Modulating the Structure and Optoelectronic Properties of Solution-Processed Bismuth-Based Nanocrystals.

Bismuth-based chalcogenides have emerged as promising candidates for next-generation, solution-processable semiconductors, mainly benefiting from their facile fabrication, low cost, excellent stability, and tunable optoelectronic properties. Particularly, the recently developed AgBiS2 solar cells have shown striking power conversion efficiencies. High performance bismuth-based photodetectors have also been extensively studied in the past few years. However, the fundamental properties of these Bi-based semiconductors have not been sufficiently investigated, which is crucial for further improving the device performance. Here, we introduce multiple time-resolved and steady-state techniques to fully characterize the charge carrier dynamics and charge transport of solution-processed Bi-based nanocrystals. It was found that the Ag-Bi ratio plays a critical role in charge transport. For Ag-deficient samples, silver bismuth sulfide thin films behave as localized state induced hopping charge transport, and the Ag-excess samples present band-like charge transport. This finding is crucial for developing more efficient Bi-based semiconductors and optoelectronic devices.

Berberine alleviates inflammation and suppresses PLA2-COX-2-PGE2-EP2 pathway through targeting gut microbiota in DSS-induced ulcerative colitis.

Berberine, isolated from Coptis chinensis and Phellodendron amurense, can attenuate colonic injury and modulate gut microbiota disorders in ulcerative colitis (UC). However, the mechanism and causal relationship between gut microbiota and the efficacy of Berberine on UC are still unclear, which were investigated by pseudo-germ-free (PGF) mice, 16S rRNA gene analysis and transcriptome analysis in this study. The results demonstrated that Berberine improved gut microbiota disorders, colon damage, tight-junction proteins, inflammatory and anti-inflammatory cytokines in DSS-induced colitis mice with intact gut microbiota but not in PGF mice. Besides, immune-related and inflammation-related pathways were closely related to the efficacy that Berberine alleviated colitis by regulating gut microbiota. Furthermore, Berberine reduced PGE2, PLA2, COX-2, Ptges, EP2 and p-Stat3 only in colitis mice with intact gut microbiota. In summary, our study confirms that Berberine inhibits PLA2-COX-2-PGE2-EP2 pathway in UC through gut microbiota, leading to the alleviation of inflammation in colon, which further elucidates the underlying mechanism and promotes the application of Berberine in UC.

Precursor Engineering of Solution-Processed Sb2 S3 Solar Cells.

Antimony-based chalcogenides have emerged as promising candidates for next-generation thin film photovoltaics. Particularly, binary Sb2 S3 thin films have exhibited great potential for optoelectronic applications, due to the facile and low-cost fabrication, simple composition, decent charge transport and superior stability. However, most of the reported efficient Sb2 S3 solar cells are realized based on chemical bath deposition and hydrothermal methods, which require large amount of solution and are normally very time-consuming. In this work, Ag ions are introduced within the Sb2 S3 sol-gel precursors, and effectively modulated the crystallization and charge transport properties of Sb2 S3 . The crystallinity of the Sb2 S3 crystal grains are enhanced and the charge carrier mobility is increased, which resulted improved charge collection efficiency and reduced charge recombination losses, reflected by the greatly improved fill factor and open-circuit voltage of the Ag incorporated Sb2 S3 solar cells. The champion devices reached a record high power conversion efficiency of 7.73% (with antireflection coating), which is comparable with the best photovoltaic performance of Sb2 S3 solar cells achieved based on chemical bath deposition and hydrothermal techniques, and pave the great avenue for next-generation solution-processed photovoltaics.

Densest subgraph-based methods for protein-protein interaction hot spot prediction.

BACKGROUND: Hot spots play an important role in protein binding analysis. The residue interaction network is a key point in hot spot prediction, and several graph theory-based methods have been proposed to detect hot spots. Although the existing methods can yield some interesting residues by network analysis, low recall has limited their abilities in finding more potential hot spots. RESULT: In this study, we develop three graph theory-based methods to predict hot spots from only a single residue interaction network. We detect the important residues by finding subgraphs with high densities, i.e., high average degrees. Generally, a high degree implies a high binding possibility between protein chains, and thus a subgraph with high density usually relates to binding sites that have a high rate of hot spots. By evaluating the results on 67 complexes from the SKEMPI database, our methods clearly outperform existing graph theory-based methods on recall and F-score. In particular, our main method, Min-SDS, has an average recall of over 0.665 and an f2-score of over 0.364, while the recall and f2-score of the existing methods are less than 0.400 and 0.224, respectively. CONCLUSION: The Min-SDS method performs best among all tested methods on the hot spot prediction problem, and all three of our methods provide useful approaches for analyzing bionetworks. In addition, the densest subgraph-based methods predict hot spots with only one residue interaction network, which is constructed from spatial atomic coordinate data to mitigate the shortage of data from wet-lab experiments.

Engineering the Non-Radiative Recombination of Mixed-Halide Perovskites with Optimal Bandgap for Indoor Photovoltaics.

Indoor photovoltaics have attracted increasing attention, since they can provide sustainable energy through the recycling of photon energy from household dim lighting. However, solar cells exhibiting high performance under sunlight may not perform well under indoor light conditions, mainly due to the mismatch of the irradiance spectrum. In particular, most of the indoor light sources emit visible photons with negligible near-infrared irradiance. According to the detailed balance theory, the optimal bandgap for indoor photovoltaics should be relatively larger, considering the trade-off between photocurrent and photovoltage losses. In this work, a systematic comparison of the theoretical limits of the conventional and indoor photovoltaics is presented. Then the non-radiative recombination losses are reduced by a synergetic treatment with Pb(SCN)2 and PEABr, resulting relatively high open circuit voltage of 1.29 V and power conversion efficiency of 17.32% under 1 sun illumination. Furthermore, the devices are fully characterized under weak indoor light (1000 lux, 4000 K LED) achieving a high efficiency of 37.18%, which is promising for real applications.

MHBSt167 induced autophagy promote cell proliferation and EMT by activating the immune response in L02 cells.

BACKGROUND: Hepatitis B virus can induce hepatocellular carcinoma (HCC) by inducing a host immune response against infected hepatocytes. C-terminally truncated middle surface protein (MHBSt) has been reported to contribute to HCC through transcriptional activation in epidemiology studies, while the underlying mechanism of MHBSt-induced HCC is unknown. METHODS: In this study, a premature stop at codon 167 in MHBS (MHBSt167) was investigated into eukaryotic expression plasmid pcDNA3.1(-). MHBSt167 expressed plasmid was transfected into the L02 cell line, cell proliferation was analyzed by CCK-8 and high-content screening assays, the cell cycle was analyzed by flow cytometry, and epithelial-to-mesenchymal transition and autophagy were analyzed by immunoblotting and immunofluorescence. NF-κB activation and the MHBSt167-induced immune response were analyzed by immunoblotting and immunofluorescence. IFN-α, IFN-ß and IL-1α expression were analyzed by qPCR. Autophagy inhibitors were used to analyze the relationship between the immune response and autophagy. RESULTS: The results showed that MHBSt167 promoted L02 cell proliferation, accelerated cell cycle progression from the S to G2 phase and promoted epithelial-to-mesenchymal transition through ER-stress, leading to autophagy and NF-κB activation and increased immune-related factor expression. The MHBSt167-induced acceleration of cell proliferation and the cell cycle was abolished by autophagy or NF-κB inhibitors. CONCLUSION: In summary, MHBSt167 could promote cell proliferation, accelerate cell cycle progression, induce EMT and activate autophagy through ER-stress to induce the host immune response, supporting a potential role of MHBSt167 in contributing to carcinogenesis.

lncRNA PVT1: a novel oncogene in multiple cancers.

Long noncoding RNAs are involved in epigenetic gene modification, including binding to the chromatin rearrangement complex in pre-transcriptional regulation and to gene promoters in gene expression regulation, as well as acting as microRNA sponges to control messenger RNA levels in post-transcriptional regulation. An increasing number of studies have found that long noncoding RNA plasmacytoma variant translocation 1 (PVT1) plays an important role in cancer development. In this review of a large number of studies on PVT1, we found that PVT1 is closely related to tumor onset, proliferation, invasion, epithelial-mesenchymal transformation, and apoptosis, as well as poor prognosis and radiotherapy and chemotherapy resistance in some cancers. This review comprehensively describes PVT1 expression in various cancers and presents novel approaches to the diagnosis and treatment of cancer.

Weighted minimum feedback vertex sets and implementation in human cancer genes detection.

BACKGROUND: Recently, many computational methods have been proposed to predict cancer genes. One typical kind of method is to find the differentially expressed genes between tumour and normal samples. However, there are also some genes, for example, 'dark' genes, that play important roles at the network level but are difficult to find by traditional differential gene expression analysis. In addition, network controllability methods, such as the minimum feedback vertex set (MFVS) method, have been used frequently in cancer gene prediction. However, the weights of vertices (or genes) are ignored in the traditional MFVS methods, leading to difficulty in finding the optimal solution because of the existence of many possible MFVSs. RESULTS: Here, we introduce a novel method, called weighted MFVS (WMFVS), which integrates the gene differential expression value with MFVS to select the maximum-weighted MFVS from all possible MFVSs in a protein interaction network. Our experimental results show that WMFVS achieves better performance than using traditional bio-data or network-data analyses alone. CONCLUSION: This method balances the advantage of differential gene expression analyses and network analyses, improves the low accuracy of differential gene expression analyses and decreases the instability of pure network analyses. Furthermore, WMFVS can be easily applied to various kinds of networks, providing a useful framework for data analysis and prediction.

Enhanced Stability of the Pharmacologically Active Lactone Form of 10-Hydroxycamptothecin by Self-Microemulsifying Drug Delivery Systems.

10-Hydroxycamptothecin (HCPT) is a DNA inhibitor of topoisomerase I and exerts antitumor activities against various types of cancer. However, reversible conversion from a pharmacologically active lactone form to an inactive carboxylate form of HCPT and poor water solubility hamper its clinical applications. To overcome these shortcomings, we designed a fine self-microemulsifying drug delivery system (SMEDDS) for HCPT to effectively protect HCPT in its active lactone form as well as improving dissolution rates. A formulation of HCPT-SMEDDS that contained ethyl oleate, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), and polyethylene glycol 400 (PEG400) was optimized by using the central composite design and response surface methodology. Following 1:100 aqueous dilution of the optimized HCPT-SMEDDS, the droplet size of resulting microemulsions was 25.6 ± 0.7 nm, and the zeta potential was - 15.2 ± 0.4 mV. The optimized HCPT-SMEDDS appeared to stabilize the lactone moiety of HCPT with 73.6% being present in the pharmacologically active lactone forms in simulated intestinal fluid, but only 45.7% for free HCPT. Furthermore, the physically stable formulation showed the active lactone form predominated in HCPT-SMEDDS (> 95%) for 6 months under the accelerated storage condition. Meanwhile, the optimized SMEDDS formulation also significantly improved dissolution rates and membrane permeability of the lactone form of HCPT. Therefore, HCPT-SMEDDS involved designing for the ease of manufacture, and provided a potent oral dosage form for preserving its active lactone form as well as enhancing the dissolution rate.

Synergistic combination of DT-13 and Topotecan inhibits aerobic glycolysis in human gastric carcinoma BGC-823 cells via NM IIA/EGFR/HK II axis.

DT-13 combined with topotecan (TPT) showed stronger antitumour effects in mice subcutaneous xenograft model compared with their individual effects in our previous research. Here, we further observed the synergistically effect in mice orthotopic xenograft model. Metabolomics analysis showed DT-13 combined with TPT alleviated metabolic disorders induced by tumour and synergistically inhibited the activity of the aerobic glycolysis-related enzymes in vivo and in vitro. Mechanistic studies revealed that the combination treatment promoted epidermal growth factor receptor (EGFR) degradation through non-muscle myosin IIA (NM IIA)-induced endocytosis of EGFR, further inhibited the activity of hexokinase II (HK II), and eventually promoted the aerobic glycolysis inhibition activity more efficiently compared with TPT or DT-13 monotherapy. The combination therapy also inhibited the specific binding of HK II to mitochondria. When using the NM II inhibitor (-)002Dblebbistatin or MYH-9 shRNA, the synergistic inhibition effect of DT-13 and TPT on aerobic glycolysis was eliminated in BGC-823 cells. Immunohistochemical analysis revealed selective up-regulation of NM IIA while specific down-regulation of p-CREB, EGFR, and HK II by the combination therapy. Collectively, these findings suggested that this regimen has significant clinical implications, warranted further investigation.

ThreaDomEx: a unified platform for predicting continuous and discontinuous protein domains by multiple-threading and segment assembly.

We develop a hierarchical pipeline, ThreaDomEx, for both continuous domain (CD) and discontinuous domain (DCD) structure predictions. Starting from a query sequence, ThreaDomEx first threads it through the PDB to identify multiple structure templates, where a profile of domain conservation score (DC-score) is derived for domain-segment assignment. To further detect DCDs that consist of separated segments along the sequence, a boundary-clustering algorithm is used to refine the DCD-linker locations. In case that the templates do not contain DCDs, a domain-segment assembly process, guided by symmetry comparison, is applied for further DCD detections. ThreaDomEx was tested a set of 1111 proteins and achieved a normalized domain overlap score of 89.3% compared to experimental data, which is significantly higher than other state-of-the-art methods. It also recalls 26.7% of DCDs with 72.7% precision on the proteins for which threading failed to detect any DCDs. The server provides facilities for users to interactively refine the domain models by adjusting DC-score threshold, deleting and adding domain linkers, and assembling domain segments, which are particularly helpful for the hard targets for which current methods have a low accuracy while human-expert knowledge and experimental insights can be used for refining models. ThreaDomEX server is available at http://zhanglab.ccmb.med.umich.edu/ThreaDomEx.

[Understanding the reasons behind the low utilization of thrombolysis in hyperacute ischemic stroke].

OBJECTIVE: The study aimed to analyze the influencing factors of thrombolysis therapy in acute ischemic stroke patients with onset time less than 4.5 hours. METHODS: We consecutively prospectively screened acute ischemic stroke patients with onset time less than 4.5 hours from emergency department, outpatients and inpatients of neurology department, and image center in our hospital over a 31-month time period (April 2012-November 2014). The rate of thrombolysis and the reasons for not receiving thrombolysis were analyzed. RESULTS: A total of 538 patients who met the inclusion criteria were included (68.2% males, mean age 67±13 years old). Only 104 (19.3%) patients received thrombolysis. The main reasons for the patients not receiving thrombolysis included minor symptoms (172 cases, 39.6%), rapidly improving symptoms and high possibility of transient ischemic attack (TIA) (59 cases, 13.6%), patients or families refusing thrombolysis (44, 10.1%), in-hospital delay (38, 8.8%), elderly people with age over than 80 years old (38, 8.8%). CONCLUSIONS: The thrombolysis rate within time window of acute ischemic stroke is remarkably higher than that of several years ago in China. The main reasons for not receiving thrombolysis are minor and rapidly improving symptoms, patients or families' refusal, in-hospital delay, elderly people with age over than 80 years old.

The relationship between the network of non-coding RNAs-molecular targets and N6-methyladenosine modification in tumors of urinary system.

N6-methyladenosine (m6A) methylation, a prevalent eukaryotic post-transcriptional modification, is involved in multiple biological functions, including mediating variable splicing, RNA maturation, transcription, and nuclear export, and also is vital for regulating RNA translation, stability, and cytoplasmic degradation. For example, m6A methylation can regulate pre-miRNA expression by affecting both splicing and maturation. Non-coding RNA (ncRNA), which includes microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), does not encode proteins but has powerful impacts on transcription and translation. Conversely, ncRNAs may impact m6A methylation by affecting the expression of m6A regulators, including miRNAs targeting mRNA of m6A regulators, or lncRNAs, and circRNAs, acting as scaffolds to regulate transcription of m6A regulatory factors. Dysregulation of m6A methylation is common in urinary tumors, and the regulatory role of ncRNAs is also important for these malignancies. This article provides a systematic review of the role and mechanisms of action of m6A methylation and ncRNAs in urinary tumors.

Synthesis of Gemini-type imidazoline quaternary ammonium salt using by-product fatty acid as corrosion inhibitor for Q235 steel.

Gemini-type imidazoline quaternary ammonium salt is a new type of environmentally friendly corrosion inhibitor has been widely used in engineering materials. However, most of them are hazardous/toxic compounds derived from petroleum-based products, which did harm to environment. In this work, an environmentally friendly Gemini-shaped imidazoline quaternary ammonium salt corrosion inhibitor (G211) was synthesized using cheap fatty acid recycled from dimer acid industry as feedstock. The corrosion inhibition effects of G211 on Q235 steel in 1 M HCl solution were investigated through weight loss experiments, potential polarization curves, and alternating current impedance spectroscopy experiments. The results show that the inhibition rate of G211 as a mixed-type inhibitor is up to 94.4% and the concentration drop as low as 500 ppm at 25 â„ƒ. The adsorption of G211 on Q235 surface follows Langmuir adsorption isothermal curve. The chemical composition of the Q235 steel surface was analyzed through scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). Furthermore, the possible corrosion inhibition mechanism of G211 on the surface of Q235 steel is proposed. This article not only presents an outstanding solution for safeguarding Q235 steel against corrosion but also introduces a feasible method for high-value utilization of monomer acid (MA).

Constructing Ultra-Shallow Near-Edge States for Efficient and Stable Perovskite Solar Cells.

Electronic band structure engineering of metal-halide perovskites (MHP) lies at the core of fundamental materials research and photovoltaic applications. However, reconfiguring the band structures in MHP for optimized electronic properties remains challenging. This article reports a generic strategy for constructing near-edge states to improve carrier properties, leading to enhanced device performances. The near-edge states are designed around the valence band edge using theoretical prediction and constructed through tailored material engineering. These states are experimentally revealed with activation energies of around 23 milli-electron volts by temperature-dependent time-resolved spectroscopy. Such small activation energies enable prolonged carrier lifetime with efficient carrier transition dynamics and low non-radiative recombination losses, as corroborated by the millisecond lifetimes of microwave conductivity. By constructing near-edge states in positive-intrinsic-negative inverted cells, a champion efficiency of 25.4% (25.0% certified) for a 0.07-cm2 cell and 23.6% (22.7% certified) for a 1-cm2 cell is achieved. The most stable encapsulated cell retains 90% of its initial efficiency after 1100 h of maximum power point tracking under one sun illumination (100 mW cm-2) at 65 °C in ambient air.

Flexible all-organic photodetectors via universal water-assisted transfer printing.

Transfer printing of small-molecular organic semiconductors often faces challenges due to surface adhesion mismatch. Here, we developed a sacrificing-layer-assisted transfer printing technique for the deposition of small-molecular thin films. High-boiling-point ethylene glycol (EG) was doped in aqueous solution poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) as the sacrificing layer to manipulate residual water in film, which allowed chlorobenzene solution to spontaneously spread and form uniform film. The residual water guaranteed film delamination from the stamp, allowing for its transfer onto various substrates and seeding layers. As a proof of concept, laterally conductive organic photodetectors using recyclable EG-PEDOT:PSS electrodes and a small-molecular active layer were consecutively fabricated via transfer printing in ambient air. The resulting device exhibited a high on/off ratio of 711 and a fast rise time of 0.5 ms. Notably, the polymer electrode and the bulk heterojunction demonstrated unique repairability and recyclability.

Charge-Carrier Dynamics of Evaporated Bismuth-Based Chalcogenide Thin Films Probed with Time-Resolved Microwave Conductivity.

Chalcogenide-based semiconductors are emerging as a set of highly promising candidates for optoelectronic devices, owing to their low toxicity, cost-effectiveness, exceptional stability, and tunable optoelectronic properties. Nonetheless, the limited understanding of charge recombination mechanisms and trap states of these materials is impeding their further development. To fill this gap, we conducted a comprehensive study of bismuth-based chalcogenide thin films and systematically investigated the influence of post-treatments via time-resolved microwave conductivity and temperature-dependent photoluminescence. The key finding in this work is that post-treatment with Bi could effectively enhance the crystallinity and charge-carrier mobility. However, the carrier density also increased significantly after the Bi treatment. On the contrary, post-treatment of evaporated Bi2S3 thin films with sulfur could effectively increase the carrier lifetime and mobility by passivating the trap states on the grain boundaries, which is also consistent with the enhanced radiative recombination efficiency.

Insulin-loaded pH-sensitive hyaluronic acid nanoparticles enhance transcellular delivery.

In the present study, we developed novel insulin-loaded hyaluronic acid (HA) nanoparticles for insulin delivery. The insulin-loaded HA nanoparticles were prepared by reverse-emulsion-freeze-drying method. This method led to a homogenous population of small HA nanoparticles with average size of 182.2 nm and achieved high insulin entrapment efficiencies (approximately 95%). The pH-sensitive HA nanoparticles as an oral delivery carrier showed advantages in protecting insulin against the strongly acidic environment of the stomach, and not destroying the junction integrity of epithelial cells which promise long-term safety for chronic insulin treatment. The results of transport experiments suggested that insulin-loaded HA nanoparticles were transported across Caco-2 cell monolayers mainly via transcellular pathway and their apparent permeability coefficient from apical to basolateral had more than twofold increase compared with insulin solution. The efflux ratio of P (app) (B to A) to P (app) (A to B) less than 1 demonstrated that HA nanoparticle-mediated transport of insulin across Caco-2 cell monolayers underwent active transport. The results of permeability through the rat small intestine confirmed that HA nanoparticles significantly enhanced insulin transport through the duodenum and ileum. Diabetic rats treated with oral insulin-loaded HA nanoparticles also showed stronger hypoglycemic effects than insulin solution. Therefore, these HA nanoparticles could be a promising candidate for oral insulin delivery.

Simultaneous determination of cyclophosphamide and 4-hydroxycyclophosphamide in human plasma by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry - application to Chinese systemic lupus erythematosus patients.

BACKGROUND: A pharmacogenomics study of cyclophosphamide in systemic lupus erythematosus patients is being conducted in our laboratory in which the plasma concentrations of cyclophosphamide and its active metabolite 4-hydroxycyclophosphamide should be assayed rapidly and sensitively. METHODS: A rapid, stable and sensitive liquid chromato-graphy/electrospray ionization tandem mass spectrometry method was developed to simultaneously determine cyclophosphamide and 4-hydroxycyclophosphamide in human plasma with ifosfomide as an internal standard. After a protein precipitation with cold acetonitrile and stabilization of 4-hydroxycyclophosphamide by ansyldrazine and extraction with ethyl acetate, separation was performed on a C18 3.5 µm 2.1 × 50 mm column with mobile phase of acetonitrile and water (50:50, v/v) with 0.1% formic acid at 200 µL/min. The chromatographic run time was 3 min. RESULTS: The linear calibration curves ranged from 5 to 5000 ng/mL for cyclophosphamide and 5-500 ng/mL for 4-hydroxycyclophosphamide. The recoveries of the liquid extraction were 54.5%-58.5% for cyclophosphamide and 103.5%-105.5% for 4-hydroxycyclophosphamide. The lower limit of quantification was 5 ng/mL for both analytes. The intra- and inter-day precision was <15% for quality control samples at 4000, 500, 50 ng/mL for cyclophosphamide and 4-hydroxycyclophosphamide at 400, 100, 20 ng/mL. The method was applied in this pharmacogenomics study in Chinese systemic lupus erythematosus patients treated with low-dose cyclophosphamide. CONCLUSIONS: The method was efficient with shorter running time and lower limit of quantification compared to previous reports and has been successfully applied in this pharmacogenomics study.