Atomic Dispersed Co on NC@Cu Core-Shells for Solar Seawater Splitting.

With freshwater resources becoming increasingly scarce, the photocatalytic seawater splitting for hydrogen production has garnered widespread attention. In this study, a novel photocatalyst consisting of a Cu core coated is introduced with N-doped C and decorated with single Co atoms (Co-NC@Cu) for solar to hydrogen production from seawater. This catalyst, without using noble metals or sacrificial agents, demonstrates superior hydrogen production effficiency of 9080 µmolg-1h-1, i.e., 4.78% solar-to-hydrogen conversion efficiency, and exceptional long-term stability, operating over 340 h continuously. The superior performance is attributed to several key factors. First, the focus-light induced photothermal effect enhances redox reaction capabilities, while the salt-ions enabled charge polarization around catalyst surfaces extends charge carrier lifetime. Furthermore, the Co─NC@Cu exhibits excellent broad light absorption, promoting photoexcited charge production. Theoretical calculations reveal that Co─NC acts as the active site, showing low energy barriers for reduction reactions. Additionally, the formation of a strong surface electric field from the localized surface plasmon resonance (LSPR) of Cu nanoparticles further reduces energy barriers for redox reactions, improving seawater splitting activity. This work provides valuable insights into intergrating the reaction environment, broad solar absorption, LSPR, and active single atoms into a core-shell photocatalyst design for efficient and robust solar-driven seawater splitting.

A splicing isoform of PD-1 promotes tumor progression as a potential immune checkpoint.

The immune checkpoint receptor, programmed cell death 1 (PD-1, encoded by PDCD1), mediates the immune escape of cancer, but whether PD-1 splicing isoforms contribute to this process is still unclear. Here, we identify an alternative splicing isoform of human PD-1, which carries a 28-base pairs extension retained from 5' region of intron 2 (PD-1^28), is expressed in peripheral T cells and tumor infiltrating lymphocytes. PD-1^28 expression is induced on T cells upon activation and is regulated by an RNA binding protein, TAF15. Functionally, PD-1^28 inhibits T cell proliferation, cytokine production, and tumor cell killing in vitro. In vivo, T cell-specific exogenous expression of PD-1^28 promotes tumor growth in both a syngeneic mouse tumor model and humanized NOG mice inoculated with human lung cancer cells. Our study thus demonstrates that PD-1^28 functions as an immune checkpoint, and may contribute to resistance to immune checkpoint blockade therapy.

N6-methyladenosine enhances the expression of TGF-ß-SMAD signaling family to inhibit cell growth and promote cell metastasis.

TGF-ß-SMAD signaling pathway plays an important role in the progression of various cancers. However, posttranscriptional regulation such as N6-methyladenosine (m6A) of TGF-ß-SMAD signaling axis remains incompletely understood. Here, we reveal that insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) is low expression as well as associated with poor prognosis in clear cell renal cell carcinoma (ccRCC) patients and inhibits proliferation as well as promotes metastasis of ccRCC cells. Mechanistically, IGF2BP2 systematically regulates TGF-ß-SMAD signaling family, including TGF-ß1/2, TGF-ßR1/2 and SMAD2/3/4, through mediating their mRNA stability in an m6A-dependent manner. Furthermore, the functional effects of IGF2BP2 on ccRCC cells is mediated by TGF-ß-SMAD signaling downstream effector SMAD4, which is identified three m6A sites in 5'UTR and CDS. Our study establishes IGF2BP2-TGF-ß-SMAD axis as a new regulatory effector in ccRCC, providing new insights for developing novel therapeutic strategies.

Construction of scalable multi-channel DNA nanoplatform for the combined detection of ctDNA biomarkers of ovarian cancer.

Single-level biomarker detection has the limitation of insufficient accuracy in cancer diagnosis. Therefore, the strategy of developing highly sensitive, multi-channel biosensors for high-throughput ctDNA determination is critical to improve the accuracy of early diagnosis of clinical tumors. Herein, in order to achieve efficient detection of up to ten targets for early diagnosis of ovarian cancer, a DNA-nanoswitch-based multi-channel (DNA-NSMC) biosensor was built based on the multi-module catalytic hairpin assembly-mediated signal amplification (CHA) and toehold-mediated DNA strand displacement (TDSD) reaction. Only two different fluorescence signals were used as outputs, combined with modular segmentation strategy of DNA-nanoswitch-based reaction platform; the multi-channel detection of up to ten targets was successfully achieved for the first time. The experimental results suggest that the proposed biosensor is a promising tool for simultaneously detecting multiple biomarkers for the early diagnosis of ovarian cancer, offering new strategies for the early screening, diagnosis, and treatment not only for ovarian cancer but also for other cancers.

WSSV early protein WSSV004 enhances viral replication by suppressing LDH activity.

White spot syndrome virus (WSSV) is known to upregulate glycolysis to supply biomolecules and energy for the virus's replication. At the viral genome replication stage, lactate dehydrogenase (LDH), a glycolytic enzyme, shows increased activity without any increase in expression. In the present study, yeast 2-hybrid screening was used to identify WSSV proteins that interacted with LvLDH isoform 1 and 2, and these included the WSSV early protein WSSV004. The interaction between WSSV004 and LvLDH1/2 was confirmed by co-immunoprecipitation. Immunofluorescence showed that WSSV004 co-localized with LvLDH1/2 in the cytoplasm. dsRNA silencing experiments showed that WSSV004 was crucial for WSSV replication. However, although WSSV004 silencing led to the suppression of total LvLDH gene expression during the viral late stage, there was nevertheless a significant increase in LvLDH activity at this time. We also used affinity purification-mass spectrometry to identify cellular proteins that interact with WSSV004, and found a total of 108 host proteins and 3 WSSV proteins with which it potentially interacts. Bioinformatics analysis revealed that WSSV004 and its interacting proteins might be responsible for various biological pathways during infection, including vesicular transport machinery and RNA-related functions. Collectively, our study suggests that WSSV004 serves as a multifunctional modulator to facilitate WSSV replication.

DRAIC mediates hnRNPA2B1 stability and m6A-modified IGF1R instability to inhibit tumor progression.

Type 1 insulin-like growth factor receptor (IGF1R) plays an important role in cancer, however, posttranscriptional regulation such as N6-methyladenosine (m6A) of IGF1R remains unclear. Here, we reveal a role for a lncRNA Downregulated RNA in Cancer (DRAIC) suppress tumor growth and metastasis in clear cell Renal Carcinoma (ccRCC). Mechanistically, DRAIC physically interacts with heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) and enhances its protein stability by blocking E3 ligase F-box protein 11 (FBXO11)-mediated ubiquitination and proteasome-dependent degradation. Subsequently, hnRNPA2B1 destabilizes m6A modified-IGF1R, leading to inhibition of ccRCC progression. Moreover, four m6A modification sites are identified to be responsible for the mRNA degradation of IGF1R. Collectively, our findings reveal that DRAIC/hnRNPA2B1 axis regulates IGF1R mRNA stability in an m6A-dependent manner and highlights an important mechanism of IGF1R fate. These findings shed light on DRAIC/hnRNPA2B1/FBXO11/IGF1R axis as potential therapeutic targets in ccRCC and build a link of molecular fate between m6A-modified RNA and ubiquitin-modified protein.

Hierarchical Hollow Carbon Particles with Encapsulation of Carbon Nanotubes for High Performance Supercapacitors.

A novel and sustainable carbon-based material, referred to as hollow porous carbon particles encapsulating multi-wall carbon nanotubes (MWCNTs) (CNTs@HPC), is synthesized for use in supercapacitors. The synthesis process involves utilizing LTA zeolite as a rigid template and dopamine hydrochloride (DA) as the carbon source, along with catalytic decomposition of methane (CDM) to simultaneously produce MWCNTs and COx -free H2 . The findings reveal a distinctive hierarchical porous structure, comprising macropores, mesopores, and micropores, resulting in a total specific surface area (SSA) of 913 m2  g-1 . The optimal CNTs@HPC demonstrates a specific capacitance of 306 F g-1 at a current density of 1 A g-1 . Moreover, this material demonstrates an electric double-layer capacitor (EDLC) that surpasses conventional capabilities by exhibiting additional pseudocapacitance characteristics. These properties are attributed to redox reactions facilitated by the increased charge density resulting from the attraction of ions to nickel oxides, which is made possible by the material's enhanced hydrophilicity. The heightened hydrophilicity can be attributed to the presence of residual silicon-aluminum elements in CNTs@HPC, a direct outcome of the unique synthesis approach involving nickel phyllosilicate in CDM. As a result of this synthesis strategy, the material possesses excellent conductivity, enabling rapid transportation of electrolyte ions and delivering outstanding capacitive performance.

A combined bioinformatics and experimental approach identifies RMI2 as a Wnt/ß-catenin signaling target gene related to hepatocellular carcinoma.

BACKGROUND: The Wnt/ß-catenin signaling pathway plays an important role in embryogenesis and tumorigenesis. In human cancer, abnormal activity of Wnt/ß-catenin signaling pathway induces overexpressed of downstream genes, and initiate oncogene. There are several target genes known to be key players in tumorigenesis, such as c-myc, cyclin D1, MMPs or survivin. Therefore, identifying the target genes of Wnt/ß-catenin signaling pathway is important to understanding Wnt/ß-catenin-mediated carcinogenesis. In this study, we developed a combined bioinformatics and experimental approach to find potential target genes. METHODS: Luciferase reporter assay was used to analyze the promoter activity of RMI2. WST1 cell proliferation assays and transwell assays were performed to determine the proliferation and migration capacities of RMI2 overexpressing or knockdown stable hepatic cells. Finally, xenograft experiments were performed to measure the tumor formation capacity in vivo. RESULTS: The results showed that RMI2 mRNA was upregulated after LiCl treatment and Wnt3a-conditioned medium in a culture of SK-hep-1 cell lines. A chromatin immunoprecipitation (ChIP) assay showed that the ß-catenin/T cell-specific factor (TCF) complex binds to the putative TCF binding site of the RMI2 promoter. We then found a TCF binding site at - 333/- 326 of the RMI2 promoter, which is crucial for ß-catenin responsiveness in liver cell lines. RMI2 was overexpressed in hepatoma tissue and cell lines, and it promoted the migration and invasion of HCC cells. Moreover, RMI2 upregulated the expression of epithelial-mesenchymal transition (EMT) markers and the Wnt3a/ß-catenin-related genes, but silencing RMI2 had the opposite effects. Notably, the expression of RMI2 was positively correlated with the clinical data of HCC patients who had significantly shorter overall survival (OS) and disease-free survival (DFS) (Both: P < 0.05). In addition, a total of 373 HCC patients' data from the Caner Genome Atlas project (TCGA) were used to validate our findings. CONCLUSIONS: Taking all these findings together, we determined that RMI2 was a new target gene of the Wnt/ß-catenin signaling pathway. We also found that RMI2 promotes EMT markers, HCC cell invasion, and metastasis, which indicated that RMI2 is a potential target for preventing or at least mitigating the progression of HCC.

Hypoxia inhibits HUNK kinase activity to induce epithelial-mesenchymal transition.

Hypoxia is a common hallmark of cancer and plays a crucial role in promoting epithelial-mesenchymal transition (EMT). Hormonally Upregulated Neu-associated Kinase (HUNK) regulates EMT through its kinase activity. However, whether hypoxia is involved in HUNK-mediated EMT is incompletely understood. This study unveils an association between HUNK kinase activity and hypoxia in colorectal cancer (CRC). Importantly, hypoxia does not alter the expression levels of HUNK, but directly affects the phosphorylation levels of downstream proteins with indication of HUNK activity. Functionally, the upregulation of migration, invasion, and expression of EMT markers in CRC cells under hypoxic conditions can be attributed, in part, to the downregulation of HUNK-mediated phosphorylation of downstream proteins. These findings highlight the intricate relationship between HUNK, hypoxia and the molecular mechanisms of cancer EMT. Understanding these mechanisms may provide valuable insights into therapeutic targets for inhibiting cancer metastasis.

Construction and validation of infection risk model for patients with external ventricular drainage: a multicenter retrospective study.

PURPOSE: External ventricular drainage (EVD) is a life-saving neurosurgical procedure, of which the most concerning complication is EVD-related infection (ERI). We aimed to construct and validate an ERI risk model and establish a monographic chart. METHODS: We retrospectively analyzed the adult EVD patients in four medical centers and split the data into a training and a validation set. We selected features via single-factor logistic regression and trained the ERI risk model using multi-factor logistic regression. We further evaluated the model discrimination, calibration, and clinical usefulness, with internal and external validation to assess the reproducibility and generalizability. We finally visualized the model as a nomogram and created an online calculator (dynamic nomogram). RESULTS: Our research enrolled 439 EVD patients and found 75 cases (17.1%) had ERI. Diabetes, drainage duration, site leakage, and other infections were independent risk factors that we used to fit the ERI risk model. The area under the receiver operating characteristic curve (AUC) and the Brier score of the model were 0.758 and 0.118, and these indicators' values were similar when internally validated. In external validation, the model discrimination had a moderate decline, of which the AUC was 0.720. However, the Brier score was 0.114, suggesting no degradation in overall performance. Spiegelhalter's Z-test indicated that the model had adequate calibration when validated internally or externally (P = 0.464 vs. P = 0.612). The model was transformed into a nomogram with an online calculator built, which is available through the website: https://wang-cdutcm.shinyapps.io/DynNomapp/ . CONCLUSIONS: The present study developed an infection risk model for EVD patients, which is freely accessible and may serve as a simple decision tool in the clinic.

Cleaner outdoor air diminishes the overall risk of intracerebral hemorrhage but brings differential benefits to subpopulations: a time-stratified case-crossover study.

BACKGROUND: Short-term air pollution exposure and intracerebral hemorrhage (ICH) risk are related. However, the impact of the pollutant levels decline on this relationship, which attributes to clean air policy implementation and the COVID-19 pandemic lockdown, is unclear. In the present research, we explored the influence of different pollutant levels on ICH risk during eight years in a southwestern China megacity. METHODS: Our research used a time-stratified case-crossover design. We retrospectively analyzed ICH patients in a teaching hospital from January 1, 2014, to December 31, 2021, and divided 1571 eligible cases into two groups (1st group: 2014-2017; 2nd group: 2018-2021). We observed the trend of every pollutant in the entire study period and compared the pollution levels in each group, using air pollutants data (PM2.5, PM10, SO2, NO2, CO, and O3) documented by the local government. We further established a single pollutant model via conditional logistic regression to analyze the association between short-term air pollutants exposure and ICH risk. We also discussed the association of pollution levels and ICH risk in subpopulations according to individual factors and monthly mean temperature. RESULTS: We found that five air pollutants (PM2.5, PM10, SO2, NO2, CO) exhibited a continuous downward trend for the whole duration, and the daily concentration of all six pollutants decreased significantly in 2018-2021 compared with 2014-2017. Overall, the elevation of daily PM2.5, SO2, and CO was associated with increased ICH risk in the first group and was not positively associated with risk escalation in the second group. For patients in subgroups, the changes in the influence of lower pollutant levels on ICH risk were diverse. In the second group, for instance, PM2.5 and PM10 were associated with lower ICH risk in non-hypertension, smoking, and alcohol-drinking participants; however, SO2 had associations with increased ICH risk for smokers, and O3 had associations with raised risk in men, non-drinking, warm month population. CONCLUSIONS: Our study suggests that decreased pollution levels diminish the adverse effects of short-term air pollutants exposure and ICH risk in general. Nevertheless, the influence of lower air pollutants on ICH risk in subgroups is heterogeneous, indicating unequal benefits among subpopulations.

White spot syndrome virus (WSSV) modulates lipid metabolism in white shrimp.

In addition to the Warburg effect, which increases the availability of energy and biosynthetic building blocks in WSSV-infected shrimp, WSSV also induces both lipolysis at the viral genome replication stage (12 hpi) to provide material and energy for the virus replication, and lipogenesis at the viral late stage (24 hpi) to complete virus morphogenesis by supplying particular species of long-chain fatty acids (LCFAs). Here, we further show that WSSV causes a reduction in lipid droplets (LDs) in hemocytes at the viral genome replication stage, and an increase in LDs in the nuclei of WSSV-infected hemocytes at the viral late stage. In the hepatopancreas, lipolysis is triggered by WSSV infection, and this leads to fatty acids being released into the hemolymph. ß-oxidation inhibition experiment reveals that the fatty acids generated by WSSV-induced lipolysis can be diverted into ß-oxidation for energy production. At the viral late stage, WSSV infection leads to lipogenesis in both the stomach and hepatopancreas, suggesting that fatty acids are in high demand at this stage for virion morphogenesis. Our results demonstrate that WSSV modulates lipid metabolism specifically at different stages to facilitate its replication.

Epitranscriptic regulation of HRAS by N6-methyladenosine drives tumor progression.

Overexpression of Ras, in addition to the oncogenic mutations, occurs in various human cancers. However, the mechanisms for epitranscriptic regulation of RAS in tumorigenesis remain unclear. Here, we report that the widespread N6-methyladenosine (m6A) modification of HRAS, but not KRAS and NRAS, is higher in cancer tissues compared with the adjacent tissues, which results in the increased expression of H-Ras protein, thus promoting cancer cell proliferation and metastasis. Mechanistically, three m6A modification sites of HRAS 3' UTR, which is regulated by FTO and bound by YTHDF1, but not YTHDF2 nor YTHDF3, promote its protein expression by the enhanced translational elongation. In addition, targeting HRAS m6A modification decreases cancer proliferation and metastasis. Clinically, up-regulated H-Ras expression correlates with down-regulated FTO and up-regulated YTHDF1 expression in various cancers. Collectively, our study reveals a linking between specific m6A modification sites of HRAS and tumor progression, which provides a new strategy to target oncogenic Ras signaling.

Potentiometric nanosensor for real-time measurement of hydrogen sulfide in single cell.

One potentiometric nanosensor for monitoring intracellular hydrogen sulfide (H2S) with fast potential response, high selectivity and excellent antifouling properties was developed. This study constructs a powerful tool to real-time track the changes of intracellular H2S in situ, promoting the future studies of physiologically relevant processes.

Hydrogel-Coated Microelectrode Resists Protein Passivation of In Vivo Amperometric Sensors.

Passivation of electrodes caused by nonspecific adsorption of protein can dramatically reduce sensing sensitivity and accuracy, which is a great challenge for in vivo neurochemical monitoring. However, most antipassivation strategies are not suitable to carbon fiber microelectrodes (CFMEs) for in vivo measurement, and these methods also do not work on electrochemical biosensors that fix biometric elements. In this study, we demonstrate that chitosan hydrogel-coated microelectrodes can avoid the current passivation caused by protein adsorption on the surface of carbon fiber because the chitosan hydrogel prepared by local pH gradient caused by hydrogen evolution reaction has three-dimensional networks containing large amounts of water. The highly hydrophilic three-dimensional structure of hydrogel not only forms a biocompatible interface to confine enzymes but also keeps the fast mass transfer of analytes, such as dopamine, ascorbic acid, and glucose. The consistency of the precalibration and postcalibration of the prepared sensor enables in vivo amperometric detection of both electroactive species based on their redox property and electroinactive species based on the enzyme. This study provides a simple and versatile strategy to constitute an amperometric sensor interface to resist passivation of protein adsorption in a complex biological environment such as the brain.

An Electrochemical Nanosensor for Monitoring the Dynamics of Intracellular H2 O2 Upon NADH Treatment.

Reactive oxygen species (ROS)-based therapeutic strategies play an important role in cancer treatment. However, in situ, real-time and quantitative analysis of intracellular ROS in cancer treatment for drug screening is still a challenge. Herein we report one selective hydrogen peroxide (H2 O2 ) electrochemical nanosensor, which is prepared by electrodeposition of Prussian blue (PB) and polyethylenedioxythiophene (PEDOT) onto carbon fiber nanoelectrode. With the nanosensor, we find that the level of intracellular H2 O2 increases with NADH treatment and that increase is dose-dependent to the concentration of NADH. High-dose of NADH (above 10 mM) can induce cell death and intratumoral injection of NADH is validated for inhibiting tumor growth in mice. This study highlights the potential of electrochemical nanosensor for tracking and understanding the role of H2 O2 in screening new anticancer drug.

Effect of thermocycling-induced stress on properties of orthodontic NiTi wires.

Background/purpose: In orthodontic applications, NiTi wires are under continuous bending stress and exposed to fluctuations in temperature over long durations. The sensitivity of NiTi to temperature can have a considerable influence on its mechanical properties. This study investigated the effects of deflected NiTi wire, presented in stress-induced (detwinned) martensite microstructure, combined with thermal cycle on the microstructure and mechanical properties. Materials and methods: We tested four types of as-received orthodontic NiTi: (1) Nitinol Classic (3 M Unitek), (2) Sentalloy (Tomy), (3) 27 °C CuNiTi (Ormco) and (4) 40 °C CuNiTi (Ormco). Each group of specimens was subjected to three different testing conditions: (1) temperature fluctuations (5000 cycles) between 5 and 55 °C, (2) continuous three-point bending force and (3) combination of thermal cycling and bending stress. Results: The specimens that underwent thermocycling as well as loading exhibited a substantial narrowing in stress hysteresis, which may be attributed to crystallinity lower than that of as-received NiTi wires. Reduced crystallinity can manifest in a number of imperfections, such as dislocations and internal stress, as well as a less-organized structure. Micro X-ray diffraction (XRD) analysis revealed the existence of martensite phase in Sentalloy wires subject to thermal and stress conditions. Under loading conditions, stress-induced martensite of NiTi wires exposed to temperature fluctuations of 5-55 °C also induced cyclic changes in bending stress. In a simulated intra-oral environment, the stability of austenite↔martensite transformation decreased. Conclusion: This study determined that bending stress in conjunction with repeated temperature fluctuations can greatly affect the microstructure and mechanical properties of NiTi wires.

Prediction of Lumbar Drainage-Related Meningitis Based on Supervised Machine Learning Algorithms.

Background: Lumbar drainage is widely used in the clinic; however, forecasting lumbar drainage-related meningitis (LDRM) is limited. We aimed to establish prediction models using supervised machine learning (ML) algorithms. Methods: We utilized a cohort of 273 eligible lumbar drainage cases. Data were preprocessed and split into training and testing sets. Optimal hyper-parameters were archived by 10-fold cross-validation and grid search. The support vector machine (SVM), random forest (RF), and artificial neural network (ANN) were adopted for model training. The area under the operating characteristic curve (AUROC) and precision-recall curve (AUPRC), true positive ratio (TPR), true negative ratio (TNR), specificity, sensitivity, accuracy, and kappa coefficient were used for model evaluation. All trained models were internally validated. The importance of features was also analyzed. Results: In the training set, all the models had AUROC exceeding 0.8. SVM and the RF models had an AUPRC of more than 0.6, but the ANN model had an unexpectedly low AUPRC (0.380). The RF and ANN models revealed similar TPR, whereas the ANN model had a higher TNR and demonstrated better specificity, sensitivity, accuracy, and kappa efficiency. In the testing set, most performance indicators of established models decreased. However, the RF and AVM models maintained adequate AUROC (0.828 vs. 0.719) and AUPRC (0.413 vs. 0.520), and the RF model also had better TPR, specificity, sensitivity, accuracy, and kappa efficiency. Site leakage showed the most considerable mean decrease in accuracy. Conclusions: The RF and SVM models could predict LDRM, in which the RF model owned the best performance, and site leakage was the most meaningful predictor.