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The report demonstrated that a member of cockroach family, Blaptica dubia (Blattodea: Blaberidae) biodegraded commercial polystyrene (PS) plastics with M n of 20.3 kDa and M w of 284.9 kDa. The cockroaches digested up to 46.6 % of ingested PS within 24 h. The biodegradation was confirmed by the 13 C isotopic shift of the residual PS in feces versus pristine PS (Δ δ 13 C of 2.28 ‰), reduction of molecular weight and formation of oxidative functional groups in the residual PS. Further tests found that B.dubia cockroaches degraded all eight high purity PS microplastics with low to ultra-high molecular weights (MW) at 0.88, 1.20, 3.92, 9.55, 62.5, 90.9, 524.0, and 1040 kDa, respectively, with superior biodegradation ability. PS depolymerization/biodegradation pattern was MW-dependent. Ingestion of PS shifted gut microbial communities and elevated abundances of plastic-degrading bacterial genes. Genomic, transcriptomic and metabolite analyses indicated that both gut microbes and cockroach host contributed to digestive enzymatic degradation. PS plastic diet promoted a highly cooperative model of gut digestive system. Weighted gene co-expression network analysis revealed different PS degradation patterns with distinct MW profiles in B. dubia. These results have provided strong evidences of plastic-degrading ability of cockroaches or Blaberidae family and new understanding of insect and their microbe mediated biodegradation of plastics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To explore changes in cerebral cortex activation and functional connectivity during resting-state and verbal fluency tasks in patients with different types of dementia., Methods: We recorded oxygenated hemoglobin concentration (HbO) signals detected by functional near-infrared spectroscopy (fNIRS) from the prefrontal cortex, partial parietal cortex, and cortex of the temporal lobe in four groups of participants: mild cognitive impairment (MCI), Lewy body dementia (LBD), Alzheimer's disease (AD), and cognitively normal (CN)., Results: The study recruited 120 older adults with MCI (n = 30), LBD (n = 28), AD (n = 30), or CN (n = 32). The mean functional connectivity of the frontal and temporal lobe in resting state was significantly less in the AD (0.19 ± 0.11) group than in the MCI (0.23 ± 0.11), LBD (0.29 ± 0.12), and CN (0.40 ± 0.11) groups (p < 0.001). Further, the mean HbO concentrations in the brain regions and channels were significantly lower in the AD group than in the LBD and MCI groups (p < 0.001). Cognitive levels correlated significantly with the mean HbO concentrations in the resting state and verbal fluency task conditions., Conclusion: The fNIRS HbO signals significantly differed in the cerebral cortex regions in participants with different types of dementia. These findings suggest that fNIRS can effectively enhance the differential diagnosis and assessment of dementia., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Epicardial adipose tissue (EAT) significantly contributes to the progression of cardiovascular diseases (CVDs). However, manually quantifying EAT volume is labor-intensive and susceptible to human error. Although there have been some deep learning-based methods for automatic quantification of EAT, they are mostly uninterpretable and fail to harness the complete anatomical characteristics. In this study, we proposed an enhanced deep learning method designed for EAT quantification on coronary computed tomography angiography (CCTA) scan, which integrated both data-driven method and specific morphological information. A total of 108 patients who underwent routine CCTA examinations were included in this study. They were randomly assigned to training set (n = 60), validation set (n = 8), and test set (n = 40). We quantified and calculated the EAT volume based on the CT attenuation values within the predicted pericardium. The automatic method demonstrated strong agreement with expert manual quantification, yielding a median Dice score coefficients (DSC) of 0.916 (Interquartile Range (IQR): 0.846-0.948) for 2D slices. Meanwhile, the median DSC for the 3D volume was 0.896 (IQR: 0.874-0.908) between these two measures, with an excellent correlation of 0.980 (p < 0.001) for EAT volumes. Additionally, our model's Bland-Altman analysis revealed a low bias of -2.39 cm³. The incorporation of pericardial anatomical structures into deep learning methods can effectively enhance the automatic quantification of EAT. The promising results demonstrate its potential for clinical application., (© 2024. The Author(s).)

The N7-methylguanosine (m7G) methyltransferase Mettl1 has been recently implicated in cardiac repair and fibrosis. In this study we investigated the role of Mettl1 in mouse cardiomyocytes injury and the underlying mechanisms. Cardiac ischemia/reperfusion (I/R) I/R model was established in mice by ligation of the left anterior descending coronary artery (LAD) for 45 min followed by reperfusion for 24 h. We showed the mRNA and protein levels of Mettl1 were significantly upregulated in mouse I/R hearts and H 2 O 2 -treated neonatal mouse cardiomyocytes (NMCMs). Mettl1 knockdown markedly ameliorated cardiac I/R injury, evidenced by decreased infarct size, apoptosis, and improved cardiac function. Overexpression of Mettl1 triggered cardiomyocytes apoptosis in vivo and in vitro. By performing RNA sequencing combined with m7G methylated RNA sequencing in Mettl1-overexpressing mouse hearts, we revealed that Mettl1 catalyzed m7G modification of the deubiquitinase cylindromatosis (CYLD) mRNA to increase the expression of CYLD, which enhanced the stability of P53 via abrogating its ubiquitination degradation. Vice versa, P53 served as a transcriptional factor to positively regulate Mettl1 expression during I/R injury. Knockdown of CYLD mitigated cardiomyocytes apoptosis induced by Mettl1 overexpression or oxidative stress. From the available drug-targets databases and literature, we identified 4 small molecule inhibitors of m7G modification. Sinefungin, one of the Mettl1 inhibitors exerted profound protection against cardiac I/R injury in vivo and in vitro. Collectively, this study has identified Mettl1 as a key regulator of cardiomyocyte apoptosis, and targeting the Mettl1-CYLD-P53 positive feedback circuit may represent a novel therapeutic avenue for alleviating cardiac I/R injury., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Benzimidazoles (BMZs) are a class of veterinary drugs with a benzimidazole ring, the abuse of which poses a serious threat to ecological balance and human health. Consequently, the development of broad-spectrum antibodies and rapid assays are crucial for detecting BMZs in food samples. Herein, we scientifically designed three hapten structures, predicted the availability of the hapten with computational chemistry, and subsequently verified the broad-spectrum with immunological experiments. A broad-spectrum monoclonal antibody (6F10) was prepared based on the predicted hapten-2. Molecular recognition studies illustrated intricate interactions between mAb 6F10 binding to BMZs attributed to halogen bonds and π-π/π-alkyl interactions, revealing key amino acid sites and demonstrating the reliability of the hapten prediction strategies. Finally, a broad-spectrum, rapid, and sensitive lateral flow immunoassay based on aggregation-induced emission microspheres with high fluorescence intensity was established. The LOD values of the proposed method for eight kinds of BMZs were 0.027, 0.032, 0.058, 0.091, 0.087, 0.246, 0.369, and 0.311 ng mL -1 , respectively. In this work, a hapten prediction strategy based on a computational chemistry method effectively guided the preparation of antibodies for broad-spectrum recognition of BMZs, and the molecular recognition studies verified the interaction of mAb 6F10 with BMZs, enabling broad-spectrum and sensitive detection of BMZs in milk., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: This study aimed to investigate cortical activation and functional connectivity in the cortex during working memory (WM) tasks in patients with Alzheimer's disease (AD) using functional near-infrared spectroscopy (fNIRS)., Methods: A total of 17 older adults with AD and 17 cognitively normal (CN) participants were recruited. fNIRS was utilized to monitor oxygenated hemoglobin (HbO) concentrations in the frontotemporal lobe, while participants performed WM tasks to examine WM impairments in subjects with AD. Student's t-test for continuous variables and the chi-square test for categorical variables were used to compare the clinical and HbO variables between the AD and CN groups. Functional connectivity was analyzed using Pearson's correlation coefficient between the time series of each channel-to-channel pair., Results: The changes in HbO concentrations and cortical activations during the WM task showed that the HbO concentration curve of the CN group was higher than that of the AD group during the encoding and maintenance phases of the WM task. Although in the brain region scale, there were no significant differences in average HbO concentrations between the two groups, many channels located in the frontal and temporal lobes showed significant differences ( p  < 0.05) in the average HbO (channels 7 and 32) and slope HbO values (channels 7, 8, 9, 23, 30, 34, and 38) during the WM task. The average functional connectivity of the AD group was significantly lower than that of the CN group ( p  < 0.05). The functional connectivity was stronger in the frontopolar (FP) region than in other areas in both groups., Conclusion: This study revealed there were significant differences in HbO concentration in older adult patients with AD compared to CN during the WM task. The characteristics of HbO measured by the fNIRS technique can be valuable for distinguishing between AD and CN in older adults., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ruan, Li, Xu, Zhao, Mei and Zheng.)

Background: Perception is frequently impaired in patients with Alzheimer's disease (AD). Several patients exhibit visual or haptic hallucinations., Case Summary: A 71-year-old Chinese man presented with visual and haptic hallucinations he had been experiencing for 2 weeks. The clinical manifestations were the feeling of insects crawling and biting the limbs and geison. He looked for the insects while itching and scratching, which led to skin breakage on the limbs. He was treated with topical and anti-allergic drugs in several dermatology departments without any significant improvement. After admission, the patient was administered risperidone (0.5 mg) and duloxetine (2 mg/day). One week later, the dose of risperidone was increased to 2 mg/day, and that of duloxetine was increased to 60 mg/day. After 2 weeks of treatment, the patient's sensation of insects crawling and biting disappeared, and his mood stabilized., Conclusion: This patient manifested psychiatric behavioral symptoms caused by AD brain atrophy. It was important to re-evaluate the patient's cognitive-psychological status when the patient repeatedly went to the hospital for treatment. Follow-up attention to cognitive function and the consideration of perceptual deficits as early manifestations of AD should be considered., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Curcumae Radix (CR) is a widely used traditional Chinese medicine with significant pharmaceutical importance, including enhancing blood circulation and addressing blood stasis. This study aims to establish an integrated and rapid quality assessment method for CR from various botanical origins, based on chemical components, antiplatelet aggregation effects, and Fourier transform near-infrared (FT-NIR) spectroscopy combined with multivariate algorithms. Firstly, ultra-performance liquid chromatography-photodiode array (UPLC-PDA) combined with chemometric analyses was used to examine variations in the chemical profiles of CR. Secondly, the activation effect on blood circulation of CR was assessed using an in vitro antiplatelet aggregation assay. The studies revealed significant variations in chemical profiles and antiplatelet aggregation effects among CR samples from different botanical origins, with constituents such as germacrone, β-elemene, bisdemethoxycurcumin, demethoxycurcumin, and curcumin showing a positive correlation with antiplatelet aggregation biopotency. Thirdly, FT-NIR spectroscopy was integrated with various machine learning algorithms, including Artificial Neural Network (ANN), K-Nearest Neighbors (KNN), Logistic Regression (LR), Support Vector Machine (SVM), and Subspace K-Nearest Neighbors (Subspace KNN), to classify CR samples from four distinct sources. The result showed that FT-NIR combined with KNN and SVM classification algorithms after SNV and MSC preprocessing successfully distinguished CR samples from four plant sources with an accuracy of 100%. Finally, Quantitative models for active constituents and antiplatelet aggregation bioactivity were developed by optimizing the partial least squares (PLS) model with interval combination optimization (ICO) and competitive adaptive reweighted sampling (CARS) techniques. The CARS-PLS model achieved the best predictive performance across all five components. The coefficient of determination (R 2 p) and root mean square error (RMSEP) in the independent test sets were 0.9708 and 0.2098, 0.8744 and 0.2065, 0.9511 and 0.0034, 0.9803 and 0.0066, 0.9567 and 0.0172 for germacrone, β-elemene, bisdemethoxycurcumin, demethoxycurcumin and curcumin, respectively. The ICO-PLS model demonstrated superior predictive capabilities for antiplatelet aggregation biotency, achieving an R 2 p of 0.9010, and an RMSEP of 0.5370. This study provides a valuable reference for the quality evaluation of CR in a more rapid and comprehensive manner., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Aconiti lateralis radix praeparata (ALRP), the sub root of Aconitum carmichaelii Debx., is a traditional Chinese medicine with good pharmacological effects. Heishunpian (HSP), prepared through the process of brine immersing, boiling, rinsing, dyeing, and steaming ALRP is one of the most widely used forms of decoction pieces in clinical practice., Objectives: This study aims to investigate the mechanisms of component changes and transformations during the processing from ALRP to HSP, and to screen for their quality markers through UHPLC-QTOF-MS analysis., Methods: Samples from ALRP to HSP during processing were prepared and analyzed by UHPLC-QTOF-MS. By comparing the differences between before and after each processing step, the purpose of processing and the transformation of components during processing were studied. In addition, multiple batches of ALRP and HSP were determined, and potential quality markers were screened., Results: Through the analysis of ALRP and five key processing samples, 55 components were identified. Immersing in brine, rinsing, and dyeing were the main factors of component loss, and boiling caused a slight loss of components. Some components were enhanced during the steaming process. Combining the screened differences components between multiple ALRP and HSP, 10 components were considered as potential quality biomarkers., Conclusion: This study found that the adjacent hydroxyl groups of the ester group may have a positive impact on the hydrolysis of the ester group, and 10 quality markers were preliminarily screened. It provides a reference for quality control and clinical application of ALRP and HSP., (© 2024 John Wiley & Sons Ltd.)

Objective: This study mainly explores (2R,6R; 2S,6S)-HNK and its compounds whether there are antidepressant effects., Methods: Four HNK compounds were obtained from 2-(Chlorophenyl) Cyclopentylmethanone. Forced swimming test, locomotor sensitization test, and conditioned location preference test were used to screen the antidepressant activity of the synthesized target compounds., Results: In the case of 10 mg HNK treatment, compared with saline, the immobile time of mice in the HNK group, I5 group and I6 group at 1 h and 7 days had statistical significance. In the case of 10 mg HNK treatment, compared with saline, the immobile time of compound C and D groups in the glass cylinder area was significantly different. In the locomotor sensitization test, the movement distance of compound C and D groups on day 15 and day 7 mice increased significantly compared with the first day. In the conditioned place preference experiment, compound C and compound D induced conditioned place preference in mice compared with the Veh group., Conclusion: The results of the forced swimming test, locomotor sensitization test, and conditioned location preference test showed that compounds C and D may have certain anti-depressant activity. However, HNK exerts a rapid and significant antidepressant effect within 1 week, but the duration is short., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Type 2 diabetes mellitus (T2DM) significantly impairs the functionality and number of endothelial progenitor cells (EPCs) and resident endothelial cells, critical for vascular repair and regeneration, exacerbating the risk of vascular complications. GLP-1 receptor agonists, like dulaglutide, have emerged as promising therapeutic agents due to their multifaceted effects, including the enhancement of EPC activity and protection of endothelial cells. This study investigates dulaglutide's effects on peripheral blood levels of CD34 + and CD133+ cells in a mouse model of lower limb ischemia and its protective mechanisms against high-glucose-induced damage in endothelial cells. Results demonstrated that dulaglutide significantly improves blood flow, reduces tissue damage and inflammation in ischemic limbs, and enhances glycemic control. Furthermore, dulaglutide alleviated high-glucose-induced endothelial cell damage, evident from improved tube formation, reduced reactive oxygen species accumulation, and restored endothelial junction integrity. Mechanistically, dulaglutide mitigated mitochondrial fission in endothelial cells under high-glucose conditions, partly through maintaining SIRT1 expression, which is crucial for mitochondrial dynamics. This study reveals the potential of dulaglutide as a therapeutic option for vascular complications in T2DM patients, highlighting its role in improving endothelial function and mitochondrial integrity., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare that are relevant to the content of this article. All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The efficacy of berberine in managing diabetes through modulation of gut microbiome has been established through fecal sample analyses. However, relying solely on fecal materials constrains our comprehension of berberine's effects on diverse gastrointestinal locations. This study specifically explores the ileocecal region, a segment characterized by higher microbial diversity than fecal samples. Berberine exhibits a robust hypoglycemic impact by significantly reducing glucose levels in blood and urine. Beyond glycemic control, berberine ameliorates various diabetes-related symptoms in serum, including increased insulin and leptin, but decreased NEFA and MDA. Notably, berberine demonstrates liver-protective functions by alleviating oxidative stress and enhancing hepatic glycogen abundance. These outcomes prompted a high-throughput sequencing analysis of the ileocecal microbiome, revealing an augmentation of beneficial bacterial genera (four genera in the Lachnospiraceae family, Erysipelatoclostridium , and Escherichia-Shigella ), along with a reduction in harmful bacterial genera ( Romboutsia ). Additionally, we predicted the impact of the ileocecal microbiome on clinically relevant factors associated with diabetes. These findings elucidate the multi-pathway mechanisms of berberine in treating T2D, underscoring its potential as a natural anti-diabetic agent or functional food, particularly through the modulation of the gut microbiota., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Small extracellular vesicles (sEVs) are a type of extracellular vesicle that carries many types of molecular information. The identification of sEVs is essential for the non-invasive detection and treatment of illnesses. Hence, there is a significant need for the development of simple, sensitive, and precise methods for sEV detection. Herein, a DNA tweezers-based assay utilizing a "turn-on" mechanism and proximity ligation was suggested for the efficient and rapid detection of sEVs through amplified fluorescence. The target facilitates the proximity combination of the C1 probe and C2 probe, resulting in the formation of a complete extended sequence. The elongated sequence can cyclically initiate the hairpin probe (HP), leading to the activation of DNA tweezers. An excellent linear correlation was achieved, with a limit of detection of 57 particles per μL. Furthermore, it has been effectively employed to analyze sEVs under intricate experimental conditions, demonstrating a promising and pragmatic prospect for future applications. Given that the identification of sEVs was successfully accomplished using a single-step method that exhibited exceptional sensitivity and strong resistance to interference, the proposed technique has the potential to provide a beneficial platform for accurate recognition of sEVs and early detection of diseases.

Surface-enhanced Raman spectroscopy (SERS), a rapid, low-cost, non-invasive, ultrasensitive, and label-free technique, has been widely used in-situ and ex-situ biomedical diagnostics questions. However, analyzing and interpreting the untargeted spectral data remains challenging due to the difficulty of designing an optimal data pre-processing and modelling procedure. In this paper, we propose a Multi-branch Attention Raman Network (MBA-RamanNet) with a multi-branch attention module, including the convolutional block attention module (CBAM) branch, deep convolution module (DCM) branch, and branch weights, to extract more global and local information of characteristic Raman peaks which are more distinctive for classification tasks. CBAM, including channel and spatial aspects, is adopted to enhance the distinctive global information on Raman peaks. DCM is used to supplement local information of Raman peaks. Autonomously trained branch weights are applied to fuse the features of each branch, thereby optimizing the global and local information of the characteristic Raman peaks for identifying diseases. Extensive experiments are performed for two different neurological disorders classification tasks via untargeted serum SERS data. The results demonstrate that MBA-RamanNet outperforms commonly used CNN methods with an accuracy of 88.24% for the classification of healthy controls, mild cognitive impairment, Alzheimer's disease, and Non-Alzheimer's dementia; an accuracy of 90% for the classification of healthy controls, elderly depression, and elderly anxiety., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Optica Publishing Group.)

Polyethylene (PE) is the most productive plastic product and includes three major polymers including high-density polyethylene (HDPE), linear low-density polyethylene (LLDPE) and low-density polyethylene (LDPE) variation in the PE depends on the branching of the polymer chain and its crystallinity. Tenebrio obscurus and Tenebrio molitor larvae biodegrade PE. We subsequently tested larval physiology, gut microbiome, oxidative stress, and PE degradation capability and degradation products under high-purity HDPE, LLDPE, and LDPE powders (<300 μm) diets for 21 days at 65 ± 5% humidity and 25 ± 0.5 °C. Our results demonstrated the specific PE consumption rates by T. molitor was 8.04-8.73 mg PE ∙ 100 larvae -1 ⋅day -1 and by T. obscurus was 7.68-9.31 for LDPE, LLDPE and HDPE, respectively. The larvae digested nearly 40% of the ingested three PE and showed similar survival rates and weight changes but their fat content decreased by 30-50% over 21-day period. All the PE-fed groups exhibited adverse effects, such as increased benzoquinone concentrations, intestinal tissue damage and elevated oxidative stress indicators, compared with bran-fed control. In the current study, the digestive tract or gut microbiome exhibited a high level of adaptability to PE exposure, altering the width of the gut microbial ecological niche and community diversity, revealing notable correlations between Tenebrio species and the physical and chemical properties (PCPs) of PE-MPs, with the gut microbiome and molecular weight change due to biodegradation. An ecotoxicological simulation by T.E.S.T. confirmed that PE degradation products were little ecotoxic to Daphnia magna and Rattus norvegicus providing important novel insights for future investigations into the environmentally-friendly approach of insect-mediated biodegradation of persistent plastics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The dried young fruit of Citrus reticulata Blanco, known as Qingpi, is commonly used in clinic both with its raw and vinegar-processed products. However, the distinctions in quality between these two products remain unclear, and the methods for identification are considerably intricate. In this study, an electronic eye technique was applied to assess the overall color of Qingpi products before and after processing. The luminosity (L*) and yellow-blue (b*) values of Qingpi decreased after vinegar processing, while red-green (a*) values increased. The discriminant function models based on color parameters were established to effectively classify the two products. The chemical compositions of different Qingpi products were characterized using ultra-high performance liquid chromatography fingerprint technology, and 10 distinct components were considered as potential chemical markers. The correlation analysis revealed a significant relationship between chromatic values and chemical components. In conclusion, the results of this study suggested that chromaticity can be effectively considered as a valuable instrument for the prediction of component content in both raw and vinegar-processed Qingpi products. This study will provide new ideas and methods for identification and quality evaluation of Qingpi processed products, as well as provide a reference for standardizing traditional Chinese medicine processing techniques., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Statins are known to be anti-inflammatory, but the mechanism remains poorly understood. Here, we show that macrophages, either treated with statin in vitro or from statin-treated mice, have reduced cholesterol levels and higher expression of Jmjd3 , a H3K27me3 demethylase. We provide evidence that lowering cholesterol levels in macrophages suppresses the adenosine triphosphate (ATP) synthase in the inner mitochondrial membrane and changes the proton gradient in the mitochondria. This activates nuclear factor kappa-B (NF-κB) and Jmjd3 expression, which removes the repressive marker H3K27me3. Accordingly, the epigenome is altered by the cholesterol reduction. When subsequently challenged by the inflammatory stimulus lipopolysaccharide (M1), macrophages, either treated with statins in vitro or isolated from statin-fed mice, express lower levels proinflammatory cytokines than controls, while augmenting anti-inflammatory Il10 expression. On the other hand, when macrophages are alternatively activated by IL-4 (M2), statins promote the expression of Arg1 , Ym1 , and Mrc1 . The enhanced expression is correlated with the statin-induced removal of H3K27me3 from these genes prior to activation. In addition, Jmjd3 and its demethylase activity are necessary for cholesterol to modulate both M1 and M2 activation. We conclude that upregulation of Jmjd3 is a key event for the anti-inflammatory function of statins on macrophages., Competing Interests: ZS, KD, YL, NV, DV, VA, JZ, KN, MC, JM, CC, AS, BS, IL, JL, JD, XZ No competing interests declared, (© 2024, Salloum et al.)

Spinal cord injury (SCI) is a traumatic neuropathic condition that results in motor, sensory and autonomic dysfunction. Mitochondrial dysfunction caused by primary trauma is one of the critical pathogenic mechanisms. Moderate levels of zinc have antioxidant effects, promote neurogenesis and immune responses. Zinc normalises mitochondrial morphology in neurons after SCI. However, how zinc protects mitochondria within neurons is unknown. In the study, we used transwell culture, Western blot, Quantitative Real-time Polymerase Chain Reaction (QRT-PCR), ATP content detection, reactive oxygen species (ROS) activity assay, flow cytometry and immunostaining to investigate the relationship between zinc-treated microglia and injured neurons through animal and cell experiments. We found that zinc promotes mitochondrial transfer from microglia to neurons after SCI through Sirtuin 3 (SIRT3) regulation of Mitofusin 2 protein (Mfn2). It can rescue mitochondria in damaged neurons and inhibit oxidative stress, increase ATP levels and promote neuronal survival. Therefore, it can improve the recovery of motor function in SCI mice. In conclusion, our work reveals a potential mechanism to describe the communication between microglia and neurons after SCI, which may provide a new idea for future therapeutic approaches to SCI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Immunochromatographic assay (ICA) has attracted widespread attention owing to its advantages of economy, simplicity, and rapidity. However, the synthesis of immunoprobes is still limited by complicated design ideas and multistep operations from preparing nanoparticles to conjugating monoclonal antibodies (mAb) onto nanoparticles. Inspired by the biomineralization of zeolitic imidazolate framework-8 (ZIF-8), we proposed a strategy for the rapid synthesis of an integrated immunoprobe (ZIF-8@QDs-mAb), achieving a one-step integration with strong fluorescent signal output capability and specific recognition ability. In addition, different fluorescent colors of ZIF-8@QDs-mAb were generated by doping red and green quantum dots (QDs) in various ratios. With a smart detection platform, the developed ZIF-8@QDs-mAb-based multiplex ICA (ZIF-8@QDs-mAb-mICA) achieved the on-site quantitative detection of enrofloxacin, sulfamethazine, and kanamycin in milk within 15 min, with the limit of detection (LOD) of 0.052, 0.186 and 0.216 ng mL -1 , which were 5.69, 2.20 and 4.40 times higher than that of gold nanoparticles-based mICA, respectively. The quantitative detection of alpha-fetoprotein and human chorionic gonadotropin was also achieved with LOD of 0.516 ng mL -1 and 0.225 mIU mL -1 , respectively, which verified the universality of the strategy. This work provides a novel idea for the design of an efficient integrated immunoprobe and has broad application prospects in ICA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The advent of immune-checkpoint inhibitors (ICIs) has revolutionized the treatment of malignant solid tumors in the last decade, producing lasting benefits in a subset of patients. However, unattended excessive immune responses may lead to immune-related adverse events (irAEs). IrAEs can manifest in different organs within the body, with pulmonary toxicity commonly referred to as immune checkpoint inhibitor-related pneumonitis (CIP). The CIP incidence remains high and is anticipated to rise further as the therapeutic indications for ICIs expand to encompass a wider range of malignancies. The diagnosis and treatment of CIP is difficult due to the large individual differences in its pathogenesis and severity, and severe CIP often leads to a poor prognosis for patients. This review summarizes the current state of clinical research on the incidence, risk factors, predictive biomarkers, diagnosis, and treatment for CIP, and we address future directions for the prevention and accurate prediction of CIP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lin, Zang, Liu, Han and Chen.)

The present study has successfully established a scientific and precise approach for distinguishing the geographical origins of young citrus fruits (Qingpi) from four primary production regions in China, using gas chromatography-mass spectrometry (GC-MS) and flash gas chromatography electronic nose (flash GC e-nose) to analyze the volatile composition and odor characteristics. Through the application of chemometric analysis, a clear differentiation among Qingpi samples was established using GC-MS. Additionally, the application of flash GC e-nose facilitated the extraction of flavor information, which enabled the discrimination of geographical origins. Several flavor components were identified as significant factors for origin certification. Furthermore, two pattern recognition algorithms were employed to achieve high accuracy in regional identification. The results of this investigation demonstrate that the amalgamation of multivariate chemometrics and algorithms can proficiently discern the sources of those young citrus fruits. The findings of this research can provide a reference for the assessment of quality control in food and other agricultural commodities in the times ahead., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The quality of traditional Chinese medicine is very important for human health, but the traditional quality control method is very tedious, which leads to the substandard quality of many traditional Chinese medicine. In order to solve the problem of time-consuming and laborious traditional quality control methods, this study takes traditional Chinese medicine Cyperus rotundus as an example, a comprehensive strategy of near-infrared (NIR) spectroscopy combined with One-dimensional convolutional neural network (1D-CNN) and chaotic map dung beetle optimization (CDBO) algorithm combined with BP neural network (BPNN) is proposed. This strategy has the advantages of fast and non-destructive. It can not only qualitatively distinguish Cyperus rotundus and various processed products, but also quantitatively predict two bioactive components. In classification, 1D-CNN successfully distinguished four kinds of processed products of Cyperus rotundus with 100 % accuracy. Quantitatively, a CDBO algorithm is proposed to optimize the performance of the BPNN quantitative model of two terpenoids, and compared with the BP, whale optimization algorithm (WOA)-BP, sparrow optimization algorithm (SSA)-BP, grey wolf optimization (GWO)-BP and particle swarm optimization (PSO)-BP models. The results show that the CDBO-BPNN model has the smallest error and has a significant advantage in predicting the content of active components in different processed products. To sum up, it is feasible to use near infrared spectroscopy to quickly evaluate the effect of processing methods on the quality of Cyperus rotundus, which provides a meaningful reference for the quality control of traditional Chinese medicine with many other processing methods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Pyroptosis is an inflammatory type of programmed cell death, and could overcome the drug-resistance induced by anti-apoptotic effect of cancers. Carvedilol (CVL), a β-adrenergic receptors antagonist, has shown anti-inflammatory response and anti-cancer effect. The aim of this study is to investigate whether pyroptosis can be activated by CVL in prostate cancer (PCa)., Methods and Results: Datasets were used to analyze the expressions of pyroptosis-related proteins. Intracellular morphological change, cell viability, LDH and Il-1β release by cells,, and Hoechst/PI staining were used to detect the occurrence of pyroptosis. Realtime-PCR, western blot, immunofluorescence, and immunohistochemistry (IHC) were used to investigate the expressions of pyroptosis-related proteins. Datasets analyze showed the expressions of NLRP3, Caspase 1, ASC and GSDMD were all decreased in PCa comparing with normal tissues, but without prognostic significance. CVL treatment weakened the viabilities of PCa cells. Cell morphology changing, cytoplasmic vacuole formation, membrane integrity loss, LDH and IL-1β release and PI positive cells increasing were observed. NLRP3, Caspase 1, ASC, GSDMD and N-GSDMD expressions were elevated after CVL treatment, accompanied by a tendency of NF-κB transferring into nucleus. In vivo, CVL inhibited the growth of subcutaneous transplanted tumor. IHC showed CVL increased the expressions of NLRP3, ASC, and GSDMD, and decreased the expression of Ki-67 in transplanted tumor tissues., Conclusion: This study demonstrated that CVL could induce pyroptosis in PCa cells through NLRP3-caspase1-ASC inflammasome by promoting nuclear translocation of NF-κB, which would lay a foundation for the application of adrenergic receptor antagonist in PCa., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Qingpi, a well-known traditional Chinese medicine for qi-regulating and commonly processed into three types of pieces, has been widely used in the clinical application of liver disease for thousands of years. In this study, an ultra-high-performance liquid chromatography-quadrupole-time of flight-mass spectrometry approach along with multivariate statistical analysis was developed to assess and characterize the differentiations of three processed products and confirm the potential quality markers of Qingpi. In addition, a systematic analysis combined with network pharmacology and molecular docking was performed to clarify the potential mechanism of Qingpi for the treatment of liver disease. As a result, 18 components were identified and an integrated network of Qingpi-Components-Target-Pathway-Liver Disease was constructed. Eight compounds were finally screened out as the potential quality markers acting on ten main targets and pathways of liver disease. Molecular docking analysis results indicated that the quality markers had a good binding activity with the targets. Overall, this work preliminarily identified the potential quality markers of three processed products of Qingpi, and predicted its targets in the prevention and treatment of liver disease, which can provide supporting information for further study of the pharmacodynamic substances and mechanisms of Qingpi., (© 2023 Wiley-VCH GmbH.)

The effects of HNK, I5, and I6 on the expression of protein in hippocampus of depressed mice were studied by isobaric tags for relative and absolute quantitation (iTRAQ) to explore the mechanism of their antidepressant action. HNK, I5, and I6 were administered intragastric administration once a day in the morning for 7 days. The drug was subsequently discontinued for 7 days (without any treatment). On the 15th day, mice in each group were given the drug (1.0, 10.0, 30.0 mg/kg) intragastric stimulation and mouse hippocampal tissues were taken to perform iTRAQ to identify differentially expressed proteins, and bioinformatics was used to analyze the functional enrichment of the differentially expressed proteins. Compared with Ctr group, the number of differentially expressed proteins in HNK, I5, and I6 treatment groups was 158, 88, and 105, respectively. The three groups shared 29 differentially expressed proteins. In addition, compared with HNK group, the number of differentially expressed proteins in I5 and I6 groups was 201 and 203, respectively. A total of 47 and 56 differentially expressed proteins were co-expressed in I5 and I6 groups. Bioinformatics analysis showed that these differentially expressed proteins mainly had the functions of binding, biocatalysis, and transport, and mainly participated in cellular process, biological regulation process, biological metabolism process, and stress reaction process. GO and KEGG pathway analysis found that these differentially expressed proteins were involved long-term potentiation, G13 pathway, platelet activation pathway, and MAPK signaling pathway. HNK, I5, and I6 antidepressants are closely related to sudden stress sensitivity, stress resistance, neurotransmitter, and metabolic pathways. This study provides a scientific basis to further elucidate the mechanism and clinical application of HNK, I5, and I6 antidepressants., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Developing of the multifunctional polymeric carrier for controlled drug release is still one of most challenging task. In this work, a pH-responsive dual drug delivery system was designed and prepared based on the zeolitic imidazolate framework-8 (ZIF-8). The poly(lactic acid)/chitosan (PLA/CS) core-shell nanofiber membranes by emulsion electrospinning, which the hydrophilic drug (Astragalus Polysacharin, APS) was encapsulated in the CS core and the hydrophobic drug (Camptothecin, CPT) was loaded into the PLA shell, respectively. Subsequently, ZIF-8 nanoparticles served as the protective layer were immobilized on the surface of PLA/CS to form multi-structural PLA/CS@ZIF-8 nanofiber membranes. In vitro drug release of nanofiber membranes were studied in the acidic and neutral medium, respectively. The results were that the hydrophilicity and surface roughness of nanofiber membranes rose with increasing of 2-MIM concentrations. The nanofiber membranes also had excellent pH-responsive and controlled release property. Furthermore, the drug release of PLA/CS@ZIF-8 for either APS or CPT were all carried out in a coexisting manner of diffusion and skeleton corrosion. In addition, in vitro cytotoxicity assay indicated nanofiber membranes with good cytocompatibility. Therefore, the multi-structured PLA/CS@ZIF-8 nanofiber membranes has been used as a potential pH-responsive dual drug release system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Delirium is an acute reversible neuropsychiatric syndrome caused by multiple factors. It is associated with many adverse clinical outcomes including cognitive impairment, functional decline, prolonged hospitalization, and increased nursing service. The prevalence of delirium was high in department of cardiology, geriatric, and intensive care unit of hospital. With the increase in the aged population, further increases in delirium seem likely. However, it remains poorly recognized in the clinical practice. This article comprehensively discusses the latest research perspectives on the epidemiological data, risk factors, preventive interventions, overlapping symptoms, and clinical measures of delirium, including specific measures to manage delirium in clinical real-world situations. This article helps readers improve their knowledge and understanding of delirium and helps clinicians quickly identify and implement timely therapeutic measures to address various delirium subtypes that occur in the clinical settings to ensure patients are treated as aggressively as possible., Competing Interests: Conflict-of-interest statement: The authors declare that they had no conflict of interests., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: The flavonoid Naringin (Nar) has been extensively investigated and found to have multiple pharmacological properties, including neuroprotection. Although recent reports have shown that Nar can effectively treat spinal cord injury (SCI), its potential mechanism remains unknown. This study aimed to investigate the effects of Nar on motor recovery and inflammatory responses after SCI and to elucidate its mechanism., Methods: SCI rat models were established using Allen's weight-drop method. The rats were intragastrically given Nar (40 mg/kg) for 21 d, and their motor function before surgery and on the 1st, 3rd, 7th, 14th, 21st days after surgery was assessed by the Basso-Beattie-Bresnahan (BBB) scale and examined by the grid walking test (GWT). The enzyme linked immunosorbent assay (ELISA) was used to detect the interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and monocyte chemoattractant protein (MCP)-1 levels in rat spinal cord tissues, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) to measure the mRNA expression levels of microglial activation markers CD68 and ionized calcium binding adaptor molecule 1 (Iba-1), M1 markers inducible nitric oxide synthase (iNOS) and IL-6, and M2 markers CD206 and Arginase 1 (Arg1). The expression levels of peroxisome proliferator-activated receptor gamma/nuclear factor kappa B (PPAR-γ/NF-κB) pathway-related proteins in rat spinal cord tissues were determined using western blotting., Results: Nar significantly increased the BBB score and decreased the mean error rate of GWT in SCI rats. Additionally, Nar effectively inhibited microglial activation and expression of M1 markers in spinal cord tissues. It also elevated M2 polarization-related gene expression and significantly lowered the levels of inflammatory factors. Further investigation showed that Nar enhanced the expression of PPAR-γ protein and inhibited NF-κB pathway activity., Conclusion: Nar promotes functional recovery by regulating microglial polarization and inhibiting the inflammatory response in SCI, and its mechanism may be related to the PPAR-γ/NF-κB signaling pathway activity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: As a non-pharmacologic treatment, bright light therapy (BLT) is often used to improve affective disorders and memory function. In this study, we aimed to determine the effect of BLT on depression and electrophysiological features of the brain in patients with Alzheimer's disease (AD) and their caregivers using a light-emitting diode device of 14000 lux. Methods: A 4-week case-control trial was conducted. Neuropsychiatric and electroencephalogram (EEG) examination were evaluated at baseline and after 4 weeks. EEG power in delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), and beta (12-30 Hz) bands was calculated for our main analysis. Demographic and clinical variables were analyzed using Student's t test and the chi-square test. Pearson's correlation was used to determine the correlation between electrophysiological features, blood biochemical indicators, and cognitive assessment scale scores. Results: In this study, 22 in-patients with AD and 23 caregivers were recruited. After BLT, the Hamilton depression scale score decreased in the fourth week. Compared with the age-matched controls of their caregivers, a higher spectral power at the lower delta and theta frequencies was observed in the AD group. After BLT, the EEG power of the delta and theta frequencies in the AD group decreased. No change was observed in blood amyloid concentrations before and after BLT. Conclusion: In conclusion, a 4-week course of BLT significantly suppressed depression in patients with AD and their caregivers. Moreover, changes in EEG power were also significant in both groups., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mei, Zou, Si, Xu, Hu, Wu and Zheng.)

Introduction: This study utilized serum proteomics with tandem mass tags (TMT) to investigate potential biomarkers associated with femoral central venous catheter (CVC) thrombosis in endstage kidney disease (ESKD) patients. TMT proteomics analysis on serum samples was conducted to identify proteins with distinct expression levels that may be linked to thrombosis. The findings have important implications for enhancing anticoagulant procedures, catheter closure techniques, and determining optimal intervention timing for post-catheterization dialysis., Methods: Thirty ESKD patients with CVC receiving hemodialysis between May 2021 and October 2022 at the First Affiliated Hospital of Chengdu Medical College were included in the study, and grouped according to vascular color Doppler ultrasound results, including 23 patients in the thrombo-positive group and 7 patients in the thrombo-negative group. Selection criteria were: 1) Patients with ESKD candidate for hemodialysis initiation; 2) no dialysis access has been placed previously, and CVC needs to be inserted as a temporary access; 3) patients volunteered to participate in this clinical study. Clinical data, blood tests, coagulation function, and biochemical parameters were collected and analyzed on the 14th day after catheterization. Color ultrasonography was conducted on the same day to categorize patients into two groups: those with thrombus-positive results and those with thrombus-negative results., Results: TMT proteomics analysis identified twenty-eight differently expressed proteins, including 16 upregulated and 12 downregulated proteins. Enrichment analysis demonstrated nine proteins that were significantly enriched in four pathways within the thrombus-positive group after CVC insertion. Enzyme-linked immunosorbent assay (ELISA) test confirmed the TMT proteomics findings, specifically highlighting significant differences in human plasma kallikrein B1 (KLKB1) and angiopoietin-like protein 3 (ANGPTL3) levels on the 14th day after CVC insertion. Additionally, KLKB1, fibrinogen (FIB), D-dimer, and fibrinogen degradation products (FDP) levels were significantly elevated, while ANGPTL3 levels were decreased on the 14th day after CVC insertion in the thrombus-positive ESKD patient group., Conclusion: Monitoring coagulation status post-CVC catheterization and evaluating potential biomarkers like KLKB1 and ANGPTL3 can contribute to the development of personalized treatment plans, improving the quality of hemodialysis and the overall quality of life for ESKD patients.  DOI: 10.52547/ijkd.7671.

The occurrence of acute thrombosis, directly related to platelet aggregation and coagulant system, is a considerable reason for the failure of small-diameter vascular grafts. Heparin is commonly used as a functional molecule for graft modification due to the strong anticoagulant effect. Unfortunately, heparin cannot directly resist the adhesion and aggregation of platelets. Therefore, we have prepared a heparin-aspirin compound by coupling heparin with aspirin, an antiplatelet drug, and covalently grafted it onto the surface of polycaprolactone/polyurethane composite tube. In this way, the graft not only showed a dual function of both anticoagulation and antiplatelet, but also effectively avoided the rapid drug release and excessive toxicity to other organs caused by simple blending the medicine with material matrix. The compound retained the original function of heparin, showing good hydrophilicity and biocompatibility, which could promote the adhesion and proliferation of endothelial cells (ECs) and facilitate the process of tissue regeneration. What's more, the compound showed more effective than heparin in reducing platelet activation and preventing thrombosis. The graft modified by this compound maintained completely unobstructed for one month of implantation, while severe obstruction or stenosis occurred in PCL/PU and PCL/PU-Hep lumen at the first week, verifying the effect of the compound on preventing acute thrombosis. In general, this study proposed a designing method for small-diameter vascular graft which could prevent acute thrombosis and promote intimal construction., Competing Interests: Declaration of competing interest All authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

In this study, CM-5 spectrophotometer and Heracles NEO ultra-fast gas-phase electronic nose were used to analyze the changes in color and odor of vinegar-processed Cyperi Rhizoma(VPCR) pieces. Various analysis methods such as DFA and partial least squares discriminant analysis(PLS-DA) were combined to identify different processing degrees and quantify the end point of processing. The results showed that with the increase in vinegar processing, the brightness parameter L~* of VPCR pieces decreased gradua-lly, while the red-green value a~* and yellow-blue value b~* initially increased and reached their maximum at 8 min of processing, followed by a gradual decrease. A discriminant model based on the color parameters L~*, a~*, and b~* was established(with a discrimination accuracy of 98.5%), which effectively differentiated different degrees of VPCR pieces. Using the electronic nose, 26 odor components were identified from VPCR samples at different degrees of vinegar processing. DFA and PLS-DA models were established for different degrees of VPCR pieces. The results showed that the 8-min processed samples were significantly distinct from other samples. Based on variable importance in projection(VIP) value greater than 1, 10 odor components, including 3-methylfuran, 2-methylbuty-raldehyde, 2-methylpropionic acid, furfural, and α-pinene, were selected as odor markers for differentiating the degrees of vinegar processing in VPCR. By combining the changes in color and the characteristic odor components, the optimal processing time for VPCR was determined to be 8 min. This study provided a scientific basis for the standardization of vinegar processing techniques for VPCR and the improvement of its quality standards and also offered new methods and ideas for the rapid identification and quality control of the end point of processing for other traditional Chinese medicine.

Objective: To investigate correlation between cognitive function, age, and sleep disturbances., Methods: This retrospective clinical study enrolled 78 patients with sleep disorders who were divided into three groups: a group of 24 patients with sleep disorders accompanied by cognitive decline (SD-CD); 54 patients with sleep disorders and no cognitive decline (SD-nCD) was divided into two groups, one of 30 patients aged between 60 and 70 years and another of 24 patients aged >70 years. Polysomnography was used to record patients' sleep indicators throughout night; these included total sleep duration, sleep efficiency (SE), sleep latency, sleep structure and percentage of N1, N2, and N3 stages, rapid eye movement (REM) stage, as well as apnea hypopnea index (AHI), and oxygen saturation (OS). Analysis of variance (ANOVA) for continuous variables and chi-square test for categorical variables were used to analyze variables between different groups. Pearson's correlation was used to analyze correlation between sleep parameters and mini-mental state examination (MMSE). Blood samples were used to determine their Aβ, Aβ 40 , Aβ 42 , total tau, phosphorylated tau protein (ptau), ptau 181 , ptau 217 , the inflammatory factor IL-1β, vitamin B12 (VB12), and melatonin levels., Results: In the SD-CD group, there was a significant decrease in SE and an increase in N1 stage sleep in older patients and a significant increase in AHI, REM stage AHI, and non-REM stage AHI. In patients with SD-nCD, the minimum OS, minimum OS in the REM period, and minimum OS in the non-REM period were significantly reduced. OS was significantly correlated with cognitive level, as evaluated by the MMSE. The addition of sleep parameters can significantly improve the accuracy of dementia diagnosis. Dementia biomarkers of Aβ and tau proteins in blood showed cognition-related differences, while ptau181 was associated with both cognition and age-related differences. Regression models revealed that age was related to higher levels of cognitive decline before (β = -0.43, P < 0.001) and after (β = -0.38, P < 0.001) adjustment of gender, BMI, and education level. There was a significant mediation effect of relationship between aging and cognitive function by sleep efficiency and N1 stage sleep., Conclusion: Sleep disorders and low OS are associated with a higher incidence of cognitive decline and dementia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mei, Zhao, Qiu, Wang, Yu and Zheng.)

Nonalcoholic fatty liver disease (NAFLD) has become a worldwide epidemic and a major public health problem, with a prevalence of approximately 25%. The pathogenesis of NAFLD is complex and may be affected by the environment and susceptible genetic factors, resulting in a highly variable disease course and no approved drugs in the clinic. Notably, 17β-hydroxysteroid dehydrogenase type 13 (HSD17B13), which belongs to the 17β-hydroxysteroid dehydrogenase superfamily (HSD17Bs), is closely related to the clinical outcome of liver disease. HSD17Bs consists of fifteen members, most related to steroid and lipid metabolism, and may have the same biological function as HSD17B13. In this review, we highlight recent advances in basic research on the functional activities, major substrates, and key roles of HSD17Bs in the progression of NAFLD to develop innovative anti-NAFLD drugs targeting HSD17Bs., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Mitochondrial damage caused by oxidative stress and energy deficiency induced by focal ischemia and hypoxia are important factors that aggravate diseases. Studies have shown that ginsenoside Rb1 has neurotrophic and neuroprotective effects. However, whether it influences energy metabolism after spinal cord injury remains unclear. In this study, we treated mouse and cell models of spinal cord injury with ginsenoside Rb1. We found that ginsenoside Rb1 remarkably inhibited neuronal oxidative stress, protected mitochondria, promoted neuronal metabolic reprogramming, increased glycolytic activity and ATP production, and promoted the survival of motor neurons in the anterior horn and the recovery of motor function in the hind limb. Because sirtuin 3 regulates glycolysis and oxidative stress, mouse and cell models of spinal cord injury were treated with the sirtuin 3 inhibitor 3-TYP. When Sirt3 expression was suppressed, we found that the therapeutic effects of ginsenoside Rb1 on spinal cord injury were remarkably inhibited. Therefore, ginsenoside Rb1 is considered a potential drug for the treatment of spinal cord injury, and its therapeutic effects are closely related to sirtuin 3., Competing Interests: None

Identification of age-related neuropsychiatric disorders, i.e., late-life depression (LDD) and mild cognitive impairment (MCI) is of imperative clinical value considering the large probability of misdiagnosis and current lack of sensitive, non-invasive and low-cost diagnostic approaches. Here, the serum surface-enhanced Raman spectroscopy (SERS) technique is proposed to identify healthy controls, LDD and MCI patients. Based on SERS peaks analysis, abnormal levels of ascorbic acid, saccharide, cell-free DNA and amino acids in serum are found to be potential biomarkers for identifying LDD and MCI. These biomarkers might be related to oxidative stress, nutritional status, lipid peroxidation and metabolic abnormalities. Moreover, partial least square analysis-linear discriminant analysis (PLS-LDA) is applied to those collected SERS spectra. Finally, the overall identification accuracy is 83.2%, and accuracies are 91.6% and 85.7% for differentiating healthy versus neuropsychiatric disorders and LDD versus MCI, respectively. Thus, the serum SERS combined with multivariate statistical analysis has proved its successful potential for rapid, sensitive and non-invasive identification of healthy, LDD and MCI, which may open new avenues for early diagnosis and timely intervention for age-related neuropsychiatric disorders., Competing Interests: The authors declare no conflicts of interest., (© 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Background: Functional near-infrared spectroscopy (fNIRS) is commonly used to study human brain function by measuring the hemodynamic signals originating from cortical activation and provides a new noninvasive detection method for identifying dementia., Aim: To investigate the fNIRS imaging technique and its clinical application in differential diagnosis of subtype dementias including frontotemporal lobe dementia, Lewy body dementia, Parkinson's disease dementia (PDD) and Alzheimer's disease (AD)., Methods: Four patients with different types of dementia were examined with fNIRS during two tasks and a resting state. We adopted the verbal fluency task, working memory task and resting state task. Each patient was compared on the same task. We conducted and analyzed the fNIRS data using a general linear model and Pearson's correlation analysis., Results: Compared with other types of dementias, fNIRS showed the left frontotemporal and prefrontal lobes to be poorly activated during the verbal fluency task in frontotemporal dementia. In Lewy body dementia, severe asymmetry of prefrontal lobes appeared during both verbal fluency and working memory tasks, and the patient had low functional connectivity during a resting state. In PDD, the patient's prefrontal cortex showed lower excitability than the temporal lobe during the verbal fluency task, while the prefrontal cortex showed higher excitability during the working memory task. The patient with AD showed poor prefrontal and temporal activation during the working memory task, and more activation of frontopolar instead of the dorsolateral prefrontal cortex., Conclusion: Different hemodynamic characteristics of four types of dementia (as seen by fNIRS imaging) provides evidence that fNIRS can serve as a potential tool for the diagnosis between dementia subtypes., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Polygonatum rhizoma polysaccharide (PP) is a main ingredient of Polygonatum rhizoma , which is both food and traditional herbal medicine. In this study, we aimed to investigate the hypoglycemic effect of PP and the underlying mechanisms in db/db mice. Our finding showed that PP significantly ameliorates diabetic symptoms by reducing glucose levels in blood and urine and increasing insulin and leptin abundance in the serum. Histopathological examination revealed that PP improved the pathological state and increased hepatic glycogen storage in liver. Additionally, RT-qPCR results indicated that PP significantly down-regulated the expression of phosphoenolpyruvate carboxykinase 1. Furthermore, 16s rRNA sequencing results demonstrated that PP intervention resulted in an increase in beneficial bacteria genus and a reduction in harmful genus. Redundancy analysis revealed the correlation between intestinal flora and clinical factors. Taken together, these results suggest that PP has a significant hypoglycemic effect on type 2 diabetes (T2D) through up-regulating serum insulin and leptin, as well as hepatic glycogen storage, and down-regulating hepatic phosphoenolpyruvate carboxykinase 1 expression, as well as modulating gut microbiota composition. In conclusion, this study investigated the mechanisms of PP in the treatment of diabetes in db/db mice. To the best of our knowledge, this is the first study to explore the positive and negative correlations between gut microbiota and clinical factors, such as oxidative stress injury in liver and glucose related indicators in the blood., (© 2023 The Authors. Published by Elsevier Ltd.)

Late-life depression (LLD) is one of the most common mental disorders among the older adults. Population aging, social stress, and the COVID-19 pandemic have significantly affected the emotional health of older adults, resulting in a worldwide prevalence of LLD. The clinical phenotypes between LLD and adult depression differ in terms of symptoms, comorbid physical diseases, and coexisting cognitive impairments. Many pathological factors such as the imbalance of neurotransmitters, a decrease in neurotrophic factors, an increase in β-amyloid production, dysregulation of the hypothalamic-pituitary-adrenal axis, and changes in the gut microbiota, are allegedly associated with the onset of LLD. However, the exact pathogenic mechanism underlying LLD remains unclear. Traditional selective serotonin reuptake inhibitor therapy results in poor responsiveness and side effects during LLD treatment. Neuromodulation therapies and complementary and integrative therapies have been proven safe and effective for the treatment of LLD. Importantly, during the COVID-19 pandemic, modern digital health intervention technologies, including socially assistive robots and app-based interventions, have proven to be advantageous in providing personal services to patients with LLD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao, Wu, Tang, Shi, Gong, Mei, Zhao, He, Huang and Cui.)

Alzheimer's disease is characterized by sustained neuroinflammation leading to memory loss and cognitive decline. The past decade has witnessed tremendous efforts in Alzheimer's disease research; however, no effective treatment is available to prevent disease progression. An increasing body of evidence suggests that neuroinflammation plays an important role in Alzheimer's disease pathogenesis, alongside the classical pathological hallmarks such as misfolded and aggregated proteins (e.g., amyloid-beta and tau). Firstly, this review summarized the clinical and pathological characteristics of Alzheimer's disease. Secondly, we outlined key aspects of glial cell-associated inflammation in Alzheimer's disease pathogenesis and provided the latest evidence on the roles of microglia and astrocytes in Alzheimer's disease pathology. Then, we revealed the double-edged nature of inflammatory cytokines and inflammasomes in Alzheimer's disease. In addition, the potential therapeutic roles of innate immunity and neuroinflammation for Alzheimer's disease were also discussed through these mechanisms. In the final section, the remaining key problems according to the current research status were discussed., Competing Interests: None

Cyperus rotundus is the dry rhizome of the Cyperaceae plant Cyperus. Although there are two types of processed products in clinics, their quality differences are not clear, and the identification methods are more complex. In this study, the chemical composition of different processed products of Cyperus rotundus was characterized using ultra-high-performance liquid chromatography-quadrupole-time of flight-mass spectrometry and molecular network analysis, to identify the potential chemical markers and to establish a quick and simple color-based discrimination method. Among the 65 compounds analyzed, 12 showed significant differences. Observing the color, the surface brightness (L*) of Cyperus rotundus decreased after vinegar processing, while red (a*) and yellow (b*) values increased. These color values correlated significantly with chemical compositions. Finally, a color discriminant function was established and verified for raw Cyperus rotundus and vinegar-processing Cyperus rotundus. Based on this study, Cyperus rotundus' quality can be effectively controlled and provides a method for the comprehensive characterization of chemical components and chemical markers of other traditional Chinese medicine and processed products, as well as new ideas and methods in identification and quality evaluation., (© 2023 Wiley-VCH GmbH.)

Wearable flexible sensors are widely used in several applications such as physiological monitoring, electronic skin, and telemedicine. Typically, flexible sensors that are made of elastomeric thin-films lack sufficient permeability, which leads to skin inflammation, and more importantly, affects signal detection and consequently, reduces the sensitivity of the sensor. In this study, we designed a flexible nanofibrous membrane with a high air permeability (6.10 mm/s), which could be effectively used to monitor human motion signals and physiological signals. More specifically, a flexible membrane with a point (liquid metal nanoparticles)-line (carbon nanotubes)-plane (liquid metal thin-film) multiscale conductive structure was fabricated by combining liquid metal (LM) and carbon nanotubes (CNTs) with a polyurethane (PU) nanofibrous membrane. Interestingly, the excellent conductivity and fluidity of the liquid metal enhanced the sensitivity and stability of the membrane. More precisely, the gauge factor (GF) values of the membrane is 3.0 at 50% strain and 14.0 at 400% strain, which corresponds to a high strain sensitivity within the whole range of deformation. Additionally, the proposed membrane has good mechanical properties with an elongation at a break of 490% and a tensile strength of 12 MPa. Furthermore, the flexible membrane exhibits good biocompatibility and can efficiently monitor human health signals, thereby indicating potential for application in the field of wearable electronic devices., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Wu, Tang, Zhou, Liang, Liu and Li.)

Objectives: Obstructive sleep apnea syndrome (OSAS) is associated with increased risk of postoperative complications, which is possibly related to increased sensitivity to opioid. However, the effect of increased sensitivity to opioids in patients with OSAS remains controversial. This study aims to investigate whether male patients with moderate to severe OSAS have increased sensitivity to opioid remifentanil and its related predictive factors, so as to provide a reference for the rational use of opioids in patients with OSAS., Methods: This study was a prospective study. From December 28, 2021 to October 15, 2022, a total of 61 male patients aged 22 to 60 years old, American Society of Anesthesiologists (ASA) status I and II, who underwent nasopharyngeal surgery under general anesthesia, were selected. According to STOP-BANG questionnaire score and apnea-hypopnea index (AHI), the patients were divided into an OSAS group ( n =39) and a control group ( n =22). The pupil diameter (PD) of the patients was measured by hand-held monocular pupillometer, and the perception threshold (PT) and pain tolerance threshold (PTT) of the patients were measured by somatosensory evoked potential stimulator. The initial PD, PT, and PTT were measured in a quiet environment and recorded as PD0, PT0, and PTT0. Changes in PD, PT, PTT, respiration, and consciousness were recorded after remifentanil infusion. Age, body mass index (BMI), smoking, AHI, minimal oxygen saturation, and percentage of sleep time spent with oxygen saturation <90% (T90) were included as independent variables in multiple linear regression equations to analyze the possible predictors of increased opioid sensitivity in patients with moderate to severe OSAS., Results: There were no significant differences in PD0, PT0 and PTT0 between the OSAS group and the control group (all P >0.05). After remifentanil infusion, there was no significant difference in the rate of PT change between the 2 groups ( P >0.05). The change rate of PTT and PD in the OSAS group was significantly higher than that in the control group ( P <0.05 and P <0.001, respectively), PD in the OSAS group was significantly lower than that in the control group ( P <0.001). During remifentanil infusion, there were no significant differences in the incidence of respiratory depression and the distribution of observer's assessment of alertness/sedation (OAA/S) scores between the 2 groups (both P >0.05), and there were no changes in mental status and airway support in the patients of the 2 groups. Multiple linear regression showed that T90 was positively correlated with miosis rate ( β =0.597, 95% CI 0.269 to 0.924, P <0.05) and the rate of PTT change ( β =0.458, 95% CI 0.116 to 0.800, P <0.05). However, minimal oxygen saturation, age, BMI, smoking, and AHI were not correlated with PD change rate and PTT change rate in the OSAS patients (all P >0.05)., Conclusions: Male patients with moderate to severe OSAS have increased sensitivity to remifentanil, the duration of nocturnal desaturation may be its predictive factor. Male patients with moderate to severe OSAS with a longer duration of nocturnal hypoxia are more sensitive to remifentanil, and the use of opioids in these patients should be more cautious in clinical.

The chemical components of Huanglian Decoction were identified by ultra-performance liquid chromatography-quadrupole-time-of-flight-tandem mass spectrometry(UPLC-Q-TOF-MS/MS) technology. The gradient elution was conducted in Agilent ZORBAX Extend-C&#95;(18) column(2.1 mm×100 mm, 1.8 μm) with the mobile phase of 0.1% formic acid aqueous solution(A)-acetonitrile(B) at a flow rate of 0.3 mL·min~(-1) and the column temperature of 35 ℃. The MS adopted the positive and negative ion mode of electrospray ionization(ESI), and the MS data were collected under the scanning range of m/z 100-1 500. Through high-resolution MS data analysis, combined with literature comparison and confirmation of reference substances, this paper identified 134 chemical components in Huanglian Decoction, including 12 alkaloids, 23 flavonoids, 22 terpenes and saponins, 12 phenols, 7 coumarins, 12 amino acids, 23 organic acids, and 23 other compounds, and the medicinal sources of the compounds were ascribed. Based on the previous studies, 7 components were selected as the index components. Combined with the network pharmacology research and analysis me-thods, the protein and protein interaction(PPI) network information of the intersection targets was obtained through the STRING 11.0 database, and 20 core targets of efficacy were screened out. In this study, UPLC-Q-TOF-MS/MS technology was successfully used to comprehensively analyze and identify the chemical components of Huanglian Decoction, and the core targets of its efficacy were discussed in combination with network pharmacology, which laid the foundation for clarifying the material basis and quality control of Huanglian Decoction.

Background: Bipolar disorder (BD) is predominantly treated with psychotropic drugs, but BD is a complex medical condition and the contribution of psychotropic drugs is not clear. The objectives of this study are: (1) to present psychotropic drugs used in patients with BD; (2) to access changes of psychotropic drug treatments in acute and maintenance episodes., Methods: The study retrospectively evaluated the medical records of inpatients in the Ningbo Kangning Hospital from January 2019 to December 2019. The medical history of each subject was collected completely, including sociodemographic (gender, age, marital status, and so on) and clinical characteristics at baseline and within 12 months of admission., Results: The study ultimately included 204 patients with BD. After 12 months, 73.0% of the patients still took drugs. Mood stabilizers (72-90%) and antipsychotics (77-95%) were still the most important drugs in patients with BD. Antidepressants (34-40%) and benzodiazepines (20-34%) were the other frequently used drug classes. For mood stabilizers, 40-56% of patients were prescribed lithium. For antipsychotic, 54-65% of patients were prescribed quetiapine. Sertraline (6-9%) and fluoxetine (5-9%) were the antidepressant that most frequently prescribed. Lorazepam (10-18%) was the most commonly used benzodiazepine. In psychotropic polypharmacy, the most frequently taken was mood stabilizer plus antipsychotic co-treatment, about 36-44% of all patients. A total of 35-48% of patients treated by two psychotropic drugs and 24-36% received three., Conclusion: The first 6 months after treatment is very important to medication adherence. Mood stabilizers and antipsychotic remained the primary treatment for BD. Antipsychotic is on the rise in the treatment of BD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jing, Su, Zheng, Mei and Zhang.)

Progressive supranuclear palsy (PSP) is a complex clinicopathologic disease which can only be definitively confirmed at autopsy. It belongs to a family of conditions exhibiting Parkinson's syndrome, including Lewy body dementia (LBD) or dementia with Lewy body (DLB), and Parkinson's disease dementia (PDD). In regards to clinical manifestations, these two dementias have many overlapping characteristics. The declines of cognition in older patients of dementia are generally accompanied by depression, anxiety, hallucinations, delusions, eating and sleep disorders. This can lead to the difficulty in distinguishing the types of dementia and accurately diagnosing the disease. Herein, we present a complex case of PSP with depression, anxiety, and fluctuating dementia in which DLB was initially suspected. Before antidepressant therapy, the patient showed extrapyramidal symptoms as well as major depression, which lead to greatly impaired movement. Moreover, this patient was an older person with depression disorders, implicating further complexities of late life depression. After two weeks of therapy with antidepressants, the patient had reduced depressive symptoms, and even the somatic symptoms were improved. This case demonstrated that antidepressant therapy can be effective in improving emotion and cognition among patients with late life depression., Competing Interests: Declaration of competing interest The authors declare that they had no conflict of interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: To investigate the potential of dual-energy computed tomography (DECT) parameters in identifying metastatic cervical lymph nodes in oral squamous cell carcinoma (OSCC) patients and to explore the relationships between DECT and pathological features., Methods: Clinical and DECT data were collected from patients who underwent radical resection of OSCC and cervical lymph node dissection between November 2019 and June 2021. Microvascular density was assessed using the Weidner counting method. The electron density (ED) and effective atomic number (Z eff ) in non - contrast phase and iodine concentration (IC), normalized IC, slope of the energy spectrum curve (λ HU ), and dual-energy index (DEI) in parenchymal phase were compared between metastatic and non - metastatic lymph nodes. Student's t-test, Pearson's rank correlation, and receiver operating characteristic curves were performed., Results: The inclusion criteria were met in 399 lymph nodes from 103 patients. Metastatic nodes (n = 158) displayed significantly decreased ED, IC, normalized IC, λ HU , and DEI values compared with non-metastatic nodes (n = 241) (all p < 0.01). Strong correlations were found between IC (r = 0.776), normalized IC (r = 0.779), λ HU (r = 0.738), DEI (r = 0.734), and microvascular density. Area under the curve (AUC) for normalized IC performed the highest (0.875) in diagnosing metastatic nodes. When combined with the width of nodes, AUC increased to 0.918., Conclusion: DECT parameters IC, normalized IC, λ HU , and DEI reflect pathologic changes in lymph nodes to a certain extent, and aid for detection of metastatic cervical lymph nodes from OSCC., Key Points: • Electron density, iodine concentration, normalized iodine concentration, λ HU , and dual-energy index values showed significant differences between metastatic and non-metastatic nodes. • Strong correlations were found between iodine concentration, normalized iodine concentration, slope of the spectral Hounsfield unit curve, dual-energy index, and microvascular density. • DECT qualitative parameters reflect the pathologic changes in lymph nodes to a certain extent, and aid for the detection of metastatic cervical lymph nodes from oral squamous cell carcinoma., (© 2022. The Author(s).)