore, the reductive organic acids in root exudates contribute to the mineral transformation of nano-BC/Fh associations by donating electrons to Fe(III) through nano-BC. Our results suggest that heteroaggregates between nano-BC and Fe minerals are subjected to partial dissociation during their co-transport, and the stably attached nano-BC is favorable to the phase transformation of poorly crystalline Fe minerals (e.g., Fh), which might have profound implications on biogeochemical cycles of carbon and Fe in the prevailing redox environments.

Effect of root exudates on the release, surface property, colloidal stability, and phytotoxicity of dissolved black carbon.

In this study, the release of dissolved black carbon (DBC) from bulk-BC, its surface properties, colloidal stability, and oxidative stress to rice seedlings in the presence and absence of rice root exudates were compared. The bulk-BCs were prepared at 550 °C and derived from wood chips and pig manure, respectively. The release of DBC from bulk-BC was significantly enhanced (20.19-23.63%) by the introduction of root exudates, where low molecular weight organic acids played a dominating role in the dissociation of DBC from carbon skeleton. The surface properties of DBC were greatly modified by root exudates including decreases in the surface area (18.13%) and mineral contents (43.90-69.57%). The O-containing groups and graphitization were also enhanced by 11.46% and 18.65%, respectively. Meanwhile, the presence of root exudates not only reduced the colloidal stability of DBC but also lowered the intensity of free radicals (19.44-22.22%) in DBC. Consequently, the oxidative stress of DBC to rice seedlings was significantly (p < 0.05) alleviated, evidenced by reduced antioxidative enzyme activities (5.67-29.25%) and soluble protein content (15.75-46.79%) in rice plants. These results indicate that the interaction between DBC and root exudates could remarkably modify the surface properties and reactivity of DBC, which has profound implications for understanding the behavior and functions of DBC in the environment.

Indirect Electrosynthesis with Halogen Ions as Mediators.

Organic electrosynthesis has gained increasing research interest as it harvests electric current as redox regents, thereby providing a sustainable alternative to conventional approaches. Compared with direct electrosynthesis, indirect electrosynthesis employs mediator(s) to lower the overpotentials for substrate activation, and enhance the reaction efficiency and functional group compatibility by shifting the heterogenous electron transfer process to be homogenous. As one of the most versatile and cost-efficient mediators, halogen mediators are always combined with an irreversible halogenation reaction. Thus, the electrochemical reaction between halogen mediators and substrates doesn't directly controlled by the two standard potentials difference. In this account, our recent developments in the area of halogen-mediated indirect electrosynthesis are summarized. The anodically generated halogen species from halogenide salts have the abilities to undergo electron-transfer (ET) or hydrogen-atom- transfer (HAT) processes. The reaction features, scopes, limitations, and mechanistic rationalisations are discussed in this account. We hope our studies will contribute to the future developments to broaden the scope of halogen-mediated electrosynthesis.

Photochemical Transformation and Catalytic Activity of Dissolved Black Nitrogen Released from Environmental Black Carbon.

Biomass combustion results in the formation and wide distribution of black carbon (BC) in soils, wherein the dissolved fractions are among the most active components. Although the presence of dissolved black nitrogen (DBN) in BC has been identified, its environmental behavior and implication are not understood. This study investigated the photochemical transformation and catalytic activity of DBN under simulated solar irradiation. DBN is more easily transformed than dissolved BC due to its photoactive heteroaromatic N structure, and the half-life of DBN produced at 500 °C (8.6 h) is two times shorter than that of the dissolved BC counterpart (23 h). Meanwhile, solar irradiation is favorable for the homoaggregation of DBN. During irradiation, DBN generates not only reactive oxygen species (e.g., 1O2, O2-, and •OH) but also reactive nitrogen species (mainly •ON), which account for its higher photocatalytic degradation of bisphenol A than dissolved BC. These findings shed new light on the impact of heteroatoms on the phototransformation and activity of BC as well as cycling of N in terrestrial systems.

A Case of Ewing Sarcoma of the Bladder Presenting in Early Infancy.

A 6-week-old female presented with gross hematuria and was diagnosed with Ewing sarcoma of the bladder through ultrasound and cystoscopic biopsies, along with a negative metastatic workup. She was treated with transurethral resection, chemotherapy consisting of with vincristine, cycolphosphamide, doxorubicin, ifosfamide and etoposide, and partial cystectomy. After completing chemotherapy, the patient has been doing well with no evidence of disease. There have been 14 other cases, 4 pediatric, of Ewing sarcoma of the bladder reported. To our knowledge, our case is the youngest patient reported with this disease.

Silicon combined with foliar melatonin for reducing the absorption and translocation of Cd and As by Oryza sativa L. in two contaminated soils.

Potentially toxic elements (PTE) toxicity has serious effects for human health. Si has been tested to investigate their ability to mitigate Cd and As contamination of rice. In this study, the combined effect of Si and melatonin (MT) on Cd and As uptake and transport in rice plants is tested in two contaminated soils via controlled pot experiments. Results showed that a combined Si and MT treatment (Si + MT) was more effective at reducing Cd and As uptake and transport than Si alone. The treatment had the strongest effect on Cd concentrations in rice grains from high-polluted soil (HP) when treated at the flowering stage (81.8% reduction) and from low-polluted soil (LP) at the tillering stage (TS, 64.9%). The greatest reduction of grain As was found when treated at TS in both soils, by 58.2% and 39.2% in HP and LP soil, respectively. The significant upregulation of CAT, SOD, and POD activities, and downregulation of MDA by Si + MT was more effective than that of Si alone; Si + MT significantly decreased expressions of Nramp1, HMA2, and IRT2 in roots in both soils, and also Nramp5, HMA3, and IRT1 in LP soil, which might result in Si+MT effect on Cd and As accumulation. However, Si + MT had little effect on the amino acid content of grains compared to Si alone. Overall, the combination of Si and MT was substantially more effective at reducing Cd and As uptake and transport than Si alone, especially in HP soil. This effect might result from the regulation of antioxidant potential and gene expression relating Cd uptake and transport.

The role of biochars in sustainable crop production and soil resiliency.

Biochar is a promising soil additive for use in support of sustainable crop production. However, the high level of heterogeneity in biochar properties and the variations in soil composition present significant challenges to the successful uptake of biochar technologies in diverse agricultural soils. An improved understanding of the mechanisms that contribute to biochar-soil interactions is required to address issues related to climate change and cultivation practices. This review summarizes biochar modification approaches (physical, chemical, and biochar-based organic composites) and discusses the potential role of biochar in sustainable crop production and soil resiliency, including the degradation of soil organic matter, the improvement of soil quality, and reductions in greenhouse gas emissions. Biochar design is crucial to successful soil remediation, particularly with regard to issues arising from soil structure and composition related to crop production. Given the wide variety of feedstocks for biochar production and the resultant high surface heterogeneity, greater efforts are required to optimize biochar surface functionality and porosity through appropriate modifications. The design and establishment of these approaches and methods are essential for the future utilization of biochar as an effective soil additive to promote sustainable crop production.

Rac-GTPase promotes fibrotic TGF-ß1 signaling and chronic kidney disease via EGFR, p53, and Hippo/YAP/TAZ pathways.

Rac-GTPases are major regulators of cytoskeletal remodeling and their deregulation contributes to numerous pathologies. Whether or how Rac promotes tubulointerstitial fibrosis and chronic kidney disease (CKD) is currently unknown. We showed that the major profibrotic cytokine, TGF-ß1 promoted rapid Rac1-GTP loading in human kidney 2 (HK-2) human renal epithelial cells. A Rac-specific chemical inhibitor, EHT 1864, blocked TGF-ß1-induced fibrotic reprogramming in kidney epithelial cells and fibroblasts. Stable Rac1 depletion in HK-2 cells, moreover, eliminated TGF-ß1-mediated non-SMAD pathway activation [e.g., Src, epidermal growth factor receptor (EGFR), p53] and subsequent plasminogen activator inhibitor-1 (PAI-1), connective tissue growth factor, fibronectin, and p21 induction. Rac1 and p22phox knockdown abrogated free radical generation by TGF-ß1 in HK-2 cells, consistent with the role of Rac1 in NAPD(H). TGF-ß1-induced renal epithelial cytostasis was also completely bypassed by Rac1, p22phox, p47phox, and PAI-1 silencing. Rac1b isoform expression was robustly induced in the fibrotic kidneys of mice and humans. Intraperitoneal administration of EHT 1864 in mice dramatically attenuated ureteral unilateral obstruction-driven EGFR, p53, Rac1b, yes-associated protein/transcriptional coactivator with PDZ-binding motif activation/expression, dedifferentiation, cell cycle arrest, and renal fibrogenesis evident in vehicle-treated obstructed kidneys. Thus, the Rac1-directed redox response is critical for TGF-ß1-driven epithelial dysfunction orchestrated, in part, via PAI-1 up-regulation. Rac pathway inhibition suppressed renal oxidative stress and maladaptive repair, identifying Rac as a novel therapeutic target against progressive CKD.-Patel, S., Tang, J., Overstreet, J. M., Anorga, S., Lian, F., Arnouk, A., Goldschmeding, R., Higgins, P. J., Samarakoon, R. Rac-GTPase promotes fibrotic TGF-ß1 signaling and chronic kidney disease via EGFR, p53, and Hippo/YAP/TAZ pathways.

Size Matters: Nano-Biochar Triggers Decomposition and Transformation Inhibition of Antibiotic Resistance Genes in Aqueous Environments.

Antibiotic resistance genes (ARGs) are considered to be a type of emerging contaminant; their interaction with biochar (BC) could affect their dissemination and fate in the environment. Although adsorption of ARGs onto bulk-BC has been reported, the interaction with nanosized BC (nano-BC) is largely unknown. In this study, the interactions of a model extracellular DNA (eDNA, calf thymus DNA) and two typical ARGs (ampC and ermB) extracted from a natural river with bulk- and nano-BCs from two pyrolysis temperatures (400 and 700 °C) were investigated. Only adsorption was observed on bulk-BCs, while not only adsorption but also fragmentation of these eDNA molecules was found to occur on nano-BCs. Also, their replication was greatly inhibited by nano-BCs. The electron paramagnetic resonance results indicated that hydroxyl radicals produced from persistent free radicals (PFRs) on nano-BCs played a major role in the damage of eDNA. Moreover, the direct contact with nonradical reacting sites and PFRs on nano-BCs also contributed to the decay of eDNA. Comparatively, PFRs in bulk-BCs were difficult to be reached by eDNA because of steric hindrance and played a negligible role in destroying eDNA. These findings highlight the importance of the size effect in evaluating the reactivity and related environmental risks of PFRs on BC and improve our understanding on the interaction between ARGs and BC.

Comparison of Ca2+ Handling for the Regulation of Vasoconstriction between Rat Coronary and Renal Arteries.

BACKGROUND: Ca2+ plays an important role in the regulation of vasoconstriction. Ca2+ signaling is regulated by a number of Ca2+-handling proteins. However, whether differences in Ca2+ handling affect the regulation of vasoconstriction in different arteries remains elusive. OBJECTIVE: To determine whether differences in Ca2+ handling affect the response to vasoconstrictors in different arteries. METHODS: Arterial ring contraction was measured using a Multi Myograph System. Vascular smooth muscle cells (VSMCs) were digested with type 2 collagenase in DMEM, then intracellular calcium concentration was measured with the Ca2+ probe fluo-4/AM in the isolated cells. Calcium-related proteins were assayed by Western blotting. RESULTS: Phenylephrine did not induce -coronary arterial contraction. There were differences in -5-hydroxytryptamine, 9,11-dideoxy-11a,9a-epoxymethano-prostaglandin F2a, and endothelin 1-induced vasoconstriction in different solutions between coronary and renal arteries. Vasoconstrictions in the presence of Bay K8644 were stronger in coronary than in renal arteries. Store-operated calcium (SOC) channels could mediate Ca2+ influx in VSMCs of both groups. SOC channels did not participate in the contraction of coronary arteries. In addition, there were significant differences in the expressions of receptors and ion channels between the two groups. CONCLUSIONS: Ca2+ handling contributed to the different responses to vasoconstrictors between coronary and renal arteries.

New Insights into Black Carbon Nanoparticle-Induced Dispersibility of Goethite Colloids and Configuration-Dependent Sorption for Phenanthrene.

Black carbon nanoparticles (nano-BC) are one of the most active components in pyrogenic carbonaceous matter and involved in many biogeochemical processes. This study investigated heteroaggregation of nano-BC with goethite (a model of natural mineral colloids) and the configuration effect of heteroaggregates on phenanthrene (PHE) sorption. Nano-BC could significantly enhance the dispersion of goethite via heteroaggregation when its concentration was higher than the critical concentration ( Cc). The Cc was dependent on the surface potential of nano-BC, which was directly measured for the first time in this study. Configuration and stability of the heteroaggregates were regulated by BC-goethite mass ratio and solution pH. At pH 5.3, oppositely charged goethite and nano-BC interacted with each other through electrostatic attraction and the configuration of heteroaggregates was dependent on BC-goethite mass ratio. At pH 7.4, where both goethite and nano-BC were negatively charged, they heteroaggregated with each other mainly through H-bonding and Lewis acid-base mechanisms, and the configuration of heteroaggregates was independent of BC-goethite mass ratio. For PHE sorption, small-sized heteroaggregates were more favorable than large ones due to the higher content of active sorption sites. Interestingly, at a higher concentration of PHE, we found that the solute molecules could probably penetrate into and/or alter the configuration of heteroaggregates and enhance its sorption capacity for PHE. These findings are useful for understanding the effect of nano-BC on colloidal stability and organic compound sorption of minerals.

Application of polymeric ferric sulfate combined with cross-frequency magnetic field in the printing and dyeing wastewater treatment.

Polymeric ferric sulfate (PFS) was pretreated with a self-made alternating frequency magnetic field for coagulation printing and dyeing (PD) wastewater treatment. The effects of PFS dosage, magnetization intensity, frequency, and time on the removal of chemical oxygen demand (COD), color and turbidity of PD wastewater were investigated. The results indicated that the magnetized PFS significantly improved the removal efficiency in wastewater treatment. When the initial COD, color and turbidity of printing and dyeing wastewater was 464 mg/L, 180 degrees, and 54.8 NTU respectively, the maximum removal rate of COD, color and turbidity was 87.9%, 80.1%, and 95.2% respectively, under the condition of cross frequency magnetic field magnetization PFS. Moreover, the PFS treatment combined with cross-frequency magnetic field could greatly reduce the pollution of iron ions released from iron-based coagulant during wastewater treatment. Characterization of magnetized PFS flocculant by fourier transform infrared spectroscopy, ultraviolet and visible spectrophotometry, and scanning electron microscopy suggested that magnetic crystal with larger size can be formed on the surface of PFS particles.

Black Carbon (Biochar) In Water/Soil Environments: Molecular Structure, Sorption, Stability, and Potential Risk.

Black carbon (BC) is ubiquitous in the environments and participates in various biogeochemical processes. Both positive and negative effects of BC (especially biochar) on the ecosystem have been identified, which are mainly derived from its diverse physicochemical properties. Nevertheless, few studies systematically examined the linkage between the evolution of BC molecular structure with the resulted BC properties, environmental functions as well as potential risk, which is critical for understanding the BC environmental behavior and utilization as a multifunctional product. Thus, this review highlights the molecular structure evolution of BC during pyrolysis and the impact of BC physicochemical properties on its sorption behavior, stability, and potential risk in terrestrial and aqueous ecosystems. Given the wide application of BC and its important role in biogeochemical processes, future research should focus on the following: (1) establishing methodology to more precisely predict and design BC properties on the basis of pyrolysis and phase transformation of biomass; (2) developing an assessment system to evaluate the long-term effect of BC on stabilization and bioavailability of contaminants, agrochemicals, and nutrient elements in soils; and (3) elucidating the interaction mechanisms of BC with plant roots, microorganisms, and soil components.

Physical, Complementary, and Alternative Medicine in the Treatment of Pelvic Floor Disorders.

PURPOSE OF REVIEW: The purpose of the study was to catalog the most recent available literature regarding the use of conservative measures in treatment of pelvic floor disorders. RECENT FINDINGS: Pelvic floor disorders encompass abnormalities of urination, defecation, sexual function, pelvic organ prolapse, and chronic pain, and can have significant quality of life implications for patients. Current guidelines recommend behavioral modifications and conservative treatments as first-line therapy for pelvic floor disorders. We have reviewed the literature for articles published on physical, complementary, and alternative treatments for pelvic floor disorders over the past 5 years. Review of pelvic floor muscle physiotherapy (PFMT) and biofeedback (BF) shows a benefit for patients suffering from bladder dysfunction (incontinence, overactive bladder), bowel dysfunction (constipation, fecal incontinence), pelvic organ prolapse, and sexual dysfunction (pelvic pain). Combination of PFMT and BF has shown improved results compared to PFMT alone, and some studies find that electrical stimulation can augment the benefit of BF and PFMT. Additionally, acupuncture and cognitive behavioral therapy has shown to be an effective treatment for pelvic floor disorders, particularly with respect to pelvic pain. This update highlights beneficial conservative treatments available for pelvic floor dysfunction, and supplements the current literature on treatment options for patients suffering from these disorders.

High Royal Jelly-Producing Honeybees (Apis mellifera ligustica) (Hymenoptera: Apidae) in China.

China is the largest producer and exporter of royal jelly (RJ) in the world, supplying >90% of the global market. The high production of RJ in China is principally owing to the high RJ-producing lineage of honeybees (Apis mellifera ligustica Spinola, 1806) established by beekeepers in the 1980s. We describe the development of high royal jelly-producing honeybees and the management of this lineage today. Previous research and recent advances in the genetic characterization of this lineage, and the molecular markers and mechanisms associated with high RJ production are summarized. The gaps in our knowledge and prospects for future research are also highlighted.

One-step synthesis of a novel N-doped microporous biochar derived from crop straws with high dye adsorption capacity.

N-doping is one of the most promising strategies to improve the adsorption capacity and selectivity of carbon adsorbents. Herein, synthesis, characterization and dye adsorption of a novel N-doped microporous biochar derived from direct annealing of crop straws under NH3 is presented. The resultant products exhibit high microporosity (71.5%), atomic percentage of nitrogen (8.81%), and adsorption capacity to dyes, which is about 15-20 times higher than that of original biochar. Specifically, for the sample NBC800-3 pyrolyzed at 800°C in NH3 for 3 h, its adsorption for acid orange 7 (AO7, anionic) and methyl blue (MB, cationic) is up to 292 mg g(-1) and 436 mg g(-1), respectively, which is among the highest ever reported for carbonaceous adsorbents. The influences of N-doping and porous structure on dye adsorption of the synthesized carbons are also discussed, where electrostatic attraction, π-π electron donor-accepter interaction, and Lewis acid-base interaction mainly contribute to AO7 adsorption, and surface area (especially pore-filling) dominates MB adsorption. The N-doped biochar can be effectively regenerated and reused through direct combustion and desorption approaches.