Multivariate Strategy Preparation of Nanoscale Ru-Doped Metal-Organic Frameworks with Boosted Photoactivity for Bioimaging and Reactive Oxygen Species Generation.

How to incorporate chromophores into MOFs is a key for the development of multifunctional photoactive systems. The poor internalization by cancer cells and low efficiency of ROS generation hamper the potential clinic application of Ru-based molecular agents. In this work, a nanoscale Ru-doped metal-organic framework Hf-UiO-Ru (Hf-Ru) with framework-boosted photoactivities was prepared via a multivariate strategy for use in bioimaging and ROS generation. The as-synthesized Hf-Ru nanocrystals not only maintain the well regular morphology and crystal structure in comparison with that of the Hf-UiO-66 prototype but also give an oxygen-independent emission with a much longer lifetime, higher quantum yield, and stronger ROS generation than molecular Ru(dcbpy)3. Additionally, the enhanced cellular uptake and high brightness in fluorescence and CT imaging of Hf-Ru nanocrystals have also been well studied in vitro. This multivariate strategy may be utilized as a general paradigm to develop a photoactive nanosystem for bioimaging and cancer treatment.

Stepwise on-surface synthesis of thiophene-based polymeric ribbons by coupling reactions and the carbon-fluorine bond cleavage.

The rational synthesis of thiophene-based cross-coupled polymers on surfaces has been attracting more attention recently. Here, we report the stepwise activation of 5,5'-(2,3-difluoro-1,4-phenylene)bis(2-bromothiophene) as a precursor to synthesize thiophene-based polymeric ribbons on the Au(111) surface. Scanning tunneling microscopy studies showed that the precursor adopted different conformations in the self-assembled structure, organometallic species, and covalent polymers. On annealing the sample at a relatively low temperature (150 °C), the conversion of the organometallic structure into a covalent product with straight lines was observed, in which the Br adatoms arranged between the neighboring chains. On further annealing the sample at 270 °C, the detached Br adatoms played a key role in promoting the C-H bond activation. The cross-linked polymer was achieved by a combination of Ullmann and dehydrogenative coupling. When the annealing temperature was up to 390 °C, the C-F bond activation was triggered, which led to the formation of polymeric ribbons resulting from the cyclodehydrogenation of the fluorinated polymer. This study further supplements the reaction mechanism of thiophene-based dehalogenative, dehydrogenative and defluorinative coupling, and provides us a rational way for synthesizing cross-linked functional materials.

A Wide-Bandgap Conjugated Polymer Based on Quinoxalino[6,5-f ]quinoxaline for Fullerene and Non-Fullerene Polymer Solar Cells.

A wide-bandgap conjugated polymer, PNQx-2F2T, based on a ring-fused unit of quinoxalino[6,5-f ]quinoxaline (NQx), is synthesized for use as electron donor in polymer solar cells (PSCs). The polymer shows intense light absorption in the range from 300 to 740 nm and favorable energy levels of frontier molecular orbitals. The polymer has afforded decent device performance when blended with either fullerene-based acceptor [6,6]-phenyl-C71 -butylric acid methyl ester ([70]PCBM) or non-fullerene acceptor 3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-indanone-methyl))-5,5,11,11-tetrakis(4-n-hexylphenyl)-dithieno[2,3-d: 2',3'-d']-s-indaceno[1,2-b:5,6-b']dithiophene (IT-M). The highest PCEs of 7.9% and 7.5% have been achieved for [70]PCBM or IT-M based PSCs, respectively. Moreover, the influence of molecular weight of PNQx-2F2T on solar cell performance has been investigated. It is found that fullerene-based devices prefer higher polymer molecular weight, while non-fullerene devices are not susceptible to the molecular weight of PNQx-2F2T. The device results are extensively explained by electrical and morphological characterizations. This work not only evidences the potential of NQx for constructing high-performance photovoltaic polymers but also demonstrates a useful structure-performance relationship for efficiency enhancement of non-fullerene PSCs via the development of new conjugated polymers.

Gadd45a gene silencing by RNAi promotes cell proliferation and inhibits apoptosis and senescence in skin squamous cell carcinoma through the p53 signaling pathway.

Skin squamous cell carcinoma (SCC) is generally considered as nonaggressive lesions and mainly caused by ultraviolet (UV) radiation. Gadd45a is a key component protecting skin against UV-induced tumors. For that, the study aims to investigate the mechanism of Gadd45a gene silencing on cell proliferation, apoptosis, and senescence in nude mice with skin SCC through the p53 signaling pathway. Healthy nude mice was collected as the normal group and 40 nude mouse models of skin SCC were successfully established as the model group, which were sub-divided into five groups. The incidence, size, and weight of SCC tumor of nude mice were observed. The mRNA expression of Gadd45a, Cyclin B1, MMP-2, Bcl-2, and Bax were determined by RT-qPCR. Cell viability, cell cycle and apoptosis, cell senescence were detected by MTT assay, flow cytometry, and ß-galactosidase staining, respectively. The levels of inflammatory factors and vascular endothelial growth factor (VEGF) were detected by using ELISA. The protein expression rate of mutant p53 was detected by immunohistochemistry. Mice transfected with siGadd45a showed increased tumor incidence, size, and weight. Cells transfected with siGadd45a showed decrease in expression of Gadd45a and Bax; and increase in expression of Cyclin B1, MMP-2, and Bcl-2, expression of mutant p53, IL-1α, IL-1ß, IL-6, TNF-α, and VEGF. Cell apoptosis and senescence were inhibited, while cell viability and proliferation were promoted after siGadd45a treatment. The results reveal that Gadd45a silencing increases tumor cell proliferation and reduces apoptosis and senescence through the p53 signaling pathway in skin SCC.

MicroRNA-29a Inhibits Growth, Migration and Invasion of Melanoma A375 Cells in Vitro by Directly Targeting BMI1.

BACKGROUND/AIMS: Melanoma is one of the most aggressive malignant tumors, with increasing incidence, poor prognosis, and lack of any effective targeted therapies. Abnormal expression of miR-29a has been found in several types of cancers, including melanoma. In this study, experiments were performed to investigate the role of miR-29a in melanoma, and the molecular mechanism by which miR-29a represses melanoma. METHODS: miR-29 and Bmi1 expression was examined by quantitative real-time polymerase chain reaction (qRT-PCR). The cell viability, apoptosis, migration and invasion were respectively determined by Cell Counting Kit-8 assay, Propidium iodide (PI) fluorescein isothiocynate (FITC)-Annexin V staining assay, wound healing assay and transwell assay. Luciferase reporter assay was performed to determine a target gene of miR-29a. Western blot was used to analyze protein expression of apoptosis-related proteins, Bmi1, Wnt/ß-catenin and Nuclear factor-κB (NF-κB) pathway target genes. RESULTS: miR-29a was down-regulated in all tested melanoma cell lines. Up-regulation of miR-29a effectively inhibited cell viability, migration, and invasion, but promoted apoptosis in A375 cells. Bmi1 was a direct target gene of miR-29a. Transfection with miR-29a mimic decreased cell migration and invasion and Bmi1 expression in Malme-3M cells, SK-MEL-2, SK-MEL-5, and M14 cell lines. Moreover, miR-29a might suppress growth, migration and invasion of A375 cells by negatively regulating Bmi1. In addition, our results demonstrated that transfection with miR-29a mimic effectively blocked Wnt/ß-catenin and NF-κB pathways via down-regulating Bmi1. CONCLUSION: miR-29a could be functioned as a potential tumor suppressor through direct regulation of Bmi1 in melanoma cells.

Mapping the developmental potential of mouse inner ear organoids at single-cell resolution.

Inner ear organoids recapitulate development and are intended to generate cell types of the otic lineage for applications such as basic science research and cell replacement strategies. Here, we use single-cell sequencing to study the cellular heterogeneity of late-stage mouse inner ear organoid sensory epithelia, which we validated by comparison with datasets of the mouse cochlea and vestibular epithelia. We resolved supporting cell sub-types, cochlear-like hair cells, and vestibular type I and type II-like hair cells. While cochlear-like hair cells aligned best with an outer hair cell trajectory, vestibular-like hair cells followed developmental trajectories similar to in vivo programs branching into type II and then type I extrastriolar hair cells. These results highlight the transcriptional accuracy of the organoid developmental program but will also inform future strategies to improve synaptic connectivity and regional specification.

Enhancing humification and microbial interactions during co-composting of pig manure and wine grape pomace: The role of biochar and Fe2O3.

Phenol-rich wine grape pomace (WGP) improves the conversion of pig manure (PM) into humic acid (HA) during composting. However, the impact of using combinations of Fe2O3 and biochar known to promote compost maturation remains uncertain. This research explored the individual and combined influence of biochar and Fe2O3 during the co-composting of PM and WGP. The findings revealed that Fe2O3 boosts microbial network symbiosis (3233 links), augments the HA yield to 3.38 by promoting polysaccharide C-O stretching, and improves the germination index to 124.82 %. Limited microbial interactions, increased by biochar, resulted in a lower HA yield (2.50). However, the combination weakened the stretching of aromatics and quinones, which contribute to the formation of HA, resulting in reduced the humification to 2.73. In addition, Bacillus and Actinomadura were identified as pivotal factors affecting HA content. This study highlights Fe2O3 and biochar's roles in phenol-rich compost humification, but combined use reduces efficacy.

Crown Ethers with Different Cavity Diameters Inhibit Ion Migration and Passivate Defects toward Efficient and Stable Lead Halide Perovskite Solar Cells.

Organic-inorganic hybrid metal halide perovskite solar cells have been considered as one of the most promising next-generation photovoltaic technologies. Nevertheless, perovskite defects and Li+ ionic migration will seriously affect the power conversion efficiency and stability of the formal device. Herein, we designed two crown ether derivatives (PC12 and PC15) with different cavity diameters, which selectively bind to different metal cations. It is found that PC15 in perovskite precursor solution can actively regulate the nucleation and crystallization processes and passivate the uncoordinated Pb2+ ions, while PC12 at the interface between the perovskite layer and hole-transporting layer can effectively inhibit the migration of Li+ ions and reduce nonradiative recombination losses. Therefore, PC12 and PC15 can act as "lubricant" and defect passivators, as well as inhibitors of ion migration, when they are synergistically applied at the surface and bulk of perovskite layer. Consequently, the optimized device achieved a champion efficiency of 24.8% with significantly improved humidity, thermal, and light stability.

A universal packaging substrate for mechanically stable assembly of stretchable electronics.

Stretchable electronics commonly assemble multiple material modules with varied bulk moduli and surface chemistry on one packaging substrate. Preventing the strain-induced delamination between the module and the substrate has been a critical challenge. Here we develop a packaging substrate that delivers mechanically stable module/substrate interfaces for a broad range of stiff and stretchable modules with varied surface chemistries. The key design of the substrate was to introduce module-specific stretchability and universal adhesiveness by regionally tuning the bulk molecular mobility and surface molecular polarity of a near-hermetic elastic polymer matrix. The packaging substrate can customize the deformation of different modules while avoiding delamination upon stretching up to 600%. Based on this substrate, we fabricated a fully stretchable bioelectronic device that can serve as a respiration sensor or an electric generator with an in vivo lifetime of 10 weeks. This substrate could be a versatile platform for device assembly.

Analysis of microbial population dynamics in a partial nitrifying SBR at ambient temperature.

In this study, a lab-scale partial nitrifying sequencing batch reactor (SBR) was developed to investigate partial nitrification at ambient temperature (16-22 °C). Techniques of denaturing gradient gel electrophoresis (DGGE), cloning, and fluorescence in situ hybridization (FISH) were utilized simultaneously to study microbial population dynamics. Partial nitrification was effectively achieved in response to shifts of influent ammonium concentrations. DGGE results showed that higher ammonia concentration referred to lower ammonia-oxidizing bacteria (AOB) diversity in the SBR. Phylogenetic analysis revealed that all the predominant AOB was affiliated with Nitrosomonas genus. FISH analysis illustrated AOB was the predominant nitrifying bacteria of microbial compositions when SBR achieved partial nitrification (PN) at ambient temperature.

Structural optimization of BODIPY photosensitizers for enhanced photodynamic antibacterial activities.

Enhancing the interactions between photosensitizers and bacteria is key to developing effective photodynamic antibacterial agents. However, the influence of different structures on the therapeutic effects has not been systematically investigated. Herein, 4 BODIPYs with distinct functional groups, including the phenylboronic acid (PBA) group and pyridine (Py) cations, were designed to explore their photodynamic antibacterial activities. The BODIPY with the PBA group (IBDPPe-PBA) exhibits potent activity against planktonic Staphylococcus aureus (S. aureus) upon illumination, while the BODIPY with Py cations (IBDPPy-Ph) or both the PBA group and Py cations (IBDPPy-PBA) can significantly minimize the growth of both S. aureus and Escherichia coli (E. coli). In particular, IBDPPy-Ph can not only eliminate the mature S. aureus biofilm and E. coli biofilm in vitro, but also promote the healing of the infected wound. Our work provides an alternative for reasonable design of photodynamic antibacterial materials.

Structural Engineering of Ionic MOF@COF Heterointerface for Exciton-Boosting Sunlight-Driven Photocatalytic Filter.

Sunlight-driven photocatalytic filters against pathogenic bioaerosols have attracted a lot of interest. However, developing an efficient interception system that shows enhanced visible-light harvesting, controllable charge dynamic, and boosted ROS generation remains a grand challenge. Here, we designed an ionic ZIF-8@iCOF nanocomposite as a sunlight-driven photocatalytic filter through elaborate structural engineering of the heterointerface between ZIF-8 and cationic iCOF layers. The photoactive experiments reveal significant improvements in the visible light absorption and sunlight-driven exciton-enhanced intersystem crossing to boost the generation of singlet oxygen (220%) and also obtain antibacterial efficiency of 99.99999% after 15 min irradiation. After combining with commercial polymer, resultant ZIF-8@iCOF/polyacrylonitrile (PAN) fibrous membranes exhibited high interception efficiency for both PM10 and PM2.5 (98%), being close to the commercial N95. This fibrous membrane also possesses good biocompatibility and strong elimination of bacteria under sunlight conditions, satisfying for the long-lasting contact usage. This finding not only showcases the promise of the porous materials-based fibrous membranes for efficient photocatalytic filter against pathogenic bioaerosols but also highlights the importance of accurate structural engineering for the advancement of sunlight-driven photocatalytic systems in environment and energy-related fields.

Different Stepwise Growth Mechanism of AIE-Active Tetraphenylethylene-Functionalized Metal-Organic Frameworks on Au(111) and Cu(111) Surfaces.

Fabricating tetraphenylethylene (TPE)-functionalized metal-organic frameworks (MOFs) with aggregation- induced emission on surfaces and understanding the growth mechanism have not yet been pursued. Herein, MOFs constructed via the Ullmann-type reaction of a C2-symmetry TPE derivative (p-BrTBE) on Au(111) and Cu(111) surfaces were thoroughly investigated using scanning tunneling microscopy. On a Au(111) surface, p-BrTBE molecules formed the self-assembled pattern at 298 K. Stepwise annealing led to a progressive evolution process, in which the stepwise debromination reaction led to organometallic intermediates, and surface-stabilized radicals and metal-organic networks were formed. By contrast, the relatively ordered MOFs were obtained by replacing the underlying substrate with the more catalytically active Cu(111) at 298 K. Density functional theory calculations demonstrated that the formation of different networks on Au(111) and Cu(111) was determined by the different conformations of the TBE unit on the different substrates due to the different adsorption energy.

Effect of biochar addition on copper and zinc passivation pathways mediated by humification and microbial community evolution during pig manure composting.

The mobility and bioavailability of Cu and Zn are the main threats associated with the land application of pig manure (PM) compost products. This study investigated the impacts of biochar (BC) concentration on passivation of Cu and Zn associated with the compost maturity. The results indicated that 15% and 10% BC favoured the passivation of Cu and Zn, respectively. BC promoted passivation of Cu by accelerating HA production and optimized the abundance of Firmicutes. BC promoted the passivation of Zn by increasing the high temperature peak and the corresponding pH (8-8.5). A higher level (15% and 20%) of BC altered the dominant bacterial phylum from Firmicutes to Proteobacteria. 20% BC inhibited the passivation of Cu and Zn by reducing the highest temperature and lowering the alkalinity of substrate. These results offer new insights into understanding how the addition of BC could reduce the risk of hazardous products during PM composting.

Matrigel is required for efficient differentiation of isolated, stem cell-derived otic vesicles into inner ear organoids.

Inner ear organoids derived from pluripotent stem cells could be a useful model system to study development, disease, and regeneration. However, there is considerable heterogeneity in the size, morphology, and efficiency of organoid production using standard protocols. Greater control of the culture microenvironment could decrease heterogeneity and increase the yield of organoids. Animal-derived otic vesicles show some autonomy during development and can differentiate into cochlear and vestibular domains in mesenchyme-free ex vivo culture. Therefore, we investigated whether stem cell-derived otic vesicles can autonomously generate inner ear organoids. Isolated, stem cell-derived vesicles grew into cyst-like organoids with high efficiency, over 90%, when embedded in droplets of the basement membrane matrix Matrigel. Though nearly all vesicles within the aggregate were competent to mature into organoids, the efficiency of organoid production depended on the stage of vesicle isolation and required supplementation with Matrigel.

Conformation modification of terthiophene during the on-surface synthesis of pure polythiophene.

On-surface coupling under ultra-high vacuum is employed as a versatile approach to synthesize pure polythiophene from a 5,5''-dibromo-2,2':5',2''-terthiophene (DBTT) precursor and the corresponding temperature-dependent stepwise reaction mechanism is systematically studied by scanning tunneling microscopy (STM). After thermal deposition of the precursor onto a Au(111) surface that is kept at room temperature, a triangle-like pattern and a linear self-assembled pattern are formed with different molecular coverages through BrBrS halogen bonds and BrBr type-I contact bonds, respectively. In the self-assembled nanostructures, the thiophene units adopt trans-conformation. Mild annealing promotes the structural transition of both nanostructures into ordered zigzag organometallic linear chains with all-cis configured thiophene units connected through coordination bonds to the Au adatoms. Such conformational variety is easily recognized by STM, particularly in the case of DBTT-CH3 with the extra -CH3 signals. The covalently coupled products from the DBTT precursor are obtained by further annealing the organometallic intermediate at higher temperatures, which leads to the removal of Au atoms and the formation of ordered polymer chains and disordered polythiophene networks. Further characterization suggests that the reaction mechanism is associated with Ullmann-type coupling to form the ordered chains as well as Ullmann-type and dehydrogenative C-C coupling to fabricate cross-linked polymer networks. Compared with the on-surface synthesis process of DBTT on the Cu(111) surface, it can be confirmed that the Au adatoms are vital to synthesize polythiophene. These findings provide important insight into the reaction mechanism of on-surface synthesized pure polythiophene and on-surface coupling can potentially be applied to synthesize other functional conjugated polymers.

Single-nucleotide polymorphisms of APE1 associated with risk and prognosis of vitiligo in a Han Chinese population.

BACKGROUND: The single-nucleotide polymorphisms (SNPs) of apurinic/apyrimidinicendonuclease 1 (APE1), which has been implicated in cancers and the DNA base excision repair (BER) process, have not been thoroughly investigated in association with the risks of oxidative stress-related vitiligo. OBJECTIVES: The aim of this study is to investigate associations between APE1 single-nucleotide polymorphisms 141T >G and 1349T >G and risk and prognosis of vitiligo. MATERIAL AND METHODS: From June 2013 to June 2015, a total of 460 vitiligo patients were randomly recruited as a case group; 200 of these patients received narrow bound ultraviolet B (NB-UVB) treatment. Meanwhile, 460 healthy controls were included as a control group. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to explore the distribution frequencies of genotypes. RESULTS: Significant differences were detected between the case group and the control group in the frequencies of the 141T >G and 1349T >G genotypes. At 141T >G, compared with patients carrying the TG + GG genotype, male patients carrying the TT genotype aged more than 20 years with active non-segmental vitiligo, without a family history of vitiligo or other autoimmune diseases, exhibited an increased risk of vitiligo. Binary logistic regression analysis demonstrated that the TT genotype at 141T >G and the non-TT genotype at 1349T >G were independent risk factors for vitiligo development. At 1349T >G, compared with patients carrying the TT genotype, male patients carrying the TG + GG genotype aged more than 20 years with active non-segmental vitiligo, without a family history of vitiligo or other autoimmune diseases, exhibited an increased risk of vitiligo. Moreover, patients carrying 141TG + GG or 1349 TT genotypes had better photochromic effects, lower cumulative radiation doses, shorter treatment times, and earlier first photochromic times.

Sequence variants in host cell factor C1 are associated with Ménière's disease.

HYPOTHESIS: There is a genetic basis for the development of Ménière's (MD) disease. BACKGROUND: The cause of MD is unknown, although many potential theories have been proposed. A genetic basis for the disease is suggested by greater prevalence in Caucasians and familial cases that display an autosomal dominant pattern of inheritance. METHODS/DESIGN: Case-control association study of selected candidate genes among patients with MD and selected control individuals. RESULTS: Several single-nucleotide polymorphisms (SNPs) within the host cell factor C1 (HCFCI) gene displayed a significant increase in prevalence of the major allele in subjects with MD disease. The most individually significant SNP is rs2266886. The minor allele at this site displays an odds ratio of 0.26 (95% confidence intervals, 0.010-0.65; p = 0.003) for disease development. CONCLUSION: The minor allele at each SNP site was significantly more common in controls, suggesting that individuals bearing these alleles are at reduced risk of developing MD. The functional consequences of the SNPs in host cell factor C1 are unknown. A viable hypothesis for disease development is presented based on the known interaction between HCFC1 and the herpes simplex viral protein VP16.

High-Performance Ternary Nonfullerene Polymer Solar Cells with Both Improved Photon Harvesting and Device Stability.

Efficiency and stability of polymer solar cells (PSCs) are the two most significant decisive factors for the purpose of actual applications. Here, highly efficient and stable ternary PSCs were fabricated by incorporating two well-compatible polymer donors (poly[4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)benzo[1,2- b;4,5- b0]dithiophene-2,6-diyl- alt-(4-(2-ethylhexyl)-3-fluorothieno[3,4- b]thiophene-)-2-carboxylate-2-6-diyl] and poly[[9-(1-octylnonyl)-9 H-carbazole-2,7-diyl]-2,5-thiophenediyl-2,1,3-benzothiadiazole-4,7-diyl-2,5-thiophenediyl]) with one narrow band gap nonfullerene acceptor (3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-indanone)-5,5,11,11-tetrakis(4-hexylphenyl)-dithieno[2,3- d:2',3'- d']- s-indaceno[1,2- b:5,6- b']dithiophene)). It is found that Förster resonance energy transfer acts as an efficient pathway to further strengthen photon harvesting in this ternary system, which results in a significant improvement in current density ( JSC) without sacrificing the strong absorption of binary blends in the near-infrared region. Meanwhile, both of the inverted and conventional ternary PSCs exhibit better stability compared with the related binary PSCs in air condition because of the interlocked morphology in ternary films. The optimized ternary PSCs exhibit an outstanding power conversion efficiency (PCE) of 9.53% resulting from the synchronous improvements in JSC and fill factor. Moreover, this ternary strategy can be further confirmed by the use of an ultranarrow-band gap nonfullerene acceptor IEICO-4F, and the champion PCE of ternary PSCs reaches to 12.15%.

Chikusetsu (CHI) triggers mitochondria-regulated apoptosis in human prostate cancer via reactive oxygen species (ROS) production.

The prostate cancer prognosis is still not fully understood. Chikusetsu saponin Iva (CHI), isolated from Aralia taibaiensis, shows anti-cancer and anti-inflammatory properties. Here, in our study, we attempted to explore the efficiency and the possible molecular mechanism by which CHI may suppress prostate cancer. CHI was found to inhibit prostate cancer cell proliferation and induce cell death without cytotoxicity in prostate normal cells. CHI resulted in intracellular reactive oxygen species (ROS) production, and induced apoptosis regulated by mitochondria in vitro studies. CHI-caused apoptosis was shown in both caspase-dependent and -independent manner, which released cyto-c, enhancing caspases expression and promoting apoptosis-inducing factors (AIF) as well as endonuclease G (Endo G) nuclear transfer, respectively. Moreover, in vivo study showed that prostate tumor was inhibited by CHI administration through apoptosis induction. Thus, the results illustrated that CHI might be an effective therapeutic strategy for prostate cancer treatment in future.