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Intervertebral disc degeneration (IVDD) is a chronic degenerative disease with a complex pathophysiological mechanism. Increasing evidence suggests that the NOD-like receptor thermal protein domain associated protein 3 (NLRP3)-mediated pyroptosis of nucleus pulposus cells (NPCs) plays a crucial role in the pathological progression of IVDD. Pyroptosis is a novel form of programmed cell death characterized by the formation of plasma membrane pores by gasdermin family proteins, leading to cell swelling, membrane rupture, and the release of inflammatory cytokines, which trigger an inflammatory response. The close relationship between pyroptosis and mitophagy has been previously described in various diseases, but the crosstalk between pyroptosis and mitophagy in IVDD remains unexplored. Cellular repressor of E1A-stimulated genes 1 (CREG1) is a secreted glycoprotein involved in cell differentiation and homeostasis regulation and has been shown to promote lysosomal biogenesis and function. However, the potential role and underlying mechanisms of CREG1 in the progression of IVDD have not yet been reported. In this study, we first observed that CREG1 is downregulated following IVDD and that pyroptosis occurs. Furthermore, CREG1 knockdown inhibited NPC proliferation and exacerbated apoptosis and degeneration. Moreover, we confirmed that CREG1 knockdown induced NLRP3 activation while also leading to mitophagy inhibition and mitochondrial dysfunction in NPCs. CREG1 overexpression ameliorated LPS-induced mitophagy inhibition and mitochondrial dysfunction by promoting PINK1/Parkin-mediated mitophagy, thereby suppressing NLRP3 inflammasome activation. However, these protective effects were reversed by pretreatment with the mitophagy inhibitor cyclosporin A (CsA). In a rat model of IVDD, imaging and histological assessments revealed that CREG1 overexpression effectively alleviated the progression of IVDD. Additionally, CREG1 overexpression reduced the expression of NLRP3, caspase-1, and IL-1β while increasing the expression of collagen II, PINK1 and LC3, delaying the course of IVDD. Overall, this study highlights the importance of the interplay between CREG1-mediated regulation of mitophagy and pyroptosis in the pathogenesis of IVDD, identifying CREG1 as a promising therapeutic target for IVDD treatment., 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 © 2025 Elsevier B.V. All rights reserved.)

Abstract: Alzheimer's disease, a devastating neurodegenerative disorder, is characterized by progressive cognitive decline, primarily due to amyloid-beta protein deposition and tau protein phosphorylation. Effectively reducing the cytotoxicity of amyloid-beta42 aggregates and tau oligomers may help slow the progression of Alzheimer's disease. Conventional drugs, such as donepezil, can only alleviate symptoms and are not able to prevent the underlying pathological processes or cognitive decline. Currently, active and passive immunotherapies targeting amyloid-beta and tau have shown some efficacy in mice with asymptomatic Alzheimer's disease and other transgenic animal models, attracting considerable attention. However, the clinical application of these immunotherapies demonstrated only limited efficacy before the discovery of lecanemab and donanemab. This review first discusses the advancements in the pathogenesis of Alzheimer's disease and active and passive immunotherapies targeting amyloid-beta and tau proteins. Furthermore, it reviews the advantages and disadvantages of various immunotherapies and considers their future prospects. Although some antibodies have shown promise in patients with mild Alzheimer's disease, substantial clinical data are still lacking to validate their effectiveness in individuals with moderate Alzheimer's disease., (Copyright © 2025 Neural Regeneration Research.)

Fig (Ficus carica L.) holds economic significance in Atushi, Xinjiang, but as fig cultivation expands, disease prevalence has risen. In July 2024, approximately 22% of harvested fig (cv. Xinjiang Zaohuang) from 20 commercial orchards (covering 40 hectares) in Atushi (39°39'37.65" N, 76°14'3.62" E) showed varying degrees of fruit rot symptoms. The initial symptoms were characterized by the appearance of small, brown lesions on the fruit surface. These lesions rapidly progressed into water-soaked spots, which expanded quickly. As the disease advanced, the affected areas became covered with dense, white, fluffy mycelia, accompanied by prominent black sporulation. In later stages, the infected tissues softened further, ultimately resulting in the complete decay of the fruit. Twenty diseased fig were collected from the sampling site. Tissue samples (5×5×5 mm) were cut at the diseased-healthy junction, surface-sterilized in 0.5% NaClO for 1 minute, rinsed twice in sterile distilled water, air-dried, and transferred aseptically onto potato dextrose agar (PDA), and incubated at 25°C for 5 days with a 12-hour photoperiod. Fifteen isolates were obtained from the infected tissues, with two representative isolates (WH 12 and WH 23) selected for further study due to morphological similarity. The fungal colonies initially appeared as white mycelium, later turning olive green to grayish-black. Colony growth was rapid (32 mm/day). Arthrospores were colorless to light brown, short columnar, aseptate, with a truncated base, 0 to 1 septate, averaging 11.9±2.3×3.6±0.8 μm (n = 50), and sometimes formed arthric chains. Chlamydospores were dark brown, round or oval, 0 to 1 septate, averaging 7.26±1.7×5.05±1.0 μm (n = 50). Genomic DNA was extracted from the two isolates. The internal transcribed spacer (ITS), translation elongation factor 1-alpha (TEF1-α), and beta-tubulin (TUB2) genes were amplified using primers ITS1/ITS4 (White et al. 1990), EF1-728F/EF1-986R (Carbone & Kohn. 1999), and BT2a/BT2b (Glass & Donaldson. 1995), respectively, and sequences were deposited in GenBank (ITS: PQ555020, PQ555021; TUB2: PQ557519, PQ557521; TEF1-α: PQ557520, PQ557522). BLAST analysis revealed 99-100% similarity to Neoscytalidium dimidiatum Arp2-D (ITS: MK813852; TUB2: MK816354; TEF1-α: MK816355). Phylogenetic analysis using IQ-Tree and MrBayes3.2.7 based on concatenated ITS-TEF1-TUB sequences showed WH 12 and WH 23 clustering with N. dimidiatum Arp2-D (99% bootstrap). Morphological and molecular data identified the isolates as N. dimidiatum (Penz.) Crous & Slippers (Crous et al. 2006). Pathogenicity tests were conducted on 20 healthy fig (cv. Xinjiang Zaohuang) by inoculating each fruit with 10 µl of a WH 12 conidial suspension (1 × 10⁶ conidia/ml) using sterile needles. The Control were treated with 10 µl of sterile distilled water. All fruits were placed in sterile plastic containers and incubated at 25 ± 1°C, 90% relative humidity, and a 12-hour light cycle. This experiment was performed twice. On the 1st day post-inoculation, brown lesions began to develop on the fruit. By the 4th day post-inoculation, the entire fruit was completely decayed and covered with white mycelia and black spores, while the control fruit showed no symptoms. The fungus was successfully reisolated from the inoculated fruits and identified as N. dimidiatum following the methods described above, fulfilling Koch's postulates. N. dimidiatum has been reported to have a wide range of hosts in China, such as Jacaranda mimosifolia, Hylocereus megalanthus, Hylocereus undatus, and Styphnolobium japonicum (Li et al. 2024; Zeng et al. 2024; Lan et al. 2022; Luo et al. 2024). To our knowledge, this study is the first report of N. dimidiatum as the causal agent of fruit rot in fig in China. Our findings have expanded the host range of N. dimidiatum in China and provide a theoretical basis for the diagnosis and treatment of the disease.

Recombinant adeno-associated viruses (rAAVs) comprise a promising viral vector for therapeutic gene delivery to treat disease. However, the current manufacturing capability of rAAVs must be improved to meet commercial demand. Previously published omics studies indicate that rAAV production through transient transfection triggers antiviral responses and endoplasmic reticulum stress responses in the host cell. Both responses negatively regulate viral production. We demonstrate that the modulation of the antiviral immune response (by blocking interferon signaling pathways) can effectively lower the production of interferon and enhance viral genome production. The use of interferon inhibitors before transfection can significantly increase rAAV production in HEK293 cells, with up to a 2-fold increase in productivity and up to a 6-fold increase in specific productivity. Compared to the untreated groups, the addition of these small molecules generally reduced viable cell density but increased vector productivity. The positive candidates were BX795 (a TBK inhibitor), TPCA-1 (an IKK2 inhibitor), Cyt387 (a JAK1 inhibitor), and ruxolitinib (another JAK1 inhibitor). These candidates were identified using deep well screening, and reproducible titer improvement was achieved in a 30mL shake flask scale. Additionally, genome titer improvement is feasible and scalable in two different media, but the extent of improvement may vary., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare that are relevant to the content of this article. This article does not contain any studies with human participants or animals performed by any of the authors., (Copyright © 2025. Published by Elsevier B.V.)

To clarify the effect of heating rate on the thermal decomposition process of 1,3,5-triamino-2,4,6-trinitrobenzene (TATB), this study employs molecular dynamic simulations to investigate the thermal decomposition of TATB at heating rates of 20, 40, 60, and 80 K/ps. The initial temperature is uniformly set to 300 K, while the final temperature is set to 3000 K. Results indicate that within the temperature range of 300-3000 K, the thermal decomposition rate of TATB decreases with increasing heating rate, whereas the initial decomposition temperature of TATB increases, consistent with the experimental pattern. Within the studied temperature range, a lower heating rate results in a higher number of decomposition fragments, leading to more effective collision between active fragments, facilitating more effective collisions between active species, and leading to the formation of more stable products such as H₂O, CO₂, and N₂. Conversely, higher heating rates reduce the quantities of these stable products. This study enhances the understanding of TATB's thermal decomposition mechanism, providing valuable insights for its safe handling and application. METHODS: The Gaussian09 software was used to calculate the BDEs of TATB molecules, while the MD simulation using the ReaxFF-lg force field was performed by the LAMMPS package. Visualization and postprocessing were conducted using the OVITO software, and a custom script was developed to analyze the reaction products and frequencies., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The albumin to fibrinogen ratio (AFR), a biomarker associated with inflammatory, nutritional, and coagulation status, and the CALLY index, a biomarker combining C-reactive protein, albumin, and lymphocyte count, have been suggested to correlate with prognosis in a variety of diseases in previous studies; however, studies of these two markers in ulcerative colitis (UC) are lacking. The aim of this study was to evaluate the clinical significance of AFR and CALLY index in UC., Methods: The study included 109 UC patients and 126 healthy controls. For UC patients treated with Vedolizumab (50 patients), they were categorized into mucosal healing group (MH group) and non- mucosal healing group (non-MH group) based on Mayo endoscopic score (MES) after 14 weeks of treatment. The differences in AFR and CALLY index were compared between the UC group and the healthy control group, and between the MH group and the non-MH group. Then, the correlation of the AFR and CALLY index with UC activity was assessed, and the predictive value of the AFR and CALLY index was evaluated using the receiver operating characteristic (ROC) curve., Results: The results showed that both AFR and CALLY index were significantly decreased in the UC group compared with the healthy control group (both p<0.001); the area under the curve (AUC) of the AFR and CALLY index differentiating between the healthy control group and the UC group were 0.782 and 0.773, respectively. For Vedolizumab treatment, the non-MH group had significantly lower baseline AFR and CALLY index compared to the MH group; the AUC for baseline AFR and CALLY index discriminating the MH group from the non-MH group were 0.665 and 0.721, respectively. In addition, AFR and CALLY index were negatively correlated with the MES and inflammatory load of UC. The results of multivariate logistic regression analysis showed that the CALLY index was an independent predictor of UC diagnosis and mucosal healing after 14 weeks of Vedolizumab treatment., Conclusion: AFR and CALLY index can be used as novel serologic markers for diagnosing UC and predicting the efficacy of Vedolizumab treatment., Competing Interests: The authors report no conflicts of interest in this work., (© 2025 Su et al.)

Background: Existing cardiovascular risk prediction models still have room for improvement in patients with type 2 diabetes who represent a high-risk population. This study evaluated whether adding metabolomic biomarkers could enhance the 10-year prediction of major adverse cardiovascular events (MACE) in these patients., Methods: Data from 10,257 to 1,039 patients with type 2 diabetes from the UK Biobank (UKB) and the German ESTHER cohort, respectively, were used for model derivation, internal and external validation. A total of 249 metabolites were measured with nuclear magnetic resonance (NMR) spectroscopy. Sex-specific LASSO regression with bootstrapping identified significant metabolites. The enhanced model's predictive performance was evaluated using Harrell's C-index., Results: Seven metabolomic biomarkers were selected by LASSO regression for enhanced MACE risk prediction (three for both sexes, three male- and one female-specific metabolite(s)). Especially albumin and the omega-3-fatty-acids-to-total-fatty-acids-percentage among males and lactate among females improved the C-index. In internal validation with 30% of the UKB, adding the selected metabolites to the SCORE2-Diabetes model increased the C-index statistically significantly (P = 0.037) from 0.660 to 0.678 in the total sample. In external validation with ESTHER, the C-index increase was higher (+ 0.043) and remained statistically significant (P = 0.011)., Conclusions: Incorporating seven metabolomic biomarkers in the SCORE2-Diabetes model enhanced its ability to predict MACE in patients with type 2 diabetes. Given the latest cost reduction and standardization efforts, NMR metabolomics has the potential for translation into the clinical routine., Competing Interests: Declarations. Competing interest: The authors declare no competing interests., (© 2025. The Author(s).)

Empathy, typically regarded as a positive attribute, is now being critically evaluated for its potential negative implications on mental health. A growing body of research indicates that excessive empathy, particularly high level of affective empathy, can lead to overwhelming emotional states, increasing susceptibility to psychological distress and psychiatric disorders. This review aims to explore the negative effects of empathy on mental health. We review both human and animal studies concerning the relationship between empathy and psychological disorders, revealing that while empathy enhances social interactions and emotional understanding, it may also heighten empathic distress and potentially contribute to the development of pain, internalizing disorders, depression, anxiety, emotional over-involvement, burnout, vicarious trauma and post-traumatic stress disorder. This review contributes to the broader discourse on empathy by delineating its dual impacts, integrating insights from neurobiology, psychology, and behavioral studies. This review may enhance our understanding of empathy's complex role in mental health, offering a nuanced perspective that acknowledges both its beneficial and detrimental impacts., (Copyright © 2025. Published by Elsevier Inc.)

Adeno-associated virus (AAV) vectors are a leading platform for gene therapy. Recently, AAV-mediated gene therapy in the inner ear has progressed from laboratory use to clinical trials, but the lower transduction rates in outer hair cells (OHCs) in the organ of Corti and in vestibular hair cells in adult mice still pose a challenge. OHCs are particularly vulnerable to inner ear insults. In this study, we demonstrated that expression of a key AAV receptor (AAVR, Kiaa0319l, or Au040320) in OHCs and vestibular hair cells decreases significantly in mature mice and AAV particles directly interact with AAVR by forming complexes. Consequently, antibody blockage of AAVR significantly inhibits AAV transduction in sensory hair cells in cochlear explants. Moreover, use of AAVR knockout mice confirms inhibition of AAV transduction in sensory hair cells in vivo. Finally, conditional overexpression of AAVR in sensory hair cells of adult mice successfully restores AAV transduction efficiency in OHCs and vestibular hair cells. In conclusion, this strong evidence that AAVR is essential for AAV transduction in sensory hair cells will help to increase the efficacy of future gene therapy in inner ear., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Within the global population, depression and anxiety are common among older adults. Tai Chi is believed to have a positive impact on these disturbances. This study examined the network structures of depression and anxiety among older Tai Chi practitioners vs non-practitioners. Propensity score matching (PSM) was used to construct a non-practitioner group based on Chinese Longitudinal Healthy Longevity Survey (CLHLS) data. 346 Tai Chi practitioners and 1019 non-practitioners were included. The prevalence and severity rates of depression were significantly lower among Tai Chi practitioners compared to non-practitioners though there was no group difference for anxiety. Network analysis showed that, among Tai Chi practitioners, "Felt sadness", "Uncontrollable worrying" and "Trouble relaxing" were the most central symptoms. In contrast, among non-practitioners, the most central symptoms were "Felt sadness", "Uncontrollable worrying", and "Nervousness". Key bridge symptoms linking depressive and anxiety symptoms were "Worry too much", "Bothered by things" and "Uncontrollable worrying" in Tai Chi practitioners and "Nervousness", "Felt nervous/fearful" and "Sleep quality" in non-practitioners. This study underscored how practising Tai Chi is associated with reduced overall prevalence and severity of depression and different interactions of depressive and anxiety symptoms among older adults. Central and bridge symptoms differed between Tai Chi practitioners and non-practitioners., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Patients with ulcerative colitis (UC) exhibit abnormal amino acid (AA) metabolism. Taste receptors play a crucial role in the detection of intestinal AAs. Nevertheless, it remains unclear whether UC patients exhibit abnormal expression of these receptors in the colon., Methods: An observational, multicenter study was conducted involving adult patients with active UC and healthy controls (HCs), recruited from July 2023 to March 2024. Fresh feces and rectosigmoid mucosal tissues were obtained from each participant. The concentrations of fecal AAs and the expression of taste receptors, including calcium-sensing receptor (CaSR), G protein-coupled receptor family C group 6 member A (GPRC6A), taste receptor type 1 member 1 (T1R1), and metabotropic glutamate receptor 4 (mGLuR4), in the colon were measured. Additionally, the correlation between colonic mucosal taste receptors and clinical characteristics was evaluated., Results: Except for GPRC6A, the expression levels of CaSR, mGLuR4, and T1R1 in the colonic mucosa of UC patients were significantly elevated compared to HC. The expression of CaSR was negatively correlated with C-reactive protein and erythrocyte sedimentation rate (ESR). T1R1 expression positively correlated with defecation frequency and an Improved Mayo Endoscopic Score. The total and subtype concentrations of fecal AAs were elevated in UC patients and demonstrated a negative correlation with ESR and fecal calprotectin., Conclusions: The increased levels of taste receptors and fecal AAs in the colon of UC patients suggest an abnormal nutrient-sensing mechanism, potentially playing a crucial role in the development of the disease., (© The Author(s) 2025. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Rationale: Chronic kidney disease (CKD) is a progressively debilitating condition leading to kidney dysfunction and severe complications. While dysbiosis of the gut bacteriome has been linked to CKD, the alteration in the gut viral community and its role in CKD remain poorly understood. Methods: Here, we characterize the gut virome in CKD using metagenome-wide analyses of faecal samples from 425 patients and 290 healthy individuals. Results: CKD is associated with a remarkable shift in the gut viral profile that occurs regardless of host properties, disease stage, and underlying diseases. We identify 4,649 differentially abundant viral operational taxonomic units (vOTUs) and reveal that some CKD-enriched viruses are closely related to gut bacterial taxa such as Bacteroides , [Ruminococcus] , Erysipelatoclostridium , and Enterocloster spp. In contrast, CKD-depleted viruses include more crAss-like viruses and often target Faecalibacterium , Ruminococcus , and Prevotella species. Functional annotation of the vOTUs reveals numerous viral functional signatures associated with CKD, notably a marked reduction in nicotinamide adenine dinucleotide (NAD + ) synthesis capacity within the CKD-associated virome. Furthermore, most CKD viral signatures are reproducible in the gut viromes of diabetic kidney disease and several other common diseases, highlighting the considerable universality of disease-associated viromes. Conclusions: This research provides comprehensive resources and novel insights into the CKD-associated gut virome, offering valuable guidance for future mechanistic and therapeutic investigations., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Metabolic syndrome (MetS) remains a significant global public health concern. However, the relationship between MetS, its individual components and melanoma metastasis remains unexplored. We analysed the clinical data of 258 Chinese melanoma patients who had not undergo systemic therapy. Binary logistic regression, adjusted for sex and age, was employed to evaluate the connection between MetS and its components and melanoma metastasis. Of the 258 melanoma patients, 92 met the MetS criteria upon diagnosis. No direct association between MetS and melanoma metastasis was identified. However, specific components of MetS, namely low HDL-cholesterol levels (OR = 2.85, 95% CI:1.50-5.41, p < 0.05) and dysglycaemia (OR = 4.23, 95% CI:1.80-8.96, p < 0.05), were associated with melanoma metastasis. In subgroup analysis, hypertriglyceridemia correlated with melanoma metastasis in non-elderly patients (< 65 years) (OR = 2.69, 95% CI: 1.14-6.33, p < 0.05). Central obesity and hypertension showed no association. A dose-response analysis further indicated that melanoma metastasis risk escalated with increasing fasting blood glucose and blood triglyceride concentrations, and with decreasing blood HDL concentration. Our results suggest that monitoring and managing individual components of the MetS, particularly HDL-cholesterol levels, fasting glucose and triglyceride levels, may have potential prognostic benefits for melanoma in the Chinese population., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Acute gastrointestinal injury (AGI) is common in intensive care unit (ICU) and worsens the prognosis of critically ill patients. The four-point grading system proposed by the European Society of Intensive Care Medicine is subjective and lacks specificity. Therefore, a more objective method is required to evaluate and determine the grade of gastrointestinal dysfunction in this patient population. Digital continuous monitoring of bowel sounds and some biomarkers can change in gastrointestinal injuries. We aimed to develop a model of AGI using continuous monitoring of bowel sounds and biomarkers., Aim: To develop a model to discriminate AGI by monitoring bowel sounds and biomarker indicators., Methods: We conducted a prospective observational study with 75 patients in an ICU of a tertiary-care hospital to create a diagnostic model for AGI. We recorded their bowel sounds, assessed AGI grading, collected clinical data, and measured biomarkers. We evaluated the model using misjudgment probability and leave-one-out cross-validation., Results: Mean bowel sound rate and citrulline level are independent risk factors for AGI. Gastrin was identified as a risk factor for the severity of AGI. Other factors that correlated with AGI include mean bowel sound rate, amplitude, interval time, Sequential Organ Failure Assessment score, Acute Physiology and Chronic Health Evaluation II score, platelet count, total protein level, blood gas potential of hydrogen (pH), and bicarbonate (HCO 3 - ) level. Two discriminant models were constructed with a misclassification probability of < 0.1. Leave-one-out cross-validation correctly classified 69.8% of the cases., Conclusion: Our AGI diagnostic model represents a potentially effective approach for clinical AGI grading and holds promise as an objective diagnostic standard for AGI., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Electrocatalyst materials play a crucial role in determining the efficiency of the hydrogen evolution reaction (HER), directly influencing the overall effectiveness of energy conversion technologies. Ni 3 S 2 /MoS 2 heterostructures hold substantial promise as bifunctional catalysts, owing to their synergistic electronic characteristics and plentiful active sites. However, their catalytic efficacy is impeded by the relatively elevated chemisorption energy of hydrogen-containing intermediates, which constrains their functionality in different pH environments. In order to mitigate this limitation, trace amounts of Pt are introduced into the heterostructure, intending to enhance electronic transport and refining chemisorption energies, thereby facilitating significant enhancements in both HER and oxygen evolution reaction (OER) activities over a wide pH range. It is revealed that the Pt-modified catalyst achieves exceptional HER performance, requiring merely 64 mV and 83 mV overpotentials to attain a current density of 100 mA cm -2 in acidic and alkaline media, respectively. Furthermore, theoretical simulations corroborate that Pt modification optimizes local electronic configurations and augments electronic transfer, contributing to its superior catalytic performance. This investigation underscores the pivotal role of Pt modification in propelling the practical application of Ni 3 S 2 /MoS 2 heterostructures as highly efficient and pH-universal bifunctional catalysts.

Background: We aimed to evaluate the incremental predictive value of metabolomic biomarkers for assessing the 10-year risk of type 2 diabetes when added to the clinical Cambridge Diabetes Risk Score (CDRS)., Methods: We utilized 86,232 UK Biobank (UKB) participants (recruited between 13 March 2006 and 1 October 2010) for model derivation and internal validation. Additionally, we included 4383 participants from the German ESTHER cohort (recruited between 1 July 2000 and 30 June 2002 for external validation). Participants were followed up for 10 years to assess the incidence of type 2 diabetes. A total of 249 NMR-derived metabolites were quantified using nuclear magnetic resonance (NMR) spectroscopy. Metabolites were selected with LASSO regression and model performance was evaluated with Harrell's C-index., Findings: 11 metabolomic biomarkers, including glycolysis related metabolites, ketone bodies, amino acids, and lipids, were selected. In internal validation within the UKB, adding these metabolites significantly increased the C-index (95% confidence interval (95% CI)) of the clinical CDRS from 0.815 (0.800, 0.829) to 0.834 (0.820, 0.847) and the continuous net reclassification index (NRI) with 95% CI was 39.8% (34.6%, 45.0%). External validation in the ESTHER cohort showed a comparable statistically significant C-index increase from 0.770 (0.750, 0.791) to 0.798 (0.779, 0.817) and a continuous NRI of 33.8% (26.4%, 41.2%). A concise model with 4 instead of 11 metabolites yielded similar results., Interpretation: Adding 11 metabolites to the clinical CDRS led to a novel type 2 diabetes prediction model, we called UK Biobank Diabetes Risk Score (UKB-DRS), substantially outperformed the clinical CDRS. The concise version with 4 metabolites performed comparably. As only very few clinical information and a blood sample are needed for the UKB-DRS, and as high-throughput NMR metabolomics are becoming increasingly available at low costs, these models have considerable potential for routine clinical application in diabetes risk assessment., Funding: The ESTHER study was funded by grants from the Baden-Württemberg state Ministry of Science, Research and Arts (Stuttgart, Germany), the Federal Ministry of Education and Research (Berlin, Germany), the Federal Ministry of Family Affairs, Senior Citizens, Women and Youth (Berlin, Germany), and the Saarland State Ministry of Health, Social Affairs, Women and the Family (Saarbrücken, Germany). The UK Biobank project was established through collaboration between various entities including the Wellcome Trust, the Medical Research Council, Department of Health, Scottish Government, and the Northwest Regional Development Agency. Additional funding was provided by the Welsh Assembly Government, British Heart Foundation, Cancer Research UK, and Diabetes UK, with support from the National Health Service (NHS). The German Diabetes Center is funded by the German Federal Ministry of Health (Berlin, Germany) and the Ministry of Culture and Science of the state North Rhine-Westphalia (Düsseldorf, Germany) and receives additional funding from the German Federal Ministry of Education and Research (BMBF) through the German Center for Diabetes Research (DZD e.V.)., Competing Interests: No potential conflicts of interest were disclosed., (© 2024 The Author(s).)

Background: Older adults with heart disease often experience higher rates of comorbid anxiety and depression. This study examined depression and anxiety network structures among older adults with heart disease and their heart disease free peers., Methods: Network analyses of secondary cross-sectional data from the 2017 to 2018 wave of CLHLS were used to construct groups of older adults with and without heart disease using propensity score matching. Depression and anxiety symptoms were assessed using Center for Epidemiological Studies Depression Scale and Generalized Anxiety Disorder Scale, respectively. Central symptoms and bridge symptoms were identified using expected influence., Results: 1689 older adults with heart disease and matched control sample of 1689 older adults without heart disease were included. The prevalence and severity of depression and anxiety were significantly higher in older adults with heart disease compared to the control group. There was no significant difference in overall structures of depression and anxiety network models between two the groups. Key central symptoms and bridge symptoms within these groups were highly similar; GAD 2 "Uncontrollable worrying" and GAD 4 "Trouble relaxing" were identified as the most central symptoms, while GAD 1 "Nervousness" and CESD 1 "Feeling bothered" were identified as key bridge symptoms across both network models., Conclusion: Depression and anxiety are more prevalent in older adults with heart disease than demographically-matched heart disease free controls. However, network structures of these symptoms do not differ between two groups. Accordingly, depression and anxiety psychosocial interventions developed for older adults without heart disease may also benefit older adults with heart disease., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Inc.)

Background: There is a scarcity of large randomized clinical trials on the efficacy and safety of high-dose amino acid supplementation (AAS) in patients with gastrointestinal tumors undergoing surgical treatment., Methods: This pragmatic, randomized, controlled, single-center, open-label, parallel-group AMIGITS trial was performed in a tertiary care teaching hospital. Patients with gastrointestinal tumors were randomly assigned to receive either AAS or standard care (SC). Amino acid targets were 2.0 g/kg per day in the AAS group and 1.2 g/kg per day in the SC group. The AAS group received additional amino acids intravenously, while the SC group received an iso-energetic 5% glucose intravenously., Results: Overall, 407 patients (AAS group, 204; SC group, 203) were included in this study. During the intervention, the actual mean daily energy intake did not differ significantly between the AAS and SC groups (25.53 vs. 25.16 kcal/kg per day, P =0.493). However, the actual mean daily amino acid intake was significantly higher in the AAS group than that in the SC group (1.81 vs. 0.94 g/kg per day, P <0.001). The infection incidence during hospitalization and within 30 days of surgery was significantly lower in the AAS group than that in the SC group ( P =0.031 and P= 0.024, respectively). The 30-day postoperative incidence of amino acid treatment-related adverse events and other complications did not significantly differ between the two groups. The postoperative hospital stay was significantly different between the two groups ( P< 0.001)., Conclusions: AAS was associated with a reduced infection incidence within 30 days of major surgery in patients with gastrointestinal tumors and can be a promising strategy., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Recombinant adeno-associated virus (rAAV) is a commonly used in vivo gene therapy vector because of its nonpathogenicity, long-term transgene expression, broad tropism, and ability to transduce both dividing and nondividing cells. However, rAAV vector production via transient transfection of mammalian cells typically yields a low fraction of filled-to-total capsids (~1%-30% of total capsids produced). Analysis of our previously developed mechanistic model for rAAV2/5 production attributed these low fill fractions to a poorly coordinated timeline between capsid synthesis and viral DNA replication and the repression of later phase capsid formation by Rep proteins. Here, we extend the model by quantifying the expression dynamics of total Rep proteins and their influence on the key steps of rAAV2/5 production using a multiple dosing transfection of human embryonic kidney 293 (HEK293) cells. We report that the availability of preformed empty capsids and viral DNA copies per cell are not limiting to the capsid-filling reaction. However, optimal expression of Rep proteins (<240 ± 13 ag per cell) enables enrichment of the filled capsid population (>12% of total capsids/cell) upstream. Our analysis suggests increased enrichment of filled capsids via regulating the expression of Rep proteins is possible but at the expense of per cell capsid titer in a triple plasmid transfection. Our study reveals an intrinsic limitation of scaling rAAV2/5 vector genome (vg) production and underscores the need for approaches that allow for regulating the expression of Rep proteins to maximize vg titer per cell upstream., (© 2024 The Author(s). Biotechnology and Bioengineering published by Wiley Periodicals LLC.)

Aberrant neurogenesis in the adult hippocampal dentate gyrus (DG) contributes to synapse remodeling during temporal lobe epilepsy (TLE). Transient receptor potential vanilloid 4 (TRPV4) is involved in the pathogenesis of TLE. Activation of TRPV4 can modulate neurogenesis in the adult hippocampal DG. The present study examined whether TRPV4 is responsible for the aberrant neurogenesis in the adult hippocampal DG during TLE. Herein, administration of a TRPV4-specific antagonist, HC-067047, attenuated the enhanced neural stem cell proliferation in the adult hippocampal DG in mice following pilocarpine‑induced status epilepticus (PISE). HC-067047 reduced the heightened hippocampal protein levels of cyclin-dependent kinase (CDK) 2, CDK6, cyclin E1, cyclin A2, and phosphorylated retinoblastoma (p-Rb) observed following PISE. Meanwhile, HC-067047 inhibited the extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK) pathways that were enhanced and responsible for the increased proliferation of stem cells and higher levels of CDKs, cyclins, and p-Rb protein. HC-067047 reduced the 28-day-old BrdU + cells but increased the ratio of 28-day-old BrdU + cells to 1-day-old BrdU + cells, indicating that TRPV4 blockage reduced the number but increased the survival rate of newborn cells following PISE. Finally, HC-067047 increased the Akt signaling that was inhibited and responsible for the decreased survival rate of newborn cells following PISE. It is concluded that TRPV4 blockage inhibits stem cell proliferation in the hippocampal DG following PISE, likely through inhibiting ERK1/2 and p38 MAPK signaling to decrease cell cycle-related protein expression, and increases newborn cell survival rate likely through increasing phosphoinositide 3 kinase-Akt signaling., Competing Interests: Declarations. Ethical Approval: This study was approved by the Ethics Committee of Nanjing Medical University (No. IACUC2009007), and all animal experiments were performed in accordance with the Guidelines for Laboratory Animal Research set by Nanjing Medical University. Competing Interests: The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Hydraulic redistribution (HR) is a critical ecological process whereby plant roots transfer water from wetter to drier soil layers, significantly impacting soil moisture dynamics and plant water and nutrient uptake. Yet a comprehensive understanding of the mechanism triggering HR and its influencing factors remains elusive. Here, we conducted a systematic meta-analysis to discuss the influence of soil conditions and plant species characteristics on HR occurrence. The threshold of HR ranges from -1.80 to -0.05 MPa, with soil hydraulic conductivity between 1.51 × 10 -13 and 6.53 × 10 -5 cm s -1 when HR occurs. HR is influenced by various factors. Soil texture plays a pivotal role, with loamy soils promoting HR more effectively than sandy and clay soils. Plant root structure and hydraulic conductivity significantly influence HR occurrence, where HR is more prevalent in deep-rooted tree species with larger root canal diameters and dimorphic roots. Additionally, mycorrhizal fungi enhance HR by expanding root uptake area, reducing water transport distances and improving soil structure. However, adverse soil conditions, inadequate plant physiological regulatory capacity, or methodological limitations can hinder HR detection. The findings highlight that HR is more likely to occur where there is a significant water potential gradient, appropriate root-soil contact, and low nocturnal transpiration. Plants can effectively replenish the water in dry root systems under drought conditions by HR by increasing the water potential of root systems to maintain normal physiological functions. Our study identifies key factors influencing HR, offering a comprehensive framework for future research aimed at improving plant drought resistance and refining ecohydrological models., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: All authors approved the final manuscript and the submission to this journal. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: Skilled Nursing residents who have cognitive impairment (CI) in heart failure(HF) have a significantly higher mortality rate. These residents' ability to self-manage their complex care upon discharge is critical for positive health outcomes., Method: We conducted a secondary data analysis of admission MDS records for 79 residents admitted for HF care from 2021 to 2022., Results: Seventy-nine eligible admission MDS records were included in the study. Only one additional with DC diagnoses of CI in HF was captured upon discharge. Twenty-seven (35.1 %) records affirming CI in HF were omitted from the discharge diagnosis list or discharge summary., Conclusion: This secondary data analysis of admission MDS records in two large mid-south metropolitan nursing facilities uncovered quality improvement opportunities, including improving facility interprofessional communication, opportunities to capture and improve diagnostic accuracy, the potential value of an evidence-based discharge planning program, opportunity for improved hand-offs back to community primary care providers., Competing Interests: Declaration of competing interest All authors attest that they have no personal, professional, or financial relationships with people or organizations that could create a conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The limited therapeutic options and inconsistent treatment efficacy of Intestinal Behçet's disease complicate its management, with the absence of standardized guidelines further exacerbating the challenges faced by clinicians., Case Presentation: In this case report, we present a patient with refractory intestinal Behçet's disease who experienced treatment failure with prior biologic agents. This case sheds light on managing this complex scenario with Janus kinase (JAK) inhibitors, the patient achieved mucosal healing after switching to Upadacitinib., Conclusion: This case underscores the potential of Upadacitinib as an effective alternative for managing difficult cases of intestinal Behçet's disease., 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 Sha, Xu, Wang, Qiao, Shi, Jiang, Quan and Liu.)

Background: Our previous study demonstrated that microRNA-409-5p (miR-409-5p) and its target ubiquitin-specific protease 7 (USP7) were involved in hypoxia-induced cardiomyocyte injury and ischemic left ventricular remodeling (LVR) in rats. This study aimed to probe into the relationship between plasma miR-409-5p and USP7 levels and LVR and dysfunction in patients with acute myocardial infarction (AMI)., Methods: Sixty patients with acute myocardial infarction (AMI) and 60 cases with chronic coronary syndrome (CCS) were enrolled. The clinical characteristics, echocardiographic/serum parameters of LVR, and circulating miR-409-5p and USP7 mRNA levels between the two groups and between admission and 6 weeks after discharge were compared. The correlations between circulating miR-409-5p/USP7 levels and serum/echocardiographic parameters were analyzed., Results: The demographic characteristics of the AMI group and CCS group were comparable. Patients with AMI admitted to the study displayed significantly higher levels of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) and growth stimulation expressed gene 2 (ST2), along with a greater left ventricular end-systolic volume (LVESV). Conversely, their left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), and global radial strain (GRS) were significantly lower compared to patients with CCS. These changes were normalized 6 weeks after discharge. Circulating miR-409-5p levels at admission were significantly decreased while circulating USP7 mRNA expression levels were significantly increased in patients with AMI compared with those with CCS (both P < 0.01). However, these changes were restored 6 weeks after discharge (both P < 0.01). Moreover, circulating miR-409-5p and USP7 mRNA levels showed varying correlations with GLS, GRS, LVESV, LVEF, and NT-proBNP in patients with AMI but not in those with CCS. Additionally, circulating miR-409-5p and USP7 levels predicted the incidence of LVR and major adverse cardiovascular events (MACE) after AMI., Conclusion: Serum miR-409-5p and USP7 may influence the occurrence and evolution of LVR and left ventricular dysfunction after AMI., (© 2024. The Author(s).)

Cutaneous melanoma is the most lethal of all skin tumors. Recently, cuproptosis, a novel form of cell death linked to oxidative phosphorylation, has emerged as an important factor. However, the precise role of cuproptosis in melanoma remains unclear. Our research explored the potential links between cuproptosis-related genes, prognosis, immune microenvironments, and melanoma treatments. Significantly, cuproptosis regulators showed remarkable differences between melanoma and normal tissues, establishing their relevance to melanoma. The newly developed cuproptosis-related gene signature (CGS) demonstrated a robust ability to predict overall survival (OS) in melanoma. We constructed a novel nomogram that combined clinical features with CGS to improve predictive accuracy. In addition, the study revealed correlations between CGS and immune cell populations, including CD8 + T cells, Tfh cells, B cells, and myeloid-derived suppressor cells. Within the CGS, Peptidylprolyl isomerase C (PPIC) emerged as the most strongly associated with poor prognosis and drug resistance in melanoma. PPIC was identified as a promoter of melanoma progression, enhancing cell invasiveness while concurrently suppressing CD8 + T cell activation. This comprehensive study not only elucidated the intricate connections between CGS, melanoma prognosis, immune microenvironment, and drug resistance but also provided compelling evidence supporting PPIC as a promising biomarker for predicting OS in melanoma treatment., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Study Aims: Adherent invasive Escherichia coli (AIEC) are enriched in IBD (inflammatory bowel disease) patients, but the role and mechanism of AIEC in the intestinal epithelial barrier is poorly defined. We evaluated the role of the AIEC strain E. coli LF82 in vitro and investigated the role of Th17 in this process., Material and Methods: After coincubation with AIEC, the epithelial barrier integrity was monitored by epithelial resistance measurements. The permeability of the barrier was evaluated by TEER (trans-epithelial electrical resistance) and mucosal-to-serosal flux rate. The presence of interepithelial tight junction proteins ZO-1 and Claudin-1 were determined by immunofluorescence and western blot analysis. Cytokines in the cell culture supernatant were assayed by enzyme-linked immunosorbent assay (ELISA)., Results: AIEC infection decreased TEER and increased the mucosal-to-serosal flux rate of Lucifer yellow in the intestinal barrier model in a time- and dose-dependent manner. AIEC infection decreased the expression and changed the distribution of ZO-1 and claudin-1. It also induced the secretion of cytokines such as TNF-α and IL-17., Conclusion: AIEC strain E. coli LF82 increased the permeability and disrupted the tight junctions of the intestinal epithelial barrier, revealing that AIEC plays an aggravative role in the inflammatory response., Competing Interests: Declaration of 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., (Copyright © 2024 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

Background: Moral distress is the inability to do the right thing due to imposed constraints., Objective: Explore the presence of moral distress among nurses., Methods: A quantitative, exploratory, cross-sectional study at a level 1 trauma center using the Measure of Moral Distress for Healthcare Professionals (MMD-HP)., Results: Ninety-seven nurses completed the MMD-HP. The top 3 items contributing to moral distress included inadequate staffing, inadequate resources, and lack of administrative support. Nurses who considered leaving had more moral distress. Moral distress explained 28.5% of the variance associated with nurses' "intent to leave" and "primary unit" ( P < 0.001). Moral distress for nurses 40 to 49 years of age was higher compared with nurses 50 years or older., Conclusions: Moral distress involved deficiencies in staffing, resources, and administrative support. Research should explore interventions to mitigate moral distress among nurses by promoting safe staffing levels, the provision of adequate resources, and increased administrative support., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The purpose of this study was to examine dimensions of the perioperative work environment and their associations with the operating room (OR) culture of safety and high-reliability characteristics., Design: A predictive correlational design using a cross-sectional survey was used., Methods: A convenience sample of perioperative nurses (N = 96) was used to evaluate strength of associations of their work environment with OR safety culture and high-reliability organizational culture. In addition, the best predictive models for OR culture of safety and high-reliability characteristics were used., Findings: Findings indicated that the five dimensions of the work environment are significant predictors of a safety culture; however, only Collegial Relationships and Nursing Foundations for Quality of Care significantly predict high reliability., Conclusions: Due to the extraordinary responsibility perioperative nurses hold to maintain safety standards for surgical patients, it is critical to fortify elements of the nurse work environment., Competing Interests: Declaration of Competing Interest None to report., (Copyright © 2024 The American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.)

Efficaciously assessing product quality remains time- and resource-intensive. Online Process Analytical Technologies (PATs), encompassing real-time monitoring tools and soft-sensor models, are indispensable for understanding process effects and real-time product quality. This research study evaluated three modeling approaches for predicting CHO cell growth and production, metabolites (extracellular, nucleotide sugar donors (NSD) and glycan profiles): Mechanistic based on first principle Michaelis-Menten kinetics (MMK), data-driven orthogonal partial least square (OPLS) and neural network machine learning (NN). Our experimental design involved galactose-fed batch cultures. MMK excelled in predicting growth and production, demonstrating its reliability in these aspects and reducing the data burden by requiring fewer inputs. However, it was less precise in simulating glycan profiles and intracellular metabolite trends. In contrast, NN and OPLS performed better for predicting precise glycan compositions but displayed shortcomings in accurately predicting growth and production. We utilized time in the training set to address NN and OPLS extrapolation challenges. OPLS and NN models demanded more extensive inputs with similar intracellular metabolite trend prediction. However, there was a significant reduction in time required to develop these two models. The guidance presented here can provide valuable insight into rapid development and application of soft-sensor models with PATs for ipurposes. Therefore, we examined three model typesmproving real-time product CHO therapeutic product quality. Coupled with emerging -omics technologies, NN and OPLS will benefit from massive data availability, and we foresee more robust prediction models that can be advantageous to kinetic or partial-kinetic (hybrid) models., Competing Interests: SS currently works at Ultragenyx Pharmaceutical. HL currently works at Alexion Pharmaceuticals. Both authors contributed to this work while they were at the University of Massachusetts Lowell, and joined their respective companies after conducting this study. The remaining 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 Liang, Sha, Wang, Liu and Yoon.)

Purpose: Ischemic colitis appears to be a rare but serious complication of COVID-19. About 33.3% hospitalized COVID-19 patients who underwent endoscopy showed features resembling ischemic colitis. The aim of this prospective study was to describe the symptoms, treatment, and outcomes of these patients, particularly their colonoscopy and histologic findings., Patients and Methods: We conducted a prospective study on ischemic bowel disease associated with COVID-19 across four centers from December 2022 to January 2023. All cases were identified through a comprehensive search of electronic medical records for procedure-related data. The initial diagnosis of ischemic bowel disease was confirmed using colonoscopy and biopsy findings. After the patients were discharged, a 12-month follow-up was conducted through regular phone interviews to assess their clinical outcomes., Results: Overall, the study included 3 male patients and 9 female patients (age range, 33-76 years). Abdominal pain and hematochezia always occurred within 2 weeks after COVID-19 infection (average 5.5 days). Gastrointestinal manifestations did not parallel the severity of COVID-19 infection. The descending colon was the most susceptible segment, which was involved in 10 patients (83.33%). Colonoscopy revealed diffuse redness, edema, bleeding, erosion, and ulceration of the intestinal mucosa, similar to the findings of ischemic colitis, and biopsy revealed crypt atrophy, reduction, and interstitial bleeding. All patients were self-limited without converting to chronic changes in the next 12 months., Conclusion: SARS-CoV-2 infection may induce transient acute colon ischemia within 2 weeks, accompanied by severe clinical symptoms such as acute abdominal pain and hematochezia, which are self-limiting and do not lead to chronic symptoms., Competing Interests: The authors declared that there were no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2024 Wu et al.)

Currently, research on Ag nanoparticles (AgNPs) predominantly focuses on UV/visible photodetection and UV emission, seemingly overlooking the significance of Ag in enhancing deep ultraviolet photon detection. In this work, (In 0.3 Ga 0.7 ) 2 O 3 thin films were fabricated by plasma-enhanced chemical vapor deposition. Due to the unique photoabsorbance characteristic and better interaction with photons of small-sized AgNPs, they effectively suppress the UVB absorbance caused by energy band engineering in the (In 0.3 Ga 0.7 ) 2 O 3 thin film while enhancing photoabsorbance in UVC due to the surface plasmon effect. Therefore, under the synergistic effect of enhanced photon absorbance and hot electron transfer, the performance of the detector is significantly improved, and its responsivity ( R ), external quantum efficiency, and detectivity ( D *) are 193 mA/W, approximately 100%, and 10 14 Jones, respectively, at a bias of -6 V. The fast response time and decay time are 634.6 and 194.1 ms, respectively; the rapid decay facilitated by AgNPs is attributed to the increased indirect recombination rate. AgNPs exhibit excellent narrowband response characteristics and absorbance properties in specific wavelength bands for the InGaO photodetector. This research lays the foundation for the practical application of localized surface plasmon resonance-enhanced photon-sensing capabilities.

Despite our increasing understanding of macrophage heterogeneity, drivers of macrophage phenotypic and functional polarization in the microenvironment are not fully elucidated. Here, our single-cell RNA sequencing data identify a subpopulation of macrophages expressing high levels of the phagocytic receptor MER proto-oncogene tyrosine kinase (MerTK + macrophages), which is closely associated with melanoma progression and immunotherapy resistance. Adoptive transfer of the MerTK + macrophages into recipient mice notably accelerated tumor growth regardless of macrophage depletion. Mechanistic studies further revealed that ALK And LTK Ligand 1 (ALKAL1), a target gene of aryl hydrocarbon receptor (AhR), facilitated MerTK phosphorylation, resulting in heightened phagocytic activity of MerTK + macrophages and their subsequent polarization toward an immunosuppressive phenotype. Specifically targeted delivery of AhR antagonist to tumor-associated macrophages with mannosylated micelles could suppress MerTK expression and improved the therapeutic efficacy of anti-programmed cell death ligand 1 therapy. Our findings shed light on the regulatory mechanism of MerTK + macrophages and provide strategies for improving the efficacy of melanoma immunotherapy.

Background: The high prevalence of poor sleep quality (PSQ) in the general population leads to negative health outcomes. Since estimates of PSQ prevalence in the Chinese general population vary widely, this meta-analysis aimed to refine these estimates and to identify moderating factors., Methods: A comprehensive literature search was undertaken in both international (PubMed, PsycINFO, Web of Science, and EMBASE) and Chinese (Wanfang, and the China National Knowledge Infrastructure databases) databases from inception to 23 November 2023. Studies were required to have used standard scales such as the Chinese version of the Pittsburgh Sleep Quality Index (PSQI). The pooled prevalence of PSQ and 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup and meta-regression analyses were performed to identify sources of heterogeneity., Results: In 32 studies with a combined 376,824 participants, the pooled prevalence of PSQ was 19.0% (95% CI 15.8-22.8%; range 6.6-43.6%). Across 22 studies that reported PSQI data, the pooled mean score was 4.32 (95%CI 3.82-4.81; SD = 0.502). The pooled mean sleep duration across 8 studies was 7.62 (95% CI 7.23-8.00; SD = 0.194) hours. Subgroup analyses showed that lower education (Q = 4.12, P = 0.042), living in less developed regions (Q = 60.28, P < 0.001), and lower PSQI cutoff values (Q = 9.80, P = 0.007) were significantly associated with PSQ. Meta-regression analyses showed that study quality was inversely associated with estimated PSQ prevalence (β = - 0.442, P = 0.004)., Limitations: Although measures such as subgroup and meta-regression analyses were performed, substantial heterogeneity remained. Information related to sleep quality, such as comorbid physical diseases or psychiatric disorders, substance use, occupational types, and employment status, were not reported in most studies., Conclusion: One in five people in the general population of China may have PSQ and people with lower education or living in western regions may be more susceptible., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

The gut microbiome has been implicated in various human diseases, though findings across studies have shown considerable variability. In this study, we reanalyzed 6314 publicly available fecal metagenomes from 36 case-control studies on different diseases to investigate microbial diversity and disease-shared signatures. Using a unified analysis pipeline, we observed reduced microbial diversity in many diseases, while some exhibited increased diversity. Significant alterations in microbial communities were detected across most diseases. A meta-analysis identified 277 disease-associated gut species, including numerous opportunistic pathogens enriched in patients and a depletion of beneficial microbes. A random forest classifier based on these signatures achieved high accuracy in distinguishing diseased individuals from controls (AUC = 0.776) and high-risk patients from controls (AUC = 0.825), and it also performed well in external cohorts. These results offer insights into the gut microbiome's role in common diseases in the Chinese population and will guide personalized disease management strategies., (© 2024. The Author(s).)

Introduction: The presence of hypoxic-ischemic brain damage (HIBD) in neonates triggers a strong neuroinflammatory reaction. Pyroptosis, a programmed cell death mechanism associated with inflammation, plays a crucial role in HIBD. Pyruvate kinase M2 (PKM2) plays a significant role in connecting metabolic processes and inflammatory responses, but whether it affects hippocampus pyroptosis in HIBD is unclear. The aim of this study is to elucidate the role of PKM2 in HIBD and to propose a novel therapeutic approach for neonatal ischemic-hypoxic encephalopathy., Methods: In this study, we employed neonatal 7-day-old Sprague Dawley rats to establish a model of HIBD using the Rice-Vannucci surgical technique and a hypoxia device. To inhibit the elevation of PKM2, we utilized the PKM2 inhibitor shikonin. The rats were categorized into four groups: Sham, Shikonin, HIBD, and Shikonin + HIBD. Behavioral tests, hematoxylin eosin staining, immunofluorescence staining, ELISA (IL-1β, IL-18), and LDH were conducted in each group to evaluate neurological function, hippocampal damage, the occurrence of neuronal pyroptosis, and the neuroinflammation. Western blot was used to assess the expression levels of PKM2, NLRP3, Caspase-1, Cleaved Caspase-1, GSDMD, GSDMDN, and IL-1β., Results: The expression of PKM2 elevated in hippocampal tissues of the HIBD model and the localization of PKM2 in the hippocampus was activated in neurons instead of microglia during the HIBD. Meanwhile, the inhibition of PKM2 improved the behavioral test scores and the body weight of rats, the neuronal damage in the CA1 region of hippocampal tissue was also attenuated. In addition, inhibiting PKM2 alleviated neuronal pyroptosis by decreasing the expression of PKM2, NLRP3, Caspase-1, Cleaved Caspase-1, GSDMD, GSDMDN. Furthermore, serum levels of LDH and inflammatory factors IL-1β and IL-18 decrease with PKM2 inhibition., Conclusions: Based on these findings, we can conclude that PKM2 plays a crucial role in regulating hippocampal neuronal pyroptosis of HIBD rats via NLRP3/Caspase-1/GSDMD pathway. Therefore, inhibiting PKM2 could be a promising therapeutic strategy for the treatment of neonatal ischemic-hypoxic encephalopathy., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Pyroptosis is an inflammation-associated programmed cell death, and neuroinflammation is strongly associated with severe neurological deficits in neonatal hypoxic-ischemic encephalopathy (HIE). Ethyl pyruvate (EP), a known anti-inflammatory agent, has shown promise in the treatment of hypoxic-ischemic brain damage (HIBD) rats; nevertheless, the therapeutic mechanism of EP and its capacity to suppress neuronal pyroptosis in HIBD rats remain unclear. In both the neonatal Rice-Vannucci rat model and the OGD/R model, this study examined alterations in the NLRP3/Caspase-1/GSDMD classical pyroptosis pathway in hippocampal neurons during HIE and the potential inhibitory impact of ethyl pyruvate on this pathway. We used HE staining, immunofluorescence double staining, transmission electron microscopy, and western blot to demonstrate that EP effectively inhibited hippocampal neuronal pyroptosis and attenuated the activation of the NLRP3/Caspase-1/GSDMD signaling pathway in HIBD rats, which resulted in a reduction of neuroinflammation and facilitated neural recovery. The results suggest that EP may be a promising neuroprotective agent for treating HIE., (© 2024 International Society for Developmental Neuroscience.)

Parkinson's disease (PD) is a complex multisystem disorder clinically characterized by motor, non-motor, and premotor manifestations. Pathologically, PD involves neuronal loss in the substantia nigra, striatal dopamine deficiency, and accumulation of intracellular inclusions containing aggregates of α-synuclein. Recent studies demonstrate that PD is associated with dysregulated metabolic flux through the kynurenine pathway (KP), in which tryptophan is converted to kynurenine (KYN), and KYN is subsequently metabolized to neuroactive compounds quinolinic acid (QA) and kynurenic acid (KA). This multicenter study used highly sensitive liquid chromatography-tandem mass-spectrometry to compare blood and cerebral spinal fluid (CSF) KP metabolites between 158 unimpaired older adults and 177 participants with PD. Results indicate that increased neuroexcitatory QA/KA ratio in both plasma and CSF of PD participants associated with peripheral and cerebral inflammation and vitamin B6 deficiency. Furthermore, increased QA tracked with CSF tau and severity of both motor and non-motor PD clinical dysfunction. Importantly, plasma and CSF kynurenine metabolites classified PD participants with a high degree of accuracy (AUC = 0.897). Finally, analysis of metabolite data revealed subgroups with distinct KP profiles, and these were subsequently found to display distinct PD clinical features. Together, these data further support the hypothesis that the KP serves as a site of brain and periphery crosstalk, integrating B-vitamin status, inflammation and metabolism to ultimately influence PD clinical manifestation., Competing Interests: Competing interests: The authors declare that they have no competing interests.

Plain carbon steel is the most widely applied steel in current engineering construction. With the increased application property needs, the service life of plain carbon steel has been severely tested. As one of the most destructive failure modes, corrosion resistance of carbon steel has attracted wide attention. Rare earth La, as the microalloying element, was employed in plain carbon steel, Q355, to improve its corrosion resistance. As the content of La increased, the microstructure was refined. The fraction of pearlite decreased, while the content of acicular increased. Within the La addition of 230 ppm, the tensile strength and impact energy were jointly improved. Furthermore, the microalloying element of La modified the inclusion types and refined the inclusion size. The modified microstructure and inclusions by La co-improved the corrosion resistance. The formula of effective La content was proposed to estimate the effect of La on corrosion. As the effective content of La increased, the relative corrosion rate decreased. La 3+ promoted the protective rust layer to increase corrosion resistance.

Background: In context of COVID-19 as a collective trauma and the intense involvement of healthcare workers (HCWs) in the pandemic, perceived stress continues to have a tremendous impact on their psychological well-being. However, few studies have attempted to delineate the underlying mechanisms. This study examined whether COVID-19-related traumatic stress symptoms and mentalization act as mediators., Methods: A sample of HCWs (N = 2610) from 22 hospitals in Beijing, China participated in this cross-sectional investigation. Data on their perceived stress, psychological well-being, the impact of event, and reflective function during the COVID-19 pandemic were collected using self-report questionnaires. Different mediating models were tested., Results: COVID-19-related stress symptoms and mentalization independently mediate the association between perceived stress and psychological well-being. These two mediators also compose a serial mediation model. In particular, higher perceived stress inhibits the psychological well-being of HCWs through increased severity of traumatic stress symptoms, which in turn is associated with hypomentalizing., Conclusion: These findings shed light on the mechanisms underlying the relationship between perceived stress and psychological well-being in HCWs. We strongly recommend incorporating a mentalization framework with trauma-informed practice in prevention and intervention work with this population during this and future healthcare crisis., Competing Interests: No authors have competing interests., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Accumulating evidence indicates that oxidative stress and the disruption of antioxidant defenses play an important role in the neurobiology of bipolar disorder (BD). Studies have found that increased oxidative stress may be associated with cell apoptosis and neuronal damage in BD patients. Hence, this study explored the research field related to BD and oxidative stress from a bibliometrics perspective., Methods: Literature search and relevant data retrieval based on the Web of Sciences Core Collection (WoSCC). R software (version 4.2.2), VOSviewer software (version 1.6.18), and CiteSpace (version 6.1.6) were used in this bibliometric analysis., Results: A total of 2081 publications related to BD and oxidative stress were published between 1986 and 2024. Bipolar Disorders was the journal that had the most publications in this area (72; 3.46%; IF = 5.9), while the United States (1285; 61.7%) and the University of Toronto (377; 18.1%) were the most productive country and institution, respectively. Apart from "oxidative stress" and "bipolar disorder," the most frequently used keywords were "schizophrenia," "prefrontal cortex," and "nitric oxide.", Conclusions: The growing number of publications related to BD and oxidative stress in recent years highlights the importance of this research field. Hot topics in research related to BD and oxidative stress included animal experiments and molecular mechanisms, psychiatric-related inflammation and biomarkers, neurodegenerative diseases, and metabolism. Furthermore, the biological mechanisms of BD, particularly biomarkers and inflammation, may be the emerging research priority area in the future., (© 2024 The Author(s). Asia‐Pacific Psychiatry published by John Wiley & Sons Australia, Ltd.)

Objectives: Electroconvulsive therapy (ECT) is an effective somatic treatment, but it may be limited by cognitive adverse effects. The existing cognitive screening instruments often lack specificity to ECT-associated cognitive deficits. The ElectroConvulsive Therapy Cognitive Assessment was developed and validated in a clinical setting, but the reliability and validity of the Chinese version of ElectroConvulsive Therapy Cognitive Assessment (ECCA-C) have not been studied in a large clinical sample., Methods: The ECCA-C and the Montreal Cognitive Assessment (MoCA) were administered to patients with major depressive disorder (MDD) undergoing ECT at 3 time points: pretreatment (baseline), before the fifth treatment, and 1 week posttreatment. The instruments were also administered to a sample of healthy subjects., Results: Sixty-five patients with MDD and 50 age- and sex-matched healthy controls were recruited in this study. Overall, the patient group had statistically significantly lower MoCA and ECCA-C scores than the control group (both P values <0.001). The Cronbach α of the ECCA-C was 0.88 at baseline. Statistically significant decreases over time were observed in ECCA-C: pre-ECT (23.9 ± 4.0) > mid-ECT (21.3 ± 3.4) > post-ECT (18.7 ± 4.8) (all P values <0.001), whereas no statistically significant changes in MoCA scores were found at these 3 time points ( F = 1.86, P = 0.165). A cutoff score of 26.5 on the ECCA-C was found to best differentiate between MDD patients and healthy controls., Conclusions: The ECCA-C showed satisfactory psychometric properties and may be a more sensitive instrument than the MoCA to assess cognitive impairment associated with ECT., 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. This study was supported by the Beijing Anding Hospital, Capital Medical University (YJ2021-05)., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Environmental tobacco smoke (ETS) exposure has been shown to be associated with a variety of diseases, but evidence regarding the association between it and urinary incontinence (UI) is limited. Cotinine, a metabolite of nicotine in the human body, can more accurately quantify the level of human exposure to tobacco smoke. The study utilized data from seven survey cycles (2007-March 2020 Pre-pandemic) of the National Health and Nutrition Examination Survey (NHANES) program. Weighted multivariable logistic regression analysis, subgroup analysis, interaction tests, smooth curve fitting, and threshold effect models were used to analyze the relationship between serum cotinine and UI. Additionally, a 1:1 nearest neighbor propensity score matching (PSM) method was employed to minimize the impact of confounding factors. Before and after PSM, serum cotinine levels were higher in individuals with UI than those without (P < 0.05). Both before and after PSM, UI was positively correlated with serum cotinine levels, with a significantly increased risk of urinary incontinence when serum cotinine levels were in the Q3 range (before PSM: OR = 1.89, 95% CI = 1.59-2.24; after PSM: OR = 1.60, 95% CI = 1.28-2.00). Smooth curve fitting before and after PSM showed an approximate J-shaped non-linear dose-response relationship between log-transformed serum cotinine levels and UI. This study indicates that among American adults, there is a positive relationship between serum cotinine levels and UI, which is also significant in self-reported non-smoking populations. Therefore, reducing exposure to environmental tobacco smoke (e.g., avoiding second-hand smoke) in work and daily life may help alleviate the occurrence of UI, and serum cotinine levels have the potential to be a tool for predicting the degree of risk of developing UI., (© 2024. The Author(s).)

Silicon carbide (SiC) single crystals have great prospects for high-temperature energy storage due to their robust structural stability, ultrahigh power output, and superior temperature stability. However, energy density is an essential challenge for SiC-based devices. Herein, a facile two-step strategy is proposed for the large-scale synthesis of a unique architecture of SiC nanowires incorporating MnO 2 for enhanced supercapacitors (SCs), arising from the synergy effect between the SiC nanowires as a highly conductive skeleton and the MnO 2 with numerous active sites. The SiC@MnO 2 integrated electrode-based SCs with ionic liquid (IL) electrolytes were assembled and delivered outstanding energy and power density, as well as a great lifespan at 150 °C. This impressive work offers a novel avenue for the practical application of SiC-based electrochemical energy storage devices with high energy density under high temperatures.

Background: Major depressive disorder (MDD) becomes one of the psychiatric disorders characteristic of a combination of cognitive, emotional, and somatic symptoms. Additionally, cognitive impairment has the most significant impact on functional results. However, the evaluation of cognitive level is still based on various subjective questionnaires as there is no objective standard assessment yet. This research focuses on resting-state alpha activity to identify cognition in MDD patients using electroencephalography (EEG) signals., Methods: Ninety-two subjects were recruited: 44 patients with MDD and 48 healthy individuals as controls. Functional outcome and cognition were assessed using standardized instruments, and the EEG resting state signal of open and closed eyes was recorded. The comparison and correlation of cognitive levels with alpha power in the bilateral frontal region, bilateral central region, bilateral occipital region, and middle line was evaluated., Results: The relative alpha power in MDD group was significantly lower than that in the control group (P < 0.05). Through correlation analysis, it was shown that the bilateral frontal and occipital alpha power of MDD patients in the closed-eyes state was positively correlated with information processing rate, verbal learning, working memory, and attention retention. The alpha power of the bilateral frontal region in the open-eyes state was positively correlated with information processing rate, working memory, and attention retention (P < 0.05)., Conclusion: The research indicates that the changes in frontal and occipital alpha activities may be a promising neurophysiological indicator of cognitive level to diagnose and treat response prediction., Competing Interests: The authors have no conflicts of interest to declare in this work., (© 2024 Xie et al.)

Our study focuses on the relationship between inflammatory biomarkers and hypertension among sedentary adults in the United States, using data from the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018. We categorized 24,614 participants into two groups based on their daily sedentary time: 9607 individuals in the sedentary group (≥7 h) and 15,007 in the non-sedentary group (<7 h). We found that the sedentary group had a significantly higher prevalence of hypertension than the non-sedentary group. Using weighted multiple logistic regression and smoothing curves, we assessed the correlation between inflammatory biomarkers and hypertension among the sedentary adults. The odds ratios for hypertension were 1.92 for the monocyte to high-density lipoprotein ratio (MHR), 1.15 for the systemic inflammation response index (SIRI), and 1.19 for the natural logarithm of the systemic immune-inflammation index (lnSII), all showing nonlinear associations. Furthermore, a significant positive correlation was found between sedentary time and inflammatory biomarkers (MHR, SIRI, and lnSII). Our findings suggest that prolonged sedentary behavior in the US significantly increases hypertension risk, likely due to marked increases in inflammation markers., (© 2024 The Author(s). The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Introduction: A previous meta-analysis indicated stable progress in cognitive functions in early psychosis, assessed through various tools. To avoid assessment-related heterogeneity, this study aims to examine the longitudinal cognitive function changes in early psychosis utilizing the MATRICS Consensus Cognitive Battery (MCCB)., Methods: Embase, PubMed, and Scopus were systematically searched from their inception to September 26th 2023. The inclusion criteria were longitudinal studies that presented follow-up MCCB data for individuals experiencing first-episode psychosis (FEP) and those with ultra-high risk for psychosis (UHR)., Results: Twelve studies with 791 participants (566 FEP patients and 225 healthy controls) were subjected to analysis. Suitable UHR studies were absent. Over time, both FEP patients and healthy controls showed significant improvements in MCCB total scores. Furthermore, FEP patients demonstrated improvements across all MCCB domains, while healthy controls only showed augmentations in specific domains such as speed of processing, attention, working memory, and reasoning and problem-solving. Visuospatial learning improvements were significantly greater in FEP patients compared to healthy controls. Subgroup analyses suggested that neither diagnostic type nor follow-up duration influenced the magnitude of cognitive improvement in FEP patients., Conclusion: The magnitude of cognitive improvement for MCCB domains was not significantly different between FEP and healthy controls other than visuospatial learning. This underscores visuospatial learning as a potentially sensitive cognitive marker for early pathologic state changes in psychotic disorders., Competing Interests: Declaration of competing interest The authors declare no conflict of interest in the current study., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Oxidative stress (OS) plays a major role in the progress of hypoxic-ischemic brain damage (HIBD). This study aimed to investigate OS-related genes and their underlying molecular mechanisms in neonatal HIBD., Methods: Microarray data sets were acquired from the Gene Expression Omnibus (GEO) database to screen the differentially expressed genes (DEGs) between control samples and HIBD samples. OS-related genes were drawn from GeneCards and OS-DEGs in HIBD were obtained by intersecting with the DEGs. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were conducted to determine the underlying mechanisms and functions of OS-DEGs in HIBD. Moreover, the hub genes were screened using the protein-protein interaction network and identified in the GSE144456 data set. CIBERSORT was then performed to evaluate the expression of immunocytes in each sample and perform a correlation analysis of the optimal OS-DEGs and immunocytes. Finally, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunohistochemistry were performed to validate the expression levels of the optimal OS-DEGs., Results: In total, 93 OS-DEGs were identified. GO, KEGG, and GSEA enrichment analyses indicated that these genes were predominantly enriched in OS and inflammation. Four OS-related biomarker genes (Jun, Fos, Tlr2, and Atf3) were identified and verified. CIBERSORT analysis revealed the dysregulation of six types of immune cells in the HIBD group. Moreover, 47 drugs that might target four OS-related biomarker genes were screened. Eventually, RT-qPCR and immunohistochemistry results for rat samples further validated the expression levels of Fos, Tlr2, and Atf3., Conclusions: Fos, Tlr2 and Atf3 are potential OS-related biomarkers of HIBD progression. The mechanisms of OS are associated with those of neonatal HIBD., (© 2024 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Tuberculosis (TB) remains a threat to human health worldwide. Mycobacterium tuberculosis (Mtb) and other nontuberculous mycobacteria (NTM) can form biofilms, and in vitro and animal experiments have shown that biofilms cause serious drug resistance and mycobacterial persistence. Deeper investigations into the mechanisms of mycobacterial biofilm formation and, consequently, the exploration of appropriate antibiofilm treatments to improve the efficiency of current anti-TB drugs will be useful for curing TB. In this review, the genes and molecules that have been recently reported to be involved in mycobacterial biofilm development, such as ABC transporter, Pks1, PpiB, GroEL1, MprB, (p)ppGpp, poly(P), and c-di-GMP, are summarized. Biofilm-induced clinical problems, including biofilm-related infections and enhanced virulence, as well as their possible mechanisms, are also discussed in detail. Moreover, we also illustrate newly synthesized anti-TB agents that target mycobacterial biofilm, as well as some assistant methods with high efficiency in reducing biofilms in hosts, such as the use of nanoparticles.

Background : Potential calcium-related adverse events of vitamin D supplement use have not been addressed in large-scale, real-world data so far. Methods: Leveraging data from the UK Biobank, encompassing 445,493 individuals aged 40-69, we examined associations of high 25-hydroxyvitamin (25(OH)D) levels ≥ 100 nmol/L and vitamin D supplementation with hypercalcemia (serum calcium > 2.6 mmol/L), kidney stones, and atherosclerosis assessments (pulse wave arterial stiffness index and carotid intima-medial thickness). Regression models were comprehensively adjusted for 49 covariates. Results: Approximately 1.5% of the participants had high 25(OH)D levels, 4.3% regularly used vitamin D supplements, and 20.4% reported regular multivitamin use. At baseline, the hypercalcemia prevalence was 1.6%, and 1.1% was diagnosed with kidney stones during follow-up. High 25(OH)D levels were neither associated with calcium-related adverse events nor atherosclerosis assessments. Vitamin D and multivitamin supplementation were associated with an increased prevalence of hypercalcemia (odds ratios and 95% confidence intervals: 1.46 [1.32-1.62] and 1.11 [1.04-1.18], respectively) but were neither associated with atherosclerosis nor future kidney stones. Conclusions: High 25(OH)D levels observable in routine care were not associated with any adverse outcome. Vitamin D users have a slightly higher prevalence of hypercalcemia, possibly due to co-supplementation with calcium, but without a higher atherosclerosis prevalence or risk of kidney stones.

Background: Major depressive disorder (MDD) is the leading cause of disability among all mental illnesses with increasing prevalence. The diagnosis of MDD is susceptible to interference by several factors, which has led to a trend of exploring objective biomarkers. Electroencephalography (EEG) is a non-invasive procedure that is being gradually applied to detect and diagnose MDD through some features such as functional connectivity (FC)., Methods: In this research, we analyzed the resting-state EEG of patients with MDD and healthy controls (HCs) in both eyes-open (EO) and eyes-closed (EC) conditions. The phase locking value (PLV) method was utilized to explore the connection and synchronization of neuronal activities spatiotemporally between different brain regions. We compared the PLV between participants with MDD and HCs in five frequency bands (theta, 4-8 Hz; alpha, 8-12 Hz; beta1, 12-16 Hz; beta2, 16-24 Hz; and beta3, 24-40 Hz) and further analyzed the correlation between the PLV of connections with significant differences and the severity of depression (via the scores of 17-item Hamilton Depression Rating Scale, HDRS-17)., Results: During the EO period, lower PLVs were found in the right temporal-left midline occipital cortex (RT-LMOC; theta, alpha, beta1, and beta2) and posterior parietal-right temporal cortex (PP-RT; beta1 and beta2) in the MDD group compared with the HC group, while PLVs were higher in the MDD group in LT-LMOC (beta2). During the EC period, for the MDD group, lower theta and beta (beta1, beta2, and beta3) PLVs were found in PP-RT, as well as lower theta, alpha, and beta (beta1, beta2, and beta3) PLVs in RT-LMOC. Additionally, in the left midline frontal cortex-right temporal cortex (LMFC-RT) and posterior parietal cortex-right temporal cortex (PP-RMOC), higher PLVs were observed in beta2. There were no significant correlations between PLVs and HDRS-17 scores when connections with significantly different PLVs (all p > 0.05) were checked., Conclusion: Our study confirmed the presence of differences in FC between patients with MDD and healthy individuals. Lower PLVs in the connection of the right temporal-left occipital cortex were mostly observed, whereas an increase in PLVs was observed in patients with MDD in the connections of the left temporal with occipital lobe (EO), the circuits of the frontal-temporal lobe, and the parietal-occipital lobe. The trends in FC involved in this study were not correlated with the level of depression., Limitations: The study was limited due to the lack of further analysis of confounding factors and follow-up data. Future studies with large-sampled and long-term designs are needed to further explore the distinguishable features of EEG FC in individuals with MDD., Competing Interests: YCu, TZ, and YY were employed by Gnosis Healthineer Co. Ltd. The remaining 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 Wang, Chen, Cui, Zhao, Wang, Zheng, Ren, Sha, Yan, Zhao, Zhang and Wang.)