The Protective Effects of Methionine on Nickel-Induced Oxidative Stress via NF-κB Pathway in the Kidneys of Mice.

Nickel (Ni) is a human carcinogen that causes oxidative damage to many organs, and methionine has been studied to protect mammals from similar toxic effects by other heavy metals possibly through sulfur metabolism. This study aimed to investigate the protective effects of methionine on Ni-induced injuries to the kidneys. In this study, the mice were randomly divided into BC (normal diet), MD (methionine deficiency diet), MN (methionine plus nickel diet), and MDN (methionine deficiency plus nickel diet) treatment groups. Their renal function, histological changes, cell cycle, apoptosis, oxidative damage, and NF-κB inflammatory cytokines were detected after 21 days by HE, immunohistochemistry, TUNEL staining, and biochemical and ELISA methods. The results showed that serum Cr, BUN, and the NAG content increased in MDN (P < 0.01), MN (P < 0.05), and MD (P < 0.05) group mice compared to BC group mice. Glomerulus atrophy and renal tubular atrophy were observed in the MDN, MN, and MD groups but less severe in MN group mice. The PCNA protein content was the highest in BC group mice followed by MD, MN, and MDN. The activities of antioxidant enzymes (SOD, CAT, GSH, GSH-Px, and GSH-ST) were lower significantly in MD, MN, and MDN group mice, and the oxidant products content (MDA, LPO, and ROS) in the BC group were higher than those in other groups with a similar trend. The contents of NF-κB, TNF-α, IFN-γ, IL-1a, and IL-6 in the BC group were found to increase significantly in MD, MN, and MDN groups. In conclusion, Ni-induced kidney injury was indicated by renal tissue and cell damage, increased kidney metabolism products release in the serum, and renal oxidative stress while methionine addition helped alleviate the injury. In addition, the NF-κB signal pathway was involved in the renal inflammatory reaction induced by Ni where methionine helped mitigate it.

A flexible dual-mode sensor with decoupled strain and temperature sensing for smart robots.

Flexible dual mode strain-temperature sensors that mimic human skin functions are highly desired for wearable devices and intelligent robots. However, integrating dual sensing characteristics into a single sensor for simultaneous and decoupled strain-temperature detection still remains a challenge. Herein, we report a flexible dual-modal sensor that uses a "neutral surface" structural design technique to integrate an independently prepared temperature sensing layer (TSL) and strain sensing layer (SSL), for simultaneous monitoring of strain and temperature, in a decoupled manner. The TSL consists of a PDMS/BaTiO3 based dielectric layer whose dielectric constant and thickness change in response to temperature fluctuations. The SSL consists of a resistive type Ni80Cr20 film whose resistance changes in response to external strain. After optimizing the temperature and strain sensing characteristics of the TSL and SSL, the obtained dual-modal flexible sensor has shown a broad temperature sensing range (30 to 200 °C), with high temperature sensitivity (-160.90 fF °C-1), excellent linearity (0.998), and highly discernible temperature resolution (0.1 °C). Additionally, the sensor has also exhibited a wide strain monitoring range (20 to 1000 µÎµ), good strain resolution (20 µÎµ or 0.002%), and a fast strain response time (54 ms). When practically demonstrated, our sensor has successfully shown independent perception of strain and temperature, which highlights its promising application potential in the fields of smart robotics and intelligent prosthetics.

Melting and Rapid Solidification of Lunar Regolith Particles Returned by Chang'E-5 Mission.

Melting and solidification of lunar regolith are pivotal for comprehending the evolutionary dynamics of lunar volcanism, geology, and impact history. Additionally, insights gained from these processes can contribute to the advancement of in situ resource utilization technologies, for instance additive manufacturing and resource extraction systems. Herein, we conduct the direct observation of the melting and rapid solidification of lunar particles returned by the Chang'E 5 mission. The melting temperature and melting sequence were obtained. Bubble generation, growth, and release were clearly observed, with a maximum bubble diameter of 5 µm, which is supposed to be according to the release of volatiles that embedded in the particles. During the solidification process, evident crystallization occurred with incremental crystal growth rate approximately of 27 nm/s. Scanning electron microscopy and energy-dispersive x-ray spectroscopy results verified that the Fe-rich mineral crystalizes first. These results would improve the understanding of the evolution of lunar volcanism, geology, and impact history.

Acupuncture-assisted therapy for prolonged disorders of consciousness: study protocol for a randomized, conventional-controlled, assessor-and-statistician-blinded trial.

Background: Acupuncture is a promising non-pharmaceutical complementary therapy in treating prolonged Disorders of consciousness (pDOC), but solid evidence to support its effectiveness and safety is still lacking. Thus, the purpose of this study is to investigate the efficacy and safety of acupuncture-assisted therapy for pDOC patients. Methods: A single-center, prospective, randomized, conventional-controlled, assessor-and-statistician-blinded trial has been designed and is being conducted at West China Hospital of Sichuan University. A total of 110 participants will be randomly assigned to the experimental group and the control group in a 1:1 allocation ratio and evaluated using Coma Recovery Scale-Revised (CRS-R) at 8 a.m., 12 p.m., and 4 p.m. on 2 consecutive days before enrollment to determine the consciousness level. The experimental group will receive acupuncture combined with conventional treatment, while the control group will receive only conventional treatment during the trial observation period. The treatment duration of both groups will be 20 days. Among them, the frequency of acupuncture-assisted therapy is once a day, with 10 consecutive sessions followed by a day's rest for a total of 24 days. Data will be collected separately during baseline and after the final treatment. For data analysis, both Full Analysis Set (FAS) and Per Protocol Set (PPS) principles will be performed together by applying SPSS 27.0 software. The primary outcome measures are the changes of CRS-R before and after treatment, while the secondary outcome measures are the changes of Full Outline of Unresponsiveness Scale (FOUR), the changes of Nociception Coma Scale-Revised (NCS-R), the changes of Disability Rating Scale (DRS), the changes of Mismatch Negativity (MMN) and P300 before and after treatment, respectively. Discussion: This trial aims to rationally assess the consciousness level from multiple 2 perspectives through subjective evaluation and objective detection by selecting several standardized clinical scales combined with Event-Related Potential (ERP) detection technology. In this way, we will be able to reduce the subjectivity of consciousness assessment and objectively evaluate the clinical efficacy of acupuncture-assisted therapy for pDOC. The study, if proven to be effective and safe enough, will provide a favorable evidence to guide medical decision-making choices and future researches. Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR2300076180.

Cupric ion coordination-mediated molecularly imprinted electrochemical sensor for the recognition and ratiometric detection of lidocaine.

Molecularly imprinted polymers (MIPs) have been widely used as artificial recognition elements in sensing applications. However, their electrochemical sensing performance is generally hampered by limited affinity and uncontrolled condition change. In this work, a novel MIP electrochemical sensor based on metal coordination interaction was prepared and used for the recognition and ratiometric detection of lidocaine (LC). The sensor was constructed by electrodepositing Cu-coordinated MIP on biomass carbon modified glassy carbon electrode. Herein, Cu2+ ions acted as anchor for the immobilization of LC during the synthesis process, enabling the orderly formation of molecular recognition sites. Reversely, the metal coordination between Cu2+ ions and LC molecules facilitated the recognition of LC. Moreover, the doped cupric ions in the polymer film could provide a reference signal for subsequent ratiometric strategy. Thus the resulting sensor exhibited high selectivity, sensitivity, satisfactory reproducibility, and anti-interference ability. Under the selected conditions, the peak current ratio of LC and cupric ion was linear to LC concentration in the range of 0.008-2.5 µmol L-1 (R2 = 0.9951), and the limit of detection was 1.9 nmol L-1 (S/N = 3). The practical feasibility of the sensor was evaluated by detecting human serum and pharmaceutical samples, and satisfactory outcomes were obtained.

Enhanced cycling of Fe(III)/Fe(II) and mass transfer strategy for efficient and stable activation of peroxydisulfate for water decontamination via a flow-through Fe-MOFs cathode.

The efficiency and stability of the electrical activation of persulfate (PS) by transition metal-based cathode are controlled by the cycling of Fe(III)/Fe(II) and the mass transfer of PS. In this study, the mixed-valence MOFs catalyst (FeII-MIL-53(Fe)) modified flow-through cathode was prepared for the first time. FeII-MIL-53(Fe) was prepared by replacing part of the iron-oxygen network structure in MIL-53(Fe) with Fe(II), resulting in the formation of coordinated unsaturated iron centers (CUICs). The increase of the Fe(III) CUICs facilitated the conversion of Fe(III) to Fe(II). Furthermore, the cycling of Fe(III)/Fe(II) was further promoted by the electric field. Meanwhile, the hydrodynamic behavior of flow-through cathode was indicated by the computational fluid dynamics (CFD) simulation. The quenching experiments and electron paramagnetic resonance (EPR) results showed that several reactive specie (SO4·-, ·OH, O2·- and 1O2) were produce. In summary, this work provided an effective strategy for the efficient and stable electrical activation of PDS.

Flexible AIE/PCM composite fiber with biosensing of alcohol, fluorescent anti-counterfeiting and body thermal management functions.

Alcohol sensing plays a critical role in medical detection and personal health management. AIE materials with high sensitivity, selectivity and fast response have been widely used in biosensing, but their application in the field of alcohol sensing still needs further research and development. Furthermore, developing flexible phase change materials (PCMs) is significant for the research of human-body thermal management. In this study, a kind of flexible polyacrylonitrile (PAN)/polyvinylpyrrolidone (PVP)/polyethylene glycol (PEG)/Py-CH (pyrene-based AIE molecule)/SiO2@h-BN composite fiber textile (PAB) with alcohol sensing performance, writable fluorescence property, and human body thermal management function has been prepared via electrospinning technique. The PAN/PVP fiber matrix successfully integrated AIE fluorescent sensing material and PCM into a multi-functional composite with great shape stability. Owing to the introduction of novel pyrene-based Py-CH with AIE characteristic, this innovative textile exhibited wonderful fluorescent properties, including sensitive alcohol fluorescence sensing, writable fluorescence performance and variable temperature fluorescence. Furthermore, proposed PAB textile delivered a high energy storage density of 87∼90 J/g, excellent thermal reliability, great comprehensive mechanical flexibility and enhanced thermal conductivity for flexible human body thermal management. Hence, this flexible multifunctional AIE/PCM composite sensing textiles can be widely used in alcohol sensing, fluorescence anti-counterfeiting and flexible body thermal management.

Hepatocyte-Specific Yap1 Knockout Maintained the Liver Homeostasis of Lipid Metabolism in Mice.

Introduction: Yes-associated protein 1 (YAP1) is a crucial molecule in the Hippo pathway. The impact of hepatocyte-specific Yap1 knockout (Yap1 LKO) on hepatic lipid droplets (LD) and pePLIN2 in metabolic fatty liver has not been reported. This study aims to explore whether Yap1 LKO could offer a protective effect in a liver injury model. Methods: Three-week-old Yap1 LKO and Yap1 Flox mice were given aristolochic acid I (AAI) combined carbon tetrachloride (CCL4) establish liver injury model. Eight-week-old Yap1 LKO and Yap1 Flox mice were fed with a high-fat diet for 18 weeks to establish obesity-related liver injury model. Further biochemical, histomorphological, immunohistochemical, and lipidomic analyses were performed on serum and liver tissues of these mice to elucidate the effects of hepatocyte-specific Yap1 knockout on hepatic lipid metabolism. Results: Yap1 LKO reduced triglyceride (TG) content and PLIN2 expression level in the liver during the intervention of AAI combined CCl4. Moreover, Yap1 LKO improved lipid metabolism homeostasis in the liver by increasing the beneficial lipid molecules and reducing the harmful lipid molecules through lipidomics. Finally, Yap1 LKO reduced TG content in the serum and liver, hepatic vacuolar degeneration, and hepatic PLIN2 expression level in mice fed with a high-fat diet (HFD). Conclusion: Yap1 LKO is protective in regulating liver and blood TG when induced with toxic substances AAI combined CCl4 and a high-fat diet.

A Highly Sensitive 3D-Printed Flexible Sensor for Sensing Small Pressures in Deep-Sea High-Pressure Environment.

The origin of life on Earth is believed to be from the ocean, which offers abundant resources in its depths. However, deep-sea operations are limited due to the lack of underwater robots and rigid grippers with sensitive force sensors. Therefore, it is crucial for deep-sea pressure sensors to be integrated with mechanical hands for manipulation. Here, a flexible stress sensor is presented that can function effectively under high water pressure in the deep ocean. Inspired by biological structures found in the abyssal zone, our sensor is designed with an internal and external pressure balance structure (hollow interlocking spherical structure). The digital light processing (DLP) three-dimensional (3D) printing technology is utilized to construct this complex structure after obtaining optimized structural parameters using finite element simulation. The sensor exhibits linear sensitivity of 0.114 kPa-1 within the range of 0-15 kPa and has an extremely short response time of 32 ms, good dynamic-static load response capability, and excellent resistance cycling stability. It shows high sensitivity of 1.74 kPa-1 even under 30 MPa static water pressures and the theoretical working pressure can exceed 110 MPa, which provides a new solution for deep-sea robots.

The Impact of Delayed Transition From Noninvasive to Invasive Mechanical Ventilation on Hospital Mortality in Immunocompromised Patients With Sepsis.

OBJECTIVE: To determine whether mortality differed between initial invasive mechanical ventilation (IMV) or noninvasive ventilation (NIV) followed by delayed IMV in immunocompromised patients with sepsis. DESIGN: Retrospective analysis using the National Data Center for Medical Service claims data in China from 2017 to 2019. SETTING: A total of 3530 hospitals across China. PATIENTS: A total of 36,187 adult immunocompromised patients with sepsis requiring ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was hospital mortality. Patients were categorized into NIV initiation or IMV initiation groups based on first ventilation. NIV patients were further divided by time to IMV transition: no transition, immediate (≤ 1 d), early (2-3 d), delayed (4-7 d), or late (≥ 8 d). Mortality was compared between groups using weighted Cox models. Over the median 9-day follow-up, mortality was similar for initial NIV versus IMV (adjusted hazard ratio [HR] 1.006; 95% CI, 0.959-1.055). However, among NIV patients, a longer time to IMV transition is associated with stepwise increases in mortality, from immediate transition (HR 1.65) to late transition (HR 2.51), compared with initial IMV. This dose-response relationship persisted across subgroups and sensitivity analyses. CONCLUSIONS: Prolonged NIV trial before delayed IMV transition is associated with higher mortality in immunocompromised sepsis patients ultimately intubated.

Clinical diagnostic value of targeted next­generation sequencing for infectious diseases (Review).

As sequencing technology transitions from research to clinical settings, due to technological maturity and cost reductions, metagenomic next­generation sequencing (mNGS) is increasingly used. This shift underscores the growing need for more cost­effective and universally accessible sequencing assays to improve patient care and public health. Therefore, targeted NGS (tNGS) is gaining prominence. tNGS involves enrichment of target pathogens in patient samples based on multiplex PCR amplification or probe capture with excellent sensitivity. It is increasingly used in clinical diagnostics due to its practicality and efficiency. The present review compares the principles of different enrichment methods. The high positivity rate of tNGS in the detection of pathogens was found in respiratory samples with specific instances. tNGS maintains high sensitivity (70.8­95.0%) in samples with low pathogen loads, including blood and cerebrospinal fluid. Furthermore, tNGS is effective in detecting drug­resistant strains of Mycobacterium tuberculosis, allowing identification of resistance genes and guiding clinical treatment decisions, which is difficult to achieve with mNGS. In the present review, the application of tNGS in clinical settings and its current limitations are assessed. The continued development of tNGS has the potential to refine diagnostic accuracy and treatment efficacy and improving infectious disease management. However, further research to overcome technical challenges such as workflow time and cost is required.

Fluorescence/visual aptasensor based on Au/MOF nanocomposite for accurate and convenient aflatoxin B1 detection.

A dual-mode fluorescence/visual aptasensor was developed for straightforward and accurate determination of aflatoxin B1 (AFB1) based on an Au/metal-organic framework (Au/MOF) composite. Aptamer-modified Au/Fe3O4 (Apt/Au/Fe3O4) served as the recognition element, and Au/MOF modified with complementary chains and 3,3',5,5'-tetramethylbenzidine (cDNA/TMB/Au/MOF) acted as the fluorescence and visual probes. These components are integrated to form conjugates (Apt/Au/Fe3O4-cDNA/TMB/Au/MOF). Upon the introduction of AFB1, some cDNA/TMB/Au/MOF dissociated from Apt/Au/Fe3O4, enabling the use of detached probes for visual detection. The undecomposed conjugates were isolated magnetically for use in fluorescence detection. As the AFB1 concentration increases, the visual signal intensifies and fluorescence intensity diminishes. Thus, the proposed aptasensor achieves the simultaneous fluorescence and visual determination of AFB1, obviating the need for material and reagent substitutions. The detection limits were established at 0.07 ng mL-1 for the fluorescence mode and 0.08 ng mL-1 for the visual mode. The effectiveness of the aptasensor was further validated by quantifying AFB1 in real samples.

Metabolites mediate the causal associations between gut microbiota and NAFLD: a Mendelian randomization study.

BACKGROUND: Although gut microbiota and serum metabolite composition have been observed to be altered in patients with non-alcoholic fatty liver disease (NAFLD), previous observational studies have demonstrated inconsistent results. As this may be influenced by factors such as confounders and reverse causality, we used Mendelian randomization to clarify the causal effect of gut microbiota and blood metabolites on NAFLD. METHODS: In this research, we performed a two-step Mendelian randomization analysis by utilizing genome-wide association study (GWAS) data obtained from MiBioGen and UK Biobank. To mitigate potential errors, we employed False Discovery Rate (FDR) correction and linkage unbalanced regression (LDSC) analysis. Sensitivity analyses including cML-MA and bidirectional Mendelian randomization were performed to ensure the robustness of the results. RESULTS: In this study, a total of nine gut microbiota and seven metabolites were found to be significantly associated with NAFLD. MR analysis of the above findings revealed a causal relationship between Ruminococcus2 and cysteine-glutathione disulfide (OR = 1.17, 95%CI = 1.006-1.369, P = 0.041), as well as 3-indoleglyoxylic acid (OR = 1.18, 95%CI = 1.011-1.370, P = 0.036). For each incremental standard deviation in Ruminococcus2 abundance, there was a corresponding 26% reduction in NAFLD risk (OR = 0.74, 95%CI = 0.61-0.89, P = 0.0012), accompanied by a 17% increase in cysteine-glutathione disulfide levels (OR = 1.17, 95%CI = 1.01-1.37, P = 0.041) and an 18% increase in 3-indoleglyoxylic acid levels (OR = 1.18, 95%CI = 0.81-1.00, P = 0.036). The proportion mediated by cysteine-glutathione disulfide is 11.2%, while the proportion mediated by 3-indoleglyoxylic acid is 7.5%. CONCLUSION: Our study suggests that increased abundance of specific gut microbiota may reduce the risk of developing NAFLD, and this relationship could potentially be mediated through blood metabolites.

Dihydroartemisinin modulated arachidonic acid metabolism and mitigated liver inflammation by inhibiting the activation of 5-LOX and COX-2.

Background: Dihydroartemisinin (DHA), a derivative of Artemisia annua, has been shown to possess anti-inflammatory properties. Besides, Yes-associated protein 1 (YAP1) plays a crucial role in maintaining liver homeostasis. Methods: This study used Yap1 Flox/Flox, Albumin-Cre mice with hepatocyte-specific Yap1 knockout (referred to as Yap1 LKO) and their control mice (Yap1 Flox/Flox, referred to as Yap1 Flox). The effect of Yap1 on lipid metabolism homeostasis was investigated through non-targeted metabolomic analysis of mouse liver. Subsequently, DHA was administered to Yap1 LKO mice to assess its potential as a treatment. Liver pathology was evaluated via H&E staining, and the levels of AST, ALT, and TG were quantified using biochemical assays. The contents of arachidonic acid (AA), prostaglandin E1 (PGE1), and leukotrienes (LT) in the liver were measured using ELISA, while the protein expressions of PLIN2, 5-lipoxygenase (5-LOX), and cyclooxygenase-2 (COX-2) were analyzed through IHC staining. Results: Hepatocyte-specific Yap1 knockout activated the AA metabolic pathway, resulting in increased elevated levels of AA, PGE1, and LT levels, along with inflammatory cytokine infiltration. DHA mitigated the elevation of metabolites such as PGE1 and LT caused by the AA metabolic pathway activation by down-regulating the levels of COX-2 and 5-LOX in the liver of Yap1 LKO mice. Moreover, it alleviated the accumulation of lipid vacuoles and reduced triglyceride (TG) and perilipin-2 (PLIN2) levels in the liver of Yap1 LKO mice. Conclusions: Excessively low YAP1 expression induces liver inflammation and disturbances in lipid metabolism, whereas DHA modulated AA metabolism and mitigated liver inflammation by inhibiting the activation of 5-LOX and COX-2.

Quasi-1D Conductive Network Composites for Ultra-Sensitive Strain Sensing.

Highly performance flexible strain sensor is a crucial component for wearable devices, human-machine interfaces, and e-skins. However, the sensitivity of the strain sensor is highly limited by the strain range for large destruction of the conductive network. Here the quasi-1D conductive network (QCN) is proposed for the design of an ultra-sensitive strain sensor. The orientation of the conductive particles can effectively reduce the number of redundant percolative pathways in the conductive composites. The maximum sensitivity will reach the upper limit when the whole composite remains only "one" percolation pathway. Besides, the QCN structure can also confine the tunnel electron spread through the rigid inclusions which significantly enlarges the strain-resistance effect along the tensile direction. The strain sensor exhibits state-of-art performance including large gauge factor (862227), fast response time (24 ms), good durability (cycled 1000 times), and multi-mechanical sensing ability (compression, bending, shearing, air flow vibration, etc.). Finally, the QCN sensor can be exploited to realize the human-machine interface (HMI) application of acoustic signal recognition (instrument calibration) and spectrum restoration (voice parsing).

Identifying new cancer genes based on the integration of annotated gene sets via hypergraph neural networks.

MOTIVATION: Identifying cancer genes remains a significant challenge in cancer genomics research. Annotated gene sets encode functional associations among multiple genes, and cancer genes have been shown to cluster in hallmark signaling pathways and biological processes. The knowledge of annotated gene sets is critical for discovering cancer genes but remains to be fully exploited. RESULTS: Here, we present the DIsease-Specific Hypergraph neural network (DISHyper), a hypergraph-based computational method that integrates the knowledge from multiple types of annotated gene sets to predict cancer genes. First, our benchmark results demonstrate that DISHyper outperforms the existing state-of-the-art methods and highlight the advantages of employing hypergraphs for representing annotated gene sets. Second, we validate the accuracy of DISHyper-predicted cancer genes using functional validation results and multiple independent functional genomics data. Third, our model predicts 44 novel cancer genes, and subsequent analysis shows their significant associations with multiple types of cancers. Overall, our study provides a new perspective for discovering cancer genes and reveals previously undiscovered cancer genes. AVAILABILITY AND IMPLEMENTATION: DISHyper is freely available for download at https://github.com/genemine/DISHyper.