Perspectives on emerging dual carbon fiber batteries: advantages, challenges and prospects.

This perspective article describes a new dual carbon fiber battery, where both the cathode and anode are made of carbon fiber. The dual carbon fiber battery combines the advantages of carbon fiber and dual graphite batteries, including a higher working potential compared to lithium-ion batteries, a high areal capacity, and easy access due to the mature manufacturing technology of carbon fibers. In this article, we discuss the mechanism, current status and potential application areas of dual carbon fiber batteries. Additionally, we highlight the challenges and prospects of these batteries.

DNA Logical Device Combining an Entropy-Driven Catalytic Amplification Strategy for the Simultaneous Detection of Exosomal Multiplex miRNAs In Situ.

Exosomal miRNAs are considered promising biomarkers for cancer diagnosis, but their accuracy is severely compromised by the low content of miRNAs and the large amount of exosomal miRNAs released from normal cells. Here, we presented a dual-specific miRNA's logical recognition triggered by an entropy-driven catalysis (EDC)-enhanced system in exosomes for accurate detection of liver cancer-cell-derived exosomal miR-21 and miR-122. Taking advantage of the accurate analytical performance of the logic device, the excellent membrane penetration of gold nanoparticles, and the outstanding amplification ability of the EDC reaction, this method exhibits high sensitivity and selectivity for the detection of tumor-derived exosomal miRNAs in situ. Moreover, due to its excellent performance, this logic device can effectively distinguish liver cancer patients from healthy donors by determining the amount of cancer-cell-derived exosomal miRNAs. Overall, this strategy has great potential for analyzing various types of exosomes and provides a viable tool to improve the accuracy of cancer diagnosis.

Spatiotemporal control of DNAzyme activity for fluorescent imaging of telomerase RNA in living cells.

BACKGROUND: Human telomerase is a ribonucleoprotein complex that includes proteins and human telomerase RNA (hTR). Emerging evidence suggested that the expression level of hTR was high related with the development of tumor, so it is important to accurately detect the content of hTR. Optical control of DNAzyme activity shows a promising strategy for precise biosensing, biomedical imaging and modulation of biological processes. Although DNAzyme-based sensors can be controlled spatiotemporally by light, its application in the detection of hTR in living cells is still rare. Therefore, designing DNAzyme activity spatiotemporal controllable sensors for hTR detection is highly needed. RESULTS: We developed a UV light-activated DNAzyme-based nanoprobe for spatially accurate imaging of intracellular hTR. The proposed nanoprobe was named MDPH, which composed of an 8-17 DNAzyme (D) inactivated by a protector strand (P), a substrate strand (H), and MnO2 nanosheets. The MnO2 nanosheets can enhance the cellular uptake of DNA strands, so that MDPH probe can enter cells autonomously through endocytosis. Under the high concentration of GSH in cancer cells, MnO2 nanosheets can self-generate cofactors to maintain the catalytic activity of DNAzyme. When exposing UV light and in presence of target hTR, DNAzyme could cleave substrate H, resulting in the recovery of fluorescence of the system. The cells imaging results show that MDPH probe could be spatiotemporally controlled to image endogenous hTR in cancer cells. SIGNIFICANCE: With this design, telomerase RNA-specific fluorescent imaging was achieved by MDPH probe in both cancer and normal cells. Our probe made a promising new platform for spatiotemporal controllable intracellular hTR monitoring. This current method can be applied to monitor a variety of other biomarkers in living cells and perform medical diagnosis, so it may has broad applications in the field of medicine.

GraphVAMPnets for uncovering slow collective variables of self-assembly dynamics.

Uncovering slow collective variables (CVs) of self-assembly dynamics is important to elucidate its numerous kinetic assembly pathways and drive the design of novel structures for advanced materials through the bottom-up approach. However, identifying the CVs for self-assembly presents several challenges. First, self-assembly systems often consist of identical monomers, and the feature representations should be invariant to permutations and rotational symmetries. Physical coordinates, such as aggregate size, lack high-resolution detail, while common geometric coordinates like pairwise distances are hindered by the permutation and rotational symmetry challenges. Second, self-assembly is usually a downhill process, and the trajectories often suffer from insufficient sampling of backward transitions that correspond to the dissociation of self-assembled structures. Popular dimensionality reduction methods, such as time-structure independent component analysis, impose detailed balance constraints, potentially obscuring the true dynamics of self-assembly. In this work, we employ GraphVAMPnets, which combines graph neural networks with a variational approach for Markovian process (VAMP) theory to identify the slow CVs of the self-assembly processes. First, GraphVAMPnets bears the advantages of graph neural networks, in which the graph embeddings can represent self-assembly structures in high-resolution while being invariant to permutations and rotational symmetries. Second, it is built upon VAMP theory, which studies Markov processes without forcing detailed balance constraints, which addresses the out-of-equilibrium challenge in the self-assembly process. We demonstrate GraphVAMPnets for identifying slow CVs of self-assembly kinetics in two systems: the aggregation of two hydrophobic molecules and the self-assembly of patchy particles. We expect that our GraphVAMPnets can be widely applied to molecular self-assembly.

An Efficient Path Classification Algorithm Based on Variational Autoencoder to Identify Metastable Path Channels for Complex Conformational Changes.

Conformational changes (i.e., dynamic transitions between pairs of conformational states) play important roles in many chemical and biological processes. Constructing the Markov state model (MSM) from extensive molecular dynamics (MD) simulations is an effective approach to dissect the mechanism of conformational changes. When combined with transition path theory (TPT), MSM can be applied to elucidate the ensemble of kinetic pathways connecting pairs of conformational states. However, the application of TPT to analyze complex conformational changes often results in a vast number of kinetic pathways with comparable fluxes. This obstacle is particularly pronounced in heterogeneous self-assembly and aggregation processes. The large number of kinetic pathways makes it challenging to comprehend the molecular mechanisms underlying conformational changes of interest. To address this challenge, we have developed a path classification algorithm named latent-space path clustering (LPC) that efficiently lumps parallel kinetic pathways into distinct metastable path channels, making them easier to comprehend. In our algorithm, MD conformations are first projected onto a low-dimensional space containing a small set of collective variables (CVs) by time-structure-based independent component analysis (tICA) with kinetic mapping. Then, MSM and TPT are constructed to obtain the ensemble of pathways, and a deep learning architecture named the variational autoencoder (VAE) is used to learn the spatial distributions of kinetic pathways in the continuous CV space. Based on the trained VAE model, the TPT-generated ensemble of kinetic pathways can be embedded into a latent space, where the classification becomes clear. We show that LPC can efficiently and accurately identify the metastable path channels in three systems: a 2D potential, the aggregation of two hydrophobic particles in water, and the folding of the Fip35 WW domain. Using the 2D potential, we further demonstrate that our LPC algorithm outperforms the previous path-lumping algorithms by making substantially fewer incorrect assignments of individual pathways to four path channels. We expect that LPC can be widely applied to identify the dominant kinetic pathways underlying complex conformational changes.

PAS Domain-Containing Chemoreceptors Influence the Signal Sensing and Intestinal Colonization of Vibrio cholerae.

Bacterial chemotaxis is the phenomenon in which bacteria migrate toward a more favorable niche in response to chemical cues in the environment. The methyl-accepting chemotaxis proteins (MCPs) are the principal sensory receptors of the bacterial chemotaxis system. Aerotaxis is a special form of chemotaxis in which oxygen serves as the signaling molecule; the process is dependent on the aerotaxis receptors (Aer) containing the Per-Arnt-Sim (PAS) domain. Over 40 MCPs are annotated on the genome of Vibrio cholerae; however, little is known about their functions. We investigated six MCPs containing the PAS domain in V. cholerae El Tor C6706, namely aer2, aer3, aer4, aer5, aer6, and aer7. Deletion analyses of each aer homolog gene indicated that these Aer receptors are involved in aerotaxis, chemotaxis, biofilm formation, and intestinal colonization. Swarming motility assay indicated that the aer2 gene was responsible for sensing the oxygen gradient independent of the other five homologs. When bile salts and mucin were used as chemoattractants, each Aer receptor influenced the chemotaxis differently. Biofilm formation was enhanced by overexpression of the aer6 and aer7 genes. Moreover, deletion of the aer2 gene resulted in better bacterial colonization of the mutant in adult mice; however, virulence gene expression was unaffected. These data suggest distinct roles for different Aer homologs in V. cholerae physiology.

DNA Dendrimer-Based Directed 3D Walking Nanomachine for the Sensitive Detection and Intracellular Imaging of miRNA.

Taking advantage of the remarkable processivity and membrane penetrability, the gold nanoparticle (AuNP)-based three-dimensional (3D) DNA walking nanomachine has induced tremendous promise in molecular diagnostics and cancer therapy, whereas the executive ability of this nanomachine was eventually limited because of the disordered assembly between the walker and the track. Therefore, we developed a well-directed 3D DNA walking nanomachine by employing a DNA dendrimer as the track for intracellular imaging with high directionality and controllability. The nanomachine was constructed on a DNA dendrimer decorated with a substrate strand serving as the DNA track and a DNAzyme restrained by a locking strand as the walker. In this system, the distribution of the substrate strand and DNAzyme on the DNA dendrimer could be precisely regulated to achieve expected goals because of the specificity and predictability of the Watson-Crick base pairing, paving an explicit route for each walker to move along the track. Moreover, such a DNA dendrimer-based nanomachine owned prominent stability and anti-interference ability. By choosing microRNA-21 as a model analyte, the nanomachine was applied for the imaging of microRNA-21 in different cell lines and the monitoring of the dynamic microRNA-21 expression level in cancer cells. Therefore, we believe that this directed DNA walking nanomachine will have a variety of applications in molecular diagnostics and biological function modulation.

Symmetrical indoor visible light layout optimized by a modified grey wolf algorithm.

The indoor visible light communication system's LED layout and power factor affect the uniformity of the received power. To reduce the mean square error (MSE) of received power, a symmetrical optimization strategy based on the modified grey wolf optimization algorithm (mGWO) is proposed and applied in the square, rectangular, and circular rooms with different numbers of LED arrays. The received power uniformity, SNR uniformity, bit error rate, and channel capacity of the optimized layout with the proposed method are improved compared to the classical layout. The comparison results show that the mGWO can find the optimal layout efficiently.

Impact of atmospheric thermodynamic structures and aerosol radiation feedback on winter regional persistent heavy particulate pollution in the Sichuan-Chongqing region, China.

Potential relationships among heavy air pollution, weather conditions, and meteorological effects are unclear and require further investigation, especially for areas with complex terrains, such as the Sichuan Basin (SCB), one of the most polluted regions in China. In this study, air pollution in the SCB was examined and 18 regional persistent heavy pollution events (RPHEs) were identified for the winters of 2014-2018. The average persistent period of the RPHEs was 8.89 days, and the number of affected cities was 17. Based on ground-based observations, CALIPSO satellite data, reanalysis data, and backward trajectory calculations, the synergistic effects of the thermodynamic structures, synoptic circulations and the radiative feedback of aerosols on the formation of RPHEs were revealed. The results can be summarized as follows: (1) An abnormal warming center, attributing to the warm southerly advection in the upper layer and the cold air dammed by the topography near the surface, always presented around 800-700 hPa to form a deep stable layer. (2) The diurnal variations in vertical motions triggered by the thermodynamic structures could regulate the pollution episodes. During the daytime, pollutants accumulated rapidly and thoroughly mixed under the control of sinking airflow from 800 hPa layer to the ground. At night, pollutants sometimes slowly diffused when weak ascending airflow appeared. (3) Forced by the stable layer and topography of the Tibetan Plateau, the local circulation was confined within SCB, resulting in the intensive mixing of local emissions and transport pollutants from other regions. This situation could be maintained for a long time with stable synoptic circulation in winter, leading to the formation of RPHEs. (4) The pollution episodes were featured with multi-layer pollutants above SCB according to the CALIPSO observations, including the local anthropogenic aerosols near the surface, dust aerosols originating from the Taklamakan Desert, and biomass burning aerosols from Southeast Asia. Solar absorption aerosols, including black carbon and dust above the region, could cause meteorological feedback, making the vertical layer more stable and enhancing the persistence and intensity of the pollution episodes. This study highlights the appreciable effects of synoptic circulations on the vertical thermodynamic structures of the atmosphere and air quality, and raises the understanding of the environmental and climate impacts of RPHEs in complex terrains.

Regorafenib combined with transarterial chemoembolization for unresectable hepatocellular carcinoma: a real-world study.

BACKGROUND: The benefits and tolerability of transarterial chemoembolization (TACE) combined with regorafenib as a second-line therapy has not been reported for unresectable hepatocellular carcinoma (HCC). This study aimed to explore the benefits and tolerability of TACE combined with second-line regorafenib in patients with unresectable advanced HCC and failure to first-line treatment. METHODS: This was a multicenter retrospective study of patients with progression after first-line sorafenib and/or lenvatinib between 01/2019 and 04/2020 at four tertiary hospitals in China. The patients were treated with TACE. Then, 5-7 days after the first TACE, the patients started taking regorafenib for 3 weeks every 4-week cycle. The overall survival (OS), time to progression (TTP), progression-free survival (PFS), and adverse events (AEs) were observed. RESULTS: The median follow-up was 5.6 (range 0.7, 17.0) months. The median age was 60 (range 35, 79) years. There were 32 (84.2%) males. The patients underwent a median of three TACE sessions (range 1-13). The initial doses of regorafenib were 20 mg/d (n = 1, 2.6%), 80 mg/d (n = 10, 26.3%), 120 mg/d (n = 15, 39.5%), and 160 mg/d (n = 11, 28.9%). The incidence of grade 3/4 AEs was 15.8%. Two patients stopped regorafenib due to AEs. The median OS was 14.3 months. The median PFS and TTP were 9.1 (95% CI 4.0, 14.2) and 9.1 (95% CI 5.5, 12.8) months, respectively. CONCLUSIONS: The present study provides real-world evidence indicating that regorafenib combined with TACE was beneficial and tolerable in patients with unresectable HCC. Additional prospective large-scale studies are required for confirmation.

Composite prescribed performance control of small unmanned aerial vehicles using modified nonlinear disturbance observer.

An integrated control scheme composed of modified nonlinear disturbance observer and predefined-time prescribed performance control is proposed to address the high-accuracy tracking problem of the unmanned aerial vehicles (UAVs) subjected to external mismatched disturbances. By utilizing the transformation technique that incorporates the desired performance characteristic and the newly predefined-time performance function, the original controlled system can be transformed into a new unconstrained one to achieve the fixed-time convergence of the tracking error. Then, by virtual of the transformed unconstrained system, a modified nonlinear disturbance observer (NDO) which possesses fast convergence speed is established to estimate the external disturbance. With the application of the precise estimation value to compensate the normal control design in each back-stepping step, a novel composite control scheme is constructed. The light spot of the proposed scheme is that it not only has the superior capability to attenuate unknown mismatched disturbances, but also can guarantee that the output tracking errors converge to their prescribed regions within predefined time. Finally, simulation studies verify the effectiveness of the proposed control scheme.

Hydrodynamics and water quality of the Hongze Lake in response to human activities.

The hydrodynamics and water quality of a lake in response to human activities is an important yet poorly understood issue. In this study, the responses of flow field, water level, and water quality of the Hongze Lake to changes in land use, project operation, and pollution accident were investigated using the 2D hydrodynamic model, water quality model, and hydrological model. The results show that project operations have more significant effects on the hydrodynamics and water quality of the Hongze Lake than changes in land use. In addition, the construction and operation of various water conservancy projects could increase pollutant diffusion and water exchange, thus contributing to improve the water quality of the Hongze Lake, but there is a need to solve the problem of rising water level in the Lihe depression lake area. The increase of urban and farmland area can significantly affect the flow of the Hongze Lake that could increase the flood risk. The simulations of the loosely coupled model imply that the coupling among the hydrodynamic model, water quality model, and SWAT model for the lake basin is feasible. Furthermore, a model based on the space grid was proposed in the study and combined with the verified loosely coupled model to assess the flood risk in the Hongze Lake, which could improve water resources and flood retarding basin operations.

Advances in Artificial Layers for Stable Lithium Metal Anodes.

Lithium (Li) metal is considered as the most promising anode material for rechargeable high-energy batteries. Nevertheless, the practical implement of Li anodes is significantly hindered by the growth of Li dendrites, which can cause severe safety issues. To inhibit the formation of Li dendrites, coating an artificial layer on the Li metal anode has been shown to be a facile and effective approach. This review mainly focuses on recent advances in artificial layers for stable Li metal anodes. It summarizes the progress in this area and discusses the different types of artificial layers according to their mechanisms for Li dendrite inhibition, including regulation of uniform deposition of Li metal and suppression of Li dendrite growth. By doing this, it is hoped that this contribution will provide instructional guidance for the future design of new artificial layers.

Optimal coordination-site exposure engineering in porous platinum for outstanding oxygen reduction performance.

In this study, we report that optimal coordination-site exposure engineering in porous platinum brings ultrahigh activity and durability for the fuel cell oxygen reduction reaction (ORR). The porous platinum with numerous grain boundaries (GBP-Pt) consisting of 3 nm crystals exhibits 7 times higher ORR activity than commercial Pt. For fuel-cell measurements, the GBP-Pt catalyst based MEA exhibits high power density (1.49 W cm-2, 0.71 A mg-1 Pt for mass activity) and stability (12.9% loss after 30 K cycles), all of which far surpass the U.S. DOE target in 2020 (0.44 A mg-1 Pt for mass activity and 40% loss for stability). Density Functional Theory (DFT) calculation and X-ray Absorption Fine Structure (XAFS) results suggest that proper Pt coordination site exposure in grain boundaries provides optimal adsorption energies for oxygen species and high stability in the ORR, even superior to Pt(111) sites. We anticipated that coordination-site exposure engineering would open a new avenue to offer robust electrocatalysts for the fuel-cell oxygen reduction reaction.

Effects of group size and rank on mother-infant relationships and reproductive success in rhesus macaques (Macaca mulatta).

In the present study, we compared mother-infant relationships in 57 mother-infant dyads residing in two wild, semi-provisioned (22 mother-infant dyads in 2014, 35 dyads in 2015) groups of rhesus macaques (Macaca mulatta) in the Nanwan Nature Reserve for Rhesus Macaques, Hainan, China. We also compared reproductive success between these two groups. The ecology and provisioning regime for each group was similar. These groups differed however, in size. Group 1 contained ∼35 individuals and Group 2 contained ∼120 individuals. Data were collected over a 2-year period (2014-2015). We found that during the birth season, mother-infant relationships in the larger group were characterized by less time in contact and more time separated than in the smaller group. Mothers in the smaller group initiated more contact and proximity with their infants. During the mating season when infants were approximately 6 months old, mother-infant relationships in the smaller group were more rejecting. We also found that birth rates were significantly higher but infant survivorship (to 1-year-old) was significantly lower in the smaller group. Moreover, higher-ranking mothers in the larger group were characterized by a higher reproductive output than females of lower rank. In the smaller group, female rank did not affect reproductive output. There was, however, no clear relationship between infant survivorship and maternal rank. We hypothesize that differences in reproductive success and changes in mother-infant relationships between the birth and mating seasons reflect differences in the costs and benefits of group size: females in the larger group faced (i) higher intragroup feeding competition leading to a reduction in birth rate but also (ii) lower predation risk, resulting in higher infant survival rate compared to females in the smaller group. The results of this study point to the tradeoffs that primate females face in living in smaller and larger social groups.

Coating with spermine-pullulan polymer enhances adenoviral transduction of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are adult stem cells with multilineage potential, which makes them attractive tools for regenerative medicine applications. Efficient gene transfer into MSCs is essential not only for basic research in developmental biology but also for therapeutic applications involving gene-modification in regenerative medicine. Adenovirus vectors (Advs) can efficiently and transiently introduce an exogenous gene into many cell types via their primary receptors, the coxsackievirus and adenovirus receptors, but not into MSCs, which are deficient in coxsackievirus and adenovirus receptors expression. To overcome this problem, we developed an Adv coated with a spermine-pullulan (SP) cationic polymer and investigated its physicochemical properties and internalization mechanisms. We demonstrated that the SP coating could enhance adenoviral transduction of MSCs without detectable cytotoxicity or effects on differentiation. Our results argue in favor of the potentiality of the SP-coated Adv as a prototype vector for efficient and safe transduction of MSCs.

Serum soluble mesothelin-related peptide (SMRP): a potential diagnostic and monitoring marker for epithelial ovarian cancer.

PURPOSE: To explore the potential and diagnostic performance of soluble mesothelin-related peptide (SMRP) as a tumor marker for epithelial ovarian cancer (EOC). METHODS: Sera were obtained from 78 EOC patients, 84 benign ovarian tumor patients, 58 healthy volunteers, and 22/78 EOC patients 1 week after surgery. SMRP levels and diagnostic performance were assessed by ELISA using the MESOMARK kit. The combination of SMRP and CA125 in the diagnosis of EOC was assessed. RESULTS: SMRP concentrations were higher in EOC patients than in benign tumor patients and healthy volunteers, and SMRP levels were shown to decrease in EOC patients after surgery. Histological EOC subtypes showed significant differences in SMRP levels. Stage III-IV patients had a higher level of SMRP than stage I-II patients (P < 0.001). Elevated SMRP levels were also found in higher grade tumors (P < 0.001). The receiver operating characteristic curve for SMRP was 0.891. The best statistical cut-off for SMRP was 1.3109 nM, with 0.821 sensitivity and 0.979 specificity. When compared with CA125, SMRP performed better in specificity, omission diagnostic rate, positive predictive value, and correction rate, but worse for sensitivity and negative predictive value. The combination of SMRP and CA125 gave a sensitivity of 98.4 % and a specificity of 88.9 %. CONCLUSION: Serum SMRP is a promising marker for the diagnosis and monitoring of EOC, especially in combination with CA125.