Pruritus Anesis in Dystrophic Epidermolysis Bullosa Pruriginosa with Dupilumab.

ABSTRACT: Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) is a rare subtype of dystrophic epidermolysis bullosa, and traditional treatments have limited efficacy. Dupilumab has demonstrated remarkable efficacy in relieving pruritus. In this case study, after traditional treatment failed, providers recommended the patient begin dupilumab to treat his pruritus. The patient was administrated a loading dose of 600 mg of dupilumab and a dose of 300 mg every 2 weeks. The Dermatology Life Quality Index and Pruritic Numeric Rating Scale were used to assess the patient's situation. After several months, the patient's DEB-Pr was considered in remission. Dupilumab may be a better choice than immunosuppressants for the treatment of pruritus in patients with DEB-Pr.

Layer-by-Layer Organic Solar Cells Enabled by 1,3,4-Selenadiazole-Containing Crystalline Small Molecule with Double-Fibril Network Morphology.

A double-fibril network of the photoactive layer morphology is recognized as an ideal structure facilitating exciton diffusion and charge carrier transport for high-performance organic solar cells (OSCs). However, in the layer-by-layer processed OSCs (LbL-OSCs), polymer donors and small molecule acceptors (SMAs) are separately deposited, and it is challenging to realize a fibril network of pure SMAs with the absence of tight interchain entanglement as polymers. In this work, crystalline small molecule donors (SMDs), named TDZ-3TR and SeDZ-3TR, were designed and introduced into the L8-BO acceptor solution, forcing the phase separation and molecular fibrilization. SeDZ-3TR showed higher crystallinity and lower miscibility with L8-BO acceptor than TDZ-3TR, enabling more driving force to favor the phase separation and better molecular fibrilization of L8-BO. On the other hand, two donor polymers of PM6 and D18 with different fibril widths and lengths were put together to optimize the fibril network of the donor layer. The simultaneously optimization of the acceptor and donor layers resulted in a more ideal double-fibril network of the photoactive layer and an impressive power conversion efficiency (PCE) of 19.38 % in LbL-OSCs.

Potential role of the P2X7 receptor in the proliferation of human diffused large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of invasive non-Hodgkin lymphoma. 60-70% of patients are curable with current chemoimmunotherapy, whereas the rest are refractory or relapsed. Understanding of the interaction between DLBCL cells and tumor microenvironment raises the hope of improving overall survival of DLBCL patients. P2X7, a member of purinergic receptors P2X family, is activated by extracellular ATP and subsequently promotes the progression of various malignancies. However, its role in DLBCL has not been elucidated. In this study, the expression level of P2RX7 in DLBCL patients and cell lines was analyzed. MTS assay and EdU incorporation assay were carried out to study the effect of activated/inhibited P2X7 signaling on the proliferation of DLBCL cells. Bulk RNAseq was performed to explore potential mechanism. The results demonstrated high level expression of P2RX7 in DLBCL patients, typically in patients with relapse DLBCL. 2'(3')-O-(4-benzoylbenzoyl) adenosine 5-triphosphate (Bz-ATP), an agonist of P2X7, significantly accelerated the proliferation of DLBCL cells, whereas delayed proliferation was detected when administrated with antagonist A740003. Furthermore, a urea cycle enzyme named CPS1 (carbamoyl phosphate synthase 1), which up-regulated in P2X7-activated DLBCL cells while down-regulated in P2X7-inhibited group, was demonstrated to involve in such process. Our study reveals the role of P2X7 in the proliferation of DLBCL cells and implies that P2X7 may serve as a potential molecular target for the treatment of DLBCL.

Structure Influence of Amine-Containing Additives on the Solution State and Out-of-Plane Conductivity of PEDOT:PSS for Efficient Organic Solar Cells.

Additives are extensively explored for improving PEDOT:PSS performances mainly through the removal of excess PSS and as a secondary dopant. In this work, amine-containing additives are introduced to PEDOT:PSS solutions as processing additives where the interactions to the PSS are anticipated through electrostatic interactions. Such interactions affected solution property where the increased viscosity is found to significantly increase the out-of-plane conductivity of the PEDOT:PSS thin films. Organic solar cells adopting these additive-assisted processed PEDOT:PSS layers as hole transporting layers (HTL) showed the improved device performances that resulted from the reduced series resistance provided by the PEDOT:PSS HTL. A top power conversion efficiency of 18.28% is achieved with para-phenylenediamine (PPD) additive in the PEDOT:PSS HTL, which is 3.5% higher compared to devices with neat PEDOT:PSS thin film as the HTL.

Nickel(II) Nitrate Hole-Transporting Layers for Single-Junction Bulk Heterojunction Organic Solar Cells with a Record 19.02 % Efficiency.

A facile strategy was developed here to improve the film quality of nickel-based hole transporting layer (HTL) for efficient organic solar cell (OSC) applications. To prevent the agglomeration of Ni(NO3 )2 during film deposition, acetylacetonate was added into the precursor solution, which led to the formation of an amorphous and glass-like state. After thermal annealing (TA) treatment, the film-forming ability could be further improved. The additional UV-ozone (UVO) treatment continuously improved the film quality and increased the work function and conductivity of such HTL. The resulting TA & UVO modified Ni(NO3 )2 & Hacac HTL produced highly efficient organic solar cells with exciting power conversion efficiencies of 18.42 % and 19.02 % for PM6 : BTP-eC9 and D18 : BTP-Th devices, respectively, much higher than the control PEDOT : PSS devices.

Sorption of organochlorine pesticides on polyethylene microplastics in soil suspension.

As a new type of environmental pollutant, microplastics (MPs) can adsorb residual organochlorine pesticides (OCPs) in the soil and pose a severe threat to the soil ecosystems. To understand the interaction between soil MPs and OCPs, the sorption of two kinds of OCPs, including hexachlorocyclohexanes (HCHs) and dichlorodiphenyltrichloroethanes (DDTs), on polyethylene (PE) microplastics in soil suspension was studied through sorption kinetics and isotherm models. The effects of solution/soil ratio and MPs diameter on sorption were examined. The kinetic experiment results show that the sorption equilibrium was 12 h， and the sorption process of OCPs on MPs can be well described by a pseudo-second-order model. The Freundlich model (R2 = 0.942-0.997) provides a better fit to the sorption isotherm data than the Langmuir model (R2 = 0.062-0.634), indicating that the sorption process takes place on the nonuniform surface of MPs. The MPs had a good sorption effect on OCPs when the solution/soil ratio was from 75:1 to 100:1. As the diameter of MPs increases, the sorption capacity decreases. These results provide support for further research on microplastic pollution in soil.

Direct Antimicrobial Susceptibility Testing on Clinical Urine Samples by Optical Tracking of Single Cell Division Events.

With the increasing prevalence of antibiotic resistance, the need to develop antimicrobial susceptibility testing (AST) technologies is urgent. The current challenge has been to perform the antibiotic susceptibility testing in short time, directly with clinical samples, and with antibiotics over a broad dynamic range of clinically relevant concentrations. Here, a technology for point-of-care diagnosis of antimicrobial-resistant bacteria in urinary tract infections, by imaging the clinical urine samples directly with an innovative large volume solution scattering imaging (LVSi) system and analyzing the image sequences with a single-cell division tracking method is developed. The high sensitivity of single-cell division tracking associated with large volume imaging enables rapid antibiotic susceptibility testing directly on the clinical urine samples. The results demonstrate direct detection of bacterial infections in 60 clinical urine samples with a 60 min LVSi video, and digital AST of 30 positive clinical samples with 100% categorical agreement with both the clinical culture results and the on-site agar plating validation results. This technology provides opportunities for precise antibiotic prescription and proper treatment of the patient within a single clinic visit.

Rapid antibiotic susceptibility testing based on bacterial motion patterns with long short-term memory neural networks.

Antibiotic resistance is an increasing public health threat. To combat it, a fast method to determine the antibiotic susceptibility of infecting pathogens is required. Here we present an optical imaging-based method to track the motion of single bacterial cells and generate a model to classify active and inactive cells based on the motion patterns of the individual cells. The model includes an image-processing algorithm to segment individual bacterial cells and track the motion of the cells over time, and a deep learning algorithm (Long Short-Term Memory network) to learn and determine if a bacterial cell is active or inactive. By applying the model to human urine specimens spiked with an Escherichia coli lab strain, we show that the method can accurately perform antibiotic susceptibility testing as fast as 30 minutes for five commonly used antibiotics.

Rapid Antimicrobial Susceptibility Testing of Patient Urine Samples Using Large Volume Free-Solution Light Scattering Microscopy.

The emergence of antibiotic resistance has prompted the development of rapid antimicrobial susceptibility testing (AST) technologies that will enable evidence-based treatment and promote antimicrobial stewardship. To date, many rapid AST methods have been developed, but few are able to be performed on clinical samples directly. Here we developed a large volume light scattering microscopy technique that tracks phenotypic features of single bacterial cells directly in clinical urine samples without sample enrichment or culturing. The technique demonstrated rapid (90 min) detection of Escherichia coli in 24 clinical urine samples with 100% sensitivity and 83% specificity and rapid (90 min) AST in 12 urine samples with 87.5% categorical agreement with two antibiotics, ampicillin and ciprofloxacin.

A method for particulate matter 2.5 (PM2.5) biotoxicity assay using luminescent bacterium.

The ability to analyze biotoxicity of atmospheric pollution plays an important role in public health. It provides the potential to directly analyze the health information of at-risk individuals. Although air quality standards have received significant attention in many countries, the potential for better biotoxicity assessment has remained largely unexplored. Here we propose a method using one kind of luminescent bacterium Photobacterium phosphereum to detect the biotoxicity of atmospheric particulate matter ≤ 2.5 µm (PM2.5). Combined with the results of air pollution data of the year 2013-2014, this method has been proven to have good biotoxicity detection performance, and can evaluate the severity of at least 85% of PM2.5 related biotoxicity in Shanghai during this time period. Based on an established algorithm of this detection system, the biotoxicity of twelve PM2.5 real samples (collected over a month) were tested and divided into different biotoxicity levels. It allows an effective evaluation of biotoxicity of PM2.5 due to the quick and sensitive response of bioluminescence to the concentration of toxic components, which provides a valuable reference to evaluate the biotoxicity of PM2.5. This established method can be easily applied to the analysis and evaluation of any other PM2.5 samples assay by following the steps.

Phenotypic Antimicrobial Susceptibility Testing with Deep Learning Video Microscopy.

Timely determination of antimicrobial susceptibility for a bacterial infection enables precision prescription, shortens treatment time, and helps minimize the spread of antibiotic resistant infections. Current antimicrobial susceptibility testing (AST) methods often take several days and thus impede these clinical and health benefits. Here, we present an AST method by imaging freely moving bacterial cells in urine in real time and analyzing the videos with a deep learning algorithm. The deep learning algorithm determines if an antibiotic inhibits a bacterial cell by learning multiple phenotypic features of the cell without the need for defining and quantifying each feature. We apply the method to urinary tract infection, a common infection that affects millions of people, to determine the minimum inhibitory concentration of pathogens from human urine specimens spiked with lab strain E. coli (ATCC 43888) and an E. coli strain isolated from a clinical urine sample for different antibiotics within 30 min and validate the results with the gold standard broth macrodilution method. The deep learning video microscopy-based AST holds great potential to contribute to the solution of increasing drug-resistant infections.

First airborne pathogen direct analysis system.

We report a portable "sample to answer" system for the rapid detection of airborne pathogens for the first time. The system contains a key microfluidic chip which fulfills both pathogen enrichment and biological identification functions. The system realizes simple operation and less human intervention as well as minimum reagent contamination. The operation is user-friendly and suitable for field and point-of-care applications. The system is capable of handling detection of different pathogens by changing the primers.

Microfluidic platform for direct capture and analysis of airborne Mycobacterium tuberculosis.

Airborne Mycobacterium tuberculosis is the main source of tuberculosis infection, which is known as one of the worldwide infectious diseases. Direct capture and analysis of airborne Mycobacterium tuberculosis is essential for disease prevention and control. At present, low concentration of pathogens directly collected from the air is the major drawback for rapid analysis. Herein an integrated microfluidic system capable of airborne Mycobacterium tuberculosis capture, enrichment, and rapid bacteriological immunoassay was developed. The whole detection time was decreased to less than 50 min including 20 min of enrichment and 30 min of immunoreaction analysis. It had the advantages of low detection limit, fast detection speed, and low reagent consumption compared with conventional techniques, showing the potential to become a new airborne pathogen analysis platform.

Characteristics of a microcystin-LR biodegrading bacterial isolate: Ochrobactrum sp. FDT5.

Mass growth of blue-green algae in eutrophic water bodies leads to a large amount of toxins, e.g. microcystins (MCs). How to remove MCs from water bodies is an environmental problem. In this study, an algicidal bacterium Ochrobactrum sp. FDT5 was isolated and found to have microcystin-LR (MC-LR) degradation capacity, which could be enhanced by a domestication process. The FDT5 cell density, MC-LR initial concentration, temperature, and pH on the degradation of MC-LR were investigated. The results indicated that the initial cell density of FDT5 and the initial concentration of MC-LR could influence MC-LR degradation. The optimum conditions were under the temperature of 35°C with pH of 7.0. After FDT5 was exposed to MC-LR for 2 days, FDT5 cells produced active cellular components that degraded MC-LR. These cellular components were heat-inactivated and removed when FDT5 cells were removed by filtration.

Novel anti-Acanthamoeba effects elicited by a repurposed poly (ADP-ribose) polymerase inhibitor AZ9482.

Introduction: Acanthamoeba infection is a serious public health concern, necessitating the development of effective and safe anti-Acanthamoeba chemotherapies. Poly (ADP-ribose) polymerases (PARPs) govern a colossal amount of biological processes, such as DNA damage repair, protein degradation and apoptosis. Multiple PARP-targeted compounds have been approved for cancer treatment. However, repurposing of PARP inhibitors to treat Acanthamoeba is poorly understood. Methods: In the present study, we attempted to fill these knowledge gaps by performing anti-Acanthamoeba efficacy assays, cell biology experiments, bioinformatics, and transcriptomic analyses. Results: Using a homology model of Acanthamoeba poly (ADP-ribose) polymerases (PARPs), molecular docking of approved drugs revealed three potential inhibitory compounds: olaparib, venadaparib and AZ9482. In particular, venadaparib exhibited superior docking scores (-13.71) and favorable predicted binding free energy (-89.28 kcal/mol), followed by AZ9482, which showed a docking score of -13.20 and a binding free energy of -92.13 kcal/mol. Notably, the positively charged cyclopropylamine in venadaparib established a salt bridge (through E535) and a hydrogen bond (via N531) within the binding pocket. For comparison, AZ9482 was well stacked by the surrounding aromatic residues including H625, Y652, Y659 and Y670. In an assessment of trophozoites viability, AZ9482 exhibited a dose-and time-dependent anti-trophozoite effect by suppressing Acanthamoeba PARP activity, unlike olaparib and venadaparib. An Annexin V-fluorescein isothiocyanate/propidium iodide apoptosis assay revealed AZ9482 induced trophozoite necrotic cell death rather than apoptosis. Transcriptomics analyses conducted on Acanthamoeba trophozoites treated with AZ9482 demonstrated an atlas of differentially regulated proteins and genes, and found that AZ9482 rapidly upregulates a multitude of DNA damage repair pathways in trophozoites, and intriguingly downregulates several virulent genes. Analyzing gene expression related to DNA damage repair pathway and the rate of apurinic/apyrimidinic (AP) sites indicated DNA damage efficacy and repair modulation in Acanthamoeba trophozoites following AZ9482 treatment. Discussion: Collectively, these findings highlight AZ9482, as a structurally unique PARP inhibitor, provides a promising prototype for advancing anti-Acanthamoeba drug research.

KLF7 promotes neuroblastoma differentiation through the GTPase signaling pathway by upregulating neuroblast differentiation-associated protein AHNAKs and glycerophosphodiesterase GDPD5.

The arrest of neural crest-derived sympathoadrenal neuroblast differentiation contributes to neuroblastoma formation, and overriding this blocked differentiation is a clear strategy for treating high-risk neuroblastoma. A better understanding of neuroblast or neuroblastoma differentiation is essential for developing new therapeutic approaches. It has been proposed that Krueppel-like factor 7 (KLF7) is a neuroblastoma super-enhancer-associated transcription factor gene. Moreover, KLF7 was found to be intensely active in postmitotic neuroblasts of the developing nervous system during embryogenesis. However, the role of KLF7 in the differentiation of neuroblast or neuroblastoma is unknown. Here, we find a strong association between high KLF7 expression and favorable clinical outcomes in neuroblastoma. KLF7 induces differentiation of neuroblastoma cells independently of the retinoic acid (RA) pathway and acts cooperatively with RA to induce neuroblastoma differentiation. KLF7 alters the GTPase activity and multiple differentiation-related genes by binding directly to the promoters of neuroblast differentiation-associated protein (AHNAK and AHNAK2) and glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5) and regulating their expression. Furthermore, we also observe that silencing KLF7 in neuroblastoma cells promotes the adrenergic-to-mesenchymal transition accompanied by changes in enhancer-mediated gene expression. Our results reveal that KLF7 is an inducer of neuroblast or neuroblastoma differentiation with prognostic significance and potential therapeutic value.

Microfluidic device for efficient airborne bacteria capture and enrichment.

Highly efficient capture and enrichment is always the key for rapid analysis of airborne pathogens. Herein we report a simple microfluidic device which is capable of fast and efficient airborne bacteria capture and enrichment. The device was validated with Escherichia coli (E. coli) and Mycobacterium smegmatis. The results showed that the efficiency can reach close to 100% in 9 min. Compared with the traditional sediment method, there is also great improvement with capture limit. In addition, various flow rate and channel lengths have been investigated to obtain the optimized condition. The high capture and enrichment might be due to the chaotic vortex flow created in the microfluidic channel by the staggered herringbone mixer (SHM) structure, which is also confirmed with flow dynamic mimicking. The device is fabricated from polydimethylsiloxane (PDMS), simple, cheap, and disposable, perfect for field application, especially in developing countries with very limited modern instruments.

Sequential Deposition of Multicomponent Bulk Heterojunctions Increases Efficiency of Organic Solar Cells.

Constructing tandem and multi-blend organic solar cells (OSCs) is an effective way to overcome the absorption limitations of conventional single-junction devices. However, these methods inevitably require tedious multilayer deposition or complicated morphology-optimization procedures. Herein, sequential deposition is utilized as an effective and simple method to fabricate multicomponent OSCs with a double-bulk heterojunction (BHJ) structure of the active layer to further improve photovoltaic performance. Two efficient donor-acceptor pairs, D18-Cl:BTP-eC9 and PM6:L8-BO, are sequentially deposited to form the D18-Cl:BTP-eC9/PM6:L8-BO double-BHJ active layer. In these double-BHJ OSCs, light absorption is significantly improved, and optimal morphology is also retained without requiring a more complicated morphology optimization involved in quaternary blends. Compared to the quaternary blend devices, energy loss (Eloss ) is also reduced by rationally matching each donor with an appropriate acceptor. Consequently, the power conversion efficiency (PCE) is improved from 18.25% for D18-Cl:BTP-eC9 and 18.69% for PM6:L8-BO based binary blend OSCs to 19.61% for the double-BHJ OSCs. In contrast, a D18-Cl:PM6:L8-BO:BTP-eC9 quaternary blend of OSCs exhibited a dramatically reduced PCE of 15.83%. These results demonstrate that a double-BHJ strategy, with a relatively simple processing procedure, can potentially enhance the device performance of OSCs and lead to more widespread use.

Efficacy and safety of dupilumab in pediatric patients with moderate to severe atopic dermatitis: a real-world study.

Dupilumab is the first human monoclonal antibody that treats atopic dermatitis (AD) by blocking interleukin 4 (IL-4) and interleukin 13 (IL-13), which can suppress the Th2 inflammatory reaction. Effective treatments for pediatric AD patients are limited; therefore, we aimed to assess the efficacy and safety of dupilumab in pediatric AD patients. Fifteen pediatric patients diagnosed with moderate to severe AD and treated with dupilumab were enrolled in this study. SPSS was used to analyze data and obtain the average values of Eczema Area and Severity Index (EASI), SCORing AD (SCORAD), and Children's Dermatology Life Quality Index (CDLQI). GRAPHPAD was used to analyze and plot the statistics. The average EASI values were 19.23 ± 3.03 and 1.69 ± 0.54 at baseline and at following up for 6 months after standardized treatment protocol, respectively. The average SCORAD values were 43.27 ± 4.63 and 6.13 ± 1.41 at baseline and at following up for 6 months after standardized treatment protocol, respectively. The average CDLQI value at baseline was 13.53 ± 2.88 and following up for 6 months after standardized treatment protocol was 1.60 ± 0.63. The most frequent adverse event was conjunctivitis. No serious adverse events occurred during the treatment period. Dupilumab could reduce symptoms and improve pruritus in pediatric AD patients, and the frequent adverse events were reversible. It has a definite therapeutic effect on AD; nevertheless, further studies should be conducted to obtain information on its the long-term efficacy and safety.