Nanofluidic ion transport holds high promise in bio‐sensing and energy conversion applications. However, smart nanofluidic devices with high ion flux and modulable ion transport capabilities remain ...to be realised. Herein, we demonstrate smart nanofluidic devices based on oriented two‐dimensional covalent organic framework (2D COF) membranes with vertically aligned nanochannel arrays that achieved a 2–3 orders of magnitude higher ion flux compared with that of conventional single‐channel nanofluidic devices. The surface‐charge‐governed ion conductance is dominant for electrolyte concentration up to 0.01 M. Moreover, owing to the customisable pH‐responsivity of imine and phenol hydroxyl groups, the COF‐DT membranes attained an actively modulable ion transport with a high pH‐gating on/off ratio of ≈100. The customisable structure and rich chemistry of COF materials will offer a promising platform for manufacturing nanofluidic devices with modifiable ion/molecular transport features.
We report smart nanofluidic devices based on oriented two‐dimensional covalent organic framework membranes that offer vertically aligned nanofluidic channel arrays, leading to an ultrahigh ion flux and pH‐gating nanofluidic transport.
•The ML-RSD model mitigates subjective judgment when assessing regional sustainability and drawing the brownfield redevelopment strategies.•This model employs machine learning algorithms to predict ...comprehensive evaluation ratings for regional development.•The primary drivers of sustainable development at the regional level encompass SDG1, SDG2, SDG3, SDG4, SDG6, SDG7, and SDG8.
Brownfield redevelopment and land sustainable management have many interconnected aspects, which could be evaluated by regional development. Most contaminated sites in Taiwan often lack comprehensive consideration during remediation for land reuse planning; therefore, they are operated independently from regional development. Regional development is a dynamic process; however, there is a research gap in understanding how regional development can serve as an incentive for brownfield redevelopment. This study established a model for assessing regional sustainability using machine learning (ML-RSD), that model used principal component analysis (PCA) and support vector machine (SVM) to predict the comprehensive evaluation rating of regional development at the township level and to explore the trends of regional governance sustainability. The results of ML-RSD that are compared to commonly used methods (driver-pressure-state-impact-response and entropy weight method) were consistent. Indicators such as the protection of vulnerable groups (SDG1), food security (SDG2), good health and well-being (SDG3), inclusive and equitable quality education (SDG4), environmental protection (SDG6), accessible and reliable energy (SDG7), and sustainable economic growth (SDG8) were identified as the main factors affecting regional development. Additionally, the model achieved an accuracy value exceeding 80%. Additionally, the results showed that there was no significant correlation between the delisted site (completed remediation) and regional development in southern Taiwan. The model underscored the overall lower comprehensive sustainable values for regions affected by inadequate land rehabilitation governance (SDG15). The results present that brownfield redevelopment strategies should enhance their effectiveness in land adaptation and integrating brownfield redevelopment with regional sustainable development is essential for it to become a win–win solution.
Nanofluidic membranes have been demonstrated as promising candidates for osmotic energy harvesting. However, it remains a long-standing challenge to fabricate high-efficiency ion-permselective ...membranes with well-defined channel architectures. Here, we demonstrate high-performance osmotic energy conversion membranes based on oriented two-dimensional covalent organic frameworks (COFs) with ultrashort vertically aligned nanofluidic channels that enabled efficient and selective ion transport. Experiments combined with molecular dynamics simulations revealed that exquisite control over channel orientation, charge polarity, and charge density contributed to high ion selectivity and permeability. When applied to osmotic energy conversion, a pair of 100 nm thick oppositely charged COF membranes achieved an ultrahigh output power density of 43.2 W m–2 at a 50-fold salinity gradient and up to 228.9 W m–2 for the Dead Sea and river water system. The achieved power density outperforms the state-of-the-art nanofluidic membranes, suggesting the great potential of oriented COF membranes in the fields of advanced membrane technology and energy conversion.
Abstract
The Chelonid herpesvirus 5 (ChHV5) infection possibly associated to the fibropapillomatosis (FP) disease in sea turtles worldwide remains largely unknown and limited studies have used ...serological approaches to detection of antibodies against ChHV5 in sea turtles with or without FP. We aimed to develop diagnostic platforms based on the viral glycoprotein B (gB) for ChHV5 infection. In this study, five recombinant sub-fragments of the gB protein were successfully expressed and subsequently served as antigens for both seroprevalence and antibody production. The results indicated that the five expressed proteins harbored antigenicity, shown by the results of using sera from sea turtles that were PCR-positive for ChHV5. Moreover, seropositive sea turtles were significantly associated with FP (p < 0.05). We further used the expressed protein to produce antibodies for immunohistochemical analysis, and found that the in-house-generated sera specifically stained FP lesions while normal epithelium tissues remained negative. Of major importance, the reactivity in the ballooning degeneration area was much stronger than that in other regions of the FP lesion/tumour, thus indicating ChHV5 viral activities. In summary, the developed serological test and specific anti-gB antibodies for IHC analysis could be applied for further understanding of epidemiological distributions of ChHV5 infection in sea turtles, and studies of ChHV5 pathogenesis.
Ever since the introduction of thrombolysis and the subsequent expansion of endovascular treatments for acute ischemic stroke, it remains to be identified why the actual outcomes are less favorable ...despite recanalization. Here, by high spatio-temporal resolution imaging of capillary circulation in mice, we introduce the pathological phenomenon of dynamic flow stalls in cerebral capillaries, occurring persistently in salvageable penumbra after reperfusion. These stalls, which are different from permanent cellular plugs of no-reflow, were temporarily and repetitively occurring in the capillary network, impairing the overall circulation like small focal traffic jams. In vivo microscopy in the ischemic penumbra revealed leukocytes traveling slowly through capillary lumen or getting stuck, while red blood cell flow was being disturbed in the neighboring segments under reperfused conditions. Stall dynamics could be modulated, by injection of an anti-Ly6G antibody specifically targeting neutrophils. Decreased number and duration of stalls were associated with improvement in penumbral blood flow within 2–24 h after reperfusion along with increased capillary oxygenation, decreased cellular damage and improved functional outcome. Thereby, dynamic microcirculatory stall phenomenon can be a contributing factor to ongoing penumbral injury and is a potential hyperacute mechanism adding on previous observations of detrimental effects of activated neutrophils in ischemic stroke.
Biological cell membranes can efficiently switch Na
/K
selectivity in response to external stimuli, but achieving analogous functions in a single artificial membrane is challenging. Here, we report ...highly crystalline covalent organic framework (COF) membranes with well-defined nanochannels and coordinative sites (i. e., amino acid) that act as ion-selective switches to manipulate Na
and K
transport. The ion selectivity of the COF membrane is dynamic and can be switched between K
-selective and Na
-selective in a single membrane by applying a pH stimulus. The experimental results combined with molecular dynamics simulations reveal that the switchable Na
/K
selectivity originates from the differentiated coordination interactions between ions and amino acids. Benefiting from the switchable Na
/K
selectivity, we further demonstrate the membrane potential switches by varying electrolyte pH, miming the membrane polarity reversal during neural signal transduction in vivo, suggesting the great potential of these membranes for in vitro biomimetic applications.
Metaplastic breast carcinoma (MpBC) typically consists of carcinoma of no special type (NST) with various metaplastic components. Although previous transcriptomic and proteomic studies have reported ...subtype-related heterogeneity, the intracase transcriptomic alterations between metaplastic components and paired NST components, which are critical for understanding the pathogenesis underlying the metaplastic processes, remain unclear.
Fifty-nine NST components and paired metaplastic components (spindle carcinomatous SPS, matrix-producing, rhabdoid RHA, and squamous carcinomatous SQC components) were microdissected from specimens obtained from 27 patients with MpBC for gene expression profiling using the NanoString Breast Cancer 360 Panel on a NanoString nCounter FLEX platform. BC360-defined signatures were scored using nSolver software.
Hierarchical clustering and principal component analysis revealed a heterogeneous gene expression profile (GEP) corresponding to the NST components, but the GEP of metaplastic components exhibited subtype dependence. Compared with the paired NST components, the SPS components demonstrated the upregulation of genes related to stem cells and epithelial-mesenchymal transition and displayed enrichment in claudin-low and macrophage signatures. Despite certain overlaps in the enriched functions and signatures between the RHA and SPS components, the specific differentially expressed genes differed. We observed the RHA-specific upregulation of genes associated with vascular endothelial growth factor signaling. The chondroid matrix-producing components demonstrated the upregulation of hypoxia-related genes and the downregulation of the immune-related MHC2 signature and the TIGIT gene. In the SQC components, TGF-β and genes associated with cell adhesion were upregulated. The differentially expressed genes among metaplastic components in the 22 MpBC cases with one or predominantly one metaplastic component clustered paired NST samples into clusters with correlation with their associated metaplastic types. These genes could be used to separate the 31 metaplastic components according to respective metaplastic types with an accuracy of 74.2%, suggesting that intrinsic signatures of NST may determine paired metaplastic type. Finally, the EMT activity and stem cell traits in the NST components were correlated with specimens displaying lymph node metastasis.
We presented the distinct transcriptomic alterations underlying metaplasia into specific metaplastic components in MpBCs, which contributes to the understanding of the pathogenesis underlying morphologically distinct metaplasia in MpBCs.
Obesity is associated with chronic, low-grade inflammation, which can disrupt homeostasis within tissue microenvironments. Given the correlation between obesity and relative risk of death from ...cancer, we investigated whether obesity-associated inflammation promotes metastatic progression. We demonstrate that obesity causes lung neutrophilia in otherwise normal mice, which is further exacerbated by the presence of a primary tumour. The increase in lung neutrophils translates to increased breast cancer metastasis to this site, in a GM-CSF- and IL5-dependent manner. Importantly, weight loss is sufficient to reverse this effect, and reduce serum levels of GM-CSF and IL5 in both mouse models and humans. Our data indicate that special consideration of the obese patient population is critical for effective management of cancer progression.
Aim
The study investigated the electroencephalography (EEG) functional connectivity (FC) profiles during rest and tasks of young children with attention deficit hyperactivity disorder (ADHD) and ...typical development (TD).
Methods
In total, 78 children (aged 5–7 years) were enrolled in this study; 43 of them were diagnosed with ADHD and 35 exhibited TD. Four FC metrics, coherence, phase‐locking value (PLV), pairwise phase consistency, and phase lag index, were computed for feature selection to discriminate ADHD from TD.
Results
The support vector machine classifier trained by phase‐locking value (PLV) features yielded the best performance to differentiate the ADHD from the TD group and was used for further analysis. In comparing PLVs with the TD group at rest, the ADHD group exhibited significantly lower values on left intrahemispheric long interelectrode lower‐alpha and beta as well as frontal interhemispheric beta frequency bands. However, the ADHD group showed higher values of central interhemispheric PLVs on the theta, higher‐alpha, and beta bands. Regarding PLV alterations within resting and task conditions, left intrahemispheric long interelectrode beta PLVs declined from rest to task in the TD group, but the alterations did not differ in the ADHD group. Negative correlations were observed between frontal interhemispheric beta PLVs and the Disruptive Behavior Disorder Rating Scale as rated by teachers.
Conclusions
These results, which complement the findings of other sparse studies that have investigated task‐related brain FC dynamics, particularly in young children with ADHD, can provide clinicians with significant and interpretable neural biomarkers for facilitating the diagnosis of ADHD.
Epithelial ovarian cancer (EOC) is usually diagnosed at an advanced stage and has poor prognosis. Theranostic agents are the current trend in drug development, but are lacking in EOC. YKL40 is ...predominantly expressed and involved in tumorigenesis in EOC. In this study, we developed a companion theranostic agent targeting YKL40. We measured YKL40 expression levels in ascites using ELISA and correlated them with the clinical outcomes of patients with EOC. We developed radionuclide labeled In-111/Lu-177-DTPA-YKL40 neutralizing antibodies and investigated their radiochemical purity, SPECT/CT imaging, bio-distribution, and therapeutic responses in ovarian cancer xenograft mice. We demonstrated that YKL40 expression levels in ascites were significantly higher in EOC patients with serous histological type, high tumor grade, advanced stage, tumor recurrence, chemoresistance, and tumor-related death. The radiochemical purity of In-111/Lu-177-DTPA-YKL40 neutralizing antibodies reached more than 90% after 24 h of labeling. SPECT/CT imaging showed significant accumulation of In-111-DTPA-YKL40 and Lu-177-DTPA-YKL40 antibodies at the tumor site of ovarian cancer xenograft mice 24 h after administration. Lu-177-DTPA-YKL40 antibodies significantly inhibited tumor growth in ovarian cancer xenograft mice. Our study indicated that In-111/Lu-177-DTPA-YKL40 neutralizing antibodies could be potential companion theranostic agents for patients with EOC.
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•High YKL40 levels in ascites were associated with poor prognosis of EOC patients.•The tomographic ability of In-111/Lu-177-DTPA-YKL40 antibodies in xenograft mice.•The tumor-suppressing ability of Lu-177-DTPA-YKL40 antibodies in xenograft mice.•In-111/Lu-177-DTPA-YKL40 antibodies are potential theranostic agents for EOC.
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