Search

Antimony (Sb) pollution is considered an environmental problem, since Sb is toxic and carcinogenic to humans. Here, a novel biochar supported magnesium ferrite (BC@MF) was adopted for Sb(III) removal from groundwater. The maximum adsorption capacity was 77.44 mg g -1 . Together with characterization, batch experiments, kinetics, isotherms, and thermodynamic analyses suggested that inner-sphere complexation, H-bonding, and electrostatic interactions were the primary mechanisms. C-C/CC, C-O, and O-CO groups and Fe/Mg oxides might have acted as adsorption sites. The adsorbed Sb(III) was oxidized to Sb(V). The generation of reactive oxygen species, iron redox reaction, and oxidizing functional groups all contributed to Sb(III) oxidation. Furthermore, the fixed-bed column system demonstrated a satisfactory Sb removal performance; BC@MF could treat ∼6060 BV of simulated Sb-polluted groundwater. This research provides a promising approach to sufficiently remove Sb(III) from contaminated groundwater, providing new insights for the development of innovative strategies for heavy metal removal., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Salt stress, as a principal abiotic stress, harms the growth and metabolism of rice, thus affecting its yield and quality. The tillering stage is the key growth period that controls rice yield. Prohexadione-calcium (Pro-Ca) can increase the lodging resistance of plants by reducing plant height, but its effects on rice leaves and roots at the tillering stage under salt stress are still unclear. This study aimed to evaluate the ability of foliar spraying of Pro-Ca to regulate growth quality at the rice tillering stage under salt stress. The results showed that salt stress reduced the tillering ability of the rice and the antioxidant enzyme activity in the roots. Salt stress also reduced the net photosynthetic rate (Pn), stomatal conductance (Gs) and intercellular CO2 concentration (Ci) of the rice leaves and increased the contents of osmotic regulatory substances in the leaves and roots. The application of exogenous Pro-Ca onto the leaves increased the tiller number of the rice under salt stress and significantly increased the photosynthetic capacity of the leaves. Additionally, it increased the activities of antioxidant enzymes and the AsA content. The contents of an osmotic regulation substance, malondialdehyde (MDA), and H2O2 in the leaves and roots also decreased. These results suggested that Pro-Ca can increase the tillering ability, photosynthetic capacity, osmotic adjustment substance content levels and antioxidant enzyme activity levels in rice and reduce membrane lipid peroxidation, thus improving the salt tolerance of rice at the tillering stage., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Two-dimensional nanoporous membranes hold great promise for the design of state-of-the-art desalination architectures to alleviate the increasing global water scarcity. Herein, by employing molecular dynamics simulations, we demonstrate the great potential of two recently reported metal-organic frameworks (MOF) membranes, namely NiIT and NiAT, as efficient desalination membranes that reach super high water flux and high salt rejection. The desalination performance of the MOF membrane is highly tunable through controlling the membrane thickness from one layer to five layers. Double layer NiIT membrane exhibits excellent salt rejection of 100% for NaCl, and meanwhile achieving high water permeability of ∼45 L/cm 2 /MPa/day. While for the convertible double-layer NiAT, it effectively rejects ∼96% ions with an improved water permeation of over 70 L/cm 2 /MPa/day. Quantitative analysis of water distribution reveals a denser water solvation shell around NiAT membrane than NiIT and a higher water velocity through the nanopore of NiAT than that of NiIT, contributing to the enhanced water permeability. Through calculating free energy for water/ions translocating through two membranes, a clear energy barrier is observed for ions to penetrate through the sub-nanosized pores in both membranes, leading to the high salt rejection. The present study suggests that these two MOF membranes can serve as a promising semipermeable membrane for energy-efficient desalination which is highly prospective in industrial applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Coronary microvascular dysfunction (CMD) is a leading cause of ischemic heart disease. Over the past few decades, considerable progress has been made with respect to research on CMD. The present study summarized the current research hotspots and trends on CMD by applying a bibliometric approach., Methods: Relevant publications between 2002 and 2022 were extracted from the Web of Science Core Collection. Visualization network maps of countries, institutions, authors, and co-cited authors were built using VOSviewer. CiteSpace was used for keyword analysis and the construction of a dual-map overlay of journals and a timeline view of co-cited references., Results: 1539 CMD-related publications were extracted for bibliometric analysis. The annual publications generally showed an upward trend. The United States of America was the most prolific country, with 515 publications (33.5%). Camici P. G. was the most influential author, whereas the European Heart Journal, Circulation, and Journal of the American College of Cardiology were the most authoritative journals. Research hotspot analysis revealed that endothelial dysfunction as well as reduced nitric oxide production or bioavailability played critical roles in CMD development. Positron emission tomography was the most widely used imaging method for diagnosis. In addition, microvascular angina, hypertrophic cardiomyopathy, and heart failure have attracted much attention as the main clinical implications. Furthermore, international standards for CMD diagnosis and management may be the future research directions., Conclusions: This study offers a comprehensive view about the hotspots and development trends of CMD, which can assist subsequent researchers and guide future directions., (© 2022. The Author(s).)

Brown adipose tissue (BAT) activity contributes to cardiovascular health by its energy-dissipating capacity but how BAT modulates vascular function and atherosclerosis through endocrine mechanisms remains poorly understood. Here we show that BAT-derived neuregulin-4 (Nrg4) ameliorates atherosclerosis in mice. BAT-specific Nrg4 deficiency accelerates vascular inflammation and adhesion responses, endothelial dysfunction and apoptosis and atherosclerosis in male mice. BAT-specific Nrg4 restoration alleviates vascular inflammation and adhesion responses, attenuates leukocyte homing and reduces endothelial injury and atherosclerosis in male mice. In endothelial cells, Nrg4 decreases apoptosis, inflammation and adhesion responses induced by oxidized low-density lipoprotein. Mechanistically, protein kinase B (Akt)-nuclear factor-κB signaling is involved in the beneficial effects of Nrg4 on the endothelium. Taken together, the results reveal Nrg4 as a potential cross-talk factor between BAT and arteries that may serve as a target for atherosclerosis., (© 2022. The Author(s).)

Some small cell lung cancers (SCLCs) are highly sensitive to inhibitors of the histone demethylase LSD1. LSD1 inhibitors are thought to induce their anti-proliferative effects by blocking neuroendocrine differentiation, but the mechanisms by which LSD1 controls the SCLC neuroendocrine phenotype are not well understood. To identify genes required for LSD1 inhibitor sensitivity in SCLC, we performed a positive selection genome-wide CRISPR/Cas9 loss of function screen and found that ZFP36L1, an mRNA-binding protein that destabilizes mRNAs, is required for LSD1 inhibitor sensitivity. LSD1 binds and represses ZFP36L1 and upon LSD1 inhibition, ZFP36L1 expression is restored, which is sufficient to block the SCLC neuroendocrine differentiation phenotype and induce a non-neuroendocrine "inflammatory" phenotype. Mechanistically, ZFP36L1 binds and destabilizes SOX2 and INSM1 mRNAs, two transcription factors that are required for SCLC neuroendocrine differentiation. This work identifies ZFP36L1 as an LSD1 target gene that controls the SCLC neuroendocrine phenotype and demonstrates that modulating mRNA stability of lineage transcription factors controls neuroendocrine to non-neuroendocrine plasticity., (© 2022. The Author(s).)

Wireless body area networks (WBANs) is a new research hotspot with great development prospects. The non-contact sensing based on radio frequency signal can solve the issues of personal comfort and privacy. Detection of cervical motion range and cervical strain in time are important in diagnosis and prevention of cervical spondylosis. In this paper, channel state information is used to achieve smart perception and monitoring, timely and efficient detection of different postures and abnormal bending of the neck. It provides an efficient way for protecting cervical health, and also some help for doctors to understand the causes of cervical vertebral disease in a timely manner. The classification accuracy of the four activities reached 99.4%, 99.7%, 99.5% and 99.3%, respectively.

Background: Nanoscale drug delivery systems have emerged as broadly applicable approach for chemo-photothermal therapy. However, these nanoscale drug delivery systems suffer from carrier-induced toxicity, uncontrolled drug release and low drug carrying capacity issues. Thus, to develop carrier-free nanoparticles self-assembled from amphiphilic drug molecules, containing photothermal agent and anticancer drug, are very attractive., Results: In this study, we conjugated camptothecin (CPT) with a photothermal agent new indocyanine green (IR820) via a redox-responsive disulfide linker. The resulting amphiphilic drug-drug conjugate (IR820-SS-CPT) can self-assemble into nanoparticles (IR820-SS-CPT NPs) in aqueous solution, thus remarkably improving the membrane permeability of IR820 and the aqueous solubility of CPT. The disulfide bond in the IR820-SS-CPT NPs could be cleaved in GSH rich tumor microenvironment, leading to the on demand release of the conjugated drug. Importantly, the IR820-SS-CPT NPs displayed an extremely high therapeutic agent loading efficiency (approaching 100%). Besides, in vitro experimental results indicated that IR820-SS-CPT NPs displayed remarkable tumor cell killing efficiency. Especially, the IR820-SS-CPT NPs exhibited excellent anti-tumor effects in vivo. Both in vitro and in vivo experiments were conducted, which have indicated that the design of IR820-SS-CPT NPs can provide an efficient nanotherapeutics for chemo-photothermal therapy., Conclusion: A novel activatable amphiphilic small molecular prodrug IR820-SS-CPT has been developed in this study, which integrated multiple advantages of GSH-triggered drug release, high therapeutic agent content, and combined chemo-photothermal therapy into one drug delivery system., (© 2021. The Author(s).)

Advanced prostate cancer (PCa) often develops bone metastasis, for which therapies are very limited and the underlying mechanisms are poorly understood. We report that bone-borne TGF-β induces the acetylation of transcription factor KLF5 in PCa bone metastases, and acetylated KLF5 (Ac-KLF5) causes osteoclastogenesis and bone metastatic lesions by activating CXCR4, which leads to IL-11 secretion, and stimulating SHH/IL-6 paracrine signaling. While essential for maintaining the mesenchymal phenotype and tumorigenicity, Ac-KLF5 also causes resistance to docetaxel in tumors and bone metastases, which is overcome by targeting CXCR4 with FDA-approved plerixafor. Establishing a mechanism for bone metastasis and chemoresistance in PCa, these findings provide a rationale for treating chemoresistant bone metastasis of PCa with inhibitors of Ac-KLF5/CXCR4 signaling.

Aims/hypothesis: Myeloid-derived growth factor (MYDGF), mainly secreted by bone marrow-derived cells, has been known to promote glucagon-like peptide-1 production and improve glucose/lipid metabolism in mouse models of diabetes, but little is known about the functions of MYDGF in diabetic kidney disease (DKD). Here, we investigated whether MYDGF can prevent the progression of DKD., Methods: In vivo experiments, both loss- and gain-of-function strategies were used to evaluate the effect of MYDGF on albuminuria and pathological glomerular lesions. We used streptozotocin-treated Mydgf knockout and wild-type mice on high fat diets to induce a model of DKD. Then, albuminuria, glomerular lesions and podocyte injury were evaluated in Mydgf knockout and wild-type DKD mice treated with adeno-associated virus-mediated Mydgf gene transfer. In vitro and ex vivo experiments, the expression of slit diaphragm protein nephrin and podocyte apoptosis were evaluated in conditionally immortalised mouse podocytes and isolated glomeruli from non-diabetic wild-type mice treated with recombinant MYDGF., Results: MYDGF deficiency caused more severe podocyte injury in DKD mice, including the disruption of slit diaphragm proteins (nephrin and podocin) and an increase in desmin expression and podocyte apoptosis, and subsequently caused more severe glomerular injury and increased albuminuria by 39.6% compared with those of wild-type DKD mice (p < 0.01). Inversely, MYDGF replenishment attenuated podocyte and glomerular injury in both wild-type and Mydgf knockout DKD mice and then decreased albuminuria by 36.7% in wild-type DKD mice (p < 0.01) and 34.9% in Mydgf knockout DKD mice (p < 0.01). Moreover, recombinant MYDGF preserved nephrin expression and inhibited podocyte apoptosis in vitro and ex vivo. Mechanistically, the renoprotection of MYDGF was attributed to the activation of the Akt/Bcl-2-associated death promoter (BAD) pathway., Conclusions/interpretation: The study demonstrates that MYDGF protects podocytes from injury and prevents the progression of DKD, providing a novel strategy for the treatment of DKD. Graphical abstract.

Prostate development depends on balanced cell proliferation and differentiation, and acetylated KLF5 is known to alter epithelial proliferation. It remains elusive whether post-translational modifications of transcription factors can differentially determine adult stem/progenitor cell fate. Here we report that, in human and mouse prostates, Klf5 is expressed in both basal and luminal cells, with basal cells preferentially expressing acetylated Klf5. Functionally, Klf5 is indispensable for maintaining basal progenitors, their luminal differentiation, and the proliferation of their basal and luminal progenies. Acetylated Klf5 is also essential for basal progenitors' maintenance and proper luminal differentiation, as deacetylation of Klf5 causes excess basal-to-luminal differentiation; attenuates androgen-mediated organoid organization; and retards postnatal prostate development. In basal progenitor-derived luminal cells, Klf5 deacetylation increases their proliferation and attenuates their survival and regeneration following castration and subsequent androgen restoration. Mechanistically, Klf5 deacetylation activates Notch signaling. Klf5 and its acetylation thus contribute to postnatal prostate development and regeneration by controlling basal progenitor cell fate.

Objective: Perivascular adipose tissue (PVAT) regulates vascular function in a paracrine manner and the vasodilatory effect of PVAT on vessels is completely abolished in obesity. In addition, autophagy is required for maintaining biological function of PVAT and has been shown to be inhibited in obesity. The aim of this study was to explore whether alogliptin improves endothelial function by promoting autophagy in PVAT in obese mice., Methods: C57BL/6 mice were maintained on high fat diet with or without alogliptin intervention for 3 months. Vasorelaxation function of thoracic aorta with or without PVAT was determined. Autophagy related protein level of p62 and LC3B, along with phosphorylated mTOR (p-mTOR) were evaluated. In addition, the effects of alogliptin on autophagy were also investigated in cultured adipocytes., Results: The presence of PVAT significantly impaired endothelium-dependent vasodilation in obese mice and alogliptin intervention corrected this defect. Autophagy in PVAT was decreased in obese mice and alogliptin intervention activated autophagy. Activating autophagy in PVAT improved endothelium-dependent vasodilation while blocking it in PVAT impaired vasodilation function. Further, addition of glucagon-like peptide-1 (GLP-1) but not alogliptin alone activated autophagy. Moreover, GLP-1 and alogliptin co-treatment did not show additive effect on activating autophagy., Conclusions: These results revealed that promoting autophagy in PVAT improved endothelial function in response to alogliptin intervention. Additionally, the beneficial effect of alogliptin intervention on PVAT was GLP-1 dependent., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To investigate that short-term treatment of sildenafil can induce browning of subcutaneous white adipose tissue (sWAT) in human adults., Design: A randomized, double-blinded, placebo-controlled, parallel group trial., Methods: Sixteen eligibility overweight male subjects were recruited, comparing 100mg/day sildenafil versus an identical placebo therapy for 7days. sWAT samples were collected from subjects before and after 7-day sildenafil or placebo interventions., Results: The results showed that multilocular UCP1-positive adipocytes existed in sWAT samples from subjects after sildenafil treatment. Compared to before treatment in both group as well as after treatment in placebo, sildenafil significantly decreased adipocyte size, increased the expressions of UCP1 protein and mRNA, mitochondrial density, and leak respiratory capacity in sWAT (p<0.05). Sildenafil also increased plasma cyclic guanosine-3',5'-monophosphate (cGMP) and catecholamine concentrations (p<0.05), and consequently activated the expressions of vasodilator-stimulated phosphoprotein (VASP) and p70 ribosomal S6 kinase 1 (S6K1) (p<0.05). Sildenafil did not activate typical brown fat., Conclusions: The current findings demonstrate that sildenafil can induce browning of sWAT in human, and this action may be through cGMP-dependent protein kinase I and mechanistic/mammalian target of rapamycin (mTOR) signaling pathways. Sldenafil may be a promising treatment for metabolic disease., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Anti-microtubule therapy represents one of the most strategic cancer therapeutics. Tublin inhibitor such as paclitaxel (PTX) is well known to disturb the dynamic nature of microtubules, being considered as the first-line drug for various malignancies. However, PTX does not show favorable clinical outcomes due to serious systemic toxicities and low selectivity. The development of PTX delivery systems and combinational therapies has been conducted to enhance PTX efficacy with poorly defined mechanisms. Herein, we introduced a reactive oxygen species producible composite liposome based on a new photosensitizer sinoporphyrin sodium (DVDMS) to enhance the therapeutic effect of PTX through photochemical stimulation, and more importantly, the pivotal molecular regulation mechanisms were specifically explored. Compared with DVDMS-liposome (DL) or PTX-liposome (PL), the composite liposome DVDMS-PTX-liposome (PDL) exhibited a superior anti-tumor advantage following laser irradiation against MCF-7 breast cancer. The localized PTX release after PDL administration greatly decreased the drug dosage and laser power required, leading to much higher safety and lower costs. In vitro, the combined treatment significantly suppressed cell viability and potentiated cell apoptosis. The apoptotic central regulator Mcl-1 as a favorable target, was evaluated in association with photochemically enhanced sensitivity to anti-tubulin chemotherapeutics. Phosphorylation of Mcl-1 led to its direct degradation with the proteasome system, making it relatively unstable and potentiating cell death resulting from photochemical synergy via PDL plus laser irradiation. Further, a decrease in ATP production and glycolysis after PDL plus laser would prevent the possible energy-switch and apoptosis-escape by PTX alone treatment, thereby resulted in increased cell death in combinational therapy. Systemic administration of PDL followed by in vivo photochemotherapy achieved significantly improved therapeutic effects compared to either alone. And, the intrinsic fluorescence of DVDMS facilitated real-time imaging of PDL in tumors. Therefore, the present strategy with details at the molecular regulation could be a promising platform for antitublin chemotherapeutics., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Ultrasound and microbubbles-mediated drug delivery has become a promising strategy to promote drug delivery and its therapeutic efficacy. The aim of this research was to assess the effects of microbubbles (MBs)-combined low-intensity pulsed ultrasound (LPUS) on the delivery and cytotoxicity of curcumin (Cur) to human breast cancer MDA-MB-231 cells. Under the experimental condition, MBs raised the level of acoustic cavitation and enhanced plasma membrane permeability; and cellular uptake of Cur was notably improved by LPUS-MBs treatment, aggravating Cur-induced MDA-MB-231 cells death. The combined treatment markedly caused more obvious changes of cell morphology, F-actin cytoskeleton damage and cell migration inhibition. Our results demonstrated that combination of MBs and LPUS may be an efficient strategy for improving anti-tumor effect of Cur, suggesting a potential effective method for antineoplastic therapy., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The aim of this paper was to investigate whether sinoporphyrin sodium (DVDMS) could be a novel sonosensitizer in sonodynamic therapy. We used two kinds of leukemia cells (K562, U937) as main tumor cell models and cells (peripheral blood mononuclear cells, spleen lymphocytes) separated from healthy ICR mice as normal cell models. The multivolume spectrophotometer system and fluorescence spectrophotometer were used to determine the spectral characteristics of DVDMS. The uptake of DVDMS by tumor cells and normal cells was measured by flow cytometry. The MTT assay was used to examine the cytotoxicity and sonotoxicity of DVDMS. The absorption spectra showed that DVDMS had five distinct peaks at 359, 514, 548, 580, and 631 nm, respectively, and the maximum peak was at ∼359 nm. The fluorescence emission spectra showed that DVDMS fluorescence emission was at 642 nm. DVDMS showed an advantage of quick cellular uptake and selectively accumulated in tumor cells compared with normal healthy cells. The cytotoxicity of DVDMS by the MTT method was dose dependent, and DVDMS had little cytotoxicity to normal cells. The sonotoxicity of DVDMS showed that in the presence of DVDMS, under appropriate conditions, the cell-damaging effect of ultrasound was significantly enhanced. The present study showed that the newly synthesized sensitizer, DVDMS, under appropriate experiment conditions, can act as a potential sonosensitizer for tumors in sonodynamic therapy.