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.

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.

Lipopolysaccharide induces skin scarring through the TLR4/Myd88 inflammatory signaling pathway in dermal fibroblasts.

Skin scarring is a frequent complication of the wound healing process. Bacterial contamination and prolonged inflammation in wounds are thought to play significant roles during scar formation, but little is known about their specific mechanisms of action. In this study, hypertrophic scar derived fibroblasts (HSFs) and paired normal skin derived fibroblasts (NSFs) were used to evaluate the effects of lipopolysaccharide (LPS) on inflammation-induced skin scarring and explore the inflammation-mediated mechanism of activity of LPS on dermal fibroblasts. LPS was found to significantly upregulate the expression of the proinflammatory molecules TLR4, Myd88, TRAF6, and p65, and the fibrosis-related proteins Col I, Col III, and α-SMA, in NSFs. Blocking Myd88 expression with T6167923 downregulated the expression of Col I, Col III, and α-SMA, whereas activating Myd88 expression with CL075 significantly upregulated their expression in LPS-treated NSFs. LPS was found to delay wound healing and increase skin scarring in cell and mouse models. These results showed that LPS could induce scar formation through the TLR4/Myd88 signaling pathway in dermal fibroblasts, suggesting that the downregulation of excessive inflammation in wound tissues inhibits skin scarring and improves scar appearance.

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.

Disease-associated gut microbiome and critical metabolomic alterations in patients with colorectal cancer.

BACKGROUND: Gut microbiota plays a significant role in the colorectal cancer (CRC) process. Ectopic colonization of multiple oral bacteria is reportedly associated with CRC pathogenesis and progression, but the details remain unclear. METHODS: We enrolled a cohort of 50 CRC patients and 52 healthy controls from an East China population. Taxonomic and functional analysis of the fecal microbiota were performed using 16S rDNA (50 + 52 samples) and shotgun metagenomic sequencing (8 + 6 samples), respectively, with particular attention paid to gut-colonized oral bacteria. RESULTS AND CONCLUSIONS: The results showed more detected bacterial species but lower species evenness within the samples from CRC patients. To determine the specific bacteria enriched in each group, we analyzed their possible protective, carcinogenic, or opportunistic roles in the CRC process. Among the ectopic oral bacteria, we observed a significant increase in the abundance of Fusobacterium and decreased abundance of Prevotella and Ruminococcus in the CRC group. Main differences in the functional composition of these two groups were related to energy metabolism and biosynthesis, especially the glycolytic pathway. Furthermore, we validated the colonization of Fusobacterium nucleatum subsp. animalis within CRC tissues and studied its impact on the host intestinal epithelium and tumor cells. With high selectivity for cancerous tissues, this subspecies promoted CRC cell proliferation and induced potential DNA damage.

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.

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.

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.

Multi-parametric MRI-based radiomics for the diagnosis of malignant soft-tissue tumor.

PURPOSE: To develop and validate a multiparametric magnetic resonance imaging-based radiomics nomogram for differentiating malignant and benign soft-tissue tumors. METHODS: A total of 91 patients with pathologically confirmed soft-tissue tumors were enrolled between January 2017 and October 2020. Forty-eight patients were consecutively enrolled between November 2020 and March 2022, as a time-independent cohort. All patients underwent contrast-enhanced T1-weighted and T2-weighted fat-suppression magnetic resonance scans at 3.0 T. Radiomics features were extracted and selected from the two modalities to develop the radiomics signature. Significant clinical/morphological characteristics were identified using a multivariate logistic regression analysis. The least absolute shrinkage and selection operator regression were applied to identify discriminative features. A clinical-radiomics nomogram was constructed based on clinical/morphological characteristics and radiomics features. Finally, the performance of the nomogram was validated using the receiver operating characteristic and decision curve analysis (DCA). RESULTS: Six features were selected to establish the combined RS. Size, margin, and peritumoral edema were identified as the most important clinical and morphological factors, respectively. The radiomics signature outperformed the clinical model in terms of AUC and sensitivity. The nomogram integrating the combined RS, size, margin, and peritumoral edema achieved favorable predictive efficacy, generating AUCs of 0.954 (95% confidence interval [CI]: 0.907-1.000, Sen = 0.861, Spe = 0.917), 0.962 (95% CI: 0.901-1.000, Sen = 0.944, Spe = 0.923), and 0.935 (95% CI: 0.871-0.998, Sen = 0.815, Spe = 0.952) in the training (n = 60), validation (n = 31) and time-independent (n = 48) cohorts, respectively. The DCA curve indicated good clinical usefulness of the nomogram. CONCLUSIONS: Our study demonstrated the clinical potential of multiparametric MRI-based radiomics in distinguishing malignant from benign soft-tissue tumors, which can be considered as a noninvasive tool for individual treatment management.

Three-Dimensional Tracking of Tethered Particles for Probing Nanometer-Scale Single-Molecule Dynamics Using a Plasmonic Microscope.

Three-dimensional (3D) tracking of surface-tethered single particles reveals the dynamics of the molecular tether. However, most 3D tracking techniques lack precision, especially in the axial direction, for measuring the dynamics of biomolecules with a spatial scale of several nanometers. Here, we present a plasmonic imaging technique that can track the motion of ∼100 tethered particles in 3D simultaneously with sub-nanometer axial precision and single-digit nanometer lateral precision at millisecond time resolution. By tracking the 3D coordinates of a tethered particle with high spatial resolution, we are able to determine the dynamics of single short DNA and study its interaction with enzymes. We further show that the particle motion pattern can be used to identify specific and nonspecific interactions in immunoassays. We anticipate that our 3D tracking technique can contribute to the understanding of molecular dynamics and interactions at the single-molecule level.

A Three-Dimensional Micromixer Using Oblique Embedded Ridges.

A micromixer is one of the most significant components in a microfluidic system. A three-dimensional micromixer was developed with advantages of high efficiency, simple fabrication, easy integration, and ease of mass production. The designed principle is based on the concepts of splitting-recombination and chaotic advection. A numerical model of this micromixer was established to characterize the mixing performance for different parameters. A critical Reynolds number (Re) was obtained from the simulation results. When the Re number is smaller than the critical value, the fluid mixing is mainly dependent on the mechanism of splitting-recombination, therefore, the length of the channel capable of complete mixing (complete mixing length) increases as the Re number increases. When the Re number is larger than the critical value, the fluid mixing is dominated by chaotic advection, and the complete mixing length decreases as the Re number increases. For normal fluids, a complete mixing length of 500 µm can be achieved at a very small Re number of 0.007 and increases to 2400 µm as the Re number increases to the critical value of 4.7. As the Re number keep increasing and passes the critical Re number, the complete mixing length continues to descend to 650 µm at the Re number of 66.7. For hard-to-mix fluids (generally referring to fluids with high viscosity and low diffusion coefficient, which are difficult to mix), even though no evidence of strong chaotic advection is presented in the simulation, the micromixer can still achieve a complete mixing length of 2550 µm. The mixing performance of the micromixer was also verified by experiments. The experimental results showed a consistent trend with the numerical simulation results, which both climb upward when the Re number is around 0.007 (flow rate of 0.03 µm/min) to around 10 (flow rate of 50 µm/min), then descend when the Re number is around 13.3 (flow rate of 60 µm/min).

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.

Charge-Sensitive Optical Detection of Small Molecule Binding Kinetics in Normal Ionic Strength Buffer.

Most label-free detection technologies detect the masses of molecules, and their sensitivities thus decrease with molecular weight, making it challenging to detect small molecules. To address this need, we have developed a charge-sensitive optical detection (CSOD) technique, which detects the charge rather than the mass of a molecule with an optical fiber. However, the effective charge of a molecule decreases with the buffer ionic strength. For this reason, the previous CSOD works with diluted buffers, which could affect the measured molecular binding kinetics. Here, we show a technique capable of detecting molecular binding kinetics in normal ionic strength buffers. An H-shaped sample well was developed to increase the current density at the sensing area to compensate the signal loss due to ionic screening at normal ionic strength buffer, while keeping the current density low at the electrodes to minimize the electrode reaction. In addition, agarose gels were used to cover the electrodes to prevent electrode reaction generated bubbles from entering the sensing area. With this new design, we have measured the binding kinetics between G-protein-coupled receptors (GPCRs) and their small molecule ligands in normal buffer. We found that the affinities measured in normal buffer are stronger than those measured in diluted buffer, likely due to the stronger electrostatic repulsion force between the same charged ligands and receptors in the diluted buffer.

Gradient-Based Rapid Digital Immunoassay for High-Sensitivity Cardiac Troponin T (hs-cTnT) Detection in 1 µL Plasma.

Rapid and sensitive detection of biomarkers is the key to the diagnosis of acute diseases. One example is the detection of troponin in myocardial infarction. Here, we report a gradient-based digital immunoassay method, which can achieve high-sensitivity cardiac troponin T (hs-cTnT) detection with only 1 µL of plasma sample. We designed a multizone microfluidic channel functionalized with capture antibody specific to troponin. Taking advantage of limited sample volume, a troponin concentration gradient is created along the channel because of binding induced depletion. We quantified the concentration gradient by counting the detection antibody conjugated gold nanoparticles bound to different test zones with optical imaging. Differential counting between the zones removes most common noises and nonspecific bindings. The total analytical time is about 30 min, and the limit of quantification is 6.2 ng/L. We examined 41 clinical plasma samples from 15 patients and the change in hs-cTnT concentration in serial samples showed good linear correlation with clinical results (R2 = 0.98). Therefore, this simple and sensitive gradient-based digital immunoassay method is a promising technology for clinical hs-cTnT detection and could be adapted for detection of other biomarkers.

Probing Single-Molecule Binding Event by the Dynamic Counting and Mapping of Individual Nanoparticles.

Measuring binding processes at the single-molecule level underpin significant functions in understanding biological events. Single-nanoparticle imaging techniques are providing a new concept for mapping the heterogeneous behaviors and characterizations of individual dynamics such as molecule-molecule interactions. Here, we develop the optical imaging techniques for directly counting and monitoring the binding and motion events of single nanoparticles linked to the substrate via the specific and reversible interactions between biomolecules. The one-step digital immunoassay realizes the biomolecular detection based on dynamic counting of the single nanoparticle binding event to substrate with the bright-field imaging. The detection limit achieves 8.4 pg/mL for procalcitonin with detection time of 14 min. Meanwhile, we map the accurate trajectory of single nanoparticle switching between different target molecules among the x-y plane with the total internal reflection imaging technique, which reveals the spatial coordinates of single target molecules on the substrate surface with high spatial and temporal resolutions.

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.

Simultaneous Quantification of Protein Binding Kinetics in Whole Cells with Surface Plasmon Resonance Imaging and Edge Deformation Tracking.

Most drugs work by binding to receptors on the cell surface. Quantification of binding kinetics between drug and membrane protein is an essential step in drug discovery. Current methods for measuring binding kinetics involve extracting the membrane protein and labeling, and both have issues. Surface plasmon resonance (SPR) imaging has been demonstrated for quantification of protein binding to cells with single-cell resolution, but it only senses the bottom of the cell and the signal diminishes with the molecule size. We have discovered that ligand binding to the cell surface is accompanied by a small cell membrane deformation, which can be used to measure the binding kinetics by tracking the cell edge deformation. Here, we report the first integration of SPR imaging and cell edge tracking methods in a single device, and we use lectin interaction as a model system to demonstrate the capability of the device. The integration enables the simultaneous collection of complementary information provided by both methods. Edge tracking provides the advantage of small molecule binding detection capability, while the SPR signal scales with the ligand mass and can quantify membrane protein density. The kinetic constants from the two methods were cross-validated and found to be in agreement at the single-cell level. The variation of observed rate constant between the two methods is about 0.009 s-1, which is about the same level as the cell-to-cell variations. This result confirms that both methods can be used to measure whole-cell binding kinetics, and the integration improves the reliability and capability of the measurement.

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.

One-Step Digital Immunoassay for Rapid and Sensitive Detection of Cardiac Troponin I.

A rapid and sensitive method to detect cardiac troponin I (cTnI) in human blood is critical to the diagnosis and treatment of acute myocardial infarction (AMI). Here, we describe a simple one-step digital immunoassay for single-molecule detection without washing steps. A sample containing cTnI mixed with detection antibody-conjugated gold nanoparticles (AuNPs) is added to a capture antibody-coated sensor surface and the formation of the antibody-cTnI-antibody sandwich is detected by digitally counting the binding of the individual gold nanoparticles to the sensor surface in real time using a bright-field optical imaging setup together with a differential imaging algorithm. The digital immunoassay detects cTnI in undiluted human plasma, which achieves a detection limit of 5.7 ng/L within a detection time of only 10 min, which meets the requirement of current clinical high-sensitivity troponin assay (∼70 ng/L cutoff). We anticipate that the one-step and real-time digital immunoassay can be applied to the detection of other disease biomarkers in blood.