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The authors have advised there are errors in the Y-axis of Figures 1, 2 and 4 on pages 1097, 1099 and 1101, respectively. The Y-axis label “Body weight (kg)” in figure parts 1B, 2C and 4c should read “Body weight (g)”. The Y-axis label “Th2 cell counts (×103)” in figure parts 1G, 2H and 4H should read “Proportion of Th2 cells (%)”. The correct figures are as follows. Figure 1 Continued. Figure 1 CQ relieved MC903-induced type 2 inflammatory response in AD mice. (A) The severity of ear skin lesions; (B) dermatitis severity score; (C) left ear thickness; (D) H&E staining; (E) TB staining; (F) ELISA measurements of serum TSLP, IL-4, IL-13, IFN-γ, and IgE levels; (G) flow cytometry to determine the content of peripheral blood Th2 cells (CD3+CD4+CD193+). N = 6. Data were represented as mean ± standard deviation, one-way ANOVA was for data comparisons in panels A/D-G, with Tukey’s test serving for post hoc testing. ns represented P > 0.05, *P < 0.05, **P < 0.01, and ***P < 0.001. Two-way ANOVA was adopted in panels B-C, and Tukey’s multiple comparisons test was implemented for post hoc test. *Represented comparisons with the Control group, *P < 0.05, ***P < 0.001, #Represented comparisons with the AD group, #P < 0.05, ##P < 0.01. Figure 2 Continued. Figure 2 CQ abated type 2 inflammatory response in AD mice by inactivating TLR3. (A) Western blot detection of TLR3 protein expression; (B) the severity of ear skin lesions; (C) dermatitis severity score; (D) left ear thickness; (E) H&E staining; (F) TB staining; (G) ELISA detections of serum TSLP, IL-4, IL-13, IFN-γ, and IgE levels; (H) flow cytometry to assess the content of Th2 cells (CD3+CD4+CD193+). N = 6. Data were represented as mean ± standard deviation. Data in panel A were tested by one-way ANOVA, followed by post hoc testing using Tukey’s test. Two-way ANOVA was used for panels (C and D), and Šídák’s multiple comparisons test was used for post hoc test. Data in panels B/E-H were examined by independent sample t-test. ns represented P > 0.05, *P < 0.05, **P < 0.01, ***P < 0.001. Figure 4 Continued. Figure 4 Activation of NLRP3 partially averted the alleviating effect of CQ on type 2 inflammatory response in AD mice. (A) Western blot to test the expression levels of NLRP3, ASC and cleaved caspase-1 proteins; (B) the severity of ear skin lesions; (C) dermatitis severity score; (D) left ear thickness; (E) H&E staining; (F) TB staining; (G) ELISA detection of serum TSLP, IL-4, IL-13, IgE, IL-1β and IL-18 levels; (H) flow cytometry to assess the content of Th2 cells (CD3+CD4+CD193+). N = 6. Data were represented as mean ± standard deviation, and independent sample t-test was employed for comparisons in panels A-B/E-H. Two-way ANOVA was used in panels C-D, and Šídák’s multiple comparisons test was conducted for post hoc test. *P < 0.05, **P < 0.01. These corrections do not significantly impact the overall findings and conclusions of the paper. We would like to assure readers that the corrected values and labels do not alter the interpretations or validity of the research. The authors sincerely apologize for any confusion these errors may have caused.

Brain region- and cell-specific transcriptomic and epigenomic features are associated with heritability for neuropsychiatric traits, but a systematic view, considering cortical and subcortical regions, is lacking. Here, we provide an atlas of chromatin accessibility and gene expression profiles in neuronal and non-neuronal nuclei across 25 distinct human cortical and subcortical brain regions from 6 neurotypical controls. We identified extensive gene expression and chromatin accessibility differences across brain regions, including variation in alternative promoter-isoform usage and enhancer-promoter interactions. Genes with distinct promoter-isoform usage across brain regions were strongly enriched for neuropsychiatric disease risk variants. Moreover, we built enhancer-promoter interactions at promoter-isoform resolution across different brain regions and highlighted the contribution of brain region-specific and promoter-isoform-specific regulation to neuropsychiatric disorders. Including promoter-isoform resolution uncovers additional distal elements implicated in the heritability of diseases, thereby increasing the power to fine-map risk genes. Our results provide a valuable resource for studying molecular regulation across multiple regions of the human brain and underscore the importance of considering isoform information in gene regulation., Competing Interests: Competing interests: Boehringer Ingelheim Pharma GmbH & Co. KG supported this work only by providing financial support. S.A. and N.L. are employees of Boehringer Ingelheim Pharma GmbH & Co. KG. Aside from financial support, the industrial sponsors had no role in the design of this study, the sample collection, analysis, or interpretation of data, the writing of the report, or in the decision to submit the article for publication. The remaining authors declare no conflicts of interest., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Although the incidence of cervical cancer (CC) has been reduced in high-income countries due to human papillomavirus (HPV) vaccination and screening strategies, it remains a significant public health issue that poses a threat to women's health in low-income countries. Here, we perform a comprehensive proteogenomic profiling of CC tumors obtained from 139 Chinese women. Integrated proteogenomic analysis links genetic aberrations to downstream pathogenesis-related pathways and reveals the landscape of HPV-associated multi-omic changes. EP300 is found to enhance the acetylation of FOSL2-K222, consequently accelerating the malignant proliferation of CC cells. Proteomic stratification identifies three patient subgroups with distinct features in prognosis, genetic alterations, immune infiltration, and post-translational modification regulations. PRKCB is further identified as a potential radioresponse-related biomarker of CC patients. This study provides a valuable public resource for researchers and clinicians to delve into the molecular basis of CC, to identify potential treatments and to ultimately advance clinical practice., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Research has identified a link between the triglyceride-glucose index (TyG-i) and the risk of mortality in severely ill patients. However, it remains uncertain if the TyG-i affects mortality by influencing heart rate (HR)., Methods: This study enrolled 3,509 severely ill participants from the Medical Information Mart for Intensive Care (MIMIC-IV) database who had triglyceride, glucose, and HR data upon entering the ICU. Cox regression models were applied to estimate the effect of the TyG-i and HR on 28-day all-cause mortality (ACM) and 28-day in-hospital mortality (IHM). Additionally, Kaplan-Meier (K-M) survival analysis was employed to explore outcome variations among different patient groups. The association of the TyG-i with HR, Sequential Organ Failure Assessment (SOFA) score, and Simplified Acute Physiology Score (SAPS) II was explored through linear regression analysis. Subgroup analysis explored potential interactions among patient characteristics, while sensitivity analysis gauged the robustness of the findings. Additionally, mediation analysis was conducted to assess whether elevated HR acts as an intermediary factor linking the TyG-i to both 28-day ACM and 28-day IHM., Results: During the 28-day follow-up, 586 cases (16.7%) died from all causes, and 439 cases (12.5%) died during hospitalisation. Cox results showed that individuals with a heightened TyG-i and elevated HR had the highest 28-day ACM (Hazard Ratio 1.70, P-value below 0.001) and 28-day IHM (Hazard Ratio 1.72, P-value below 0.001) compared to those with a reduced TyG-i and HR. The K-M curves showed that individuals with low TyG-i and low HR had the lowest incidence of 28-day ACM and 28-day IHM. The linear analysis results evidenced that the TyG-i was independently connected to HR (beta = 3.05, P-value below 0.001), and the TyG-i was also independently associated with SOFA score (beta = 0.39, P-value below 0.001) and SAPS II (beta = 1.79, P-value below 0.001). Subgroup analysis revealed a significant association in participants without hypertension, the interaction of an elevated TyG-i and HR strongly correlated with a higher 28-day death risk (interaction P-value below 0.05). Furthermore, HR mediated 29.5% of the connection between the TyG-i and 28-day ACM (P-value = 0.002), as well as 20.4% of the connection between the TyG-i and 28-day IHM (P-value = 0.002)., Conclusion: For severely ill patients, the TyG-i is distinctly correlated with HR, and elevated levels of both are strongly connected to greater 28-day ACM and 28-day IHM risks, especially in patients without hypertension. Furthermore, elevated HR mediates the connection between the TyG-i and 28-day mortality., Competing Interests: Declarations. Ethics approval and consent to participate: This research was conducted in compliance with the Helsinki Declaration’s guidelines. Approval for using the MIMIC-IV database was obtained from the IRBs of both MIT and BIDMC. The ethical approval previously granted for the MIMIC database covers the data used in this study, obviating the need for further ethical approval or informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Injectable hydrogels offer a minimally invasive approach to treating intervertebral disc degeneration, a prevalent condition that affects 90% of individuals and often leads to significant pain and disability. Despite being a critical yet often overlooked issue that could lead to suboptimal therapeutic outcomes, the mechanical integrity of these gels frequently diminishes postinjection due to the injection process itself. To address this challenge, our research developed a silk-nanofibril-based hydrogel enhanced through simple in situ polymerization of dopamine. The resulting hydrogel not only effectively preserved its modulus at over 1000 Pa postinjection, matching the mechanical properties of the nucleus pulposus, but also significantly enhanced its antioxidative properties to four times that of the original silk nanofibril-based hydrogel. Furthermore, both cell-based and animal studies substantiated that such a silk nanofibril-based hydrogel integrated with polydopamine exhibited significant therapeutic efficacy in the injectable treatment of intervertebral disc degeneration. Therefore, this work introduced a new perspective on the design of injectable hydrogels that could effectively address both the mechanical and biochemical challenges of degenerative disc diseases, providing a platform for subsequent therapeutic interventions.

In the context of liver cirrhosis, the incidence of myocardial inflammation and apoptosis escalates, contributing to the development and progression of cirrhotic cardiomyopathy. The P2X7 receptor, a purinergic receptor linked to inflammatory processes, has been identified in the etiology of a range of autoinflammatory, autoimmune, chronic inflammatory, and metabolic disorders. Despite this, the specific role of the P2X7 receptor in the etiology of cirrhotic cardiomyopathy remains to be elucidated. In our research, a cirrhotic cardiomyopathy animal model was established using mice subjected to bile duct ligation. The expression of the P2X7 receptor was suppressed via intraperitoneal administration of Brilliant Blue G. Cardiac function was evaluated using echocardiographic techniques, while histopathological examination and enzyme-linked immunosorbent assays were employed to assess the presence of inflammation and apoptosis in liver and cardiac tissues. The expression of key proteins, including P2X7, NLRP3, and IL-1β, in the myocardial tissue was quantified by Western blot analysis. Our research has unveiled significant findings in a murine model of liver fibrosis induced by two weeks of bile duct ligation. Notably, we detected escalated levels of liver fibrosis coupled with disruptions in liver blood flow dynamics. Concurrently, there was a marked increase in myocardial inflammation and apoptosis, which adversely affected heart function. Intriguingly, the expression of P2X7 receptors (P2X7R) in cardiac and hepatic tissues was found to be significantly elevated. Targeting and inhibiting the expression of P2X7R not only alleviated myocardial inflammation and apoptosis but also enhanced cardiac performance. Furthermore, this intervention resulted in a noticeable reduction in liver fibrosis. The interplay between the P2X7 and NLRP3 pathways emerges as a pivotal mechanism in the etiology and progression of cirrhotic cardiomyopathy. Our findings suggest that modulating the P2X7-NLRP3 axis could offer promising therapeutic avenues for managing cirrhotic cardiomyopathy., Competing Interests: Declaration of Competing Interest Zhenhao Shao and Xu Ding contributed equally to this work. The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Neurotoxic effects of general anesthetics, particularly sevoflurane, on pediatric neurodevelopment are a global concern. This study investigated the molecular and metabolic impacts of repeated short exposures to sevoflurane in neonatal rats. Metabolomics analysis revealed significant changes in fatty acid and mitochondrial energy metabolism. Transcriptomic analysis identified altered gene expression related to neurodevelopment and mitochondrial function. Various analyses emphasized upregulation in oxidative phosphorylation and DNA repair pathways. Weighted gene co-expression network analysis (WGCNA) identified key gene modules associated with sevoflurane exposure. Despite these acute changes, no significant long-term memory impairments were detected. These findings highlight the impact of sevoflurane on mitochondrial energy metabolism, oxidative stress, and neuroinflammation, emphasizing its relevance to pediatric neurodevelopment. The absence of substantial long-term memory impairments provides insights into the safety and implications of sevoflurane use in pediatric anesthesia, calling for further research., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Motion sickness (MS) is a common physiological response that often occurs when individuals are exposed to environments with repeated acceleration stimuli. MS results from a mismatch between the vestibular system and visual and proprioceptive inputs. As a crucial organ for sensing acceleration stimuli, the vestibular system is closely related to the onset of MS. However, the complex pathogenesis of MS has led to its diagnosis primarily relying on subjective questionnaires, with a lack of objective indicators for evaluation. To identify objective indicators for evaluating MS, we conducted rotating chair stop experiments based on the principle of vestibulo-ocular reflex with 65 volunteers, obtaining their nystagmus slow-phase velocity and related time constants. Additionally, we conducted detailed MS questionnaires with these volunteers to assess their MS susceptibility. Through correlation analysis, we explored whether the nystagmus slow-phase velocity and related time constants significantly correlated with the MS questionnaire scores. The results showed significant positive correlations between the maximal nystagmus slow-phase velocity, cupula time constant, velocity storage time constant, and the nystagmus duration with the MS questionnaire scores in the 65 volunteers. These results indicated that these nystagmus parameters could serve as objective indicators for assessing MS susceptibility. Using K-Means clustering analysis, we classified MS susceptibility into categories I, II, III, and IV, and conducted K-Means clustering analysis on the corresponding nystagmus slow-phase velocity, cupula time constant, velocity storage time constant, and nystagmus duration. The magnitude and range of these indicators at different levels was quantified, offering objective and quantitative indicators for the clinical diagnosis of MS., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Osteoarthritis (OA) is characterized primarily by the degeneration of articular cartilage, with a high prevalence and disability rate. The functional phenotype of chondrocytes, as the sole cell type within cartilage, is vital for OA progression. Due to the avascular nature of cartilage and its limited regenerative capacity, repair following injury poses significant challenges. Various cellular stressors, including hypoxia, nutrient deprivation, oxidative stress, and collagen mutations, can lead to the accumulation of misfolded proteins in the endoplasmic reticulum (ER), resulting in ER stress (ERS). In response to restore ER homeostasis as well as cellular vitality and function, a series of adaptive mechanisms are triggered, including the unfolded protein response (UPR), ER-associated degradation (ERAD), and ER-phagy. Prolonged or severe ERS may exceed the adaptive capacity of cells, leading to dysregulation in apoptosis and autophagy-key pathogenic factors contributing to chondrocyte damage and OA progression. This review examines the relationship between ERS in OA chondrocytes and both apoptosis and autophagy in order to identify potential therapeutic targets and strategies for prevention and treatment of OA., Competing Interests: Competing interests The authors declare that there is no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Silk fibroin is a naturally abundant biomaterial renowned for its excellent biocompatibility and biodegradability, making it a promising candidate for biomedical applications like wound dressings. However, traditional silk fibroin materials often lack sufficient mechanical strength, adhesion, and the ability to modulate inflammation and oxidative stress-factors crucial for effective wound healing. To address these limitations, regenerated silk fibroin/magnesium ion [RSF/Mg(II)] composite films were developed by incorporating Mg(II) ions into RSF solutions. These films were characterized using Raman spectroscopy, mechanical testing, and biocompatibility assessments, and their wound-healing efficacy was evaluated in a mouse skin defect model. The RSF/Mg(II) composite films exhibited superior adhesion, higher transparency, and enhanced mechanical flexibility compared to pristine RSF films. They also demonstrated anti-inflammatory and antioxidative properties, effectively reducing cell apoptosis and reactive oxygen species levels in vitro . In vivo , the RSF/Mg Mg(II) composite films significantly accelerated wound healing in mice, improving epidermal thickness, collagen deposition, and promoting blood vessel formation. This study highlights the potential of RSF/Mg(II) composite films as advanced wound dressings with improved biocompatibility and biological activity, offering valuable insights for the development of Mg(II) ion-based biomaterials in wound healing and tissue regeneration applications.

G protein-coupled receptor 39 (GPR39), a member of the growth hormone-releasing peptide family, exhibits widespread expression across various tissues and demonstrates high constitutive activity, primarily activated by zinc ions. It plays critical roles in cell proliferation, differentiation, survival, apoptosis, and ion transport through the recruitment of Gq/11, Gs, G12/13, and β-arrestin proteins. GPR39 is involved in anti-inflammatory and antioxidant responses, highlighting its diverse pathophysiological functions. Recent discoveries of endogenous ligands have enhanced our understanding of GPR39's physiological roles. Aberrant expression and reactivation of GPR39 have been implicated in a range of diseases, particularly central nervous system disorders, endocrine disruptions, cardiovascular diseases, cancers, and liver conditions. These findings position GPR39 as a promising therapeutic target, with the efficacy of synthetic ligands validated in various in vivo models. Nonetheless, their clinical applicability remains uncertain, necessitating further exploration of novel agonists-especially biased agonists-and antagonists. This review examines the unique residues contributing to the high constitutive activity of GPR39, its endogenous and synthetic ligands, and its pathophysiological implications, aiming to elucidate its pharmacological potential for clinical application in disease treatment., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: The discovery of the glymphatic system, crucial for cerebrospinal and interstitial fluid exchange, has enhanced our grasp of brain protein balance and its potential role in neurodegenerative disease prevention and therapy. Detecting early neurodegenerative shifts via noninvasive biomarkers could be key in identifying at-risk individuals for Alzheimer's disease (AD). Our research explores a diffusion tensor imaging (DTI) method that measures cortical mean diffusivity (cMD), potentially a more sensitive indicator of neurodegeneration than traditional macrostructural methods., Materials and Methods: We analyzed 67 post-traumatic stress disorder (PTSD)-diagnosed veterans from the Alzheimer's Disease Neuroimaging Initiative database. Participants underwent structural MRI, DTI, Aβ PET imaging, and cognitive testing. We focused on the DTI-ALPS technique to assess glymphatic function and its relation to cMD, cortical Aβ accumulation, and thickness, accounting for age and APOE ε4 allele variations., Results: The cohort, all male with an average age of 68.1 (SD 3.4), showed a strong inverse correlation between DTI-ALPS and cMD in AD-affected regions, especially in the entorhinal, parahippocampal, and fusiform areas. Higher DTI-ALPS readings were consistently linked with greater cortical thickness, independent of Aβ deposits and genetic risk factors. Age and cMD emerged as inversely proportional predictors of DTI-ALPS, indicating a complex interaction with age., Conclusion: The study confirms a meaningful association between glymphatic efficiency and cMD in AD-sensitive zones, accentuating cortical microstructural alterations in PTSD. It positions DTI-ALPS as a viable biomarker for assessing glymphatic function in PTSD, implicating changes in DTI-ALPS as indicative of glymphatic impairment., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Photon upconversion through lanthanide-doped nanoparticles is of great significance for various applications. However, the current development of upconversion nanoparticles is hindered by the low quantum efficiency and long radiative lifetimes of lanthanide ions, restricting their applications in time-dependent nanophotonics. Herein, we report ultrafast upconversion superfluorescence with a lifetime of sub-2.5 ns in lanthanide-doped nanoparticles at room temperature. Upon excitation with an 800-nm fs-pulsed laser, we achieve a large number (N = 912) of correlated dipoles in Nd 3+ -concentrated nanoparticles, resulting in collective coherent emission with two orders of magnitude amplification in intensity and more than three orders of magnitude improvement in the radiative decay rate. Furthermore, we demonstrate that the control of excitation power and emitting sample length enables the lifetime manipulation of upconversion emission in a wide range from μs to sub-ns, accompanied by the typical superfluorescence signature of Burnham-Chiao ringing. These findings may benefit applications in many advanced technologies such as quantum counting and high-speed super-resolution bioimaging., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

IscBs, as hypercompact ancestry proteins of Cas9 nuclease, are suitable for in vivo gene editing via single adeno-associated virus (AAV) delivery. Due to the low activity of natural IscBs in eukaryotic cells, recent studies have been focusing on improving OgeuIscB's gene editing efficiency via protein engineering. However, in vivo gene editing efficacy of IscBs for disease correction remained to be demonstrated. Here, we showed effective gene knockout and base editing in mouse embryos. To further improve IscB activity, we performed systematic engineering of IscB-associated ωRNA and identified a variant, ωRNA ∗ -v2, with enhanced gene editing efficiency. Furthermore, our study demonstrated the efficacy of an engineered IscB-ωRNA system for robust gene knockout and base editing in vivo. Single AAV delivery of IscB-derived cytosine and adenine base editors achieved disease correction in a mouse model of tyrosinemia. Therefore, our results indicated the great potential of miniature IscBs for developing single-AAV-based gene editing therapeutics., Competing Interests: Declaration of interests A patent application pertaining to this study has been submitted., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer, the most common type of breast cancer, is facing challenges such as endocrine therapy resistance and distant relapse. Immunotherapy has shown progress in treating triple-negative breast cancer, but immunological research on HR+/HER2- breast cancer is still in its early stages. Here, we performed a multi-omics analysis of a large cohort of HR+/HER2- breast cancer patients (n = 351) and revealed that HR+/HER2- breast cancer possessed a highly heterogeneous tumor immune microenvironment. Notably, the immunological heterogeneity of HR+/HER2- breast cancer was related to MAP3K1 mutation and we validated experimentally that MAP3K1 mutation could attenuate CD8+ T cell-mediated antitumor immunity. Mechanistically, MAP3K1 mutation suppressed MHC-I-mediated tumor antigen presentation through promoting the degradation of antigen peptide transporter 1/2 (TAP1/2) mRNAs, thereby driving tumor immune escape. In preclinical models, the postbiotics tyramine could reverse the MAP3K1 mutation-induced MHC-I reduction, thereby augmenting the efficacy of immunotherapy. Collectively, our study identified the vital biomarker driving the immunological heterogeneity of HR+/HER2- breast cancer and elucidated the underlying molecular mechanisms, which provided the promise of tyramine as a novel therapeutic strategy to enhance the efficacy of immunotherapy.

Aim: To investigate the prognostic value of inflammatory markers in esophageal squamous cell carcinoma (ESCC) patients treated with immune checkpoint inhibitors (ICIs). Materials & methods: The infiltration of CD3 + and CD8 + T cells in tissue microarrays from 180 patients who underwent radical esophagectomy was detected using immunohistochemistry. A separate cohort of 351 patients with metastatic/recurrent or unresectable ESCC treated with ICIs was enrolled for further investigation. The overall survival difference among groups was assessed using Kaplan-Meier analysis. Cox proportional hazards models were employed to investigate the prognostic impact of the inflammatory markers, along with other factors. Results: Decreased inflammation was found to be associated with increased CD3 + and CD8 + T-cell infiltration and a better prognosis. Then, the value of inflammatory markers in predicting survival in 351 ESCC patients receiving immunotherapy was validated. Ultimately, the systemic immune-inflammation index was identified as an independent prognostic factor for overall survival. Additionally, the patients with no distant organ metastasis, or treated by first-line immunotherapy combined with concurrent chemoradiotherapy can considerably prolong survival. Conclusion: Inflammation is associated with the level of tumor infiltrating lymphocytes and that the systemic immune-inflammation index is an effective prognostic predictor for ESCC patients treated with ICIs.

Potassium ion channels play a fundamental role in regulating cell membrane repolarization, modulating the frequency and shape of action potentials, and maintaining the resting membrane potential. A growing number of studies have indicated that dysfunction in potassium channels associates with the pathogenesis and treatment of depression. However, the involvement of potassium channels in the onset and treatment of depression has not been thoroughly summarized. In this review, we performed a comprehensive analysis of the association between multiple potassium channels and their roles in depression, and compiles the SNP loci of potassium channels associated with depression, as well as antidepressant drugs that target these channels. We discussed the pivotal role of potassium channels in the treatment of depression, provide valuable insights into new therapeutic targets for antidepressant treatment and critical clues to future drug discovery., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication With the submission of this manuscript, we would like to undertake that all authors of this paper have read and approved the final version submitted. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

What Is Already Known About This Topic?: Lipooligosaccharides from Campylobacter jejuni ( C. jejuni ) have a mimicry antigen structure with gangliosides, which explains the mechanism by which C. jejuni caused Guillain-Barré syndrome (GBS)., What Is Added by This Report?: All 12 C. jejuni strains with class R LOSs and specific serotypes were isolated from seagulls in south China. These emerging C. jejuni strains had ganglioside-mimicry antigen structures and possessed a high potential for triggering GBS., What Are the Implications for Public Health Practice?: Sialylated lipooligosaccharides (LOS) class R with GBS-associated serotypes isolated from seagulls highlight the risk of induced GBS around coastal or lakeside areas., Competing Interests: No conflicts of interest., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2024.)

Background: Erastin has been found to induce ferroptosis; however, whether erastin may have roles other than ferroptosis inducer in cells is unknown. Nutrient deficiency is one of the major causes of many diseases including intervertebral disc (IVD) degeneration., Purpose: The current study investigates the effect of erastin in nucleus pulposus cells under nutrient deprivation condition., Study Design: Experiment in vitro and ex vivo., Methods: The effect of erastin on the cell survival of nucleus pulposus cells was evaluated in fetal bovine serum (FBS) and glucose deprivation condition. RSL3 and ferrostatin-1 were applied to illustrate whether the effect of erastin is ferroptosis dependent. The involvement of solute carrier family 7, membrane 11(SLC7A11), autophagy as well as mechanistic target of rapamycin kinase complex 1(mTORC1) and transcription factor EB (TFEB) were assessed to demonstrate the working mechanism of erastin., Results: Erastin may induce cell death at the concentration of ≥ 5μM; however, it may protect nucleus pulposus cells against nutrient deprivation induced cell death at lower concentration (0.25-1μM) and the effect of erastin is ferroptosis independent. The mechanism study showed that the effect of erastin may relate to its SCL7A11 regulation, as SCL7A11 knock-down may have the similar effect as erastin. Furthermore, it was also demonstrated that mTORC1-TFEB mediated autophagy was involved in protective effect of erastin., Conclusions: Low dose erastin may promote cell survival under nutrient deprivation condition, and its effect is ferroptosis independent; erastin may exert its protective effect through mTORC1-TFEB mediated autophagy regulation., Clinical Significance: Nutrient deprivation is a major contributor to intervertebral disc degeneration. Our in vitro and ex vivo study showed that low dose of erastin may suppress nutrient deprivation induced cell death in IVD degeneration. Although it was not validated in vivo model due to lack of in vivo nutrient deprivation induced IVD degeneration model currently, this study may still provide a potential therapeutic option for IVD degeneration, which of cause need further validation., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Maps are fundamental medium to visualize and represent the real word in a simple and philosophical way. The emergence of the big data tide has made a proportion of maps generated from multiple sources, significantly enriching the dimensions and perspectives for understanding the characteristics of the real world. However, a majority of these map datasets remain undiscovered, unacquired and ineffectively used, which arises from the lack of numerous well-labelled benchmark datasets, which are of significance to implement the deep learning techniques into identifying complicated map content. To address this issue, we develop a large-scale benchmark dataset involving well-labelled datasets to employ the state-of-the-art machine intelligence technologies for map text annotation recognition, map scene classification, map super-resolution reconstruction, and map style transferring. Furthermore, these well-labelled datasets would facilitate map feature detection, map pattern recognition and map content retrieval. We hope our efforts would provide well-labelled data resources for advancing the ability to recognize and discover valuable map content., (© 2024. The Author(s).)

Osteonecrosis of the femoral head (ONFH) is a common complication of glucocorticoid (GC) therapy. Recent advances demonstrate that sympathetic nerves regulate bone homeostasis, and GCs lower the sympathetic tone. Here, we show that the dramatically decreased sympathetic tone is closely associated with the pathogenesis of GC-induced ONFH. GCs activate the glucocorticoid receptor (GR) but hinder the activation of the mineralocorticoid receptor (MR) on neurons in the hypothalamic paraventricular nucleus (PVN). This disrupts the balance of corticosteroid receptors (GR/MR) and subsequently reduces the sympathetic outflow in the PVN. Vascular endothelial cells rapidly react to inhibition of sympathetic tone by provoking endothelial apoptosis in adult male mice treated with methylprednisolone (MPS) daily for 3 days, and we find substantially reduced H-type vessels in the femoral heads of MPS-treated ONFH mice. Importantly, treatment with a GR inhibitor (RU486) in the PVN promotes the activation of MR and rebalances the ratio of GR and MR, thus effectively boosting sympathetic outflow, as shown by an increase in tyrosine hydroxylase expression in both the PVN and the sympathetic postganglionic neurons and an increase in norepinephrine levels in both the serum and bone marrow of the femoral head of MPS-treated mice. Rebalancing the corticosteroid receptors mitigates GC-induced endothelial impairment and ONFH and promotes angiogenesis coupled with osteogenesis in the femoral head, while these effects are abolished by chemical sympathectomy with 6-OHDA or adrenergic receptor-β2 (Adrb2) knockout. Furthermore, activating Adrb2 signaling in vivo is sufficient to rescue the GC-induced ONFH phenotype. Mechanistically, norepinephrine increases the expression of the key glycolytic gene 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) via Adrb2-cyclic AMP response element-binding protein (CREB) signaling. Endothelial-specific overexpression of PFKFB3 attenuates endothelial impairment and prevents severe osteonecrosis in MPS-treated Adrb2 knockout mice. Thus, GC inhibits sympathetic tone via the hypothalamic descending pathway, which, in turn, acts as a mediator of GC-induced ONFH., (© 2024. The Author(s).)

The central nervous system (CNS) is increasingly recognized as a critical modulator in the oncogenesis of glioblastoma multiforme (GBM), with interactions between cancer and local neuronal circuits frequently leading to epilepsy; however, the relative contributions of these factors remain unclear. Here, we report a coordinated intratumor shift among distinct cancer subtypes within progenitor-like families of epileptic GBM patients, revealing an accumulation of oligodendrocyte progenitor (OPC)-like subpopulations at the cancer-neuron interface along with heightened electrical signaling activity in the surrounding neuronal networks. The OPC-like cells associated with epilepsy express KCND2, which encodes the voltage-gated K + channel K V 4.2, enhancing neuronal excitability via accumulation of extracellular K + , as demonstrated in patient-derived ex vivo slices, xenografting models, and engineering organoids. Together, we uncovered the essential local circuitry, cellular components, and molecular mechanisms facilitating cancer-neuron interaction at peritumor borders. KCND2 plays a crucial role in mediating nervous system-cancer electrical communication, suggesting potential targets for intervention., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Mechanoluminescence (ML) materials, known for their ability to convert mechanical energy into light, are increasingly recognized for their potential applications, such as in intelligent stress sensing, in vivo bioimaging, and stress non-destructive monitoring. However, the low signal-to-noise ratio (SNR) and narrow-band emission of single-defect-induced ML materials usually limit their biological-related practical applications. Here, these limitations will be addressed by modulating the microstructure evolution in Y 3 Ga 3 MgSiO 12 :Cr 3+ through the [Si 4+ +Mg 2+ ] → [Ga 3+ +Ga 3+ ] chemical substitution strategy. Density functional theory (DFT) calculation reveals the defect types and dynamic charge migration processes. In addition, Y 3 Ga 3 MgSiO 12 : Cr 3+ with continuously distributed "shallow-deep" defects (0.68-1.61 eV) can avoid persistent luminescence (PersL) and bright-field environment interference. Herein, such high SNR near-infrared broadband ML emission may provide a reliable way for high-quality biological non-destructive sensing and detection. Finally, benefiting from the different absorption of ML signals in glucose/lipid, one may find a novel non-invasive blood glucose/lipid testing technology in patients., (© 2024 Wiley‐VCH GmbH.)

Inflammatory bowel disease (IBD) is a considerable threat to human health with a significant risk for colorectal cancer (CRC). However, currently, both the molecular pathogenesis and therapeutic treatment of IBD remain limited. In this report, using both systemic and intestinal epithelium-specific gene knockout mouse models, we demonstrate that FBXO22, a substrate receptor within the SKP1-Cullin 1-F-box family of E3 ubiquitin ligases, plays an inhibitory role in the Azoxymethane / Dextran Sodium Sulfate-induced colorectal inflammatory responses and CRC. FBXO22 targets the serine 2448-phosphorylated form of mammalian mechanistic target of rapamycin (pS2448-mTOR) for ubiquitin-dependent degradation. This proteolytic targeting effect is established based on multiple lines of evidence including the results of colon tissue immunoblots, analysis of cultured cells with altered abundance of FBXO22 by depletion or overexpression, comparison of protein decay rate, effects on mTOR substrates S6K1 and 4E-BP1, analysis of protein-protein interactions, phosphor-peptide binding and competition, as well as reconstituted and cellular ubiquitination. Finally, we have shown that mTOR inhibitor rapamycin (RAPA) was able to alleviate the effects of fbxo22 deletion on colorectal inflammatory response and CRC. These RAPA effects are correlated with the ability of RAPA to inhibit pS2448-mTOR, pS6K1, and p4E-BP1. Collectively, our data support a suppressive role for FBXO22 in colorectal inflammation signaling and CRC initiation by targeting pS2448-mTOR for degradation., Competing Interests: Competing interests statement:The authors declare no competing interest.

The near-infrared (NIR) phosphor-converted light-emitting diode (pc-LED) is heavily reliant upon the performance of NIR phosphors. However, the current NIR pc-LEDs suffer from low photoelectric efficiency and insufficient near-infrared output power. In this study, Cr 3+ -doped Ca 3 MgZrGe 3 O 12 phosphors leading to high-performance NIR pc-LEDs were developed for the first time. They feature robust and wide NIR emission that extends over the spectrum from 650 to 1100 nm with a full width at half maximum of 120 nm, a high quantum yield of 82% and excellent thermal stability of T 50% = 250 °C and I 150 °C = 80% when excited at 460 nm. The NIR pc-LED was constructed by combining the Ca 3 MgZrGe 3 O 12 :0.04Cr 3+ phosphor with a blue LED chip, resulting in a device that exhibits a photoelectric conversion efficiency of 20% and a near-infrared output power of 54.19 mW when operated at a current of 100 mA. The obtained luminous efficacy is superior to that of the vast majority of current broadband near-infrared pc-LEDs. In addition, this NIR pc-LED exhibits strong penetration and its applications in bio-imaging are demonstrated. The results indicate that Ca 3 MgZrGe 3 O 12 :Cr 3+ NIR broadband phosphors are efficient for NIR pc-LEDs.

Heavy metal pollution causes irreversible damage to plants, animals, and humans. Therefore, it is meaningful to develop facile, fast, and efficient strategies for heavy metal ion (HMI) detection. Here, a portable composite film (CPSE) was designed for HMI detection with high sensitivity and wide detection range. The CPSE was prepared by using cellulose nanofibers (CNF)/polyvinyl alcohol (PVA) as the matrix and utilizing modified starch (HPS) to assist disodium calcium ethylenediaminetetraacetate (EDTA-Ca) to form stable complexes with HMI. The R, G and B values (the three primary colors of light) were captured using an image acquisition system to produce an HMI standard color card successfully. Specifically, the composite film can effectively distinguish Cu 2+ , Pb 2+ and Fe 3+ . The response time of the composite film to HMI was 2-4 s, and the detection ranges of Cu 2+ and Fe 3+ were 5-700 ppm and 10-1000 ppm, respectively. Additionally, the synergistic effect of HPS and EDTA-Ca led to the increase in tensile strength (1.59-1.71 times), tear strength (3.29-3.57 times), and glass transition temperature (~ 6 °C) compared to CNF/PVA/HPS and CNF/PVA/EDTA-Ca films. This study confirms the value of CPSE films as materials for HMI detection and suggests innovative ideas for designing similar biomass detection materials in the future., 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 B.V.)

Intrinsically flexible micro-/nano-electronics are increasingly in demand for wearable/implantable bio-machine interfacing optical electronics and soft robots. In this work, we developed intrinsically flexible and soft wearable micro-/nano-electronics by femtosecond laser direct writing Bombyx mori sericin-based nanocomposites. Sericin was used as the biomacromolecular reductant to photo-reduce metal ions into nanoparticles and the molecular matrix for in situ nano-compositing. The two/three-dimensional fabrication realized ∼350 nm minimum line width, customizable Young's modulus (∼0.22-3.35 GPa in air), and nano-scale morphology (∼12.1 nm average roughness). The electrical percolation and adjustable conductivity up to 10 5 S m -1 were studied. Within the sericin/Ag-nanocomposite percolation-threshold range, a miniaturized electro-mechano-sensor was prototyped with gauge factors (GF ∼ 16.95) and linearity ( R 2 ∼ 0.996), short response/recovery time (200 ms/120 ms), low detection limit (∼0.06% deformation) and power consumption (<0.1 mW), and remarkable intrinsic flexible performances ( e.g. , ∼10 4 time outward bendings). Cell/skin biocompatibilities and detections of human muscle/joint movements and sounds were demonstrated, promising its practical potential towards in vivo or in vitro bio-integrated electronics.

Non-alcoholic fatty liver disease (NAFLD) poses a serious global health threat, with its progression mechanisms not yet fully understood. While several molecular markers for NAFLD have been developed in recent years, a lack of robust evidence hampers their clinical application. Therefore, identifying novel and potent biomarkers would directly aid in the prediction, prevention, and personalized treatment of NAFLD. We downloaded NAFLD-related datasets from the Gene Expression Omnibus (GEO). Differential expression analysis and functional analysis were initially conducted. Subsequently, Weighted Gene Co-expression Network Analysis (WGCNA) and multiple machine learning strategies were employed to screen and identify key genes, and the diagnostic value was assessed using Receiver Operating Characteristic (ROC) analysis. We then explored the relationship between genes and immune cells using transcriptome data and single-cell RNA sequencing (scRNA-seq) data. Finally, we validated our findings in cell and mouse NAFLD models. We obtained 23 overlapping differentially expressed genes (DEGs) across three NAFLD datasets. Enrichment analysis revealed that DEGs were associated with Apoptosis, Parathyroid hormone synthesis, secretion and action, Colorectal cancer, p53 signaling pathway, and Biosynthesis of unsaturated fatty acids. After employing machine learning strategies, we identified one gene, pleckstrin homology like domain family A member 1 (PHLDA1), downregulated in NAFLD and showing high diagnostic accuracy. CIBERSORT analysis revealed significant associations of PHLDA1 with various immune cells. Single-cell data analysis demonstrated downregulation of PHLDA1 in NAFLD, with PHLDA1 exhibiting a significant negative correlation with macrophages. Furthermore, we found PHLDA1 to be downregulated in an in vitro hepatic steatosis cell model, and overexpression of PHLDA1 significantly reduced lipid accumulation, as well as the expression of key molecules involved in hepatic lipogenesis and fatty acid uptake, such as FASN, SCD-1, and CD36. Additionally, gene set enrichment analysis (GSEA) pathway enrichment analysis suggested that PHLDA1 may influence NAFLD progression through pathways such as Cytokine Cytokine Receptor Interaction, Ecm Receptor Interaction, Parkinson's Disease, and Ribosome pathways. Our conclusions were further validated in a mouse model of NAFLD. Our study reveals that PHLDA1 inhibits the progression of NAFLD, as overexpression of PHLDA1 significantly reduces lipid accumulation in cells and markedly decreases the expression of key molecules involved in liver lipogenesis and fatty acid uptake. Therefore, PHLDA1 may emerge as a novel potential target for future prediction, diagnosis, and targeted prevention of NAFLD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

An effective strategy to facilitate oxygen redox chemistry in metal-air batteries is to introduce a redox mediator into the liquid electrolyte. The rational utilization of redox mediators to accelerate the charging kinetics while ensuring the long lifetime of alkaline Zn-air batteries is challenging. Here, we apply commercial acetylene black catalysts to achieve an I 3 - -mediated Zn-air battery by using ZnI 2 additives that provide I 3 - to accelerate the cathodic redox chemistry and regulate the uniform deposition of Zn 2+ on the anode. The Zn-air battery performs an ultra-long cycle life of over 600 h at 5 mA cm -2 with a final charge voltage of 1.87 V. We demonstrate that I - mainly generates I 3 - on the surface of carbon catalysts during the electrochemically charging process, which can further chemically react with OH - to generate oxygen and further revert to I - , thus obtaining a stable electrochemical system. This work offers a strategy to simultaneously improve the cycling life and reduce the charging voltage of Zn-air batteries through redox mediator methods., (© 2024 Wiley-VCH GmbH.)

Here, we report a strategy enabling triple switchable chemo-, regio-, and stereodivergence in newly developed palladium-catalyzed cycloadditions of allenes. An asymmetric pseudo-stereodivergent cycloaddition of allenes bearing a primary leaving group at the α-position, where a dynamic kinetic asymmetric hydroalkoxylation of racemic unactivated allenes was the enantio-determining step, is realized, providing four stereoisomers [(Z,R), (Z,S), (E,S), and (E,R)] containing a di-substituted alkene scaffold and a stereogenic center. By tuning reaction conditions, a mechanistically distinctive cycloaddition is uncovered selectively with the same set of substrates. By switching the position of the leaving group of allenes, a cycloaddition involving an intermolecular O-attack is disclosed. Diverse mechanisms of the cycloaddition reactions of allenes enable rapid access to structurally and stereochemically diverse 3,4-dihydro-2H-1,4-benzoxazines in high efficiency and selectivity., (© 2024 Wiley-VCH GmbH.)

Objectives: Our study aimed to assess the associations between meal-replacement (MR) drinking and risks of all-cause, cardiovascular and cerebrovascular disease (CVD), and cancer mortality., Methods: The study was based on 6770 adults aged 20 years or older from the National Health and Nutrition Examination (NHANES) 2003-2006 with linked mortality data from the National Death Index for linked mortality records (until 31 December 2019). Respondents were categorized into four groups according to the frequency of MR drinking: ≤1 time per month (seldom), 2-3 times per month (monthly), 1-6 times per week (weekly), and ≥1 time per day (daily). The adjusted hazard ratios (aHRs) of MR drinking with all-cause, CVD, and cancer mortality were estimated by Cox proportional hazards regression models. Likelihood ratio tests were used to find potential interactions of MR drinking with age, sex, and BMI., Results: During a median follow-up of 14.4 years, a total of 1668 death events were recorded among the study population. Compared to respondents who seldom drank MR, daily and weekly drinkers had greater risks of all-cause mortality (aHRs and 95% confidence intervals [CI]: 1.52 [1.17-1.97] for daily; 1.54 [1.24-1.91] for weekly). Stratified analyses indicated that the effects of MR on all-cause mortality were different between females and males and were more substantial among females ( P for interaction: 0.003; daily female drinkers vs. daily male drinkers: 2.01 [1.40-2.90] vs. 1.24 [0.85-1.81]; weekly female drinkers vs. weekly male drinkers: 1.68 [1.26-2.24] vs. 1.36 [0.97-1.91])., Conclusions: Daily and weekly MR drinking might increase the risk of all-cause mortality.

The widespread bacterial genus Sulfurimonas is metabolically versatile and occupies a key ecological niche in different habitats, but its interaction with bacteriophages remains unexplored. Here we systematically investigated the genetic diversity, taxonomy and interaction patterns of Sulfurimonas-associated phages based on sequenced microbial genomes and metagenomes. High-confidence phage contigs related to Sulfurimonas were retrieved from various ecosystems, clustered into 61 viral operational taxonomic units across three viral realms, including Duplodnaviria, Monodnaviria and Varidnaviria. Head-tail phages of Caudoviricetes were assigned to 19 genus-level viral clusters, the majority of which were distantly related to known viruses. Notably, diverse double jelly-roll viruses and inoviruses were also linked to Sulfurimonas, representing two commonly overlooked phage groups. Historical and current phage infections were revealed, implying viral impact on the evolution of host adaptive immunity. Additionally, phages carrying auxiliary metabolic genes might benefit hosts by compensating or augmenting sulfur metabolism. This study highlights the diversity and novelty of Sulfurimonas-associated phages with divergent tailless lineages, providing basis for further investigation of phage-host interactions within this genus., (© 2024. The Author(s).)

Sine oculis homeobox homolog 1 (SIX1) is a new identified cancer driver in the development of prostate cancer (PC). However, the upstream regulatory mechanisms for SIX1 reactivation in cancer remains elusive. Here, we found that Ku70 robustly interacts with SIX1 in the nucleus of PC cells. The HD domain of SIX1 and the DBD domain of Ku70 are required for formation of Ku70-SIX1 complex. 20 groups of hydrogen bonds were identified in this complex by molecular dynamics simulation. Depletion of Ku70/SIX1 notably abrogates the proliferation and migration of PC. Further studies revealed that SIX1 is recruited to the promoter region on glutamate-pyruvate transaminase 2 (GPT2). Ku70 enhances the SIX1-mediated transcriptional activation on GPT2, thereby facilitating the generation of alpha-ketoglutarate (α-KG). In addition, formation of the Ku70-SIX1 complex promotes GPT2-dependent cell proliferation and migration in PC. Moreover, the expression of GPT2 is upregulated and strongly correlated with the expression of Ku70/SIX1 in PC tissues. In summary, our findings not only provide insight into the mechanistic interactions between Ku70 and SIX1, but also highlight the significance of the Ku70-SIX1-GPT2 axis for α-KG metabolism and PC carcinogenesis., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Ischemic stroke is one of the major diseases causing varying degrees of dysfunction and disability worldwide. The current management of ischemic stroke poses significant challenges due to short therapeutic windows and limited efficacy, highlighting the pressing need for novel neuroprotective treatment strategies. Previous studies have shown that fingolimod (FIN) is a promising neuroprotective drug. Here, we report the rational development of FIN nano-embedded nasal powders using full factorial design experiments, aiming to provide rapid neuroprotection after ischemic stroke. Flash nanoprecipitation was employed to produce FIN nanosuspensions with the aid of polyvinylpyrrolidone and cholesterol as stabilizers. The optimized nanosuspension (particle size = 134.0 ± 0.6 nm, PDI = 0.179 ± 0.021, physical stability = 72 ± 0 h, and encapsulation efficiency of FIN = 90.67 ± 0.08%) was subsequently spray-dried into a dry powder, which exhibited excellent redispersibility (RdI = 1.09 ± 0.04) and satisfactory drug deposition in the olfactory region using a customized 3D-printed nasal cast (45.4%) and an Alberta Idealized Nasal Inlet model (8.6%) at 15 L/min. The safety of the optimized FIN nano-embedded dry powder was confirmed in cytotoxicity studies with nasal (RPMI 2650 and Calu-3 cells) and brain related cells (SH-SY5Y and PC 12 cells), while the neuroprotective effects were demonstrated by observed behavioral improvements and reduced cerebral infarct size in a middle cerebral artery occlusion mouse stroke model. The neuroprotective effect was further evidenced by increased expression of anti-apoptotic protein BCL-2 and decreased expression of pro-apoptotic proteins CC3 and BAX in brain peri-infarct tissues. Our findings highlight the potential of nasal delivery of FIN nano-embedded dry powder as a rapid neuroprotective treatment strategy for acute ischemic stroke., (© 2024. The Author(s).)