An Antiferromagnetic Neuromorphic Memory Based on Perpendicularly Magnetized CoO.

Antiferromagnets (AFMs) are ideal materials to boost neuromorphic computing toward the ultrahigh speed and ultracompact integration regime. However, developing a suitable AFM neuromorphic memory remains an aspirational but challenging goal. In this work, we construct such a memory based on the CoO/Pt heterostructure, in which the collinear insulating AFM CoO shows a strong perpendicular anisotropy facilitating its electrical readout and writing. Utilizing the unique nonlinear response and bipolar fading memory properties of the device, we demonstrate a multidimensional reservoir computing beyond the traditional binary paradigm. These results are expected to pave the way toward next-generation fast and massive neuromorphic computing.

Investment and financing maturity mismatch: Moderating role of financialization in regulatory context for A-share listed Chinese companies.

As the financialization issue is getting more and more attention, the behavioral motives and effects behind this appearance should not be ignored, and it is of great practical significance for the high-quality development of China's real economy to explore the impact and mechanism of the financialization trend on the investment and financing maturity mismatch of China's real enterprises. Using sample data of Chinese A-share listed companies from 2013 to 2020, this article empirically examines the impact of financialization on the investment and financing maturity structure from a new perspective of asset classification by using a fixed-effect model, and explores the mechanism of the financial regulatory environment's moderating effect on the relationship between the two mentioned above. The study shows that: there is an inverted U-shaped nonlinear relationship between the financialization of investment income and fixed income and "maturity mismatch ". The term mismatch of investment and financing increases with the degree of financialization, after reaching the critical point, it eases with the deepening of financialization. However, the specific point of view is different. In the sample interval, the investment income financialization exacerbates the investment and financing maturity mismatch more obviously; the fixed income financialization inhibits the investment and financing maturity mismatch more obviously. Under the different perspectives of the firms' ownership nature, financing constraints, and principal-agent problems, there are differences in the impact of firms' allocation of different types of financial assets on the investment and financing term structure. In addition, the regulatory effect of financial supervision weakens the inverted U-shaped relationship of investment income financialization with investment and financing maturity mismatch; it enhances the inverted U-shaped relationship between fixed income financialization and investment and financing maturity mismatch. In general, financial supervision has had a significant positive effect on investment and financing maturity mismatches. The findings have important policy implications in terms of corporate real investment, financial market development, and financial regulation, which can help promote China's economic development and stability.

The arginine and nitric oxide metabolic pathway regulate the gut colonization and expansion of Ruminococcous gnavus.

BACKGROUND: Ruminococcus gnavus is a mucolytic commensal bacterium whose increased gut colonization has been associated with chronic inflammatory and metabolic diseases in humans. Whether R. gnavus metabolites can modulate host intestinal physiology remains largely understudied. METHODS: We performed untargeted metabolomic and bulk RNA sequencing analyses using R. gnavus mono-colonization in germ free mice. Based on transcriptome-metabolome correlations, we tested the impact of specific arginine metabolites on intestinal epithelial production of nitric oxide (NO) and examined the effect of NO on the growth of various strains of R. gnavus in vitro and in Nos2-deficient mice. RESULTS: R. gnavus produces specific arginine, tryptophan and tyrosine metabolites, some of which are regulated by the environmental richness of sialic acid and mucin. R. gnavus colonization promotes expression of amino acid transporters and enzymes involved in metabolic flux of arginine and associated metabolites into NO. R. gnavus induced elevated levels of Nitric Oxide Synthase 2 (NOS2) while Nos2 ablation resulted in R. gnavus expansion in vivo. The growth of various R. gnavus strains can be inhibited by NO. Specific R. gnavus metabolites modulate intestinal epithelial cell NOS2 abundance and reduce epithelial barrier function at higher concentrations. CONCLUSIONS: Intestinal colonization and interaction with R. gnavus are partially regulated by an arginine-NO metabolic pathway, whereby a balanced control by the gut epithelium may restrain R. gnavus growth in healthy individuals. Disruption in this arginine metabolic regulation will contribute to the expansion and blooming of R. gnavus.

A dual-functional electrolyte additive displaying hydrogen bond fusion enables highly reversible aqueous zinc ion batteries.

In recent years, aqueous zinc-ion batteries (AZIBs) have attracted significant attention in energy storage due to their notable advantages, including high safety, low cost, high capacity, and environmental friendliness. However, side reactions like hydrogen evolution and zinc (Zn) dendrites can significantly impact their Coulombic efficiency (CE) and lifespan. Effectively addressing these issues has become a focus of research in this field. In our study, dimethyl sulfoxide (DMSO) and nanodiamonds (NDs) were used to optimize the electrolyte of AZIBs. Benefiting from the hydrogen bond fusion of DMSO and NDs, which regulates the Zn deposition behavior, effectively inhibiting the growth of Zn dendrites, hydrogen evolution, and corrosion. The Zn | |Zn symmetric cells using NDs-DMSO-ZS demonstrate exceptional cycling stability for over 1500 h at 1 mA cm-2, while the Zn//Cu asymmetric cells achieve up to 99.8% CE at 2 mA cm-2. This study not only shows the application prospects of electrolyte optimization in enhancing AZIBs performance, but also provides a reference for the advancement of electrolyte technology in advanced AZIBs technology.

Electronic and magnetic properties of Au-doped diamond surfaces by first-principles calculation.

The electronic and magnetic properties of the Au-doped diamond surface are investigated by first-principles calculation. After Au-doping, diamond shows surface p-type conductivity with an areal electron density of 6.34 × 1013 cm-2. Unlike the non-magnetic feature of intrinsic diamond, magnetism is induced for diamond (100), (110) and (111) surfaces as well as at different terminations (H, F, N and O). The magnetism originates from the s-p hybridization between the Au-6s state and the C-2p state, and the spin charge density and magnetic moments of Au-doped diamond originate mainly from the Au atoms and their surrounding C atoms. Further studies show that the magnetic properties still maintain under different doping concentrations (0.125-0.5 monolayer). Therefore, this study would provide great potential applications of diamond in novel magnetic semiconductors and transistors.

Development and psychometric testing of the nursing practice difficulty scale for nurses caring for patients with dementia in general hospitals.

Objective: As aging in the Chinese population increases, the hospitalization rates of patients with dementia have also risen. Research on the difficulties of nurses who care for patients with dementia in Chinese general hospitals is limited. This study aimed to develop a scale to measure the difficulties nurses face in nursing patients with dementia in Chinese general hospitals and to verify its reliability and validity. Methods: Guided by the biopsychosocial theory, an initial scale was created through a literature review, qualitative interviews, and expert consultation. A web-based survey for psychometric testing was conducted with 394 nurses from 11 general hospitals during September to November 2021. Validity was verified using content validity, exploratory factor analysis, the known-groups method, and concurrent validity. Cronbach's α coefficient and split-half reliability were used to assess reliability. Results: The Item-level Content Validity Index was 0.833-1.000. The Scale-level Content Validity Index was 0.929. Twenty-one items with four factors were extracted from the item analysis and exploratory factor analysis. According to the known-groups method, the difficulty of the experienced group and the group with training experience was significantly lower than that of the less experienced group and the group without training experience. Based on external standards, the correlation coefficient was 0.387 with the Nursing Job Stress Scale and -0.239 with the Dementia Care Attitude Scale. Cronbach's α coefficient for each factor ranged from 0.889 to 0.905, and the total was 0.959. The split-half reliability for each factor ranged from 0.814 to 0.894, and the total was 0.911. Conclusion: This study discovered a four-factor structure related to the difficulty scale of dementia nursing practice, and the scale's reliability and validity were confirmed. The scale can be utilized to assess the difficulty of dementia nursing practice in general hospitals and may be employed in future research to improve dementia nursing practices.

Interactions between Inhibitors and 5-Lipoxygenase: Insights from Gaussian Accelerated Molecular Dynamics and Markov State Models.

Inflammation is a protective stress response triggered by external stimuli, with 5-lipoxygenase (5LOX) playing a pivotal role as a potent mediator of the leukotriene (Lts) inflammatory pathway. Nordihydroguaiaretic acid (NDGA) functions as a natural orthosteric inhibitor of 5LOX, while 3-acetyl-11-keto-ß-boswellic acid (AKBA) acts as a natural allosteric inhibitor targeting 5LOX. However, the precise mechanisms of inhibition have remained unclear. In this study, Gaussian accelerated molecular dynamics (GaMD) simulation was employed to elucidate the inhibitory mechanisms of NDGA and AKBA on 5LOX. It was found that the orthosteric inhibitor NDGA was tightly bound in the protein's active pocket, occupying the active site and inhibiting the catalytic activity of the 5LOX enzyme through competitive inhibition. The binding of the allosteric inhibitor AKBA induced significant changes at the distal active site, leading to a conformational shift of residues 168-173 from a loop to an α-helix and significant negative correlated motions between residues 285-290 and 375-400, reducing the distance between these segments. In the simulation, the volume of the active cavity in the stable conformation of the protein was reduced, hindering the substrate's entry into the active cavity and, thereby, inhibiting protein activity through allosteric effects. Ultimately, Markov state models (MSM) were used to identify and classify the metastable states of proteins, revealing the transition times between different conformational states. In summary, this study provides theoretical insights into the inhibition mechanisms of 5LOX by AKBA and NDGA, offering new perspectives for the development of novel inhibitors specifically targeting 5LOX, with potential implications for anti-inflammatory drug development.

Assessment of toxic effects of thallium on the earthworm Eisenia fetida using the biomarker response index.

Thallium (Tl), though not essential for biological systems, is widely used in industrial activities, resulting in soil pollution and adverse effects on soil biota. Systematic toxicological studies on Tl, especially concerning soil organisms, are relatively rare. This research evaluates the toxic effects of Tl on earthworms by measuring oxidative stress biomarkers, such as superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG), and by assessing the expression of functional genes, such as heat shock protein 70 (Hsp70), metallothionein (MT), and annetocin (ANN). Additionally, this study employs the Biomarker Response Index (BRI) and two-way ANOVA to comprehensively assess the cumulative toxicity of Tl in earthworms. The findings indicate that Tl exposure significantly exacerbates oxidative stress and cellular damage in earthworms, particularly under conditions of high concentration and prolonged exposure. BRI results demonstrate a continuous decline in the physiological state of earthworms with increasing Tl concentration and exposure duration. Two-way ANOVA reveals significant dose-responsive increases in SOD and CAT activities, as well as in ANN gene expression. Apart from GST activity, other biomarkers significantly increased over time, and the changes in biomarkers such as SOD, CAT, MDA, and 8-OHdG were significantly influenced by dose and time. LSD post hoc tests show significant effects of dose, time, and their interactions on all biomarkers except for GST. These findings are valuable for gaining a deeper understanding of the ecological risks of Tl in soil environments and its potential threats to soil biota, aiding in the management of ecological risks associated with Tl-contaminated soils.

Combination Nanomedicine Strategy for Preventing High-Risk Corneal Transplantation Rejection.

High-risk (HR) corneal transplantation presents a formidable challenge, with over 50% of grafts experiencing rejection despite intensive postoperative care involving frequent topical eyedrop administration up to every 2 h, gradually tapering over 6-12 months, and ongoing maintenance dosing. While clinical evidence underscores the potential benefits of inhibiting postoperative angiogenesis, effective antiangiogenesis therapy remains elusive in this context. Here, we engineered controlled-release nanomedicine formulations comprising immunosuppressants (nanoparticles) and antiangiogenesis drugs (nanowafer) and demonstrated that these formulations can prevent HR corneal transplantation rejection for at least 6 months in a clinically relevant rat model. Unlike untreated corneal grafts, which universally faced rejection within 2 weeks postsurgery, a single subconjunctival injection of the long-acting immunosuppressant nanoparticle alone effectively averted graft rejection for 6 months, achieving a graft survival rate of ∼70%. Notably, the combination of an immunosuppressant nanoparticle and an anti-VEGF nanowafer yielded significantly better efficacy with a graft survival rate of >85%. The significantly enhanced efficacy demonstrated that a combination nanomedicine strategy incorporating immunosuppressants and antiangiogenesis drugs can greatly enhance the ocular drug delivery and benefit the outcome of HR corneal transplantation with increased survival rate, ensuring patient compliance and mitigating dosing frequency and toxicity concerns.

Residue-Free Orally Administered Drug Carrier Based on a Porous Aromatic Framework for Efficient Multisite Treatment.

Nowadays, oral medications are the primary method of treating disease due to their convenience, low cost, and safety, without the need for complex medical procedures. To maximize treatment effectiveness, almost all oral medications utilize drug carriers, such as capsules, liposomes, and sugar coatings. However, these carriers rely on dissolution or fragmentation to achieve drug release, which leads to drugs and carriers coabsorption in the body, causing unnecessary adverse drug reactions, such as nausea, vomiting, abdominal pain, and even death caused by allergy. Therefore, the ideal oral drug carrier should avoid degradation and absorption and be totally excreted after drug release at the desired location. Herein, a gastrointestinally stable oral drug carrier based on porous aromatic framework-1 (PAF-1) is constructed, and it is modified with famotidine (a well-known gastric drug) and mesalazine (a well-known ulcerative colitis drug) to verify the excellent potential of PAF-1. The results demonstrate that PAF-1 can accurately release famotidine in stomach, mesalazine in the intestine, and finally be completely excreted from the body without any residue after 12 h. The use of PAF materials for the construction of oral drug carriers with no residue in the gastrointestinal tract provides a new approach for efficient disease treatment.

Environment-responsive dendrobium polysaccharide hydrogel embedding manganese microsphere as a post-operative adjuvant to boost cascaded immune cycle against melanoma.

Rationale: Surgical resection is a primary treatment for solid tumors, but high rates of tumor recurrence and metastasis post-surgery present significant challenges. Manganese (Mn2+), known to enhance dendritic cell-mediated cancer immunotherapy by activating the cGAS-STING pathway, has potential in post-operative cancer management. However, achieving prolonged and localized delivery of Mn2+ to stimulate immune responses without systemic toxicity remains a challenge. Methods: We developed a post-operative microenvironment-responsive dendrobium polysaccharide hydrogel embedded with Mn2+-pectin microspheres (MnP@DOP-Gel). This hydrogel system releases Mn2+-pectin microspheres (MnP) in response to ROS, and MnP shows a dual effect in vitro: promoting immunogenic cell death and activating immune cells (dendritic cells and macrophages). The efficacy of MnP@DOP-Gel as a post-surgical treatment and its potential for immune activation were assessed in both subcutaneous and metastatic melanoma models in mice, exploring its synergistic effect with anti-PD1 antibody. Result: MnP@DOP-Gel exhibited ROS-responsive release of MnP, which could exert dual effects by inducing immunogenic cell death of tumor cells and activating dendritic cells and macrophages to initiate a cascade of anti-tumor immune responses. In vivo experiments showed that the implanted MnP@DOP-Gel significantly inhibited residual tumor growth and metastasis. Moreover, the combination of MnP@DOP-Gel and anti-PD1 antibody displayed superior therapeutic potency in preventing either metastasis or abscopal brain tumor growth. Conclusions: MnP@DOP-Gel represents a promising drug-free strategy for cancer post-operative management. Utilizing this Mn2+-embedding and ROS-responsive delivery system, it regulates surgery-induced immune responses and promotes sustained anti-tumor responses, potentially increasing the effectiveness of surgical cancer treatments.

Impact of negative emotions on upper gastrointestinal diseases: A Mendel randomization study.

Mendelian randomization method is a powerful tool in epidemiological research. The core idea is to use genetic variation as a tool to assess the causal relationship between risk factors and specific diseases. Confounding factors are important interference factors for causal inference in epidemiological studies, and genetic variation in Mendelian randomization studies follows the principle of random distribution of alleles to offspring, which is similar to randomized controlled trials. Mendel 's randomization method can effectively avoid the confounding factors, reverse causality in observational studies and the representativeness and feasibility of randomized controlled trials. Previous observational studies have reported a relationship between negative emotions and upper gastrointestinal disease. However, whether this relationship is causal remains unclear. We aimed to evaluate the causal relationship between negative emotions and upper gastrointestinal diseases using two-sample Mendelian randomization (MR). Three sets of genetic instruments from the database were obtained for analysis, including 12 anxiety-related single nucleotide polymorphisms (SNPs), 46 depression-related SNPs, and 58 nervous-related SNPs. SNPs were filtered using the Phenoscanner website, and the inverse variance weighted method, weighted median method, MR-Egger regression, MR pleiotropy residual sum, and outlier test were used for analysis. In inverse variance weighted analysis, anxiety and depression had an effect on gastroduodenal ulcer (p = 2.849×10-3, ß = 4.908, 95% CI = 1.684-8.132; and p = 6.457×10-4, ß = 1.767, 95% CI = 0.752-2.782, respectively). Additionally, depression had an effect on diseases of the esophagus, stomach, and duodenum (p = 3.498×10-5, ß = 0.926, 95% CI = 0.487-1.364). Cochran's Q-derived p-values were 0.457, 0.603, and 0.643, and MR-Egger intercept-derived p-values were 0.697, 0.294, and 0.362, respectively. Here, we show that anxiety and depression have a causal relationship with gastroduodenal ulcers, and depression has a causal relationship with diseases of the esophagus, stomach, and duodenum.

Recapitulation of HIV-1 Neutralization Breadth in Plasma by the Combination of Two Broadly Neutralizing Antibodies from Different Lineages in the Same SHIV-Infected Rhesus Macaque.

Viral infection generally induces polyclonal neutralizing antibody responses. However, how many lineages of antibody responses can fully represent the neutralization activities in sera has not been well studied. Using the newly designed stable HIV-1 Env trimer as hook, we isolated two distinct broadly neutralizing antibodies (bnAbs) from Chinese rhesus macaques infected with SHIV1157ipd3N4 for 5 years. One lineage of neutralizing antibodies (JT15 and JT16) targeted the V2-apex in the Env trimers, similar to the J038 lineage bnAbs identified in our previous study. The other lineage neutralizing antibody (JT18) targeted the V3 crown region in the Env, which strongly competed with human 447-52D. Each lineage antibody neutralized a different set of viruses. Interestingly, when the two neutralizing antibodies from different lineages isolated from the same macaque were combined, the mixture had a neutralization breath very similar to that from the cognate sera. Our study demonstrated that a minimum of two different neutralizing antibodies can fully recapitulate the serum neutralization breadth. This observation can have important implications in AIDS vaccine design.

Realized Record Capacity and Rate Performance of Dual-Carbon Batteries Constructed by Introducing Superhard Nanodiamonds.

Dual-ion batteries (DIBs) are becoming an important technology for energy storage. To overcome the disadvantages of traditional electrodes and electrolytes, here we assemble a dual-carbon DIB with nanodiamond (ND)-modified crimped graphene (DCG) and electrolyte. The DCG anode and cathode realize high capacities of 1121 mA h g-1 and 149 mA h g-1, respectively, at 0.1 A g-1. The corresponding DCG//DCG full cells present a high capacity of 143 mA h g-1 at 1 A g-1 after 3300 cycles, which is superior to most reported results. Achieving these record performances is strongly dependent on the formed DCG electrodes with expanded interlayer spacing and abundant active sites, and NDs dispersed in DCG and electrolytes are very helpful for enhancing the storage of both cations and anions, effectively suppressing the irreversible decomposition of electrolytes. This work breaks through the bottleneck of graphitic-based DIBs, paving the way for realizing high-performance DIBs applied in industry.

Novel solution-gated transistor sensor-based SnO2 epitaxial thin films grown by pulsed laser deposition for nitrite detection.

A solution-gate controlled thin-film transistor with SnO2 epitaxial thin films (SnO2-SGTFT) is successfully utilized for highly sensitive detection of nitrite. The SnO2 films are deposited as channel materials on a c-plane sapphire (c-Al2O3) substrate through pulsed laser deposition (PLD), with superior crystal quality and out-of-plane atomic ordering. PtAu NPs/rGO nanocomposites are electrodeposited on a gold electrode to function as a transistor gate to further enhance the nitrite catalytic performance of the device. The change in effective gate voltage due to the electrooxidation of nitrite on the gate electrode is the primary sensing mechanism of the device. Based on the inherent amplification effect of transistors, the superior electrical properties of SnO2, and the high electrocatalytic activity of PtAu NPs/rGO, the SnO2-SGTFT sensor has a low detection limit of 0.1 nM and a wide linear detection range of 0.1 nM ~ 50 mM at VGS = 1.0 V. Furthermore, the sensor has excellent characteristics such as rapid response time, selectivity, and stability. The practicability of the device has been confirmed by the quantitative detection of nitrite in natural lake water. SnO2 epitaxial films grown by PLD provide a simple and efficient way to fabricate nitrite SnO2-SGTFT sensors in environmental monitoring and food safety, among others. It also provides a reference for the construction of other high-performance thin-film transistor sensors.

Defective Diamane: A Superior Sensor for Toxic Gases Capture and Detection with Excellent Selectivity, Sensitivity, and Reversibility at Room Temperature.

The toxic gases emitted from industrial production have caused significant damage to the environment and human health, necessitating efficient gas sensors for their detection and removal. In this work, first-principles calculations are employed to investigate the potential application of diamanes for high-performance toxic gas sensors. The results show that nine gas molecules (CO, CO2, NO, NO2, NH3, SO2, N2, O2, and H2O) are physisorbed on pristine diamane by weak van der Waals interactions. After introducing H/F defects, diamane can effectively capture specific toxic gases (CO, NO, NO2, and SO2) in the presence of interfering gases (N2, O2, and H2O), suggesting excellent selectivity and anti-interference ability. Orbital hybridization and significant charge redistribution between gas molecules and defective diamane dominate the enhanced adsorbate-substrate interactions. More importantly, the high sensitivity and good reversibility of defective diamane for detecting CO, NO, and SO2 molecules enable its reuse as a superior resistance-type gas sensor. Our calculations provide valuable insights into the potential of defective diamane for detecting toxic gases and shed light on the practical application of novel carbon-based materials in the gas-sensing field.

Oxygen-Terminated Polycrystalline Boron-Doped Diamond Superhydrophobic Surface with Excellent Mechanical and Thermal Stabilities.

Superhydrophobic surfaces are of great interest because of their remarkable properties. Due to its maximal hardness and chemical inertness, diamond film has great potential in fabricating robust superhydrophobic surfaces. In the present study, an oxygen-terminated polycrystalline boron-doped diamond (O-PBDD) superhydrophobic surface with micro/nano-hierarchical porous structures is developed. The preparation method is very simple, requiring only sputtering and dewetting procedures. The former involves sputtering gold and copper particles onto the hydrogen-terminated polycrystalline boron-doped diamond (H-PBDD) to form gold/copper films, whereas the latter involves placing the samples in an atmospheric tube furnace to form hierarchical pores. By controlling the etching parameters, the wettability of the O-PBDD surface can be adjusted from hydrophilic to superhydrophobic, which is significantly different to the normal hydrophilicity feature of O-termination diamonds. The water contact angle of the obtained O-PBDD surface can reach 165 ± 5°, which is higher than the superhydrophobic diamond surfaces that are reported in the literature. In addition, the O-PBDD surface exhibits excellent durability; it can maintain satisfactory superhydrophobicity even after high-pressure, high-temperature, and sandpaper friction tests. This work provides a new research direction for fabricating robust superhydrophobic materials with diamond film.

Immobilized NRG1 Accelerates Neural Crest like Cell Differentiation Toward Functional Schwann Cells Through Sustained Erk1/2 Activation and YAP/TAZ Nuclear Translocation.

Neural Crest cells (NC) are a multipotent cell population that give rise to a multitude of cell types including Schwann cells (SC) in the peripheral nervous system (PNS). Immature SC interact with neuronal axons via the neuregulin 1 (NRG1) ligand present on the neuronal surface and ultimately form the myelin sheath. Multiple attempts to derive functional SC from pluripotent stem cells have met challenges with respect to expression of mature markers and axonal sorting. Here, they hypothesized that sustained signaling from immobilized NRG1 (iNRG1) might enhance the differentiation of NC derived from glabrous neonatal epidermis towards a SC phenotype. Using this strategy, NC derived SC expressed mature markers to similar levels as compared to explanted rat sciatic SC. Signaling studies revealed that sustained NRG1 signaling led to yes-associated protein 1 (YAP) activation and nuclear translocation. Furthermore, NC derived SC on iNRG1 exhibited mature SC function as they aligned with rat dorsal root ganglia (DRG) neurons in an in vitro coculture model; and most notably, aligned on neuronal axons upon implantation in a chick embryo model in vivo. Taken together their work demonstrated the importance of signaling dynamics in SC differentiation, aiming towards development of drug testing platforms for de-myelinating disorders.

DrugSK: A Stacked Ensemble Learning Framework for Predicting Drug Combinations of Multiple Diseases.

Combination therapy is an important direction of continuous exploration in the field of medicine, with the core goals of improving treatment efficacy, reducing adverse reactions, and optimizing clinical outcomes. Machine learning technology holds great promise in improving the prediction of drug synergy combinations. However, most studies focus on single disease-oriented collaborative predictive models or involve excessive feature categories, making it challenging to predict the majority of new drugs. To address these challenges, the DrugSK comprehensive model was developed, which utilizes SMILES-BERT to extract structural information from 3492 drugs and trains on reactions from 48,756 drug combinations. DrugSK is an integrated learning model capable of predicting interactions among various drug categories. First, the primary learner is trained from the initial data set. Random forest, support vector machine, and XGboost model are selected as primary learners and logistic regression as secondary learners. A new data set is then "generated" to train level 2 learners, which can be thought of as a prediction for each model. Finally, the results are filtered using logistic regression. Furthermore, the combination of the new antibacterial drug Drafloxacin with other antibacterial agents was tested. The synergistic effect of Drafloxacin and Isavuconazonium in the fight against Candida albicans has been confirmed, providing enlightenment for the clinical treatment of skin infection. DrugSK's prediction is accurate in practical application and can also predict the probability of the outcome. In addition, the tendency of Drafloxacin and antifungal drugs to be synergistic was found. The development of DrugSK will provide a new blueprint for predicting drug combination synergies.

General In Situ Engineering of Carbon-Based Materials on Carbon Fiber for In Vivo Neurochemical Sensing.

Developing real-time, dynamic, and in situ analytical methods with high spatial and temporal resolutions is crucial for exploring biochemical processes in the brain. Although in vivo electrochemical methods based on carbon fiber (CF) microelectrodes are effective in monitoring neurochemical dynamics during physiological and pathological processes, complex post modification hinders large-scale productions and widespread neuroscience applications. Herein, we develop a general strategy for the in situ engineering of carbon-based materials to mass-produce functional CFs by introducing polydopamine to anchor zeolitic imidazolate frameworks as precursors, followed by one-step pyrolysis. This strategy demonstrates exceptional universality and design flexibility, overcoming complex post-modification procedures and avoiding the delamination of the modification layer. This simplifies the fabrication and integration of functional CF-based microelectrodes. Moreover, we design highly stable and selective H+, O2, and ascorbate microsensors and monitor the influence of CO2 exposure on the O2 content of the cerebral tissue during physiological and ischemia-reperfusion pathological processes.