Worm Generator: A System for High-Throughput in Vivo Screening.

Large-scale screening of molecules in organisms requires high-throughput and cost-effective evaluating tools during preclinical development. Here, a novel in vivo screening strategy combining hierarchically structured biohybrid triboelectric nanogenerators (HB-TENGs) arrays with computational bioinformatics analysis for high-throughput pharmacological evaluation using Caenorhabditis elegans is described. Unlike the traditional methods for behavioral monitoring of the animals, which are laborious and costly, HB-TENGs with micropillars are designed to efficiently convert animals' behaviors into friction deformation and result in a contact-separation motion between two triboelectric layers to generate electrical outputs. The triboelectric signals are recorded and extracted to various bioinformation for each screened compound. Moreover, the information-rich electrical readouts are successfully demonstrated to be sufficient to predict a drug's identity by multiple-Gaussian-kernels-based machine learning methods. This proposed strategy can be readily applied to various fields and is especially useful in in vivo explorations to accelerate the identification of novel therapeutics.

Integrated assessment and prediction of ecological security in typical ecologically fragile areas.

In order to safeguard and restore ecological security in ecologically fragile regions, a regionally appropriate land use structure and ecological security pattern should be constructed. Previous ecological security research models for ecologically fragile areas are relatively homogenous, and it is necessary to establish a multi-modeling framework to consider integrated ecological issues. This study proposes a coupled "PLUS-ESI-Circuit Theory" framework for multi-scenario ecological security assessment of the Ningxia Hui Autonomous Region (NHAR). Firstly, the PLUS model was used to complete the simulation of four future development scenarios. Secondly, a new ecological security index (ESI) is constructed by synthesizing ecological service function, ecological health, and ecological risk. Finally, the Circuit Theory is applied to construct the ecological security pattern under multiple scenarios, and the optimization strategy of ecological security zoning is proposed. The results show that (1) from 2000 to 2030, the NHAR has about 80% of grassland and farmland. The built-up area is consistently growing. (2) Between 2000 and 2030, high ecological security areas are primarily located in Helan Mountain, Liupan Mountain, and the central part of NHAR, while the low ecological security areas are dominated by Shapotou District and Yinchuan City. (3) After 2010, the aggregation of high-security areas decreases, and the fragmentation of patches is obvious. Landscape fragmentation would increase under the economic development (ED) scenario and would be somewhat ameliorated by the ecological protection (EP) and balanced development (BD) scenarios. (4) The number of sources increases but the area decreases from 2000 to 2020. The quantity of ecological elements is on the rise. Ecological restoration and protection of this part of the country will improve its ecological security.

Land use and habitat quality change in the Yellow River Basin: A perspective with different CMIP6-based scenarios and multiple scales.

Studying the spatial distribution of land use/land cover (LULC) and habitat quality (HQ), influenced by both climate change and socio-economic factors, holds immense importance for fostering ecological sustainability. The previous scale setting was based on changes in granularity and division of spatial ranges, without considering the differences in land quantity structure and spatial expansion under different spatial ranges. Therefore, this study is based on climate and economic data at different spatial scales to determine the various land demands of provinces (YRB-P) and integration of provinces (YRB-I) in the Yellow River Basin, and to limit the expansion of LULC in corresponding regions. At the same time, we have also established three future scenarios representing different development speeds based on the latest path of shared socio-economic development in CMIP6. We found exhibit significant characteristics in ecological responses under combinations of different scales and scenarios. Shandong and Henan Provinces are the main gathering (38.7-41.7%, 24.1-26.5%) and expansion (68.54-85.99 × 102km2, 18.89-34.12 × 102km2) provinces of built-up land under the YRB-P scale, and their HQ (0.260-0.397) are significantly lower than the average HQ (0.619-0.654). Forest land, grassland, and high value regions of HQ show "45°" distribution at two scales, with high and low values clearly clustered (Moran's I is 0.5440-0.580). The HQ evolution region is larger and more dispersed at the YRB-P scale, but accumulates in local areas at the YRB-I scale. In addition, the highest and lowest HQ mean values appear under the low speed development scenario at the YRB-P scale (0.721) and the rapid development scenario at the YRB-I scale (0.689), respectively. This study helps decision-makers control different scales and development scenarios to improve the ecological level of the study area.

Sequencing-free Analysis of Multiple Methylations on Gene-Specific mRNAs.

RNA epigenetics is a new layer of mechanism to regulate gene expression, but limited techniques are available to profile the status of mRNA modifications. Here, we describe a molecule proximity-based technique for simultaneous analysis of multiple types of mRNA methylation with specific gene information in living cells. N6-methyladenosine (m6A) or N1-methyladenosine (m1A) modifications on multiple mRNAs can be individually or simultaneously analyzed. A chip fabricated with vertically aligned, high-aspect-ratio diamond nanoneedles was used to access the intracellular domain in a minimum-invasive format and to isolate the mRNAs out of the cell cytoplasm while keeping cells alive. In the subsequent on-chip analytical procedures, the isolated RNAs were encoded, amplified, and visualized to derive a quantitative measurement of the associated gene-specific m6A or m1A modifications. Notably, a proximity ligation approach was developed to resolve dual methylation on an individual mRNA segment. Using this method, we investigated the dynamics of mRNA methylation in mammalian cells under physical or chemical stimuli and showed that m6A and m1A in mRNAs are heavily involved in the cellular stress response. Our results also suggested the common existence of single m6A modification in the basigin (BSG) mRNA but a rare occurrence of m6A and m1A dual methylation in the same BSG transcript.

Mapping Drug-Induced Neuropathy through In-Situ Motor Protein Tracking and Machine Learning.

Chemotherapy can induce toxicity in the central and peripheral nervous systems and result in chronic adverse reactions that impede continuous treatment and reduce patient quality of life. There is a current lack of research to predict, identify, and offset drug-induced neurotoxicity. Rapid and accurate assessment of potential neuropathy is crucial for cost-effective diagnosis and treatment. Here we report dynamic near-infrared upconversion imaging that allows intraneuronal transport to be traced in real time with millisecond resolution, but without photobleaching or blinking. Drug-induced neurotoxicity can be screened prior to phenotyping, on the basis of subtle abnormalities of kinetic characteristics in intraneuronal transport. Moreover, we demonstrate that combining the upconverting nanoplatform with machine learning offers a powerful tool for mapping chemotherapy-induced peripheral neuropathy and assessing drug-induced neurotoxicity.

Biohybrid Triboelectric Nanogenerator for Label-Free Pharmacological Fingerprinting in Cardiomyocytes.

The development of new drugs requires high-throughput and cost-effective pharmacological assessment in relevant biological models. Here, we introduce a novel pharmacological screening platform that combines a biohybrid triboelectric nanogenerator (TENG) and informatic analysis for self-powered, noninvasive, and label-free biosensing in cardiac cells. The cyclic mechanical activity of functional cardiomyocytes is dynamically captured by a specially designed biohybrid TENG device and is analyzed by a custom-made machine learning algorithm to reveal distinctive fingerprints in response to different pharmacological treatment. The core of the TENG device is a multilayer mesh substrate with microscale-gapped triboelectric layers, which are induced to generate electrical outputs by the characteristic motion of cardiomyocytes upon pharmaceutical treatment. Later bioinformatic extraction from the recorded TENG signal is sufficient to predict a drug's identity and efficacy, demonstrating the great potential of this platform as a biocompatible, low-cost, and highly sensitive drug screening system.

Assessment of Waterbird Habitat Importance and Identification of Conservation Gaps in Anhui Province.

Wetlands are among the most important habitats of highly wetland-dependent waterbirds but are subject to ongoing habitat loss and degradation owing to intensified anthropogenic activities. The scarcity of human and natural resources makes effective habitat protection an important concern. Here, we aimed to investigate waterbird habitat protection methods for Anhui Province, China, a critical stopover and wintering area on the East Asian-Australasian Flyway that features rich wetland resources subject to significant habitat loss and degradation. We evaluated the status and importance of 306 wintering waterbird habitats and identified the key environmental influences and current protection gaps using the entropy weights method and generalized additive modeling. We found 73 important habitats for waterbirds in Anhui Province, which were classified into levels of importance (descending from I to V) according to the natural discontinuity method. Level I and Level II habitats were mainly located in the Yangtze River floodplain and Level IV habitats in the Huaihe River floodplain. The gap analysis showed that 42 important waterbird habitats had protection gaps, accounting for 57.53% of the total area. Waterbird habitat importance was significantly correlated with elevation, normalized vegetation index, lake area, and lake circumference but not with distance from roads or population density. The results of this study provide scientific information for waterbird habitat conservation planning, which is crucial for maintaining wetland ecosystem functions.

Perioperative management of bronchoscopy in a child patient with central core disease: A case report and literature review.

INTRODUCTION: We described the perioperative management of a child patient with central core disease for bronchoscopy with bronchoalveolar lavage. It is safe to avoid triggering agents (volatile anesthetics and succinylcholine) probably in preventing this appearance of malignant hyperthermia (MH). It is important to recognize potential complications and know how to prevent and manage them in patients with this condition. PRESENTATION OF CASE: A 5-year-old boy (weight: 8.8 kg; height: 63 cm) presented to the pediatric department after five days of intermittent fever (highest body temperature is 39.3 °C) and cough, and aggravation 1 day, meanwhile he had phlegm in throat but he couldn't cough out. The child was found to have motor retardation at his one-month-old physical examination, then genetic analysis showed central core disease. Bronchoscopy with bronchoalveolar lavage was performed for better treatment under the premise of symptomatic treatment. DISCUSSION: The patients with central core disease are particularly to develop malignant hyperthermia, so adequate precautions are in place to prevent and treat MH before anesthetic induction. The anesthesiologists need to make adequate preoperative anesthesia management strategies to ensure the safety of the child with central core disease for bronchoscopy with bronchoalveolar lavage. The child was discharged from the hospital one week after anti-inflammatory and anti-asthmatic treatment. CONCLUSION: We summarized the anesthetic precautions and management in patients with central core disease, meanwhile we offered some suggestions about anesthetic focus on bronchoscopy with bronchoalveolar lavage.

Integrated Ink Printing Paper Based Self-Powered Electrochemical Multimodal Biosensing (IFP-Multi ) with ChatGPT-Bioelectronic Interface for Personalized Healthcare Management.

Personalized healthcare management is an emerging field that requires the development of environment-friendly, integrated, and electrochemical multimodal devices. In this study, the concept of integrated paper-based biosensors (IFP-Multi ) for personalized healthcare management is introduced. By leveraging ink printing technology and a ChatGPT-bioelectronic interface, these biosensors offer ultrahigh areal-specific capacitance (74633 mF cm-2 ), excellent mechanical properties, and multifunctional sensing and humidity power generation capabilities. More importantly, the IFP-Multi devices have the potential to simulate deaf-mute vocalization and can be integrated into wearable sensors to detect muscle contractions and bending motions. Moreover, they also enable monitoring of physiological signals from various body parts, such as the throat, nape, elbow, wrist, and knee, and successfully record sharp and repeatable signals generated by muscle contractions. In addition, the IFP-Multi devices demonstrate self-powered handwriting sensing and moisture power generation for sweat-sensing applications. As a proof-of-concept, a GPT 3.5 model-based fine-tuning and prediction pipeline that utilizes recorded physiological signals through IFP-Multi is showcased, enabling artificial intelligence with multimodal sensing capabilities for personalized healthcare management. This work presents a promising and ecofriendly approach to developing paper-based electrochemical multimodal devices, paving the way for a new era of healthcare advancements.

A high-current hydrogel generator with engineered mechanoionic asymmetry.

Mechanoelectrical energy conversion is a potential solution for the power supply of miniaturized wearable and implantable systems; yet it remains challenging due to limited current output when exploiting low-frequency motions with soft devices. We report a design of a hydrogel generator with mechanoionic current generation amplified by orders of magnitudes with engineered structural and chemical asymmetry. Under compressive loading, relief structures in the hydrogel intensify net ion fluxes induced by deformation gradient, which synergize with asymmetric ion adsorption characteristics of the electrodes and distinct diffusivity of cations and anions in the hydrogel matrix. This engineered mechanoionic process can yield 4 mA (5.5 A m-2) of peak current under cyclic compression of 80 kPa applied at 0.1 Hz, with the transferred charge reaching up to 916 mC m-2 per cycle. The high current output of this miniaturized hydrogel generator is beneficial for the powering of wearable devices, as exemplified by a controlled drug-releasing system for wound healing. The demonstrated mechanisms for amplifying mechanoionic effect will enable further designs for a variety of self-powered biomedical systems.

Interpreting regional ecological security from perspective of ecological networks: a case study in Ningxia Hui Autonomous Region, China.

The rapid economic development and intense human activities have seriously restricted the sustainable development of ecology and the maintenance of ecosystem services. Ecological network can effectively connect fragmented habitats and is an important way to couple landscape structure, ecological process, and function. This study proposes a multimodel coupling framework to explore the ecological security status of Ningxia Hui Autonomous Region (NHAR) under different development scenarios from the perspective of ecological networks. The conclusions are as follows: (1) From 2000 to 2030, grassland and arable land were the main land types of NHAR. Grassland is the main expansion land type under the ecological land protection (ELP) scenario, while construction land is the main expansion land type in two other scenarios. (2) The main gather and change of the ecological sources occurred in the central region, and the ecological expansion should develop from the middle to the south. (3) The average area of ecological sources under BAU and RED scenarios is smaller than that under ELP scenario, and more ecological corridors are needed to connect. (4) The centrality of the ecological sources under the BAU scenario is generally high, but the ecological sources under ELP and RED scenarios have undergone spatial migration. In addition, the urbanization trend of NHAR is different under different scenarios, and more attention should be paid to the maintenance and protection of ecological networks in typical areas. This study can provide important reference for NHAR's ecological space planning and ecological protection policy formulation.

Self-Healing Electronics for Prognostic Monitoring of Methylated Circulating Tumor DNAs.

Methylated circulating DNAs (ctDNAs) have recently been reported as a promising biomarker for early cancer diagnostics, but limited tools are currently available for continuous and dynamic profiling of ctDNAs and their methylation levels, especially when such assays need to be conducted in point-of-care (POC) scenarios. Here, a self-healing bioelectronic patch (iMethy) is developed that combines transdermal interstitial fluid (ISF) extraction and field effect transistor-based (FET-based) biosensing for dynamic monitoring of methylated ctDNAs as a prognostic approach for cancer risk management. The projection micro-stereolithography-based 3D patterning of an Eutectic Gallium-Indium (EGaIn) circuit with an unprecedented 10 µm resolution enables the construction of self-healing EGaIn microfluidic circuits that remain conductive under 100% strain and self-healing under severe destruction. In combination with continuous transdermal ISF sampling of methylated ctDNAs, iMethy can detect ctDNAs as low as 10-16  m in cellular models and is capable of phenotypic analysis of tumor growth in rodent animals. As the first demonstration of a wearable device for real-time in vivo analysis of disease-indicative biomarkers, this proof-of-concept study well demonstrated the potential of the iMethy platform for cancer risk management based on dynamic transdermal surveillance of methylated ctDNAs via a painless and self-administrable procedure.

Discrete single-cell microRNA analysis for phenotyping the heterogeneity of acute myeloid leukemia.

Acute myeloid leukemia (AML) is a highly heterogenous cancer in hematopoiesis, and its subtype specification is greatly important in the clinical practice for AML diagnosis and prognosis. Increasing evidence has shown the association between microRNA (miRNA) phenotype and AML therapeutic outcomes, emphasizing the need for novel techniques for convenient, sensitive, and efficient miRNA profiling in clinical practices. Here, we describe a nanoneedle-based discrete single-cell microRNA profiling technique for multiplexed phenotyping of AML heterogeneity without the requirement of sequencing or polymerase chain reaction (PCR). In virtue of a biochip-based and non-destructive nature of the assay, the expression of nine miRNAs in large number of living AML cells can be simultaneously analyzed with discrete single-cell level information, thus providing a proof-of-concept demonstration of an AML subtype classifier based on the multidimensional miRNA data. We showed successful analysis of subtype-specific cellular composition with over 90% accuracy and identified drug-responsive leukemia subpopulations among a mixed suspension of cells modeling different AML subtypes. The adoption of machine learning algorithms for processing the large-scale nanoneedle-based miRNA data shows the potential for powerful prediction capability in clinical applications to assist therapeutic decisions. We believe that this platform provides an efficient and cost-effective solution to move forward the translational prognostic usage of miRNAs in AML treatment and can be readily and advantageously applied in analyzing rare patient-derived clinical samples.

Electrically switched underwater capillary adhesion.

Developing underwater adhesives that can rapidly and reversibly switch the adhesion in wet conditions is important in various industrial and biomedical applications. Despite extensive progresses, the manifestation of underwater adhesion with rapid reversibility remains a big challenge. Here, we report a simple strategy that achieves strong underwater adhesion between two surfaces as well as rapid and reversible detachment in on-demand manner. Our approach leverages on the design of patterned hybrid wettability on surfaces that selectively creates a spatially confined integral air shell to preserve the water bridge in underwater environment. The overall adhesion strength can be multiplied by introducing multiple air shells and rapidly broken by disturbing the integrity of the protective air shell in response to the applied voltage on two surfaces. Our design can be constructed on the flexible substrate with hybrid wettability, which can be applied to non-conductive substrates and adapted to more complicated morphologies, extending the choice of underlying materials.

Vascularized neural constructs for ex-vivo reconstitution of blood-brain barrier function.

Ex-vivo blood-brain barrier (BBB) model is of great value for studying brain function and drug development, but it is still challenging to engineer macroscale three-dimensional (3D) tissue constructs to recapitulate physiological and functional aspects of BBB. Here, we describe a delicate 3D vascularized neural constructs for ex-vivo reconstitution of BBB function. The tissue-engineered tissue construct is based on a multicomponent 3D co-culture of four types of cells, which typically exist in the BBB and were spatially defined and organized to mimic the in vivo BBB structure and function. A porous polycaprolactone/poly (d,l-lactide-co-glycolide) (PCL/PLGA) microfluidic perfusion system works as the vasculature network, which was made by freeze-coating a 3D-printed sacrificial template. Endothelial cells were seeded inside the channels of the network to form 3D interconnected blood vessels; while other types of cells, including pericytes, astrocytes, and neurons, were co-cultured in a collagen matrix wrapping the vasculature network to derive a vascularized neural construct that recapitulates in vivo BBB function with great complexity and delicacy. Using this model, we successfully reconstituted BBB function with parameters that are similar to the in vivo condition, and demonstrated the identification of BBB-penetrating therapeutics by examining the molecular delivery to neuronal cells when relevant biologic molecules were applied to the vasculature circulation system of the neural construct.

Self-propagating Combustion Triggered Synthesis of 3D Lamellar Graphene/BaFe12O19 Composite and Its Electromagnetic Wave Absorption Properties.

The synthesis of 3D lamellar graphene/BaFe12O19 composites was performed by oxidizing graphite and sequentially self-propagating combustion triggered process. The 3D lamellar graphene structures were formed due to the synergistic effect of the tremendous heat induced gasification as well as huge volume expansion. The 3D lamellar graphene/BaFe12O19 composites bearing 30 wt % graphene present the reflection loss peak at -27.23 dB as well as the frequency bandwidth at 2.28 GHz (< -10 dB). The 3D lamellar graphene structures could consume the incident waves through multiple Reflection and scattering within the layered structures, Prolonging the propagation path of electromagnetic waves in the absorbers.

Expanded graphite embedded with aluminum nanoparticles as superior thermal conductivity anodes for high-performance lithium-ion batteries.

The development of high capacity and long-life lithium-ion batteries is a long-term pursuing and under a close scrutiny. Most of the researches have been focused on exploring electrode materials and structures with high store capability of lithium ions and at the same time with a good electrical conductivity. Thermal conductivity of an electrode material will also have significant impacts on boosting battery capacity and prolonging battery lifetime, which is, however, underestimated. Here, we present the development of an expanded graphite embedded with Al metal nanoparticles (EG-MNPs-Al) synthesized by an oxidation-expansion process. The synthesized EG-MNPs-Al material exhibited a typical hierarchical structure with embedded Al metal nanoparticles into the interspaces of expanded graphite. The parallel thermal conductivity was up to 11.6 W·m-1·K-1 with a bulk density of 453 kg·m-3 at room temperature, a 150% improvement compared to expanded graphite (4.6 W·m-1·K-1) owing to the existence of Al metal nanoparticles. The first reversible capacity of EG-MNPs-Al as anode material for lithium ion battery was 480 mAh·g-1 at a current density of 100 mA·g-1, and retained 84% capacity after 300 cycles. The improved cycling stability and system security of lithium ion batteries is attributed to the excellent thermal conductivity of the EG-MNPs-Al anodes.