Understanding asymmetric switching times in accumulation mode organic electrochemical transistors.

Understanding the factors underpinning device switching times is crucial for the implementation of organic electrochemical transistors in neuromorphic computing, bioelectronics and real-time sensing applications. Existing models of device operation cannot explain the experimental observations that turn-off times are generally much faster than turn-on times in accumulation mode organic electrochemical transistors. Here, using operando optical microscopy, we image the local doping level of the transistor channel and show that turn-on occurs in two stages-propagation of a doping front, followed by uniform doping-while turn-off occurs in one stage. We attribute the faster turn-off to a combination of engineering as well as physical and chemical factors including channel geometry, differences in doping and dedoping kinetics and the phenomena of carrier-density-dependent mobility. We show that ion transport limits the operation speed in our devices. Our study provides insights into the kinetics of organic electrochemical transistors and guidelines for engineering faster organic electrochemical transistors.

Targeting HSP47 for cancer treatment.

Heat shock protein 47 (HSP47) serves as an endoplasmic reticulum residing collagen-specific chaperone and plays an important role in collagen biosynthesis and structural assembly. HSP47 is encoded by the SERPINH1 gene, which is located on chromosome 11q13.5, one of the most frequently amplified regions in human cancers. The expression of HSP47 is regulated by multiple cellular factors, including cytokines, transcription factors, microRNAs, and circular RNAs. HSP47 is frequently upregulated in a variety of cancers and plays an important role in tumor progression. HSP47 promotes tumor stemness, angiogenesis, growth, epithelial-mesenchymal transition, and metastatic capacity. HSP47 also regulates the efficacy of tumor therapies, such as chemotherapy, radiotherapy, and immunotherapy. Inhibition of HSP47 expression has antitumor effects, suggesting that targeting HSP47 is a feasible strategy for cancer treatment. In this review, we highlight the function and expression of regulatory mechanisms of HSP47 in cancer progression and point out the potential development of therapeutic strategies in targeting HSP47 in the future.

Catalytic Refining Lignin-Derived Monomers: Seesaw Effect between Nanoparticle and Single-Atom Pt.

Pt automatically adsorbed on oxygen vacancy of TiO2 via an in situ interfacial redox reaction, resulting in atomically dispersion of Pt on TiO2. In the upgrading of lignin-derived 4-propylguaiacol, single-atom catalyst (SAC) Pt/TiO2-H achieved a conversion of 96.9 % and a demethoxylation selectivity of 93.3 % under 3 MPa H2 at 250 °C for 3 h, markedly different from the performance of nanoparticle counterpart that gave deep deoxygenation selectivity over 99.0 %. The high demethoxylation activity of SAC Pt/TiO2-H is mainly attributed to its weak hydrogen spillover capacity that suppressed the benzene ring hydrogenation and the deep deoxygenation. Additionally, SAC Pt/TiO2-H reduced the energy barrier of CAr-OCH3 bond cleavage and accordingly lowered the Gibbs free energy of the demethoxylation reaction. This facile method could fabricate single-atom Au, Pd, Ir, and Ru supported on TiO2-H, demonstrating the generality of this strategy for the establishment of a library of SACs. Moreover, SAC exhibited versatile capacity in demethoxylation of different lignin-derived monomers and high stability. This study showcases the superiority of atomically dispersed metal catalysts for selective demethoxylation reactions and proposes a renewable alternative to fossil-based 4-alkylphenols through upgrading of lignin-derived monomers.

Accurate contactless sleep apnea detection framework with signal processing and machine learning methods.

The detection of sleep apnea is critical for assessing sleep quality. It is also a proven biometric in diagnosing cardiovascular and other diseases. Recent studies have shown that radar-based non-contact vital sign monitoring system can effectively detect sleep apnea. However, the detection accuracy in the current study still needs to be improved. In this paper, we propose a sleep apnea detection framework based on FMCW radar. First, the radar system is employed to record the sleep data throughout the night with polysomnography (PSG) comparison. Then, in order to extract more accurate respiratory signal from the raw radar data, the signal processing methods are investigated to solve the observed discontinuity phenomenon. Finally, machine learning methods are adopted. The apneic and not-apneic events are classified accurately by selecting effective features of respiratory signal. As shown in the experimental results, the proposed system could achieve a good classification performance with an accuracy of 95.53%, a sensitivity of 72.60%, a specificity of 97.32%, a Kappa of 0.68, and an F-score of 0.84.

Incorporation of Digital Modulation into Vital Sign Detection and Gesture Recognition Using Multimode Radar Systems.

The incorporation of digital modulation into radar systems poses various challenges in the field of radar design, but it also offers a potential solution to the shrinking availability of low-noise operating environments as the number of radar applications increases. Additionally, digital systems have reached a point where available components and technology can support higher speeds than ever before. These advancements present new avenues for radar design, in which digitally controlled phase-modulated continuous wave (PMCW) radar systems can look to support multiple collocated radar systems with low radar-radar interference. This paper proposes a reconfigurable PMCW radar for use in vital sign detection and gesture recognition while utilizing digital carrier modulation and compares the radar responses of various modulation schemes. Binary sequences are used to introduce phase modulation to the carrier wave by use of a field programable gate array (FPGA), allowing for flexibility in the modulation speed and binary sequence. Experimental results from the radar demonstrate the differences between CW and PMCW modes when measuring the respiration rate of a human subject and in gesture detection.

Ulinastatin inhibits the metastasis of nasopharyngeal carcinoma by involving uPA/uPAR signaling.

Distant metastasis is the primary reason for treatment failure in patients with nasopharyngeal carcinoma (NPC). In this study, we investigated the effect of ulinastatin (UTI) on NPC metastasis and its underlying mechanism. Highly-metastatic NPC cell lines S18 and 58F were treated with UTI and the effect on cell proliferation, migration, and invasion were determined by MTS and Transwell assays. S18 cells with luciferase-expressing (S18-1C3) were injected into the left hind footpad of nude mice to establish a model of spontaneous metastasis from the footpad to popliteal lymph node (LN). The luciferase messenger RNA (mRNA) was measured by quantitative polymerase chain reaction (qPCR), and the metastasis inhibition rate was calculated. Key molecular members of the UTI-related uPA, uPAR, and JAT/STAT3 signaling pathways were detected by qPCR and immunoblotting. UTI suppressed the migration and infiltration of S18 and 5-8F cells and suppressed the metastasis of S18 cells in vivo without affecting cell proliferation. uPAR expression decreased from 24 to 48 h after UTI treatment. The antimetastatic effect of UTI is partly due to the suppression of uPA and uPAR. UTI partially suppresses NPC metastasis by downregulating the expression of uPA and uPAR.

Unsymmetrically Chlorinated Non-Fused Electron Acceptor Leads to High-Efficiency and Stable Organic Solar Cells.

Searching the cost-effective organic semiconductors is strongly needed in order to facilitate the practice of organic solar cells (OSCs), yet to be fulfilled. Herein, we have succeeded in developing two non-fused ring electron acceptors (NFREAs), leading to the highest efficiency of 16.2 % for the NFREA derived OSCs. These OSCs exhibit the superior operational stabilities under one sun equivalent illumination without ultraviolet (UV) filtration. It is revealed that the modulation of halogen substituents on aromatic side chains, as the new structural tool to tune the intermolecular interaction and optoelectronic properties of acceptors, not only promotes the interlocked tic-tac-toe frame of three-dimensional stacks in solid, but also improves charge dynamics of acceptors to enable high-performance and stable OSCs.

Potential inhibitors for blocking the interaction of the coronavirus SARS-CoV-2 spike protein and its host cell receptor ACE2.

BACKGROUND: The outbreak of SARS-CoV-2 continues to pose a serious threat to human health and social. The ongoing pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made a serious threat to public health and economic stability worldwide. Given the urgency of the situation, researchers are attempting to repurpose existing drugs for treating COVID-19. METHODS: We first established an anti-coronavirus drug screening platform based on the Homogeneous Time Resolved Fluorescence (HTRF) technology and the interaction between the coronavirus spike protein and its host receptor ACE2. Two compound libraries of 2,864 molecules were screened with this platform. Selected candidate compounds were validated by SARS-CoV-2_S pseudotyped lentivirus and ACE2-overexpressing cell system. Molecular docking was used to analyze the interaction between S protein and compounds. RESULTS: We identified three potential anti-coronavirus compounds: tannic acid (TA), TS-1276 (anthraquinone), and TS-984 (9-Methoxycanthin-6-one). Our in vitro validation experiments indicated that TS-984 strongly inhibits the interaction of the coronavirus S protein and the human cell ACE2 receptor. Additionally, tannic acid showed moderate inhibitory effect on the interaction of S protein and ACE2. CONCLUSION: This platform is a rapid, sensitive, specific, and high throughput system, and available for screening large compound libraries. TS-984 is a potent blocker of the interaction between the S-protein and ACE2, which might have the potential to be developed into an effective anti-coronavirus drug.

Transition-Metal-Free Synthesis of Functionalized Quinolines by Direct Conversion of ß-O-4 Model Compounds.

Direct production of heterocyclic aromatic compounds from lignin ß-O-4 models remains a huge challenge due to the incompatible catalysis for aryl ether bonds cleavage and heterocyclic ring formation. Herein, the first example of quinoline synthesis from ß-O-4 model compounds by a one-pot cascade reaction is reported in yields up to 89 %. The reaction pathway involves selective cleavage of C-O bonds, dehydrogenation, aldol condensation, C-N bond formation along with heterocyclic aromatic ring construction. The control experiments suggest that both imine and chalcone were identified as the key intermediates, and the rate determining step as well as the preferred pathway were experimentally clarified and supported by density functional theory (DFT) calculations. Based on this protocol, the conversion of ß-O-4 polymer delivered 56 wt % yield of quinoline derivative in three steps. This transformation provides a potential petroleum-independent choice for heterocyclic aromatic chemicals.

Postponing tumor onset and tumor progression can be achieved by alteration of local tumor immunity.

BACKGROUND: It has been known for years that the same genetic defects drive breast cancer formation, yet, the onset of breast cancer in different individuals among the same population differs greatly in their life spans with unknown mechanisms. METHODS: We used a MMTV-PyMT mouse model with different genetic backgrounds (FVB/NJ vs. C57BL/6J) to generate different cancer onset phenotypes, then profiled and analyzed the gene expression of three tumor stages in both Fvb.B6 and Fvb mice to explore the underlying mechanisms. RESULTS: We found that in contrast with the FVB/N-Tg (MMTV-PyMT) 634Mul mice (Fvb mice), mammary tumor initiation was significantly delayed and tumor progression was significantly suppressed in the Fvb.B6 mice (generated by crossing FVB/NJ with C57BL/6J mice). Transcriptome sequencing and analysis revealed that the differentially expressed genes were enriched in immune-related pathways. Flow cytometry analysis showed a higher proportion of matured dendritic cells in the Fvb.B6 mice. The plasma levels of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) were significantly reduced in the Fvb.B6 mice. IL-6 also impaired the maturation of bone marrow dendritic cells (BMDCs) of the Fvb mice in vitro. CONCLUSION: All these findings suggest that immunity levels (characterized by a reduced IL-6 level and intact DC maturation in Fvb.B6 mice) are the key factors affecting tumor onset in a murine mammary cancer model.

A Review on Low-Cost Microwave Doppler Radar Systems for Structural Health Monitoring.

Portable, low-cost, microwave radars have attracted researchers' attention for being an alternative noncontact solution for structural condition monitoring. In addition, by leveraging their capability of providing the target velocity information, the radar-based remote monitoring of complex rotating structures can also be accomplished. Modern radar systems are compact, able to be easily integrated in sensor networks, and can deliver high accuracy measurements. This paper reviews the recent technical advances in low-cost Doppler radar systems for phase-demodulated displacement measurements and time-Doppler analysis for structural health information, including digital signal processing and emerging applications related to radar sensor networks.

Sustainable Production of Benzylamines from Lignin.

Catalytic conversion of lignin into heteroatom functionalized chemicals is of great importance to bring the biorefinery concept into reality. Herein, a new strategy was designed for direct transformation of lignin ß-O-4 model compounds into benzylamines and phenols in moderate to excellent yields in the presence of organic amines. The transformation involves dehydrogenation of Cα -OH, hydrogenolysis of the Cß -O bond and reductive amination in the presence of Pd/C catalyst. Experimental data suggest that the dehydrogenation reaction proceeds over the other two reactions and secondary amines serve as both reducing agents and amine sources in the transformation. Moreover, the concept of "lignin to benzylamines" was demonstrated by a two-step process. This work represents a first example of synthesis of benzylamines from lignin, thus providing a new opportunity for the sustainable synthesis of benzylamines from renewable biomass, and expanding the products pool of biomass conversion to meet future biorefinery demands.

Simple Non-Fused Electron Acceptors Leading to Efficient Organic Photovoltaics.

Despite the remarkable progress achieved in recent years, organic photovoltaics (OPVs) still need work to approach the delicate balance between efficiency, stability, and cost. Herein, two fully non-fused electron acceptors, PTB4F and PTB4Cl, are developed via a two-step synthesis from single aromatic units. The introduction of a two-dimensional chain and halogenated terminals for these non-fused acceptors plays a synergistic role in optimizing their solid stacking and orientation, thus promoting an elongated exciton lifetime and fast charge-transfer rate in bulk heterojunction blends. As a result, PTB4Cl, upon blending with PBDB-TF polymer, has enabled single-junction OPVs with power conversion efficiencies of 12.76 %, representing the highest values among the reported fully unfused electron acceptors so far.

A Reversible Structural Phase Transition by Electrochemically-Driven Ion Injection into a Conjugated Polymer.

We find that conjugated polymers can undergo reversible structural phase transitions during electrochemical oxidation and ion injection. We study poly[2,5-bis(thiophenyl)-1,4-bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)benzene] (PB2T-TEG), a conjugated polymer with glycolated side chains. Using grazing incidence wide-angle X-ray scattering (GIWAXS), we show that, in contrast to previously known polymers, this polymer switches between two structurally distinct crystalline phases associated with electrochemical oxidation/reduction in an aqueous electrolyte. Importantly, we show that this unique phase change behavior has important physical consequences for ion-polaron pair transport. Notably, using moving front experiments visualized by both optical microscopy and super-resolution photoinduced force microscopy (PiFM), we show that a laterally propagating ion-polaron pair front in PB2T-TEG exhibits non-Fickian transport, retaining a sharp step-edge profile, in stark contrast to the Fickian diffusion more commonly observed in polymers like P3MEEMT. This structural phase transition is reminiscent of those accompanying ion uptake in inorganic materials like LiFePO4. We propose that the engineering of similar properties in future conjugated polymers may enable the realization of new materials with superior performance in electrochemical energy storage or neuromorphic memory applications.

Antioxidants suppress radiation-induced apoptosis via inhibiting MAPK pathway in nasopharyngeal carcinoma cells.

Nasopharyngeal carcinoma (NPC) is relatively sensitive to ionizing radiation, and radiotherapy is the main treatment modality for non-metastatic NPC. Radiation therapy generates overproduction of reactive oxygen species (ROS), which can cause DNA damage and induce apoptosis in tumors, thereby killing the malignant cells. Although dietary antioxidant supplementation reduces oxidative stress and promotes tumor progression, the effects of antioxidants on the NPC cells upon radiation have not been reported. In the present study, we showed that antioxidants (ß-Carotene, NAC, GSH) played an anti-apoptotic role in response to radiation via decreasing ROS production and inhibiting MAPK pathway in NPC cells. Based on that, we conclude that the use of supplemental antioxidants during radiotherapy should be avoided because of the possibility of tumor protection and reduced treatment efficacy.

Highly Efficient Fullerene-Free Organic Solar Cells Operate at Near Zero Highest Occupied Molecular Orbital Offsets.

Herein, we investigated a series of fullerene-free organic solar cells (OSCs) based on six different donor:acceptor (D:A) blends with varied highest occupied molecular orbital (HOMO) offsets from -0.05 to 0.21 eV. First, to verify the energetic compatibility of a specific D:A pair, especially for HOMO offsets, we established a simple method to estimate the hole transfer tendencies between D and A by using bilayer hole-only devices. It reveals that the asymmetrical diode effect of the bilayer hole-only devices can correlate with the FF and Jsc of the relevant OSCs. Second, to find out whether HOMO offset is the main restriction of hole transfer, we measured transient absorption spectra and examined the hole transfer behavior in the blends, revealing that the occurrence of hole transfer is independent of the HOMO offsets and ultrafast in the time scale of ≤4.6 ps for those blends with ≥0 eV HOMO offsets. In contrast, a negative HOMO offset can significantly slow down the hole transfer with a half-time of ∼400 ps. Furthermore, we compare the device parameters under varied light intensities and discover that the bimolecular recombination should be one of the main restrictions for high device performance. Surprisingly, small HOMO offsets of 0 and 0.06 eV can also enable high PCEs of 10.42% and 11.75% for blend 2 (PTQ10:HC-PCIC) and blend 3 (PBDB-TF:HC-PCIC), respectively. Overall, our work demonstrates not only the validity of high-performance OSCs operating at the near zero HOMO offsets but also the charge dynamic insights of these blends, which will help gain understanding on the further improvement of OSCs.

Identification and characterization of the lamprey cathepsin genes.

Cathepsins are key mammalian proteases that play an important role in the immune response. Several studies have revealed the versatile and critical functions of cathepsins. Here, we obtained ten kinds of cathepsin homologs and identified seven homologs with complete coding sequences. Phylogenetic analysis verified their identities and supported the classification of cathepsins into seven families, which is similar to other vertebrates. Tissue-specific expression analysis showed that all lamprey cathepsins (L-cathepsins) are present in the supraneural body (SB), kidney, gill, intestine, brain, heart, and liver, but their relative abundance varied among tissues. Additionally, we focused on the lamprey cathepsin L (L-cathepsin L) and used recombinant L-cathepsin L protein (rL-cathepsin L) to prepare anti rL-cathepsin L polyclonal antibodies, which were used to detect its distribution in lamprey tissues. The L-cathepsin L protein was primarily detected in the SB, kidney, gill, intestine, brain, and liver via western blot and immunohistochemistry assays. Importantly, quantitative real-time PCR (RT-PCR) revealed that the expression level of L-cathepsins mRNA significantly increased after exposure to three different stimuli (poly I:C, Staphylococcus aureus (S.a) and Vibro anguilarum (V.an)). This suggested that L-cathepsins may participate in defense processes. These results revealed that L-cathepsins may play key roles in the immune response to exogenous stimuli. The findings provide important information for future studies aiming to understand the molecular mechanisms underlying the immune response to pathogen invasion in lamprey.

Crystal structure of a cytocidal protein from lamprey and its mechanism of action in the selective killing of cancer cells.

BACKGROUND: In previous research, we found that lamprey immune protein (LIP) possessed cytocidal activity against tumor cells, but the mechanism of the selective recognition and killing of tumor cells by LIP was not identified. METHODS: Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding. RESULTS: We determined the overall crystallographic structure of LIP at a resolution of 2.25 Å. LIP exhibits an elongated structure with dimensions of 105 Å × 30 Å × 30 Å containing an N-terminal lectin module and a C-terminal aerolysin module. Moreover, the Phe209-Gly232 region is predicted to insert into the lipid bilayer to form a transmembrane ß-barrel, in which the hydrophobic residues face the lipid bilayer, and the polar residues constitute the hydrophilic lumen of the pore. We found that LIP is able to kill various human cancer cells with minimal effects on normal cells. Notably, by coupling biochemical and computational studies, we propose a hypothetical mechanism that involves dual selective recognition and efficient binding dependent on both N-linked glycans on GPI-anchored proteins (GPI-APs) and sphingomyelin (SM) in lipid rafts. Furthermore, specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs triggers substantial conformational changes in the aerolysin module, which interacts with SM, ultimately resulting in the formation of a membrane-bound oligomer in lipid rafts. CONCLUSIONS: LIP holds great potential for the application of a marine protein towards targeted cancer therapy and early diagnosis in humans.

The role of spin in the kinetic control of recombination in organic photovoltaics.

In biological complexes, cascade structures promote the spatial separation of photogenerated electrons and holes, preventing their recombination. In contrast, the photogenerated excitons in organic photovoltaic cells are dissociated at a single donor-acceptor heterojunction formed within a de-mixed blend of the donor and acceptor semiconductors. The nanoscale morphology and high charge densities give a high rate of electron-hole encounters, which should in principle result in the formation of spin-triplet excitons, as in organic light-emitting diodes. Although organic photovoltaic cells would have poor quantum efficiencies if every encounter led to recombination, state-of-the-art examples nevertheless demonstrate near-unity quantum efficiency. Here we show that this suppression of recombination arises through the interplay between spin, energetics and delocalization of electronic excitations in organic semiconductors. We use time-resolved spectroscopy to study a series of model high-efficiency polymer-fullerene systems in which the lowest-energy molecular triplet exciton (T1) for the polymer is lower in energy than the intermolecular charge transfer state. We observe the formation of T1 states following bimolecular recombination, indicating that encounters of spin-uncorrelated electrons and holes generate charge transfer states with both spin-singlet ((1)CT) and spin-triplet ((3)CT) characters. We show that the formation of triplet excitons can be the main loss mechanism in organic photovoltaic cells. But we also find that, even when energetically favoured, the relaxation of (3)CT states to T1 states can be strongly suppressed by wavefunction delocalization, allowing for the dissociation of (3)CT states back to free charges, thereby reducing recombination and enhancing device performance. Our results point towards new design rules both for photoconversion systems, enabling the suppression of electron-hole recombination, and for organic light-emitting diodes, avoiding the formation of triplet excitons and enhancing fluorescence efficiency.

Portable Microwave Radar Systems for Short-Range Localization and Life Tracking: A Review.

Short-range localization and life tracking have been hot research topics in the fields of medical care, consumer electronics, driving assistance, and indoor robots/drones navigation. Among various sensors, microwave and mm-wave continuous-wave (CW) radar sensors are gaining more popularity in their intrinsic advantages such as simple architecture, easy system integration, high accuracy, relatively low cost, and penetration capability. This paper reviews the recent advances in CW radar systems for short-range localization and life tracking applications, including system improvement, signal processing, as well as the emerging applications integrated with machine learning.