Scalable Fabrication of Ionic-Conductive Covalent Organic Framework Fibers for Capturing of Sustainable Osmotic Energy.

High-performance covalent organic framework (COF) fibers are demanded for an efficient capturing of blue osmotic power because of their excellent durability, simple integration, and large scalability. However, the scalable production of COF fibers is still very challenging due to the poor solubility and fragile structure of COFs. Herein, for the first time, it is reported that COF dispersions can be continuously processed into macroscopic, meter-long, and pure COF fibers using a wet spinning approach. The two presented COF fibers can be directly used for capturing of osmotic energy, avoiding the production of composite materials that require other additives and face challenges such as phase separation and environmental issues induced by the additives. A COF fiber exhibits power densities of 70.2 and 185.3 W m-2 at 50-fold and 500-fold salt gradients, respectively. These values outperform those of most reported systems, which indicate the high potential of COF fibers for capturing of blue osmotic energy.

A quantitative review of nature-based solutions for urban sustainability (2016-2022): From science to implementation.

Nature-based solutions (NBS) have great potential for achieving urban sustainability. While several reviews have comprehensively examined NBS, few have focused on its role in addressing urban sustainability challenges. Here we present a systematic review of 142 case studies selected from English papers published in SCI journals (i.e., indexed by Web of Science) during 2016-2022, whose titles, abstracts or keywords contain both urban-related terms and NBS-related terms. Using multiple methods, including statistical analysis, deductive content analysis, and inductive content analysis, we found that: (1) NBS have primarily been utilized to address urban flooding (43 %) and heat stress (21 %), with green roofs (24 %) and urban forests (16 %) being the most extensively studied NBS for tackling these challenges. (2) The ecosystem services (ES) capacity of NBS has been heavily researched (57 %), while studies addressing ES flows (7 %) and ES demand (18 %) are limited. (3) Most studies involved at least one NBS implementation process (83 %), but primarily focused on selecting and assessing NBS and related actions (66 %), with fewer studies on designing and implementing NBS and transferring & upscale NBS. We suggest that future research should contribute to the establishment of a checklist to assist in identifying which NBS types are effective in addressing specific urban sustainability challenges in varying contexts. Integrating the science and practice of NBS for urban sustainability is also crucial for advancing this field.

Flipped online teaching of histology and embryology with design thinking: design, practice and reflection.

BACKGROUND: Flexible hybrid teaching has become the new normal of basic medical education in the postepidemic era. Identifying ways to improve the quality of curriculum teaching and achieve high-level talent training is a complex problem that urgently needs to be solved. Over the course of the past several semesters, the research team has integrated design thinking (DT) into undergraduate teaching to identify, redesign and solve complex problems in achieving curriculum teaching and professional talent training objectives. METHODS: This study is an observational research. A total of 156 undergraduate stomatology students from Jining Medical University in 2021 were selected to participate in two rounds of online flipped teaching using the design thinking EDIPT (empathy, definition, idea, prototype, and test) method. This approach was applied specifically to the chapters on the respiratory system and female reproductive system. Data collection included student questionnaires, teacher-student interviews, and exam scores. GraphPad Prism software was used for data analysis, and the statistical method was conducted by multiple or unpaired t test. RESULTS: According to the questionnaire results, the flipped classroom teaching design developed using design thinking methods received strong support from the majority of students, with nearly 80% of students providing feedback that they developed multiple abilities during the study process. The interview results indicated that teachers generally believed that using design thinking methods to understand students' real needs, define teaching problems, and devise instructional design solutions, along with testing and promptly adjusting the effectiveness through teaching practices, played a highly positive role in improving teaching and student learning outcomes. A comparison of exam scores showed a significant improvement in the exam scores of the class of 2021 stomatology students in the flipped teaching chapters compared to the class of 2020 stomatology students, and this difference was statistically significant. However, due to the limitation of the experimental chapter scope, there was no significant difference in the overall course grades. CONCLUSION: The study explores the application of design thinking in histology and embryology teaching, revealing its positive impact on innovative teaching strategies and students' learning experience in medical education. Online flipped teaching, developed through design thinking, proves to be an effective and flexible method that enhances student engagement and fosters autonomous learning abilities.

Substantially reducing global PM2.5-related deaths under SDG3.9 requires better air pollution control and healthcare.

The United Nations' Sustainable Development Goal (SDG) 3.9 calls for a substantial reduction in deaths attributable to PM2.5 pollution (DAPP). However, DAPP projections vary greatly and the likelihood of meeting SDG3.9 depends on complex interactions among environmental, socio-economic, and healthcare parameters. We project potential future trends in global DAPP considering the joint effects of each driver (PM2.5 concentration, death rate of diseases, population size, and age structure) and assess the likelihood of achieving SDG3.9 under the Shared Socioeconomic Pathways (SSPs) as quantified by the Scenario Model Intercomparison Project (ScenarioMIP) framework with simulated PM2.5 concentrations from 11 models. We find that a substantial reduction in DAPP would not be achieved under all but the most optimistic scenario settings. Even the development aligned with the Sustainability scenario (SSP1-2.6), in which DAPP was reduced by 19%, still falls just short of achieving a substantial (≥20%) reduction by 2030. Meeting SDG3.9 calls for additional efforts in air pollution control and healthcare to more aggressively reduce DAPP.

ROCK1 inhibition improves wound healing in diabetes via RIPK4/AMPK pathway.

Refractory wounds are a severe complication of diabetes mellitus that often leads to amputation because of the lack of effective treatments and therapeutic targets. The pathogenesis of refractory wounds is complex, involving many types of cells. Rho-associated protein kinase-1 (ROCK1) phosphorylates a series of substrates that trigger downstream signaling pathways, affecting multiple cellular processes, including cell migration, communication, and proliferation. The present study investigated the role of ROCK1 in diabetic wound healing and molecular mechanisms. Our results showed that ROCK1 expression significantly increased in wound granulation tissues in diabetic patients, streptozotocin (STZ)-induced diabetic mice, and db/db diabetic mice. Wound healing and blood perfusion were dose-dependently improved by the ROCK1 inhibitor fasudil in diabetic mice. In endothelial cells, fasudil and ROCK1 siRNA significantly elevated the phosphorylation of adenosine monophosphate-activated protein kinase at Thr172 (pThr172-AMPKα), the activity of endothelial nitric oxide synthase (eNOS), and suppressed the levels of mitochondrial reactive oxygen species (mtROS) and nitrotyrosine formation. Experiments using integrated bioinformatics analysis and coimmunoprecipitation established that ROCK1 inhibited pThr172-AMPKα by binding to receptor-interacting serine/threonine kinase 4 (RIPK4). These results suggest that fasudil accelerated wound repair and improved angiogenesis at least partially through the ROCK1/RIPK4/AMPK pathway. Fasudil may be a potential treatment for refractory wounds in diabetic patients.

Nicotine-derived NNK promotes CRC progression through activating TMUB1/AKT pathway in METTL14/YTHDF2-mediated m6A manner.

Cigarette smoking substantially promotes tumorigenesis and progression of colorectal cancer; however, the underlying molecular mechanism remains unclear. Among 662 colorectal cancer patients, our investigation revealed a significant correlation between cigarette smoking and factors, such as large tumor size, poor differentiation, and high degree of invasion. Among the nicotine-derived nitrosamines, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) emerged as the most critical carcinogen, which significantly promoted the malignant progression of colorectal cancer both in vivo and in vitro. The results of methylated RNA immunoprecipitation and transcriptome sequencing indicated that NNK upregulated transmembrane and ubiquitin-like domain-containing protein 1 (TMUB1) via N6-adenosine methylation, which was regulated by methyltransferase-like 14 (METTL14) and YTH N6-methyladenosine RNA binding protein 2 (YTHDF2). Elevated TMUB1 levels were associated with a higher risk of cancer invasion and metastasis, leading to a high mortality risk in patients with colorectal cancer. Additionally, TMUB1 promoted lysine63-linked ubiquitination of AKT by interacting with AMFR, which led to the induction of malignant proliferation and metastasis in colorectal cancer cells exposed to NNK. In summary, this study provides a new insight, indicating that targeting TMUB1 expression via METTL14/YTHDF2 mediated N6-adenosine methylation may be a potential therapeutic and prognostic target for patients with colorectal cancer who smoke.

Local Electric Potential-Driven Nanofluidic Ion Transport for Ultrasensitive Biochemical Sensing.

Nanofluidic biosensors have been widely used for detection of analytes based on the change of system resistance before and after target-probe interactions. However, their sensitivity is limited when system resistance barely changes toward low-concentration targets. Here, we proposed a strategy to address this issue by means of target-induced change of local membrane potential under relatively unchanged system resistance. The local membrane potential originated from the directional diffusion of photogenerated carriers across nanofluidic biosensors and gated photoinduced ionic current signal before and after target-probe interactions. The sensitivity of such biosensors for the detection of biomolecules such as circulating tumor DNA (ctDNA) and lysozyme exceeds that of applying a traditional strategy by more than 3 orders of magnitude under unchanged system resistance. Such biosensors can specifically detect the small molecule biomarker in the blood sample between prostate cancer patients and healthy humans. The key advantages of such nanofluidic biosensors are therefore complementary to traditional nanofluidic biosensors, with potential applications in a point-of-care analytical tool.

Role of Outer Surface Probes on Bullet-Shaped Asymmetric Solid-State Nanochannels for Lysozyme Protein Sensing.

Artificial solid-state nanochannels featuring precise partitions present a highly promising platform for biomarker detection. While the significance of probes on the outer surface (POS) has been relatively overlooked in the past, our research highlights their crucial role in biosensing. Furthermore, the contribution of POS on the bullet-shaped asymmetric nanochannels has not been extensively explored until now. Here, we fabricated a series of bullet-shaped nanochannels, each featuring a distinct asymmetric structure characterized by different tip- and base-pore diameters. These nanochannels were further modified with explicit distributions at the inner wall (PIW), the outer surface (POS), and their combination (POS + PIW) for lysozyme sensing. The impact of diameters, structural asymmetry, and surface charge density on the sensing efficacy of POS and PIW was thoroughly examined through experimental investigations and numerical simulations. POS demonstrates great individual sensing performance for lysozyme within a broad concentration range, spanning from 10 nM to 1 mM. Furthermore, it improves the sensitivity when combined with PIW, particularly within the nanochannels featuring the smaller base-pore diameter, resulting in a 2-fold increase in sensing performance for POS + PIW compared to PIW at a concentration of 10 nM. These findings are substantiated by numerical simulations that closely align with the experimental parameters. The contributions of POS are notably amplified in the presence of smaller base pores and a higher degree of asymmetry within the bullet-shaped nanochannels. These findings elucidate the mechanism underlying the role of POS within bullet-shaped asymmetric nanochannels and open up new avenues for manipulating and enhancing the sensing efficiency.

Research trends and hotspots in exercise rehabilitation for coronary heart disease: A bibliometric analysis.

Exercise rehabilitation can improve the prognosis of patients with coronary heart disease. However, a bibliometric analysis of the global exercise rehabilitation for coronary heart disease (CHD) research topic is lacking. This study investigated the development trends and research hotspots in the field of coronary heart disease and exercise rehabilitation. CiteSpace software was used to analyze the literature on exercise therapy for CHD in the Web of Science Core Collection database. We analyzed the data of countries/institutions, journals, authors, keywords, and cited references. A total of 3485 peer-reviewed papers were found, and the number of publications on the topic has steadily increased. The most productive country is the USA (1125), followed by China (477) and England (399). The top 3 active academic institutions are Research Libraries UK (RLUK) (236), Harvard University (152), and the University of California System (118). The most commonly cited journals are Circulation (2596), The most commonly cited references are "Exercise-based cardiac rehabilitation for coronary heart disease" (75), Lavie CJ had published the most papers (48). World Health Organization was the most influential author (334 citations). The research frontier trends in this field are body composition, participation, and function. Research on the effects of physical activity or exercise on patients with CHD is a focus of continuous exploration in this field. This study provides a new scientific perspective for exercise rehabilitation and CHD research and gives researchers valuable information for detecting the current research status, hotspots, and emerging trends for further research.

OsNAC2 regulates seed dormancy and germination in rice by inhibiting ABA catabolism.

Seed dormancy and germination determine the beginning of the life cycle of plants, and the phytohormone ABA plays a crucial role in regulation of seed dormancy and germination. However, the upstream regulatory mechanism of ABA metabolism during dormancy releasing is still remain elusive. In this paper, we present a novel mechanism of OsNAC2 in controlling ABA metabolism and regulation of seed dormancy. OsNAC2 highly expressed during seed development and germination, and overexpression of OsNAC2 strengthened seed dormancy and suppressed germination. Moreover, exogenous phytohormone treatment showed that OsNAC2 acted upstream of GA signaling and downstream of ABA signaling. Additionally, overexpression of OsNAC2 inhibited ABA degradation and increased ABA content during early germination. Further molecular analysis revealed that OsNAC2 directly bound to the ABA metabolism genes promoter and inhibits their transcription in rice protoplasts. These finding could help us explain the genetic regulation mechanism of ABA metabolism during dormancy release and germination in rice.

Detection of Unfolded Cellular Proteins Using Nanochannel Arrays with Probe-Functionalized Outer Surfaces.

Nanochannel technology has emerged as a powerful tool for label-free and highly sensitive detection of protein folding/unfolding status. However, utilizing the inner walls of a nanochannel array may cause multiple events even for proteins with the same conformation, posing challenges for accurate identification. Herein, we present a platform to detect unfolded proteins through electrical and optical signals using nanochannel arrays with outer-surface probes. The detection principle relies on the specific binding between the maleimide groups in outer-surface probes and the protein cysteine thiols that induce changes in the ionic current and fluorescence intensity responses of the nanochannel array. By taking advantage of this mechanism, the platform has the ability to differentiate folded and unfolded state of proteins based on the exposure of a single cysteine thiol group. The integration of these two signals enhances the reliability and sensitivity of the identification of unfolded protein states and enables the distinction between normal cells and Huntington's disease mutant cells. This study provides an effective approach for the precise analysis of proteins with distinct conformations and holds promise for facilitating the diagnoses of protein conformation-related diseases.

Enzyme Regulating the Wettability of the Outer Surface of Nanochannels.

Functional probes not only at the inner wall but also at the outer surface of nanochannel systems could be used for the recognition and detection of biotargets. Despite the advancements, the current detection mechanisms are still mainly based on the surface charge variation. We proposed a strategy of using the variation of wettability on the outer surface of nanochannels for detecting a tumor marker, herein, exemplifying matrix metalloproteinase-2 (MMP-2). The outer surface of the nanochannels were modified with amphipathic peptide probe consisting of hydrophilic unit (CRRRR), MMP-2 cleavage unit (PLGLAG), and hydrophobic unit (Fn). After recognition of MMP-2, due to the release of hydrophobic unit, the hydrophilicity of the outer surface was expected to increase, thus leading to the increase of ion current. Furthermore, the number (n) of phenylalanine (F) in the hydrophobic unit was modulated from 2, 4, to 6. By lengthening the hydrophobic unit, the limit of detection for MMP-2 detection could reach 1 ng/mL (when n = 6) and improve by 50-fold (to n = 2). This nanochannel system was utilized to successfully detect the MMP-2 secreted from cells and demonstrated that the expression of MMP-2 was related to the cell cycle and exhibited the highest level in G1/S phase. This study proved that in addition to the surface charge, wettability regulation could also be utilized as a variation factor to broaden the design strategy of a probe on OS to achieve the detection of biotargets.

How does the temporal relationship between ecosystem services and human wellbeing change in space and time? Evidence from Inner Mongolian drylands.

Studies of the ecosystem services (ES) and human wellbeing (HWB) relationship have proliferated in recent decades, but few have examined how ES affect HWB over time in a region (i.e., the temporal ES-HWB relationship) and how this relationship varies between regions. Thus, this study was intended to address these questions using data from Inner Mongolia. We first quantified multiple indicators of ES and objective HWB from 1978 to 2019, and then quantified their temporal relationship with correlation analysis over the entire duration and during four development periods, respectively. Our results showed that, depending on the time periods of analysis, geographic locations, and indicators, the temporal ES-HWB relationship varied substantially in both correlation strength and directionality (r values ranged from -0.93 to +1). Specifically, food-related provisioning services and cultural services often showed significant positive relationships with income, consumption, and basic living needs (r values ranged from +0.43 to +1), but erratic relationships with equity, employment, and social relationships (r values ranged from -0.93 to +0.96). Also, the positive correlations between food-related provisioning services and HWB were generally weaker in the urbanized regions. Cultural services and HWB were more strongly correlated in later development periods, whereas the relationship between regulating services and HWB was quite variable in space and time. The variations in the relationship over different development periods may be attributable to changing environmental and socioeconomic conditions, while the variations between regions were likely due to spatial heterogeneity of influencing factors. Our findings have an important policy implication for Inner Mongolia and beyond: sustainable management based on the ES and HWB relationship must be temporally adaptive and spatially tailored.

A high-resolution transcriptomic atlas depicting nitrogen fixation and nodule development in soybean.

Although root nodules are essential for biological nitrogen fixation in legumes, the cell types and molecular regulatory mechanisms contributing to nodule development and nitrogen fixation in determinate nodule legumes, such as soybean (Glycine max), remain incompletely understood. Here, we generated a single-nucleus resolution transcriptomic atlas of soybean roots and nodules at 14 days post inoculation (dpi) and annotated 17 major cell types, including six that are specific to nodules. We identified the specific cell types responsible for each step in the ureides synthesis pathway, which enables spatial compartmentalization of biochemical reactions during soybean nitrogen fixation. By utilizing RNA velocity analysis, we reconstructed the differentiation dynamics of soybean nodules, which differs from those of indeterminate nodules in Medicago truncatula. Moreover, we identified several putative regulators of soybean nodulation and two of these genes, GmbHLH93 and GmSCL1, were as-yet uncharacterized in soybean. Overexpression of each gene in soybean hairy root systems validated their respective roles in nodulation. Notably, enrichment for cytokinin-related genes in soybean nodules led to identification of the cytokinin receptor, GmCRE1, as a prominent component of the nodulation pathway. GmCRE1 knockout in soybean resulted in a striking nodule phenotype with decreased nitrogen fixation zone and depletion of leghemoglobins, accompanied by downregulation of nodule-specific gene expression, as well as almost complete abrogation of biological nitrogen fixation. In summary, this study provides a comprehensive perspective of the cellular landscape during soybean nodulation, shedding light on the underlying metabolic and developmental mechanisms of soybean nodule formation.

Enzymatic Protein Immobilization on Amino-Functionalized Nanoparticles.

The immobilization of proteins on nanoparticles has received much attention in recent years. Among different approaches, enzymatic protein immobilization shows unique advantages because of its site-specific connection. OaAEP1 is a recently engineered peptide ligase which can specifically recognize an N-terminal GL residue (NH2-Gly-Leu) and a C-terminal NGL amino acid residue (Asn-Gly-Leu-COOH) and ligates them efficiently. Herein, we report OaAEP1-mediated protein immobilization on synthetic magnetic nanoparticles. Our work showed that OaAEP1 could mediate C-terminal site-specific protein immobilization on the amino-functionalized Fe3O4 nanoparticles. Our work demonstrates a new method for site-specific protein immobilization on nanoparticles.

Distributional environmental justice of residential walking space: The lens of urban ecosystem services supply and demand.

Urban ecosystem services (UES), as an important concept in nature-based solutions, can effectively mitigate adverse environmental burdens and have great potential in addressing environmental justice issues. However, few studies linking UES with environmental justice have considered both supply and demand sides of UES, particularly at the spatial scale of residential walking space. Against this backdrop, we investigated the distributional justice of supply and demand for urban cooling, flood mitigation, air purification, and outdoor recreation in residential walking spaces in Shanghai among socially vulnerable groups (i.e., elderly residents, children, females, low-income residents, no-hukou residents, and ethnic minorities). We found that (1) the UES supply of residential walking space was much lower than that of non-residential walking space, while the UES demand was much higher than that of non-residential walking space. (2) Higher proportions of ethnic minorities, no-hukou residents, and females in Shanghai were positively correlated with several UES demands but were not positively correlated with ES supply, indicating a higher possibility of unsatisfied UES demand for these disadvantaged groups. Future urban blue-green space planning should pay more attention to the spatial allocation of blue-green space, especially placing more blue-green space around residential walking spaces with high UES demand and with a high proportion of socially disadvantaged groups.

Pyruvate Dehydrogenase Kinase 2 Accelerates Endotoxin Shock by Promoting Mitogen-Activated Protein Kinase Activation.

Endotoxin shock remains one of the major causes of mortality worldwide. Pyruvate dehydrogenase kinase (PDK) 2 is an important regulatory enzyme involved in glucose metabolism. The purpose of this study was to determine the regulatory effect of PDK2 on LPS-induced endotoxin shock and explore the mechanisms in vivo and in vitro. Here, we showed that PDK2 contributed to Toll-like receptor (TLR)-mediated inflammation. Lipopolysaccharide (LPS) activation of TLR4 pathways resulted in PDK2 upregulation in macrophages and dendritic cells (DCs). PDK2 overexpression enhanced TLR4 signaling pathway activation, whereas downregulating PDK2 expression inhibited TLR4 signaling pathway activation. Pharmacological inhibition of PDK2 significantly decreased the mortality rate and alleviated pathological injury in the lungs and livers of LPS-challenged mice, while significantly suppressing proinflammatory cytokine production. Thus, we confirmed that PDK2 is involved in LPS-induced endotoxin shock by modulating TLR4-mitogen-activated protein kinase signaling and inducing the production of proinflammatory cytokines in macrophages and DCs. Our findings highlight the importance of PDK2 as a novel target to treat septic shock.

Belowground bud banks and land use change: roles of vegetation and soil properties in mediating the composition of bud banks in different ecosystems.

Introduction: Belowground bud banks play integral roles in vegetation regeneration and ecological succession of plant communities; however, human-caused changes in land use severely threaten their resilience and regrowth. Although vegetation attributes and soil properties mediate such anthropogenic effects, their influence on bud bank size and composition and its regulatory mechanisms under land use change have not been explored. Methods: We conducted a field investigation to examine impacts of land use change on bud bank size and composition, vegetation attributes, and soil properties in wetlands (WL), farmlands (FL), and alpine meadow (AM) ecosystems in Zhejiang Province, China. Results: Overall, 63 soil samples in close proximity to the vegetation quadrats were excavated using a shovel, and samples of the excavated soil were placed in plastic bags for onward laboratory soil analysis. The total bud density (1514.727 ± 296.666) and tiller bud density (1229.090 ± 279.002) in wetland ecosystems were significantly higher than in farmland and alpine meadow ecosystems [i.e., total (149.333 ± 21.490 and 573.647 ± 91.518) and tiller bud density (24.666 ± 8.504 and 204.235 ± 50.550), respectively]. While vegetation attributes critically affected bud banks in WL ecosystems, soil properties strongly influenced bud banks in farmland and alpine meadow ecosystems. In wetland ecosystems, total and tiller buds were predominantly dependent on soil properties, but vegetation density played a significant role in farmlands and alpine meadow ecosystems. Root sprouting and rhizome buds significantly correlated with total C in the top 0 - 10 cm layer of farmland and alpine meadow ecosystems, respectively, and depended mainly on soil properties. Discussion: Our results demonstrate that land use change alters bud bank size and composition; however, such responses differed among bud types in wetland, farmland, and alpine meadow ecosystems.

Inner Wall and Outer Surface Distinguished Solid-State Nanopores for Sensing.

Solid-state nanopores, inspired by biological nanopores, have the advantages of good mechanical properties, stability, and easy modification. They have attracted wide attention in the fields of sequencing, sensing, molecular sieving, nanofluidic devices, nanoelectrochemistry, and energy conversion. Because of the ion/molecule transport characteristic of the pore, the research on solid-state nanopores mainly focuses on the functional modification of its inner wall. In recent years, the outer surface of nanopores has also attracted the attention of researchers, and the functional elements on the outer surface have the functions of anti-interference and ionic signal enhancement. In this perspective, we review research progress of inner wall and outer surface distinguished solid-state nanopores, highlight their processing and advantages, summarize their functions and applications in sensing, and give insight into further research.