Single-molecule FRET probes allosteric effects on protein-translocating pore loops of a AAA+ machine.

AAA+ proteins (ATPases associated with various cellular activities) comprise a family of powerful ring-shaped ATP-dependent translocases that carry out numerous vital substrate-remodeling functions. ClpB is a AAA+ protein disaggregation machine that forms a two-tiered hexameric ring, with flexible pore loops protruding into its center and binding to substrate proteins. It remains unknown whether these pore loops contribute only passively to substrate-protein threading or have a more active role. Recently, we have applied single-molecule FRET spectroscopy to directly measure the dynamics of substrate-binding pore loops in ClpB. We have reported that the three pore loops of ClpB (PL1-3) undergo large-scale fluctuations on the microsecond timescale that are likely to be mechanistically important for disaggregation. Here, using single-molecule FRET, we study the allosteric coupling between the pore loops and the two nucleotide-binding domains of ClpB (NBD1-2). By mutating the conserved Walker B motifs within the NBDs to abolish ATP hydrolysis, we demonstrate how the nucleotide state of each NBD tunes pore-loop dynamics. This effect is surprisingly long-ranged; in particular, PL2 and PL3 respond differentially to a Walker B mutation in either NBD1 or NBD2, as well as to mutations in both. We characterize the conformational dynamics of pore loops and the allosteric paths connecting NBDs to pore loops by molecular dynamics simulations and find that both principal motions and allosteric paths can be altered by changing the ATPase state of ClpB. Remarkably, PL3, which is highly conserved in AAA+ machines, is found to favor an upward conformation when only NBD1 undergoes ATP hydrolysis but a downward conformation when NBD2 is active. These results explicitly demonstrate a significant long-range allosteric effect of ATP hydrolysis sites on pore-loop dynamics. Pore loops are therefore established as active participants that undergo ATP-dependent conformational changes to translocate substrate proteins through the central pores of AAA+ machines.

Fabrication of black phosphorus/CdS heterostructure with enhancement photocatalytic degradation activity for tetrabromobisphenol A and toxicity prediction of intermediates.

Black phosphorus nanosheets (BPNs)/CdS heterostructure was successfully synthesized via hydrothermal method. The experimental results indicated that BPNs modified the surface of CdS nanoparticles uniformly. Meanwhile, the BPNs/CdS heterostructure exhibited a distinguished high rate of photocatalytic activity for Tetrabromobisphenol A (TBBPA) degradation under visible light irradiation (λ > 420 nm), the kinetic constant of TBBPA degradation reached 0.0261 min-1 was approximately 5.68 and 9.67 times higher than that of CdS and P25, respectively. Moreover, superoxide radical (•O2-) is the main active component in the degradation process of TBBPA (the relative contribution is 91.57%). The photocatalytic mechanism and intermediates of the TBBPA was clarified, and a suitable model and pathway for the degradation of TBBPA were proposed. The results indicated that the toxicities of some intermediates were higher than the parent pollutant. This research provided an efficient approach by a novel photocatalyst for the removal of TBBPA from wastewater, and the appraisal methods for the latent risks from the intermediates were reported in this paper.

Surface softening regulates size-dependent stiffness of diamond nanowires.

Diamond nanowires (NWs) belong to an important class of nanoscale materials for their outstanding potential in mechanical, electrical, and thermal applications. However, their mechanical behavior under pristine and defective conditions remains less understood. This paper reveals a comprehensive understanding of the effective elastic behavior of diamond NWs, and it uncovers surface-softening as the dominant mechanism that regulates their effective behavior. We applied the force-based and energy-based approaches and constructed a comparative analysis to reveal the atomistic basis behind the diameter-dependent elastic properties of the nanowires. Our findings suggest the energy-based approach to produce physically meaningful results, whereas the widely used force-based scheme produces inconsistent size-dependent behavior. Results show that, with increasing diameter, the softening of the surface and the defective regimes decreases. As a direct consequence of the alteration in the softening state, the first-order elastic modulus increases with increasing diameter, whereas the second-order modulus decreases. Also, vacancy defects, even in very dilute concentrations, are found to substantially affect the elastic behavior of the nanowire. Furthermore, surface, core, and defective regimes exhibit very different roles in nanowires of different diameters: the surface regime acts as a softer regime and the core as stiffer, regardless of the diameter. Their cumulative effect is however dominated by the surface in smaller-diameter nanowire-but in wider diameter nanowires it is dominated by the core. As a result, the size-dependent behavior is strictly controlled by the softening state of the surface. The diameter-dependent elastic moduli show a power-law relation, which deviates substantially from the simple surface-to-volume ratio. These findings suggest surface-engineering as an important tool for modulating the effective behavior of brittle nanowires.

Wnt/ß-Catenin Signaling Determines the Vasculogenic Fate of Postnatal Mesenchymal Stem Cells.

Vasculogenesis is the process of de novo blood vessel formation observed primarily during embryonic development. Emerging evidence suggest that postnatal mesenchymal stem cells are capable of recapitulating vasculogenesis when these cells are engaged in tissue regeneration. However, the mechanisms underlining the vasculogenic differentiation of mesenchymal stem cells remain unclear. Here, we used stem cells from human permanent teeth (dental pulp stem cells [DPSC]) or deciduous teeth (stem cells from human exfoliated deciduous teeth [SHED]) as models of postnatal primary human mesenchymal stem cells to understand mechanisms regulating their vasculogenic fate. GFP-tagged mesenchymal stem cells seeded in human tooth slice/scaffolds and transplanted into immunodeficient mice differentiate into human blood vessels that anastomize with the mouse vasculature. In vitro, vascular endothelial growth factor (VEGF) induced the vasculogenic differentiation of DPSC and SHED via potent activation of Wnt/ß-catenin signaling. Further, activation of Wnt signaling is sufficient to induce the vasculogenic differentiation of postnatal mesenchymal stem cells, while Wnt inhibition blocked this process. Notably, ß-catenin-silenced DPSC no longer differentiate into endothelial cells in vitro, and showed impaired vasculogenesis in vivo. Collectively, these data demonstrate that VEGF signaling through the canonical Wnt/ß-catenin pathway defines the vasculogenic fate of postnatal mesenchymal stem cells. Stem Cells 2016;34:1576-1587.

Emotion regulation, emotional eating and the energy-rich dietary pattern. A population-based study in Chinese adolescents.

Research investigating the influence of emotion regulation (ER) strategies on emotional eating and diet among Chinese adolescents is scarce. The aim of this study was to test associations between two ER strategies (suppression/cognitive reappraisal), emotional eating, and an energy-rich dietary pattern. A total of 4316 adolescents from 10 high schools were surveyed. Dietary patterns were derived using factor analysis. Bivariate correlations were analyzed to examine associations between ER strategies, emotional eating behavior and an energy-rich dietary pattern, by gender. The mediating effect of emotional eating in the relationship between ER and energy-rich food consumption by gender was estimated using structural equation modeling. A higher level of suppression, but no lack of cognitive reappraisal, was associated with emotional eating in boys and girls. A higher level of suppression and lack of cognitive reappraisal were associated with a greater intake of energy-rich foods in girls only. Emotional eating mediated the relationship between a higher level of suppression and a greater intake of energy-rich food in girls. This study revealed significant associations between two ER strategies and an energy-rich dietary pattern in girls, and provided evidence that higher levels of suppression may put girls at risk for emotional eating, potentially affecting the energy-rich dietary pattern.

Endothelial cell-derived interleukin-6 regulates tumor growth.

BACKGROUND: Endothelial cells play a complex role in the pathobiology of cancer. This role is not limited to the making of blood vessels to allow for influx of oxygen and nutrients required for the high metabolic demands of tumor cells. Indeed, it has been recently shown that tumor-associated endothelial cells secrete molecules that enhance tumor cell survival and cancer stem cell self-renewal. The hypothesis underlying this work is that specific disruption of endothelial cell-initiated signaling inhibits tumor growth. METHODS: Conditioned medium from primary human dermal microvascular endothelial cells (HDMEC) stably transduced with silencing RNA for IL-6 (or controls) was used to evaluate the role of endothelial-derived IL-6 on the activation of key signaling pathways in tumor cells. In addition, these endothelial cells were co-transplanted with tumor cells into immunodefficient mice to determine the impact of endothelial cell-derived IL-6 on tumor growth and angiogenesis. RESULTS: We observed that tumor cells adjacent to blood vessels show strong phosphorylation of STAT3, a key mediator of tumor progression. In search for a possible mechanism for the activation of the STAT3 signaling pathway, we observed that silencing interleukin (IL)-6 in tumor-associated endothelial cells inhibited STAT3 phosphorylation in tumor cells. Notably, tumors vascularized with IL-6-silenced endothelial cells showed lower intratumoral microvessel density, lower tumor cell proliferation, and slower growth than tumors vascularized with control endothelial cells. CONCLUSIONS: Collectively, these results demonstrate that IL-6 secreted by endothelial cells enhance tumor growth, and suggest that cancer patients might benefit from targeted approaches that block signaling events initiated by endothelial cells.

Cortisol reactivity, delay discounting and percent body fat in Chinese urban young adolescents.

The purpose of this study is to test the relation of cortisol reactivity, delay discounting and percent body fat (PBF) in adolescents aged 12-13 years (N=87), and evaluate the delay discounting as potential components in models of adolescent obesity. Anthropometry and body composition measurements were assessed in adolescents. The cortisol reactivity to Trier Social Stress Test for Children (TSST-C) and delay discounting were measured. The result showed increased cortisol reactivity and greater delay discounting were associated with higher PBF in girls. Structural equation modeling supported greater delay discounting as a mediator of relations between increased cortisol reactivity and PBF in adolescent girls. The proposed mediation model indicated that cortisol reactivity is linked to PBF through delay discounting, thereby supporting a significant indirect relationship. The direct relationship between increased cortisol reactivity and higher PBF was significant in a model that did not include delay discounting, and was still significant in the mediation model that included delay discounting. This study provides the first evidence that greater delay discounting may partially account for the relationship of hyperactivity of the HPA-axis and higher PBF in girls.

Semaphorin 4D Induces Vasculogenic Differentiation of Dental Pulp Stem Cells.

This work aimed to evaluate the effect of Semaphorin 4D (SEMA4D) signaling through Plexin B1 on the vasculogenic differentiation of dental pulp stem cells. We assessed the protein expression of SEMA4D and Plexin B1 in dental pulp stem cells (DPSC) from permanent human teeth and stem cells from human exfoliated deciduous (SHED) teeth using Western blots. Their expression in human dental pulp tissues and DPSC-engineered dental pulps was determined using immunofluorescence. We then exposed dental pulp stem cells to recombinant human SEMA4D (rhSEMA4D), evaluated the expression of endothelial cell differentiation markers, and assessed the vasculogenic potential of rhSEMA4D using an in vitro sprouting assay. Lastly, Plexin B1 was silenced to ascertain its role in SEMA4D-mediated vasculogenic differentiation. We found that SEMA4D and Plexin B1 are expressed in DPSC, SHED, and human dental pulp tissues. rhSEMA4D (25-100 ng/mL) induced the expression of endothelial markers, i.e., vascular endothelial growth factor receptor (VEGFR)-2, cluster of differentiation (CD)-31, and tyrosine kinase with immunoglobulin-like and EGF-like domains (Tie)-2, in dental pulp stem cells and promoted capillary-like sprouting in vitro (p < 0.05). Furthermore, Plexin B1 silencing abrogated the vasculogenic differentiation of dental pulp stem cells and significantly inhibited capillary sprouting upon exposure to rhSEMA4D. Collectively, these data provide evidence that SEMA4D induces vasculogenic differentiation of dental pulp stem cells through Plexin B1 signaling.

Recent Developments in Semiconductor-Based Photocatalytic Degradation of Antiviral Drug Pollutants.

The prevalence of antiviral drugs (ATVs) has seen a substantial increase in response to the COVID-19 pandemic, leading to heightened concentrations of these pharmaceuticals in wastewater systems. The hydrophilic nature of ATVs has been identified as a significant factor contributing to the low degradation efficiency observed in wastewater treatment plants. This characteristic often necessitates the implementation of additional treatment steps to achieve the complete degradation of ATVs. Semiconductor-based photocatalysis has garnered considerable attention due to its promising potential in achieving efficient degradation rates and subsequent mineralization of pollutants, leveraging the inexhaustible energy of sunlight. However, in recent years, there have been few comprehensive reports that have thoroughly summarized and analyzed the application of photocatalysis for the removal of ATVs. This review commences by summarizing the types and occurrence of ATVs. Furthermore, it places a significant emphasis on delivering a comprehensive summary and analysis of the characteristics pertaining to the photocatalytic elimination of ATVs, utilizing semiconductor photocatalysts such as metal oxides, doped metal oxides, and heterojunctions. Ultimately, the review sheds light on the identified research gaps and key concerns, offering invaluable insights to steer future investigations in this field.

Surface-strain-enhanced oxygen dissociation on gold catalysts.

The excellent low-temperature oxidation performance and stability of nanogold catalysts have attracted significant interest. However, the main active source of the low-temperature oxidation of gold remains to be determined. In situ electron microscopy and mass spectrometry results show that nitrogen is oxidized, and the catalyst surface undergoes reconstruction during the process. Strain analysis of the catalyst surface and first-principles calculations show that the tensile strain of the catalyst surface affects the oxidation performance of gold catalysts by enhancing the adsorption ability and dissociation of O2. The newly formed active oxygen atoms on the gold surface act as active sites in the nitrogen oxidation reaction, significantly enhancing the oxidation ability of gold catalysts. This study provides evidence for the dissociation mechanism of oxygen on the gold surface and new design concepts for improving the oxidation activity of gold catalysts and nitrogen activation.

Recent Advances in Black Phosphorous-Based Photocatalysts for Degradation of Emerging Contaminants.

The recalcitrant nature of emerging contaminants (ECs) in aquatic environments necessitates the development of effective strategies for their remediation, given the considerable impacts they pose on both human health and the delicate balance of the ecosystem. Semiconductor-based photocatalytic technology is recognized for its dual benefits in effectively addressing both ECs and energy-related challenges simultaneously. Among the plethora of photocatalysts, black phosphorus (BP) stands as a promising nonmetallic candidate, offering a host of advantages including its tunable direct band gap, broad-spectrum light absorption capabilities, and exceptional charge mobility. Nevertheless, pristine BP frequently underperforms, primarily due to issues related to its limited ambient stability and the rapid recombination of photogenerated electron-hole pairs. To overcome these challenges, substantial research efforts have been devoted to the creation of BP-based photocatalysts in recent years. However, there is a noticeable absence of reviews regarding the advancement of BP-based materials for the degradation of ECs in aqueous solutions. Therefore, to fill this gap, a comprehensive review is undertaken. In this review, we first present an in-depth examination of the fabrication processes for bulk BP and BP nanosheets (BPNS). The review conducts a thorough analysis and comparison of the merits and limitations inherent in each method, thereby delineating the most auspicious avenues for future research. Then, in line with the pathways followed by photogenerated electron-hole pairs at the interface, BP-based photocatalysts are systematically categorized into heterojunctions (Type I, Type II, Z-scheme, and S-scheme) and hybrids, and their photocatalytic performances against various ECs and the corresponding degradation mechanisms are comprehensively summarized. Finally, this review presents personal insights into the prospective avenues for advancing the field of BP-based photocatalysts for ECs remediation.

Therapeutic inhibition of Bmi-1 ablates chemoresistant cancer stem cells in adenoid cystic carcinoma.

OBJECTIVES: Adenoid Cystic Carcinomas (ACC) typically show modest responseto cytotoxic therapy. Cancer stem cells (CSC) have been implicated in chemoresistance and tumor relapse. However, their role in ACC remains unknown. The purpose of this work was to evaluate the impact of targeting ACC CSCs with Bmi-1 inhibitors on resistance to cytotoxic therapy and tumor relapse. MATERIALS AND METHODS: Therapeutic efficacy of a small molecule inhibitor of Bmi-1 (PTC596; Unesbulin) and/or Cisplatin on ACC stemness was evaluated in immunodeficient mice harboring PDX ACC tumors (UM-PDX-HACC-5) and in human ACC cell-lines (UM-HACC-2A,-14) or low passage primary human ACC cells (UM-HACC-6). The effect of therapy on stemness was examined by salisphere assays, flow cytometry for ALDH activity and CD44 expression, and Western blots for Bmi-1 (self-renewal marker) and Oct4 (embryonic stem cell marker) expression. RESULTS: Platinum-based agents (Cisplatin, Carboplatin) induced Bmi-1 and Oct4 expression, increased salisphere formation and the CSC fraction in vitro and in vivo. In contrast, PTC596 inhibited expression of Bmi-1, Oct4 and pro-survival proteins Mcl-1 and Claspin; decreased the number of salispheres, and the fraction of ACC CSCs in vitro. Silencing Claspin decreased salisphere formation and CSC fraction. Both, single agent PTC596 and PTC596/Cisplatin combination decreased the CSC fraction in PDX ACC tumors. Notably, short-term combination therapy (2 weeks) with PTC596/Cisplatin prevented tumor relapse for 150 days in a preclinical trial in mice. CONCLUSION: Therapeutic inhibition of Bmi-1 ablates chemoresistant CSCs and prevents ACC tumor relapse. Collectively, these results suggest that ACC patients might benefit from Bmi-1-targeted therapies.

Pivotal Role of the Granularity Uniformity of the WO3 Film Electrode upon the Cyclic Stability during Cation Insertion/Extraction.

Delicate design and precise manipulation of electrode morphology has always been crucial in electrochemistry. Generally, porous morphology has been preferred due to the fast kinetic transport characteristics of cations. Nevertheless, more refined design details such as the granularity uniformity that usually goes along with the porosity regulation of film electrodes should be taken into consideration, especially in long-term cation insertion and extraction. Here, inorganic electrochromism as a special member of the electrochemical family and WO3 films as the most mature electrochromic electrode material were chosen as the research background. Two kinds of WO3 films were prepared by magnetron sputtering, one with a relatively loose morphology accompanied by nonuniform granularity and one with a compact morphology along with uniform particle size distribution, respectively. Electrochemical performances and cyclic stability of the two film electrodes were then traced and systematically compared. In the beginning, except for faster kinetic transport characters of the 50 W-deposited WO3 film, the two electrodes showed equivalent optical and electrochemical performances. However, after 5000 CV cycles, the 50 W-deposited WO3 film electrode cracked seriously. Strong stress distribution centered among boundaries of the nonuniform particle clusters together with the weak bonding among particles induced the mechanical damage. This discovery provides a more solid background for further delicate film electrode design.

Amorphous K-Buserite Microspheres for High-Performance Aqueous Zn-Ion Batteries and Hybrid Supercapacitors.

Aqueous Zn-ion batteries (AZIBs) and Zn-ion hybrid supercapacitors (AZHSCs) are considered promising energy-storage alternatives to Li-ion batteries due to the attractive merits of low-price and high-safety. However, the lack of suitable cathode materials always hinders their large-scale application. Herein, amorphous K-buserite microspheres (denoted as K-MnOx ) are reported as cathode materials for both AZIBs and AZHSCs, and the energy-storage mechanism is systematically revealed. It is found that K-MnOx is composed of rich amorphous K-buserite units, which can irreversibly be transformed into amorphous Zn-buserite units in the first discharge cycle. Innovatively, the transformed Zn-buserite acts as active materials in the following cycles and is highly active/stable for fast Zn-diffusion and superhigh pseudocapacitance, enabling the achievement of high-efficiency energy storage. In the AZIBs, K-MnOx delivers 306 mAh g-1 after 100 cycles at 0.1 A g-1 with 102% capacity retention, while in the AZHSCs, it shows 515.0/116.0 F g-1 at 0.15/20.0 A g-1 with 92.9% capacitance retention at 5.0 A g-1 after 20 000 cycles. Besides, the power/energy density of AZHSCs device can reach up to 16.94 kW kg-1 (at 20 A g-1 )/206.7 Wh kg-1 (at 0.15 A g-1 ). This work may provide some references for designing next-generation aqueous energy-storage devices with high energy/power density.

Gelatin methacryloyl hydrogel as an injectable scaffold with multi-therapeutic effects to promote antimicrobial disinfection and angiogenesis for regenerative endodontics.

Regenerative endodontics represents a paradigm shift in dental pulp therapy for necrotic young permanent teeth. However, there are still challenges associated with attaining maximum root canal disinfection while supporting angiogenesis and preserving resident stem cells viability and differentiation capacity. Here, we developed a hydrogel system by incorporating antibiotic-eluting fiber-based microparticles in gelatin methacryloyl (GelMA) hydrogel to gather antimicrobial and angiogenic properties while prompting minimum cell toxicity. Minocycline (MINO) or clindamycin (CLIN) was introduced into a polymer solution and electrospun into fibers, which were further cryomilled to attain MINO- or CLIN-eluting fibrous microparticles. To obtain hydrogels with multi-therapeutic effects, MINO- or CLIN-eluting microparticles were suspended in GelMA at distinct concentrations. The engineered hydrogels demonstrated antibiotic-dependent swelling and degradability while inhibiting bacterial growth with minimum toxicity in dental-derived stem cells. Notably, compared to MINO, CLIN hydrogels enhanced the formation of capillary-like networks of endothelial cells in vitro and the presence of widespread vascularization with functioning blood vessels in vivo. Our data shed new light onto the clinical potential of antibiotic-eluting gelatin methacryloyl hydrogel as an injectable scaffold with multi-therapeutic effects to promote antimicrobial disinfection and angiogenesis for regenerative endodontics.

Endothelial cell Bcl-2 and lymph node metastasis in patients with oral squamous cell carcinoma.

BACKGROUND: Loco-regional spread of disease causes high morbidity and is associated with the poor prognosis of malignant oral tumors. Better understanding of mechanisms underlying the establishment of lymph node metastasis is necessary for the development of more effective therapies for patients with oral cancer. The aims of this work were to evaluate a possible correlation between endothelial cell Bcl-2 and lymph node metastasis in patients with oral squamous cell carcinoma (OSCC), and to study signaling pathways that regulate Bcl-2 expression in lymphatic endothelial cells. METHODS: Endothelial cells were selectively retrieved from paraffin-embedded tissue sections of primary human OSCC from patients with or without lymph node metastasis by laser capture microdissection. RT-PCR was used to evaluate Bcl-2 expression in tumor-associated endothelial cells and in tumor cells. In vitro, mechanistic studies were performed to examine the effect of vascular endothelial growth factor (VEGF)-C on the expression of Bcl-2 in primary human lymphatic endothelial cells. RESULTS: We observed that Bcl-2 expression is upregulated in the endothelial cells of human oral tumors with lymph node metastasis as compared to endothelial cells from stage-matched tumors without metastasis. VEGF-C induced Bcl-2 expression in lymphatic endothelial cells via VEGFR-3 and PI3k/Akt signaling. Notably, OSCC cells express VEGF-C and induce Bcl-2 in lymphatic endothelial cells. CONCLUSIONS: Collectively, this work unveiled a mechanism for the induction of Bcl-2 in lymphatic endothelial cells and suggested that endothelial cell Bcl-2 contributes to lymph node metastasis in patients with oral squamous cell carcinoma.

PDGF-BB signaling via PDGFR-ß regulates the maturation of blood vessels generated upon vasculogenic differentiation of dental pulp stem cells.

A functional vascular network requires that blood vessels are invested by mural cells. We have shown that dental pulp stem cells (DPSC) can undergo vasculogenic differentiation, and that the resulting vessels anastomize with the host vasculature and become functional (blood carrying) vessels. However, the mechanisms underlying the maturation of DPSC-derived blood vessels remains unclear. Here, we performed a series of studies to understand the process of mural cell investment of blood vessels generated upon vasculogenic differentiation of dental pulp stem cells. Primary human DPSC were co-cultured with primary human umbilical artery smooth muscle cells (HUASMC) in 3D gels in presence of vasculogenic differentiation medium. We observed DPSC capillary sprout formation and SMC recruitment, alignment and remodeling that resulted in complex vascular networks. While HUASMC enhanced the number of capillary sprouts and stabilized the capillary network when co-cultured with DPSC, HUASMC by themselves were unable to form capillary sprouts. In vivo, GFP transduced human DPSC seeded in biodegradable scaffolds and transplanted into immunodeficient mice generated functional human blood vessels invested with murine smooth muscle actin (SMA)-positive, GFP-negative cells. Inhibition of PDGFR-ß signaling prevented the SMC investment of DPSC-derived capillary sprouts in vitro and of DPSC-derived blood vessels in vivo. In contrast, inhibition of Tie-2 signaling did not have a significant effect on the SMC recruitment in DPSC-derived vascular structures. Collectively, these results demonstrate that PDGF-BB signaling via PDGFR-ß regulates the process of maturation (mural investment) of blood vessels generated upon vasculogenic differentiation of human dental pulp stem cells.

Visible-light-driven photocatalytic disinfection by S-scheme α-Fe2O3/g-C3N4 heterojunction: Bactericidal performance and mechanism insight.

High-performance photocatalytic applications require to develop heterostructures between two semiconductors with matched band energy levels to facilitate charge-carrier separation. The S-scheme photocatalytic system has great potential to be explored, in terms of the improvement of charge separation, however, small efforts have been made in photocatalytic disinfection application. In this study, a non-toxic and low-cost S-scheme photocatalytic system composed of α-Fe2O3 and g-C3N4 was fabricated by in-suit production of g-C3N4 and firstly applied into water disinfection. The α-Fe2O3/g-C3N4 junction demonstrated an enhanced activity for photocatalytic bacterial inactivation, with the complete inactivation of 7 log10 cfu·mL-1 of Escherichia coli K-12 cells within 120 min under visible light irradiation. Its logarithmic bacterial inactivation efficiency was nearly 7 times better than that of single g-C3N4. The experimental results suggested that the effective prevention of charge-carrier recombination led to an improved generation of reactive oxygen species (ROSs), resulting in impressive disinfection performance. Moreover, the DNA gel electrophoresis experiments validated the reason for the irreversible death of bacteria, which was the leakage and destruction of chromosomal DNA. In addition, this S-scheme heterojunction also showed excellent photocatalytic disinfection performance in authentic water matrices (including tap water, secondary treated sewage effluent, and surface water) under visible light irradiation. Hence, the α-Fe2O3/g-C3N4 composite has great potential for sustainable and efficient photocatalytic disinfection applications.

Preparation of metal-free BP/CN photocatalyst with enhanced ability for photocatalytic tetracycline degradation.

The successful application of photocatalysis in practical water treatment opreations relies greatly on the development of highly efficient, stable and low-cost photocatalysts. The low-cost metal-free photocatalyst made up of black phosphorus (BP) and graphitic carbon nitride (CN) was successfully constructed and firstly used for the photocatalytic treatment of antibiotic contaminants in this work. Compared with bare CN, the BP/CN photocatalyst exhibited the enhanced photocatalytic performance for tetracycline hydrochloride (HTC) degradation, that 99% of HTC was removed by 6BP/CN (doping amount of BP was 6%) within 30 min under the simulated visible-light irradiation. The efficiency was even comparable to those of some high-efficiency photocatalysts recently-reported such as Fe0@POCN, CuInS2/Bi2MoO6 and Cu2O@HKUST-1. Under natural sunlight illumination, the determined apparent rate constant for degradation of HTC by BP/CN was 2.7 times as that by P25 TiO2. The experimental results indicated that loading BP on CN could enhance the separation of charge carriers and promote the ability of light absorption for visible-light, thus leading to a greater catalytic activity. Meanwhile, the influences of different operating variables (pH, water, ion and HTC concentration) on HTC degradation were studied in detail. Furthermore, the degradation pathway of HTC was also proposed. In addition, the photocatalytic activity of the BP/CN for production of hydrogen peroxide (H2O2) was also studied, which could reach up to 501.04 µmol g-1h-1. It is anticipated that BP/CN photocatalyst could be used for practical water treatment.

p53 Inhibits Bmi-1-driven Self-Renewal and Defines Salivary Gland Cancer Stemness.

PURPOSE: Mucoepidermoid carcinoma (MEC) is a poorly understood salivary gland malignancy with limited therapeutic options. Cancer stem cells (CSC) are considered drivers of cancer progression by mediating tumor recurrence and metastasis. We have shown that clinically relevant small molecule inhibitors of MDM2-p53 interaction activate p53 signaling and reduce the fraction of CSC in MEC. Here we examined the functional role of p53 in the plasticity and self-renewal of MEC CSC. EXPERIMENTAL DESIGN: Using gene silencing and therapeutic activation of p53, we analyzed the cell-cycle profiles and apoptosis levels of CSCs in MEC cell lines (UM-HMC-1, -3A, -3B) via flow cytometry and looked at the effects on survival/self-renewal of the CSCs through sphere assays. We evaluated the effect of p53 on tumor development (N = 51) and disease recurrence (N = 17) using in vivo subcutaneous and orthotopic murine models of MEC. Recurrence was followed for 250 days after tumor resection. RESULTS: Although p53 activation does not induce MEC CSC apoptosis, it reduces stemness properties such as self-renewal by regulating Bmi-1 expression and driving CSC towards differentiation. In contrast, downregulation of p53 causes expansion of the CSC population while promoting tumor growth. Remarkably, therapeutic activation of p53 prevented CSC-mediated tumor recurrence in preclinical trials. CONCLUSIONS: Collectively, these results demonstrate that p53 defines the stemness of MEC and suggest that therapeutic activation of p53 might have clinical utility in patients with salivary gland MEC.