RNA m6A detection using raw current signals and basecalling errors from Nanopore direct RNA sequencing reads.

MOTIVATION: Nanopore direct RNA sequencing (DRS) enables the detection of RNA N6-methyladenosine (m6A) without extra laboratory techniques. A number of supervised or comparative approaches have been developed to identify m6A from Nanopore DRS reads. However, existing methods typically utilize either statistical features of the current signals or basecalling-error features, ignoring the richer information of the raw signals of DRS reads. RESULTS: Here, we propose RedNano, a deep-learning method designed to detect m6A from Nanopore DRS reads by utilizing both raw signals and basecalling errors. RedNano processes the raw-signal feature and basecalling-error feature through residual networks. We validated the effectiveness of RedNano using synthesized, Arabidopsis, and human DRS data. The results demonstrate that RedNano surpasses existing methods by achieving higher area under the ROC curve (AUC) and area under the precision-recall curve (AUPRs) in all three datasets. Furthermore, RedNano performs better in cross-species validation, demonstrating its robustness. Additionally, when detecting m6A from an independent dataset of Populus trichocarpa, RedNano achieves the highest AUC and AUPR, which are 3.8%-9.9% and 5.5%-13.8% higher than other methods, respectively. AVAILABILITY AND IMPLEMENTATION: The source code of RedNano is freely available at https://github.com/Derryxu/RedNano.

Integration of valence and conflict processing through cellular-field interactions in human subgenual cingulate during emotional face processing in treatment-resistant depression.

The subgenual anterior cingulate cortex (sgACC) has been identified as a key brain area involved in various cognitive and emotional processes. While the sgACC has been implicated in both emotional valuation and emotional conflict monitoring, it is still unclear how this area integrates multiple functions. We characterized both single neuron and local field oscillatory activity in 14 patients undergoing sgACC deep brain stimulation for treatment-resistant depression. During recording, patients were presented with a modified Stroop task containing emotional face images that varied in valence and congruence. We further analyzed spike-field interactions to understand how network dynamics influence single neuron activity in this area. Most single neurons responded to both valence and congruence, revealing that sgACC neuronal activity can encode multiple processes within the same task, indicative of multifunctionality. During peak neuronal response, we observed increased spectral power in low frequency oscillations, including theta-band synchronization (4-8 Hz), as well as desynchronization in beta-band frequencies (13-30 Hz). Theta activity was modulated by current trial congruency with greater increases in spectral power following non-congruent stimuli, while beta desynchronizations occurred regardless of emotional valence. Spike-field interactions revealed that local sgACC spiking was phase-locked most prominently to the beta band, whereas phase-locking to the theta band occurred in fewer neurons overall but was modulated more strongly for neurons that were responsive to task. Our findings provide the first direct evidence of spike-field interactions relating to emotional cognitive processing in the human sgACC. Furthermore, we directly related theta oscillatory dynamics in human sgACC to current trial congruency, demonstrating it as an important regulator during conflict detection. Our data endorse the sgACC as an integrative hub for cognitive emotional processing through modulation of beta and theta network activity.

Linkage-Mixed Covalent Organic Frameworks Synthesized by a Liquid-Solid Two-Phase Strategy for Photoenhanced Uranium Extraction.

Synthesizing COFs with hybrid linkage coupling with both reversible and irreversible natures remains a challenging issue. Herein, we report the synthesis of two rare COFs constructed by both reversible and irreversible linkages through a liquid-solid two-phase strategy. A systematic study reveals a one-pot, two-step reaction mechanism for the two COFs, the first step being a reversible Schiff base reaction and the second step being an irreversible Knoevenagel reaction. Interestingly, this hybrid linkage COF is found to show an outstanding photoenhanced uranium extraction performance. The results not only provide a general and green approach to develop the linkage chemistry of COFs but also enrich the synthesis toolboxes and application of COFs.

Regulating Benzene Ring Number as Connector in Covalent Organic Framework for Boosting Photosynthesis of H2O2 from Seawater.

Photosynthesis of H2O2 from seawater represents a promising pathway to acquire H2O2, but it is still restricted by the lack of a highly active photocatalyst. In this work, we propose a convenient strategy of regulating the number of benzene rings to boost the catalytic activity of materials. This is demonstrated by ECUT-COF-31 with adding two benzene rings as the connector, which can result in 1.7-fold enhancement in the H2O2 production rate relative to ECUT-COF-30 with just one benzene ring as the connector. The reason for enhancement is mainly due to the release of *OOH from the surface of catalyst and the final formation of H2O2 being easier in ECUT-COF-31 than in ECUT-COF-30. Moreover, ECUT-COF-31 provides a stable photogeneration of H2O2 for 70 h, and a theoretically remarkable H2O2 production of 58.7 mmol per day from seawater using one gram of photocatalyst, while the cost of the used raw material is as low as 0.24 $/g.

Controllable Synthesis of Transferable Ultrathin Bi2Ge(Si)O5 Dielectric Alloys with Composition-Tunable High-κ Properties.

Two-dimensional (2D) alloys hold great promise to serve as important components of 2D transistors, since their properties allow continuous regulation by varying their compositions. However, previous studies are mainly limited to the metallic/semiconducting ones as contact/channel materials, but very few are related to the insulating dielectrics. Here, we use a facile one-step chemical vapor deposition (CVD) method to synthesize ultrathin Bi2SixGe1-xO5 dielectric alloys, whose composition is tunable over the full range of x just by changing the relative ratios of the GeO2/SiO2 precursors. Moreover, their dielectric properties are highly composition-tunable, showing a record-high dielectric constant of >40 among CVD-grown 2D insulators. The vertically grown nature of Bi2GeO5 and Bi2SixGe1-xO5 enables polymer-free transfer and subsequent clean van der Waals integration as the high-κ encapsulation layer to enhance the mobility of 2D semiconductors. Besides, the MoS2 transistors using Bi2SixGe1-xO5 alloy as gate dielectrics exhibit a large Ion/Ioff (>108), ideal subthreshold swing of ∼61 mV/decade, and a small gate hysteresis (∼5 mV). Our work not only gives very few examples on controlled CVD growth of insulating dielectric alloys but also expands the family of 2D single-crystalline high-κ dielectrics.

Enhanced Alkaline Hydrogen Evolution Reaction via Electronic Structure Regulation: Activating PtRh with Rare Earth Tm Alloying.

Developing high-performance electrocatalysts for alkaline hydrogen evolution reaction (HER) is crucial for producing green hydrogen, yet it remains challenging due to the sluggish kinetics in alkaline environments. Pt is located near the peak of HER volcano plot, owing to its exceptional performance in hydrogen adsorption and desorption, and Rh plays an important role in H2O dissociation. Lanthanides (Ln) are commonly used to modulate the electronic structure of materials and further influence the adsorption/desorption of reactants, intermediates, and products, and noble metal-Ln alloys are recognized as effective platforms where Ln elements regulate the catalytic properties of noble metals. Here Pt1.5Rh1.5Tm alloy is synthesized using the sodium vapor reduction method. This alloy demonstrates superior catalytic activity, being 4.4 and 6.6 times more effective than Pt/C and Rh/C, respectively. Density Functional Theory (DFT) calculations reveal that the upshift of d-band center and the charge transfer induced by alloying promote adsorption and dissociation of H2O, making Pt1.5Rh1.5Tm alloy more favorable for the alkaline HER reaction, both kinetically and thermodynamically.

Enhancement of solar blind full band absorption in photodetector with Ga2O3 nanopore and Al nanograting.

In this paper, we presented a novel double-layer light-trapping structure consisting of nanopores and nanograting positioned on both the surface and bottom of a gallium oxide-based solar-blind photodetector. Utilizing the finite element method (FEM), we thoroughly investigated the light absorption enhancement capabilities of this innovative design. The simulation results show that the double-layer nanostructure effectively combines the light absorption advantages of nanopores and nanogratings. Compared with thin film devices and devices with only nanopore or nanograting structures, double-layer nanostructured devices have a higher light absorption, achieving high light absorption in the solar blind area.

The scaffold of neutrophil extracellular traps promotes CCA progression and modulates angiogenesis via ITGAV/NFκB.

Neutrophil extracellular traps (NETs) have garnered attention for their dual role in host defense and tumor promotion. With their involvement documented across a spectrum of tumors, their influence on the progression of cholangiocarcinoma (CCA) is of paramount interest. We employed immunohistochemistry and immunofluorescence to detect NET deposition in CCA tissues. Through in vitro and in vivo investigation, including CCA organoid and transposon-based models in PAD4 KO mice, we explored the effects of NETs on cell proliferation and metastasis. Molecular insights were gained through RNA sequencing, enzyme linked immunosorbent assay, and chromatin immunoprecipitation. Elevated intratumoral NET deposition within CCA tissues was associated with poor survival. The influence of NETs on CCA proliferation, migration and invasion was primarily mediated by NET-DNA. RNA sequencing unveiled the activation of the NFκB signaling pathway due to NET-DNA stimulation. NET-DNA pull-down assay coupled with mass spectrometry revealed the interaction between NET-DNA and αV integrin (ITGAV), culmination in the activation of the NFκB pathway. Furthermore, NET-DNA directly upregulated the expression of VEGF-A in cancer cells. The study unequivocally establishes NETs as facilitators of CCA progression, orchestrating proliferation, metastasis, and angiogenesis through ITGAV/NFκB pathway activation. This novel insight positions NETs as prospective therapeutic targets for managing CCA patients. By implementing a variety of methodologies and drawing intricate connections between NETs, DNA interactions, and signaling pathways, this research expands our comprehension of the complex interplay between the immune system and cancer progression, offering promising avenues for intervention.

Cancer-associated fibroblasts mediate resistance to anti-EGFR therapies in cancer.

Over the last decade, epidermal growth factor receptor (EGFR)-targeted therapies have transformed the treatment landscape for patients with advanced solid tumors. Despite these advances, resistance to anti-EGFR therapies is still a significant clinical challenge. While cell-autonomous mechanisms of resistance are well-documented, they do not fully elucidate the complexity of drug resistance. Cancer-associated fibroblasts (CAFs), key mediators within the tumor microenvironment (TME), have emerged as pivotal players in cancer progression and chemoresistance. Recent evidence implicates CAFs in resistance to anti-EGFR therapies, suggesting they may undermine treatment efficacy. This review synthesizes current data, highlighting the critical role of CAFs in resistance pathogenesis and summarizing recent therapeutic strategies targeting CAFs. We underscore the challenges and advocate for the exploration of CAFs as a potential dual-targeted approach.

Extraction of Uranium by a Cheap Phosphite-Derived Polymer under Light Condition.

Uranium, as the main fuel of today's nuclear energy, is crucial to the development of nuclear energy. Therefore, the development of low-cost and powerful adsorbents is very important for the removal or recovery of uranium from uranium-containing solutions. Herein, we report the synthesis of a cheap phosphite-derived polymer for such use. Under visible-light irradiation, this phosphite-derived polymer was found to enable selective adsorption of uranium with an adsorption capacity as high as 1030 mg/g, suggesting its great potential in handling nuclear waste.

Extraction of Uranium by a Pyrazole-Based Porous Organic Polymer.

In this work, we report a pyrazole-based porous organic polymer (namely, ECUT-POP-2) for extraction of uranium. ECUT-POP-2 affords a high uranium extraction capacity of up to 1851 mg/g, excellent selectivity, and good reusability, suggesting its superior application in treating uranium-containing wastewater and acquring nuclear fuel.

Separation of Palladium by an Imine-Linked Cu(I)-Organic Framework.

Selective capture of palladium (Pd) is one of the important works in science due to its high application and low content in the Earth's crust. To this end, we present herein a new Cu(I)-organic framework (ECUT-MOF-1) by introducing pyridine N active sites to chelate Pd(II). ECUT-MOF-1 demonstrated that the maximal adsorption capacity of Pd(II) was 350 mg/g in pH = 3 solution. In addition, kinetic analysis, cycle performance, selectivity, and adsorption mechanisms were also investigated. All of the results suggested its superior application in the recovery of Pd(II).

Strong Electron Transfer in Covalently Integrating Cu(I)-Organic Frameworks Enabling Effective Radionuclide Capture.

Rational construction of strong electron-transfer materials remains a challenging task. Herein, we show a design rule for the construction of strong electron-transfer materials through covalently integrating electron-donoring Cu(I) clusters and electron-withdrawing triazine monomers together. As expected, Cu-CTF-1 (Cu(I)-triazine framework) was found to enable strong electron transfer up to 0.46|e| from each Cu(I) metal center to each adjacent triazine fragment. This finally leads to good spatial separation in both photogenerated electron-hole pairs and function units for photocatalytic uranium reduction under ambience and no sacrificial agent and to good charge separation of [I+][I5-] for I2 immobilization under extremely rigorous conditions. The results have not only opened up a structural design principle to access electron-transfer materials but also solved several challenging tasks in the field of radionuclide capture and CTFs.

Dual-Color Visual Ratiometric Fluorescence Sensing for H2O and D2O Mixtures Using a Hexanuclear Ln(III) Cluster-Based Metal-Organic Framework.

High-purity heavy water (D2O) is a strategic material owing to its important application in the fields of nuclear energy and scientific research. D2O always tends to get contaminated by H2O owing to its strong hygroscopicity. Herein, a bimetallic hexanuclear Ln(III) cluster-based metal-organic framework (Eu0.5Tb0.5-TZB-MOF) has been synthesized for fluorescence sensing of the D2O-H2O binary mixtures. Eu0.5Tb0.5-TZB-MOF can be used to immediately differentiate D2O or H2O via fluorescent color responses that are obvious to the naked eye and allow for quantitative ratiometric analysis using simple spectrophotometry. Fluorescence titration experiments demonstrate that both trace H2O in D2O and trace D2O in H2O can be quantitatively detected. Mechanistic studies demonstrate that the weaker vibrational quenching of the O-D oscillator compared to the O-H oscillator, in addition to the terbium-to-europium energy transfer, triggered the fluorescence signal response.

Electronic structures and quantum capacitance of twisted bilayer graphene with defects based on three-band tight-binding model.

Twisted bilayer graphene (tBLG) with C vacancies would greatly improve the density of states (DOS) around the Fermi level (EF) and quantum capacitance; however, the single-band tight-binding model only considering pz orbitals cannot accurately capture the low-energy physics of tBLG with C vacancies. In this work, a three-band tight-binding model containing three p orbitals of C atoms is proposed to explore the modulation mechanism of C vacancies on the DOS and quantum capacitance of tBLG. We first obtain the hopping integral parameters of the three-band tight-binding model, and then explore the electronic structures and the quantum capacitance of tBLG at a twisting angle of θ = 1.47° under different C vacancy concentrations. The impurity states contributed by C atoms with dangling bonds located around the EF and the interlayer hopping interaction could induce band splitting of the impurity states. Therefore, compared with the quantum capacitance of pristine tBLG (∼18.82 µF cm-2) at zero bias, the quantum capacitance is improved to ∼172.76 µF cm-2 at zero bias, and the working window with relatively large quantum capacitance in the low-voltage range is broadened in tBLG with C vacancies due to the enhanced DOS around the EF. Moreover, the quantum capacitance of tBLG is further increased at zero bias with an increase of the C vacancy concentration induced by more impurity states. These findings not only provide a suitable multi-band tight-binding model to describe tBLG with C vacancies but also offer theoretical insight for designing electrode candidates for low-power consumption devices with improved quantum capacitance.

PM2.5 regulates the progression of lung adenocarcinoma through the axis of HCG18, miR-195 and ATG14.

Relevant studies have indicated the association of HCG18 with tumour occurrence and progression. In this study, we observed that PM2.5 can enhance the growth of lung adenocarcinoma cells by modulating the expression of HCG18. Further investigations, including overexpression and knockout experiments, elucidated that HCG18 suppresses miR-195, which in turn upregulates the expression of ATG14, resulting in the upregulation of autophagy. Consequently, exposure to PM2.5 leads to elevated HCG18 expression in lung tissues, which in turn increases Atg14 expression and activates autophagy pathways through inhibition of miR-195, thereby contributing to oncogenesis.

Total intracorporeal laparoscopic ileal ureter replacement in a single position for ureteral stricture based on membrane anatomy.

PURPOSE: The aim of this study was to present our initial experience and prove the feasibility of total intracorporeal laparoscopic ileal ureter replacement (TILIUR) in a single position for ureteral stricture based on membrane anatomy. MATERIALS AND METHODS: Between January 2021 and April 2023, six patients underwent TILIUR in a single position for ureteral strictures based on membrane anatomy. All patients with a past medical history underwent radical hysterectomy with bilateral pelvic lymph node dissection as well as extensive ureteral stricture due to radiotherapy. The procedure is performed completely laparoscopically. Dissection of the digestive system as well as ureteral stricture or renal pelvis is based on membrane anatomy. The surgery is performed in a single position. RESULTS: TILIUR in a single position for ureteral stricture based on membrane anatomy was successfully performed without open conversion in all patients. Among the 6 patients, 3 patients underwent combined ileal ureter replacement (IUR) and abdominal wall ostomy, 2 underwent unilateral IUR, and 1 underwent bilateral IUR. The mean length of the ileal substitution was 22.83 cm (range: 15-28). The average operative time was 458 ± 72.77 min (range 385-575 min), and the average intraoperative blood loss was 158 mL (range 50-400 mL). The median postoperative hospital stay was 15.1 d (range: 8-32). The median duration of postoperative follow-up was 15 months (range: 3-29 months). The success rate was 100%. CONCLUSIONS: TILIUR in a single position may be a promising option for ureteral stricture based on membrane anatomy in selected patients. Moreover, it has a positive effect on patients with renal insufficiency and urinary incontinence. Although IUR is difficult and risky, proficient surgeons can perform the procedure safely and effectively.

Facile Fabrication of Large-Area CuO Flakes for Sodium-Ion Energy Storage Applications.

CuO is recognized as a promising anode material for sodium-ion batteries because of its impressive theoretical capacity of 674 mAh g-1, derived from its multiple electron transfer capabilities. However, its practical application is hindered by slow reaction kinetics and rapid capacity loss caused by side reactions during discharge/charge cycles. In this work, we introduce an innovative approach to fabricating large-area CuO and CuO@Al2O3 flakes through a combination of magnetron sputtering, thermal oxidation, and atomic layer deposition techniques. The resultant 2D CuO flakes demonstrate excellent electrochemical properties with a high initial reversible specific capacity of 487 mAh g-1 and good cycling stability, which are attributable to their unique architectures and superior structural durability. Furthermore, when these CuO flakes are coated with an ultrathin Al2O3 layer, the integration of the 2D structures with outer nanocoating leads to significantly enhanced electrochemical properties. Notably, even after 70 rate testing cycles, the CuO@Al2O3 materials maintain a high capacity of 525 mAh g-1 at a current density of 50 mA g-1. Remarkably, at a higher current density of 2000 mA g-1, these materials still achieve a capacity of 220 mAh g-1. Moreover, after 200 cycles at a current density of 200 mA g-1, a high charge capacity of 319 mAh g-1 is sustained. In addition, a full cell consisting of a CuO@Al2O3 anode and a NaNi1/3Fe1/3Mn1/3O2 cathode is investigated, showcasing remarkable cycling performance. Our findings underscore the potential of these innovative flake-like architectures as electrode materials in high-performance sodium-ion batteries, paving the way for advancements in energy storage technologies.

Factors influencing fatigue, mental workload and burnout among Chinese health care workers during public emergencies: an online cross-sectional study.

OBJECTIVES: The purpose of this study was to investigate fatigue, mental workload, and burnout among health care workers (HCWs) and explore the possible underlying factors. MATERIALS AND METHODS: An online cross-sectional survey design was used to collect data from HCWs in Chongqing, China. The online survey included the Fatigue Severity Scale, NASA Task Load Index, and Chinese version of the Maslach Burnout Inventory-General Survey to assess fatigue, mental workload, and burnout, respectively, and was conducted from February 1 to March 1, 2023. RESULTS: In this study, the incidence of fatigue and burnout among HCWs was 76.40% and 89.14%, respectively, and the incidence of moderate to intolerable mental workloads was 90.26%. Work-family conflict, current symptoms, number of days of COVID-19 positivity, mental workload, burnout and reduced personal accomplishment were significantly associated with fatigue. Mental workload was affected by fatigue and reduced personal accomplishment. Furthermore, burnout was influenced by marital status and fatigue. Moreover, there was a correlation among mental workload, fatigue, and burnout. CONCLUSIONS: Fatigue, mental workload and burnout had a high incidence and were influenced by multiple factors during COVID-19 public emergencies in China.

[Preparation and Performance of a Novel Polyurethane Microporous Film on Polypropylene Medical Mesh Surface]. / ä¸€ç§èšæ°¨é ¯å¾®å­”è–„è†œåŒ»ç”¨è¡¥ç‰‡è¡¨å±‚ææ–™çš„åˆ¶å¤‡åŠå ¶æ€§èƒ½ç ”ç©¶.

Objective: This study aims to develop a medical patch surface material featuring a microporous polyurethane (PU) membrane and to assess the material's properties and biological performance. The goal is to enhance the clinical applicability of pelvic floor repair patch materials. Methods: PU films with a microporous surface were prepared using PU prepolymer foaming technology. The films were produced by optimizing the PU prepolymer isocyanate index (R value) and the relative humidity (RH) of the foaming environment. The surface morphology of the PU microporous films was observed by scanning electron microscopy, and the chemical properties of the PU microporous films, including hydrophilicity, were analyzed using infrared spectroscopy, Raman spectroscopy, and water contact angle measurements. In vitro evaluations included testing the effects of PU microporous film extracts on the proliferation of L929 mouse fibroblasts and observing the adhesion and morphology of these fibroblasts. Additionally, the effect of the PU microporous films on RAW264.7 mouse macrophages was studied. Immune response and tissue regeneration were assessed in vivo using Sprague Dawley (SD) rats. Results: The PU films exhibited a well-defined and uniform microporous structure when the R value of PU prepolymer=1.5 and the foaming environment RH=70%. The chemical structure of the PU microporous films was not significantly altered compared to the PU films, with a significantly lower water contact angle ([55.7±1.5]° ) compared to PU films ([69.5±1.7]° ) and polypropylene (PP) ([ 104.3±2.5]°), indicating superior hydrophilicity. The extracts from PU microporous films demonstrated good in vitro biocompatibility, promoting the proliferation of L929 mouse fibroblasts. The surface morphology of the PU microporous films facilitated fibroblast adhesion and spreading. The films also inhibited the secretion of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1ß by RAW264.7 macrophages while enhancing IL-10 and IL-4 secretion. Compared to 24 hours, after 72 hours of culture, the expression levels of TNF-α and IL-1ß were reduced in both the PU film and PU microporous film groups and were significantly lower than those in the PP film group (P<0.05), with the most notable decreases observed in the PU microporous film group. IL-10 and IL-4 levels increased significantly in the PU microporous film group, surpassing those in the PP film group (P<0.01), with the most pronounced increase in IL-4. The PU microporous film induced mild inflammation with no significant fibrous capsule formation in vivo. After 60 days of implantation, the film partially degraded, showing extensive collagen fiber growth and muscle formation in its central region. Conclusion: The PU microporous film exhibits good hydrophilicity and biocompatibility. Its surface morphology enhances cell adhesion, regulates the function of RAW264.7 macrophages, and promotes tissue repair, offering new insights for the design of pelvic floor repair and reconstruction patch materials.