A three-dimensional liquid diode for soft, integrated permeable electronics.

Wearable electronics with great breathability enable a comfortable wearing experience and facilitate continuous biosignal monitoring over extended periods1-3. However, current research on permeable electronics is predominantly at the stage of electrode and substrate development, which is far behind practical applications with comprehensive integration with diverse electronic components (for example, circuitry, electronics, encapsulation)4-8. Achieving permeability and multifunctionality in a singular, integrated wearable electronic system remains a formidable challenge. Here we present a general strategy for integrated moisture-permeable wearable electronics based on three-dimensional liquid diode (3D LD) configurations. By constructing spatially heterogeneous wettability, the 3D LD unidirectionally self-pumps the sweat from the skin to the outlet at a maximum flow rate of 11.6 ml cm-2 min-1, 4,000 times greater than the physiological sweat rate during exercise, presenting exceptional skin-friendliness, user comfort and stable signal-reading behaviour even under sweating conditions. A detachable design incorporating a replaceable vapour/sweat-discharging substrate enables the reuse of soft circuitry/electronics, increasing its sustainability and cost-effectiveness. We demonstrated this fundamental technology in both advanced skin-integrated electronics and textile-integrated electronics, highlighting its potential for scalable, user-friendly wearable devices.

Mutations in CLCN6 as a Novel Genetic Cause of Neuronal Ceroid Lipofuscinosis in a Murine Model.

OBJECTIVE: The aim of this study was to explore the pathogenesis of CLCN6-related disease and to assess whether its Cl-/H+-exchange activity is crucial for the biological role of ClC-6. METHODS: We performed whole-exome sequencing on a girl with development delay, intractable epilepsy, behavioral abnormities, retinal dysfunction, progressive brain atrophy, suggestive of neuronal ceroid lipofuscinoses (NCLs). We generated and analyzed the first knock-in mouse model of a patient variant (p.E200A) and compared it with a Clcn6-/- mouse model. Additional functional tests were performed with heterologous expression of mutant ClC-6. RESULTS: We identified a de novo heterozygous p.E200A variant in the proband. Expression of disease-causing ClC-6E200A or ClC-6Y553C mutants blocked autophagic flux and activated transcription factors EB (TFEB) and E3 (TFE3), leading to autophagic vesicle and cholesterol accumulation. Such alterations were absent with a transport-deficient ClC-6E267A mutant. Clcn6E200A/+ mice developed severe neurodegeneration with typical features of NCLs. Mutant ClC-6E200A, but not loss of ClC-6 in Clcn6-/- mice, increased lysosomal biogenesis by suppressing mTORC1-TFEB signaling, blocked autophagic flux through impairing lysosomal function, and increased apoptosis. Carbohydrate and lipid deposits accumulated in Clcn6E200A/+ brain, while only lipid storage was found in Clcn6-/- brain. Lysosome dysfunction, autophagy defects, and gliosis were early pathogenic events preceding neuron loss. INTERPRETATION: CLCN6 is a novel genetic cause of NCLs, highlighting the importance of considering CLCN6 mutations in the diagnostic workup for molecularly undefined forms of NCLs. Uncoupling of Cl- transport from H+ countertransport in the E200A mutant has a dominant effect on the autophagic/lysosomal pathway. ANN NEUROL 2024;96:608-624.

A systematic study on the phase diagram and superconductivity of ternary clathrate Ca-Sc-H at high pressures.

This work explores potential high-temperature superconductor materials in hydrogen-rich systems. Here, the crystal structure stabilities of ternary Ca-Sc-H systems under high-pressure (P = 100-250 GPa) and their superconductivities are investigated using the particle swarm optimization methodology combined with first-principles calculations. For the predicted candidate structures of Ca-Sc-H systems, the pressure-dependent phase diagram and thermodynamic convex hull were investigated across a wide range of compositions; the electronic properties of all the predicted phases were analyzed in detail to study the bonding behavior of these stable phases. We identified the crystal structures of four thermodynamically stable compounds: R3̄m-CaScH6, Immm-CaSc2H9,C2/m-Ca2ScH10, and R3̄m-CaScH12. Among them, R3̄m-CaScH12 was predicted to have the highest Tc value (i.e., 173 K) at 200 GPa. The discovery of this previously unreported pressure-induced decomposition of Ca-Sc-H systems will pave the way for investigations on the nature of hydrogen-metal interactions.

Prediction and positioning of UWSN mobile nodes based on tidal motion model.

As the node positioning of underwater wireless sensor networks is easily affected by tidal motion, ocean current motion and multipath effect, the node positioning accuracy is low. In order to better improve the positioning accuracy of moving nodes of underwater wireless sensor networks, a method of locating mobile nodes of underwater wireless sensor based on tidal motion model is proposed. Firstly, the Time Difference of Arrival (TDOA) localization optimized by niche genetic algorithm is used to initialize each node. The integration of niche technology can effectively find multiple excellent solutions in the solution space, thus providing more abundant solution choices. This algorithm has excellent performance in multi-modal optimization problems, and can avoid the algorithm falling into local optimal solutions, so as to obtain more comprehensive optimization results. The simulation results show that the proposed algorithm has better positioning accuracy than the traditional Chan algorithm and Taylor algorithm. Then, each node is updated in real time by the optimized tidal movement model formula predicted by Kalman filter algorithm. The prediction algorithm is used to compare the real-time predicted update position of the node with the actual position. The positioning distance error of the prediction algorithm is also enough to meet the practical application requirements.

Cyanobacteria-cyanophage interactions between freshwater and marine ecosystems based on large-scale cyanophage genomic analysis.

The disparities in harmful algal blooms dynamics are largely attributed to variations in cyanobacteria populations within aquatic ecosystems. However, cyanobacteria-cyanophage interactions and their role in shaping cyanobacterial populations has been previously underappreciated. To address this knowledge gap, we isolated and sequenced 42 cyanophages from diverse water sources in China, with the majority (n = 35) originating from freshwater sources. We designated these sequences as the "Novel Cyanophage Genome sequence Collection" (NCGC). NCGC displayed notable genetic variations, with 95 % (40/42) of the sequences representing previously unidentified taxonomic ranks. By integrating NCGC with public data of cyanophages and cyanobacteria, we found evidence for more frequent historical cyanobacteria-cyanophage interactions in freshwater ecosystems. This was evidenced by a higher prevalence of prophage integrase-related genes in freshwater cyanophages (37.97 %) than marine cyanophages (7.42 %). In addition, freshwater cyanophages could infect a broader range of cyanobacteria orders (n = 4) than marine ones (n = 0). Correspondingly, freshwater cyanobacteria harbored more defense systems per million base pairs in their genomes, indicating more frequent phage infections. Evolutionary and cyanophage epidemiological studies suggest that interactions between cyanobacteria and cyanophages in freshwater and marine ecosystems are interconnected, and that brackish water can act as a transitional zone for freshwater and marine cyanophages. In conclusion, our research significantly expands the genetic information database of cyanophage, offering a wider selection of cyanophages to control harmful cyanobacterial blooms. Additionally, we represent a pioneering large-scale and comprehensive analysis of cyanobacteria and cyanophage sequencing data, and it provides theoretical guidance for the application of cyanophages in different environments.

Genetic polymorphism of IL-17 influences susceptibility to recurrent pregnancy loss in a Chinese population.

The current research aims to investigate the relationship between Interleukin-17 (IL-17) polymorphism and the risk of recurrent pregnancy loss (RPL) within a Chinese population. Totally, 120 patients with RPL were selected and enrolled as the experiment group. Additionally, 210 healthy individuals undergoing routine physical examinations during the same period served as the control group. The IL-17 gene polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism method. The IL-17 rs2275913 polymorphism exhibited 3 genotypes: GG, GA, and AA. Significant associations were observed with the AA genotype and A allele (all P < .05), indicating women with the AA genotype were 2.06 times more likely to experience RPL compared to those with the GG genotype. Similarly, women carrying the A allele faced a 1.63 times higher risk of RPL than those with the G allele. Regarding the IL-17 rs763780 polymorphism, which also presented 3 genotypes (TT, TC, CC), significant associations were noted for the CC genotype and C allele (all P < .05). Women with the CC genotype had a 1.84 times greater risk of suffering from RPL compared to those with the TT genotype, and those with the C allele were 1.51 times more likely to experience RPL than those with the T allele. The IL-17 rs2275913 and rs763780 polymorphisms contribute an increased risk to RPL in the Chinese population. Further studies, with larger sample sizes and more rigorous designs, are necessary to validate or replicate our current results.

Extracellular volume-based scoring system for tracking tumor progression in pancreatic cancer patients receiving intraoperative radiotherapy.

OBJECTIVES: To investigate the value of extracellular volume (ECV) derived from portal-venous phase (PVP) in predicting prognosis in locally advanced pancreatic cancer (LAPC) patients receiving intraoperative radiotherapy (IORT) with initial stable disease (SD) and to construct a risk-scoring system based on ECV and clinical-radiological features. MATERIALS AND METHODS: One hundred and three patients with LAPC who received IORT demonstrating SD were enrolled and underwent multiphasic contrast-enhanced CT (CECT) before and after IORT. ECV maps were generated from unenhanced and PVP CT images. Clinical and CT imaging features were analyzed. The independent predictors of progression-free survival (PFS) determined by multivariate Cox regression model were used to construct the risk-scoring system. Time-dependent receiver operating characteristic (ROC) curve analysis and the Kaplan-Meier method were used to evaluate the predictive performance of the scoring system. RESULTS: Multivariable analysis revealed that ECV, rim-enhancement, peripancreatic fat infiltration, and carbohydrate antigen 19-9 (CA19-9) response were significant predictors of PFS (all p < 0.05). Time-dependent ROC of the risk-scoring system showed a satisfactory predictive performance for disease progression with area under the curve (AUC) all above 0.70. High-risk patients (risk score ≥ 2) progress significantly faster than low-risk patients (risk score < 2) (p < 0.001). CONCLUSION: ECV derived from PVP of conventional CECT was an independent predictor for progression in LAPC patients assessed as SD after IORT. The scoring system integrating ECV, radiological features, and CA19-9 response can be used as a practical tool for stratifying prognosis in these patients, assisting clinicians in developing an appropriate treatment approach. CRITICAL RELEVANCE STATEMENT: The scoring system integrating ECV fraction, radiological features, and CA19-9 response can track tumor progression in patients with LAPC receiving IORT, aiding clinicians in choosing individual treatment strategies and improving their prognosis. KEY POINTS: Predicting the progression of LAPC in patients receiving IORT is important. Our ECV-based scoring system can risk stratifying patients with initial SD. Appropriate prognostication can assist clinicians in developing appropriate treatment approaches.

Prognostic performance of MRI LI-RADS version 2018 features and clinical-pathological factors in alpha-fetoprotein-negative hepatocellular carcinoma.

PURPOSE: To evaluate the role of the magnetic resonance imaging (MRI) Liver Imaging Reporting and Data System (LI-RADS) version 2018 features and clinical-pathological factors for predicting the prognosis of alpha-fetoprotein (AFP)-negative (≤ 20 ng/ml) hepatocellular carcinoma (HCC) patients, and to compare with other traditional staging systems. METHODS: We retrospectively enrolled 169 patients with AFP-negative HCC who received preoperative MRI and hepatectomy between January 2015 and August 2020 (derivation dataset:validation dataset = 118:51). A prognostic model was constructed using the risk factors identified via Cox regression analysis. Predictive performance and discrimination capability were evaluated and compared with those of two traditional staging systems. RESULTS: Six risk factors, namely the LI-RADS category, blood products in mass, microvascular invasion, tumor size, cirrhosis, and albumin-bilirubin grade, were associated with recurrence-free survival. The prognostic model constructed using these factors achieved C-index of 0.705 and 0.674 in the derivation and validation datasets, respectively. Furthermore, the model performed better in predicting patient prognosis than traditional staging systems. The model effectively stratified patients with AFP-negative HCC into high- and low-risk groups with significantly different outcomes (p < 0.05). CONCLUSION: A prognostic model integrating the LI-RADS category, blood products in mass, microvascular invasion, tumor size, cirrhosis, and albumin-bilirubin grade may serve as a valuable tool for refining risk stratification in patients with AFP-negative HCC.

A microfluidic chip platform based on Pt nanozyme and magnetized phage composite probes for dual-mode detecting and imaging pathogenic bacteria viability.

The detection of pathogen viability is critically important to evaluate its infectivity. In the study, an integrated microfluidic chip based on dual-mode analytical strategy was developed to rapidly realize detection of bacteria activity (with Salmonella typhimurium, S.T, as a model analyte). Firstly, the composite probes, including deactivated phage modified magnetic beads and nano Pt-antimicrobial peptide (AMP) which can specifically recognize Gram-negative bacteria as nanozyme were prepared. When the composite probes are introduced into the chip together with target bacteria, after enrichment, oscillating and magnetic separation, they will conjugate with S.T and produce a magnetic sandwich complex. The complex can catalyze tetramethylbenzidine (TMB)-H2O2 to produce visible colorimetric signals which is correspondent to the total S.T content. Simultaneously, PtNPs in the complex can produce hydroxyl radical oxidation (∙OH) by decomposing H2O2. Under the synergistic action of ∙OH and AMP, the captured live S.T can be lysed to release ATP and emit bioluminescence signals which corresponds to the live S.T concentration. Therefore, the chip can simultaneously detect and image S.T at different viability in one test. The dual-mode assay demonstrated high sensitivity (≤33 CFU/mL), high specificity (identifying strain), signal amplification (5 folds) and short time (≤40min). The chip array can detect four samples in one test and exhibited advantages of high-integration, -sensitivity, -specificity and miniaturization, which are suitable to rapidly detect and image pathogen's viability in trace level. The replacement of phage probes can detect other bacteria. It has a wide prospect in pathogens screening.

Boosting Thermoelectric Performance via Weakening Carrier-Phonon Coupling in BiCuSeO-Graphene Composites.

BiCuSeO is a promising oxygen-containing thermoelectric material due to its intrinsically low lattice thermal conductivity and excellent service stability. However, the low electrical conductivity limits its thermoelectric performance. Aliovalent element doping can significantly improve their carrier concentration, but it may also impact carrier mobility and thermal transport properties. Considering the influence of graphene on carrier-phonon decoupling, Bi0.88 Pb0.06 Ca0.06 CuSeO (BPCCSO)-graphene composites are designed. For further practical application, a rapid preparation method is employed, taking less than 1 h, which combines self-propagating high-temperature synthesis with spark plasma sintering. The incorporation of graphene simultaneously optimizes the electrical properties and thermal conductivity, yielding a high ratio of weighted mobility to lattice thermal conductivity (144 at 300 K and 95 at 923 K). Ultimately, BPCCSO-graphene composites achieve exceptional thermoelectric performance with a ZT value of 1.6 at 923 K, bringing a ≈40% improvement over BPCCSO without graphene. This work further promotes the practical application of BiCuSeO-based materials and this facile and effective strategy can also be extended to other thermoelectric systems.

ANXA9 facilitates S100A4 and promotes breast cancer progression through modulating STAT3 pathway.

Breast cancer has the highest global incidence and mortality rates among all cancer types. Abnormal expression of the Annexin family has been observed in different malignant tumors, including upregulated ANXA9 in breast cancer. We found highly expressed ANXA9 in metastatic breast cancer tissues, which is correlated with breast cancer progression. In vitro, the functional experiments indicated ANXA9 influenced breast cancer proliferation, motility, invasion, and apoptosis; in vivo, downregulation of ANXA9 suppressed breast cancer xenograft tumor growth and lung metastasis. Mechanically, on one side, we found that ANXA9 could mediate S100A4 and therefore regulate AKT/mTOR/STAT3 pathway to participate p53/Bcl-2 apoptosis; on the other side, we found ANXA9 transferred S100A4 from cells into the tumor microenvironment and mediated the excretion of cytokines IL-6, IL-8, CCL2, and CCL5 to participate angiogenesis via self- phosphorylation at site Ser2 and site Thr69. Our findings demonstrate significant involvement of ANXA9 in promoting breast cancer progression, thereby suggesting that therapeutic intervention via targeting ANXA9 may be effective in treating metastatic breast cancer.

Multiomics Analyses Identify AKR1A1 as a Biomarker for Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease. Because many genes associate with DKD, multiomics approaches were used to narrow the list of functional genes, gene products, and related pathways providing insights into the pathophysiological mechanisms of DKD. The Kidney Precision Medicine Project human kidney single-cell RNA-sequencing (scRNA-seq) data set and Mendeley Data on human kidney cortex biopsy proteomics were used. The R package Seurat was used to analyze scRNA-seq data and data from a subset of proximal tubule cells. PathfindR was applied for pathway analysis in cell type-specific differentially expressed genes and the R limma package was used to analyze differential protein expression in kidney cortex. A total of 790 differentially expressed genes were identified in proximal tubule cells, including 530 upregulated and 260 downregulated transcripts. Compared with differentially expressed proteins, 24 genes or proteins were in common. An integrated analysis combining protein quantitative trait loci, genome-wide association study hits (namely, estimated glomerular filtration rate), and a plasma metabolomics analysis was performed using baseline metabolites predictive of DKD progression in our longitudinal Diabetes Heart Study samples. The aldo-keto reductase family 1 member A1 gene (AKR1A1) was revealed as a potential molecular hub for DKD cellular dysfunction in several cross-linked pathways featured by deficiency of this enzyme.

Mammalian PIWI-piRNA-target complexes reveal features for broad and efficient target silencing.

The PIWI-interacting RNA (piRNA) pathway is an adaptive defense system wherein piRNAs guide PIWI family Argonaute proteins to recognize and silence ever-evolving selfish genetic elements and ensure genome integrity. Driven by this intensive host-pathogen arms race, the piRNA pathway and its targeted transposons have coevolved rapidly in a species-specific manner, but how the piRNA pathway adapts specifically to target silencing in mammals remains elusive. Here, we show that mouse MILI and human HILI piRNA-induced silencing complexes (piRISCs) bind and cleave targets more efficiently than their invertebrate counterparts from the sponge Ephydatia fluviatilis. The inherent functional differences comport with structural features identified by cryo-EM studies of piRISCs. In the absence of target, MILI and HILI piRISCs adopt a wider nucleic-acid-binding channel and display an extended prearranged piRNA seed as compared with EfPiwi piRISC, consistent with their ability to capture targets more efficiently than EfPiwi piRISC. In the presence of target, the seed gate-which enforces seed-target fidelity in microRNA RISC-adopts a relaxed state in mammalian piRISC, revealing how MILI and HILI tolerate seed-target mismatches to broaden the target spectrum. A vertebrate-specific lysine distorts the piRNA seed, shifting the trajectory of the piRNA-target duplex out of the central cleft and toward the PAZ lobe. Functional analyses reveal that this lysine promotes target binding and cleavage. Our study therefore provides a molecular basis for the piRNA targeting mechanism in mice and humans, and suggests that mammalian piRNA machinery can achieve broad target silencing using a limited supply of piRNA species.

Battery-free, wireless, and electricity-driven soft swimmer for water quality and virus monitoring.

Miniaturized mobile electronic system is an effective candidate for in situ exploration of confined spaces. However, realizing such system still faces challenges in powering issue, untethered mobility, wireless data acquisition, sensing versatility, and integration in small scales. Here, we report a battery-free, wireless, and miniaturized soft electromagnetic swimmer (SES) electronic system that achieves multiple monitoring capability in confined water environments. Through radio frequency powering, the battery-free SES system demonstrates untethered motions in confined spaces with considerable moving speed under resonance. This system adopts soft electronic technologies to integrate thin multifunctional bio/chemical sensors and wireless data acquisition module, and performs real-time water quality and virus contamination detection with demonstrated promising limits of detection and high sensitivity. All sensing data are transmitted synchronously and displayed on a smartphone graphical user interface via near-field communication. Overall, this wireless smart system demonstrates broad potential for confined space exploration, ranging from pathogen detection to pollution investigation.

An ingestible, battery-free, tissue-adhering robotic interface for non-invasive and chronic electrostimulation of the gut.

Ingestible electronics have the capacity to transform our ability to effectively diagnose and potentially treat a broad set of conditions. Current applications could be significantly enhanced by addressing poor electrode-tissue contact, lack of navigation, short dwell time, and limited battery life. Here we report the development of an ingestible, battery-free, and tissue-adhering robotic interface (IngRI) for non-invasive and chronic electrostimulation of the gut, which addresses challenges associated with contact, navigation, retention, and powering (C-N-R-P) faced by existing ingestibles. We show that near-field inductive coupling operating near 13.56 MHz was sufficient to power and modulate the IngRI to deliver therapeutically relevant electrostimulation, which can be further enhanced by a bio-inspired, hydrogel-enabled adhesive interface. In swine models, we demonstrated the electrical interaction of IngRI with the gastric mucosa by recording conductive signaling from the subcutaneous space. We further observed changes in plasma ghrelin levels, the "hunger hormone," while IngRI was activated in vivo, demonstrating its clinical potential in regulating appetite and treating other endocrine conditions. The results of this study suggest that concepts inspired by soft and wireless skin-interfacing electronic devices can be applied to ingestible electronics with potential clinical applications for evaluating and treating gastrointestinal conditions.

Thin, soft, 3D printing enabled crosstalk minimized triboelectric nanogenerator arrays for tactile sensing.

With the requirements of self-powering sensors in flexible electronics, wearable triboelectric nanogenerators (TENGs) have attracted great attention due to their advantages of excellent electrical outputs and low-cost processing routes. The crosstalk effect between adjacent sensing units in TENGs significantly limits the pixel density of sensor arrays. Here, we present a skin-integrated, flexible TENG sensor array with 100 sensing units in an overall size of 7.5 cm × 7.5 cm that can be processed in a simple, low-cost, and scalable way enabled by 3D printing. All the sensing units show good sensitivity of 0.11 V/kPa with a wide range of pressure detection from 10 to 65 kPa, which allows to accurately distinguish various tactile formats from gentle touching (as low as 2 kPa) to hard pressuring. The 3D printing patterned substrate allows to cast triboelectric layers of polydimethylsiloxane in an independent sensing manner for each unit, which greatly suppresses the cross talk arising from adjacent sensing units, where the maximum crosstalk output is only 10.8%. The excellent uniformity and reproducibility of the sensor array offer precise pressure mapping for complicated pattern loadings, which demonstrates its potential in tactile sensing and human-machine interfaces.