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Skin trauma often results from pain, swelling, and scarring and can significantly interfere with daily activities. Extracts from the American cockroach, a rapidly reproducing insect, have been recognized for therapeutic properties in wound management. Traditional extraction methods use solvents such as ethanol to obtain the active compounds, but these methods may compromise the intrinsic biological properties of American cockroach extracts. In this study, we investigated the use of nanovesicles isolated from fresh American cockroaches in skin wound treatment and focused on their biological characteristics and therapeutic efficacy. Fresh and dried American cockroach nanovesicles (F-ACNVs and D-ACNVs, respectively) were procured via ultrahigh-speed centrifugation. We found that F-ACNVs exhibited superior cell proliferation-promoting activity. By employing metabolomics, proteomics, and long noncoding RNA (lncRNA) omics, we identified a rich repertoire of metabolites, proteins, and lncRNAs within F-ACNVs. In vitro and in vivo experiments demonstrated that F-ACNVs significantly enhanced the proliferation and migration of human umbilical vein endothelial cells (HUVECs) and human skin keratinocytes (HACATs) as well as the repair of skin mechanical trauma. These effects may be mediated through the activation of angiogenic signaling pathways. Our research introduces a novel therapeutic strategy for treating skin trauma and offers insight into the medicinal potential of insects such as the American cockroach while emphasizing the importance of preserving the intrinsic biological properties of insects for optimal therapeutic outcomes.

Argonaute proteins are categorized into AGO and PIWI clades. Across most animal species, AGO-clade proteins are widely expressed in various cell types, and regulate normal gene expression 1 . By contrast, PIWI-clade proteins predominantly function during gametogenesis to suppress transposons and ensure fertility 1,2 . Both clades use nucleic acid guides for target recognition by means of base pairing, crucial for initiating target silencing, often through direct cleavage. AGO-clade proteins use a narrow channel to secure a tight guide-target interaction 3 . By contrast, PIWI proteins feature a wider channel that potentially allows mismatches during pairing, broadening target silencing capability 4,5 . However, the mechanism of PIWI-mediated target cleavage remains unclear. Here we demonstrate that after target binding, PIWI proteins undergo a conformational change from an 'open' state to a 'locked' state, facilitating base pairing and enhancing target cleavage efficiency. This transition involves narrowing of the binding channel and repositioning of the PIWI-interacting RNA-target duplex towards the MID-PIWI lobe, establishing extensive contacts for duplex stabilization. During this transition, we also identify an intermediate 'comma-shaped' conformation, which might recruit GTSF1, a known auxiliary protein that enhances PIWI cleavage activity 6 . GTSF1 facilitates the transition to the locked state by linking the PIWI domain to the RNA duplex, thereby expediting the conformational change critical for efficient target cleavage. These findings explain the molecular mechanisms underlying PIWI-PIWI-interacting RNA complex function in target RNA cleavage, providing insights into how dynamic conformational changes from PIWI proteins coordinate cofactors to safeguard gametogenesis., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature Limited.)

Aims/hypothesis: Brown adipose tissue (BAT) consumes excess energy through heat production by uncoupling protein 1 (UCP1) to regulate the metabolic profile, but the UCP1-independent mechanisms of BAT, such as in endocrine function, are largely unknown. Our previous study showed that BAT-derived neuregulin 4 (NRG4) displays anti-atherosclerotic properties. Thus, we hypothesised that BAT could regulate diabetic nephropathy, a diabetic microvascular complication, via NRG4., Methods: To investigate the influence of NRG4 from BAT on podocyte apoptosis, both loss- and gain-of-function approaches were used in in vivo experiments. Diabetic nephropathy models were created using BAT-specific Nrg4-knockout (BKO) mice, global Nrg4-knockout (KO) mice and wild-type (WT) mice. In in vitro studies, podocytes (MPC5) were exposed to glucose and recombinant NRG4 (rNrg4). Additionally, brown adipocytes were co-cultured with MPC5 podocytes using a transwell system. The expression levels of proteins associated with podocyte apoptosis and signalling pathways were measured., Results: BAT-specific NRG4 deficiency aggravated podocyte apoptosis (increased by 47.46%) and increased the urinary albumin/creatinine ratio (increased by 41.71%), decreased nephrin expression and increased desmin expression. As expected, these changes were reversed by NRG4 replenishment using adeno-associated virus-NRG4 interscapular BAT injection and BAT transplantation assays in KO mice. Additionally, co-culture experiments demonstrated that brown adipocytes from WT mice could alleviate high-glucose-induced podocyte apoptosis. In in vitro experiments, recombinant NRG4 inhibited high-glucose-induced podocyte apoptosis. Mechanistically, the Akt-glycogen synthase kinase 3 β (GSK-3β) pathway is crucial for the protection that BAT-derived NRG4 provides to podocytes in diabetic nephropathy., Conclusions/interpretation: Our data show that BAT had a protective effect on podocyte apoptosis in diabetic nephropathy through BAT-derived NRG4, and the Akt-GSK‑3β signalling pathway may mediate the inhibition of BAT-derived NRG4 on podocyte apoptosis in diabetic nephropathy., Competing Interests: Acknowledgements: The authors thank X. Gong and Y. Zhu from Chronic Disease Management Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China for their help with statistics and graphs. Data availability: All data generated or analysed during this study are included in this published article and ESM files. Funding: This work was funded by grants from the National Natural Science Foundation of China (no. 82170857, 81870573), Natural Science Foundation of Project of Hubei Province (no. 2022CFC022), Research Project of Hubei Administration of Traditional Chinese Medicine (no. ZY2023F060), Wuhan Medical Science Research Project (no. WX23A56) and policy supported by Wuhan Municipal Health Youth Talent Training Program. Authors’ relationships and activities: The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: SD, JLX, JYT, YYC, LFS, WW, LMZ, JJZ, BYM, XYP, LX and SGL were responsible for data acquisition and interpretation. SD, JLX and JYT conducted the experiments. SD, LY, ZJW and GDX focused on the conception and design of the study and analysis of data. SD drafted the manuscript. All authors contributed to its revision and approved the final manuscript for submission. GDX is the guarantor of this work., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Quinazolinones, essential quinazoline derivatives, exhibit diverse biological activities with applications in pharmaceuticals and insecticides. Some derivatives have already been developed as commercial drugs. Given the rising cancer incidence, there is a critical need for new anticancer agents, and quinazolinones show promising potential in this domain. The present review focuses on novel advances in the synthesis of these important scaffolds and other medicinal aspects involving drug design, the structure-activity relationship, and action mechanisms of quinazoline and quinazolinone derivatives, to help in the development of new quinazoline and quinazolinone derivatives.

Stretchable sensors that can conformally interface with the skins for wearable and real-time monitoring of skin deformations, temperature, and sweat biomarkers offer critical insights for early disease prediction and diagnosis. Integration of multiple modalities in a single stretchable sensor to simultaneously detect these stimuli would provide a more comprehensive understanding of human physiology, which, however, has yet to be achieved. Here, this work reports, for the first time, a stretchable multimodal photonic sensor capable of simultaneously detecting and discriminating strain deformations, temperature, and sweat pH. The multimodal sensing abilities are enabled by realization of multiple sensing mechanisms in a hydrogel-coated polydimethylsiloxane (PDMS) optical fiber (HPOF), featured with high flexibility, stretchability, and biocompatibility. The integrated mechanisms are designed to operate at distinct wavelengths to facilitate stimuli decoupling and employ a ratiometric detection strategy for improved robustness and accuracy. To simplify sensor interrogation, spectrally-resolved multiband emissions are generated upon the excitation of a single-wavelength laser, utilizing upconversion luminescence (UCL) and radiative energy transfer (RET) processes. As proof of concept, this work demonstrates the feasibility of simultaneous monitoring of the heartbeat, respiration, body temperature, and sweat pH of a person in real-time, with only a single sensor., (© 2024 Wiley‐VCH GmbH.)

Pancreatic ductal adenocarcinoma (PDAC) remains a particularly aggressive disease with few effective treatments. The PDAC tumor immune microenvironment (TIME) is known to be immune suppressive. Oncolytic viruses can increase tumor immunogenicity via immunogenic cell death (ICD). We focused on tumor-selective (vvDD) and cytokine-armed Western-reserve vaccinia viruses (vvDD-IL2 and vvDD-IL15) and infected carcinoma cell lines as well as patient-derived primary PDAC cells. In co-culture experiments, we investigated the cytotoxic response and the activation of human natural killer (NK). Infection and virus replication were assessed by measuring virus encoded YFP. We then analyzed intracellular signaling processes and oncolysis via in-depth proteomic analysis, immunoblotting and TUNEL assay. Following the co-culture of mock or virus infected carcinoma cell lines with allogenic PBMCs or NK cell lines, CD56 + NK cells were analyzed with respect to their activation, cytotoxicity and effector function. Both, dose- and time-dependent release of danger signals following infection were measured. Viruses effectively entered PDAC cells, emitted YFP signals and resulted in concomitant oncolysis. The proteome showed reprogramming of normally active core signaling pathways in PDAC (e.g., MAPK-ERK signaling). Danger-associated molecular patterns were released upon infection and stimulated co-cultured NK cells for enhanced effector cytotoxicity. NK cell subtyping revealed enhanced numbers and activation of a rare CD56 dim CD16 dim population. Tumor cell killing was primarily triggered via Fas ligands rather than granule release, resulting in marked apoptosis. Overall, the cytokine-armed vaccinia viruses induced NK cell activation and enhanced cytotoxicity toward human PDAC cells in vitro. We could show that cytokine-armed virus targets the carcinoma cells and thus has great potential to modulate the TIME in PDAC., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Sepsis is regarded as a dysregulated immune response to infections. Recent study showed partially reversal of immunosuppression by trained immunity, which fosters an enhanced immune response towards a secondary challenge. However, the role of trained immunity in sepsis has not been fully understood., Methods: We profiled the characteristics of peripheral blood mononuclear cells from septic patients using single-cell RNA sequencing (scRNA-seq) analyses. Murine double-hit models (pretreatment or post-treatment of β-glucan in septic mice) and murine monocyte/macrophage cell line RAW264.7 were used then., Results: scRNA-seq revealed that Ring finger protein 146 (RNF146) and protein kinase B (Akt) were downregulated in the immunosuppression period of septic patients and were verified to be decreased in bone marrow and spleen monocytes from septic mice. While β-glucan pretreatment improved the immunosuppressed state in septic mice and increased dectin-1/Akt/RNF146 expressions in monocytes, along with the increased survival rate, inflammatory factors and aerobic glycolysis, indicating a change from immunosuppression to immune training. Moreover, RNF146 regulated dectin-1-Akt-mTOR signaling in the trained immune state of murine monocyte/macrophage RAW264.7 cell line and the expression of RNF146 was dependent on dectin-1-Akt activation. The inhibition of dectin-1 by its antagonist laminarin downregulated Akt-RNF146 signaling and partially reversed β-glucan induced trained immunity in septic mice., Conclusion: RNF146 and Akt are downregulated in the immunosuppression period of sepsis, while increased after β-glucan pretreatment induced trained immunity in septic mice. Moreover, RNF146 regulates the immune trained state of monocyte through dectin-1-Akt-mTOR pathway, suggesting a possible target in reversal of immunosuppression in sepsis., Competing Interests: The authors report no conflicts of interest in this work., (© 2025 Guo et al.)

Objective: This study aims to explore the interactions between social capital, positive psychological capital, and health-promoting behaviors among elderly residents in nursing homes in the Xiangxi region of China., Methods: A random cluster sampling method was employed to select elderly individuals from 27 nursing homes in the Xiangxi area. Data were collected using the general information questionnaire, the Social Capital Scale, the Positive Psychological Capital Scale, and the Health-Promoting Behaviors Scale. The mediating role of positive psychological capital between social capital and health-promoting behaviors was analyzed., Results: A total of 341 questionnaires were collected from 27 nursing homes. The data reveals mean scores of 46.83 ± 10.26 for social capital, 72.48 ± 6.39 for positive psychological capital, and 68.25 ± 10.85 for health-promoting behaviors. Mediation analysis shows that the total effect of social capital on health-promoting behaviors was 0.800 (95% CI: 0.726, 0.873), with a direct effect of 0.478 (95% CI: 0.379, 0.577), accounting for 59.75% of the total effect. The indirect effect, mediated by positive psychological capital, was 0.321 (95% CI: 0.233, 0.409), contributing to 40.13% of the total effect., Conclusion: Positive psychological capital acts as a mediating variable between social capital and health-promoting behaviors. Future interventions designed to enhance health-promoting behaviors must consider both social and psychological capitals to fully leverage their interplay and further promote healthy aging., 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 © 2025 Liao, Li, Tian, Wu, Zhong, He and Li.)

Objectives: To investigate the protective effect of Yiqi Yangyin Huazhuo Tongluo Formula (YYHT) against high glucose-induced injury in mouse renal podocytes (MPC5 cells) and the possible mechanism., Methods: Adult Wistar rats were treated with 19, 38, and 76 g/kg YYHT or saline via gavage for 7 days to prepare YYHT-medicated or blank sera for treatment of MPC5 cells cultured in high glucose (30 mmol/L) prior to transfection with a miR-21a-5p inhibitor or a miR-21a-5p mimic. The changes in miR-21a-5p expressions and the mRNA levels of FoxO1, PINK1, and Parkin in the treated cells were detected with qRT-PCR, and the protein levels of nephrin, podocin, FoxO1, PINK1, and Parkin were detected with Western blotting. Autophagic activity in the cells were evaluated with MDC staining. The effect of miR-21a-5p mimic on FoxO1 transcription and the binding of miR-21a-5p to FoxO1 were examined with luciferase reporter gene assay and radioimmunoprecipitation assay., Results: MPC5 cells exposed to high glucose showed significantly increased miR-21a-5p expression, lowered expressions of FoxO1, PINK1, and Parkin1 mRNAs, and reduced levels of FoxO1, PINK1, parkin, nephrin, and podocin proteins and autophagic activity. Treatment of the exposed cells with YYHT-medicated sera and miR-21a-5p inhibitor both significantly enhanced the protein expressions of nephrin and podocin, inhibited the expression of miR-21a-5p, increased the mRNA and protein expressions of FoxO1, PINK1 and Parkin, and upregulated autophagic activity of the cells. Transfection with miR-21a-5p mimic effectively inhibited the transcription of FoxO1 and promoted the binding of miR-21a-5p to FoxO1 in MPC5 cells, and these effects were obviously attenuated by treatment with YYHT-medicated sera., Conclusions: YYHT-medicated sera alleviate high glucose-induced injury in MPC5 cells by regulating miR-21a-5p/FoxO1/PINK1-mediated mitochondrial autophagy.

Cyclin-dependent kinases (CDK) 14 regulates cell cycle, tumor expansion by influencing the downstream targets of the canonical Wnt signaling pathway. However, the function of CDK14 during organ development and regeneration has not been investigated in genetically-modified animals. Here, we found that genetic ablation of Cdk14 influenced pulmonary vascular endothelial cells and alveolar epithelial cells during mice embryonic development as well as repair of lung after bleomycin or lipopolysaccharide induced injury. Genetic knockout of Cdk14 and the CDK14 covalent inhibitor FMF-04-159-2 resulted in reduction of pulmonary vessel covered area and epithelial cell number, exhibiting increased mortality and more severe lung damage after injury. Mechanistically, Cdk14 ablation inhibited the proliferation of epithelial and vascular endothelial cells, inducing cell cycle arrest at the G 2 /M phase. Through RNA-seq analysis of both endothelial and epithelial cells, we found that knockdown of Cdk14 controls the expression of signal transducers and activator of transcription 1 (STAT1) as well as associated genes in interferon signaling. Disruption of Cdk14 interferes with IFN-γ induced lung repair in vivo, suggesting potential crosstalk of CDK14 signaling and IFN-γ pathway. Our work highlights the importance of Cdk14 in lung development and regenerative repair through an uncharacterized CDK14- IFN-γ signaling axis., Competing Interests: Competing interests: The authors declare no competing interests. Ethical approval: Animals were housed in the animal facility of Guangzhou Institutes of Biomedicine and Health. Animal experiments were performed according to the institutional guidelines and laws, following the protocols (2024028) approved by local animal ethics committees., (© 2025. The Author(s).)

Background: Management of persistent inflammation, immunosuppression, and catabolism syndrome (PICS) after sepsis remains challenging for patients in the intensive care unit, experiencing poor quality of life and death. However, immune-cell signatures in patients with PICS after sepsis remain unclear., Methods: We determined immune-cell signatures of PICS after sepsis at single-cell resolution. Murine cecal ligation and puncture models of PICS were applied for validation., Findings: Immune functions of two enriched monocyte subpopulations, Mono1 and Mono4, were suppressed substantially in patients with sepsis and were partially restored in patients with PICS after sepsis and exhibited immunosuppressive and pro-apoptotic effects on B and CD8T cells. Patients with PICS and sepsis had reduced naive and memory B cells and proliferated plasma cells. Besides, naive and memory B cells in patients with PICS showed an active antigen processing and presentation gene signature compared to those with sepsis. PICS patients with better prognoses exhibited more active memory B cells and IGHA1-plasma cells. CD8TEMRA displayed signs of proliferation and immune dysfunction in the PICS-death group in contrast with the PICS-alive group. Megakaryocytes proliferation was more pronounced in patients with PICS and sepsis than in healthy controls, with notable changes in the anti-inflammatory and immunomodulatory effects observed in patients with PICS and verified in mice models., Conclusions: Our study evaluated PICS after sepsis at the single-cell level, identifying the heterogeneity present within immune-cell subsets, facilitating the prediction of disease progression and the development of effective intervention., Funding: This work was supported by the National Natural Science Foundation of China, Shanghai Municipal Health Commission "Yiyuan New Star" Youth Medical Talent Cultivating Program, and Shanghai Clinical Research Center for Anesthesiology., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

This research demonstrates that DCC-2036 (Rebastinib), a potent third-generation tyrosine kinase inhibitor (TKI), effectively suppresses tumor growth in colorectal cancer (CRC) models with functional immune systems. The findings underscore the capacity of DCC-2036 to enhance both the activation and cytotoxic functionality of CD8 + T cells, which are crucial for facilitating anti-tumor immune responses. Through comprehensive multi-omics investigations, significant shifts in both gene and protein expression profiles were detected, notably a marked decrease in DKK1 levels. This reduction in DKK1 was linked to diminished CD8 + T cell effectiveness, correlating with decreased FGR expression. Moreover, our findings identify FGR as a pivotal modulator that influences DKK1 expression via the PI3K-AKT-SP1 signaling cascade. Correlative analysis of clinical specimens supports the experimental data, showing that increased levels of FGR and DKK1 in CRC tissues are associated with inferior clinical outcomes and reduced efficacy of immunotherapeutic interventions. Consequently, targeting the FGR-AKT-SP1-DKK1 pathway with DCC-2036 could potentiate immunotherapy by enhancing CD8 + T cell functionality and their tumor infiltration. This strategy may contribute significantly to the refinement of therapeutic approaches for CRC, potentially improving patient prognoses., Competing Interests: Competing interests: No conflict of interest exists in the submission of this manuscript, and the manuscript is approved by all authors for publication. Ethics approval: The National Institutes of Health (NIH)‘s Guide for the Care and Use of Laboratory Animals served as the basis for this study. All efforts were made to minimize animal suffering during anesthesia with sodium pentobarbital (3.5% [w/v], 1 ml/kg). The experiments adhered to institutional guidelines and were approved by the ethics committee of the University of South China(# USC202209XS02). Consent for publication: Written informed consent for publication was obtained from all participants., (© 2025. The Author(s).)

Purpose: Fungal keratitis (FK) remains a treatment challenge, necessitating new therapeutic targets. Piezo1, a mechanosensitive ion channel, regulates calcium signaling and immune cell function. This study investigates its role in macrophage-mediated antifungal responses in FK., Methods: Piezo1 and Pyrin expression in corneas and bone marrow-derived macrophages (BMDMs) were assessed by RNAseq, quantitative real-time PCR (qRT-PCR), Western blot, and immunofluorescence. Intracellular calcium ion concentration was detected by Fluo-4 AM fluorescent probe staining. Heterozygous Piezo1 deficiency (Piezo1+/-) mice and Yoda1 were performed to regulate the expression of Piezo1., Results: Our investigation demonstrates elevated expression of Piezo1 in the corneas of patients with FK and infected mice. This upregulation of Piezo1 corresponded with the swift recruitment of macrophages via the limbus. Additionally, Piezo1+/- mice exacerbate the progression of FK in the infection model. Furthermore, Piezo1 knockdown in macrophages exhibit a notable reduction phagocytic capacity, accompanied by an increase in viable colony-forming units in an in vitro model of fungal infection. Moreover, using a pharmacologic activator of Piezo1 (Yoda1), a calcium ion (Ca2+) chelator of BAPTA or Piezo1+/- mice, we demonstrate that Piezo1 activation triggers the Pyrin inflammasome via augmented calcium ion influx, which is required for protection against FK in murine hosts., Conclusions: Piezo1 is crucial for innate immunity in FK, enhancing macrophage recruitment, activation, and Pyrin inflammasome-mediated antifungal activity via calcium signaling. Using Piezo1+/- mice and Yoda1, we confirm Piezo1's role in fungal clearance. Targeting Piezo1 offers a novel strategy to improve FK outcomes by boosting macrophage function and immune response.

Purpose: The absence of effective treatment strategies in Fungal Keratitis (FK) emphasizes the critical need to understand the pathogenic mechanisms to enhance therapeutic outcomes. Sphingolipids have been proved to play a pivotal role in the pathogenesis of fungal infections, but the specific alteration in sphingolipids and regulatory pathways remain elusive. Our aim is to gain insight into the pathophysiological mechanisms of sphingolipid homeostasis in FK through multi-omics analysis., Methods: Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) was performed in FK patients and mouse model. Furthermore, time-course RNA-seq was performed and Weighted gene co-expression network analysis (WGCNA) was used to reveal the driver genes in FK. We further investigated the effect of FTY-720, a mimetic of sphingosine 1-phosphate (S1P), on the progression of FK., Results: MALDI-MSI analysis of FK patients revealed a downregulation of sphingolipids, with sphingolipid metabolism identified as the most prominently enriched pathway. These alterations were validated in mouse model, in which S1P, ceramide, ceramide 1-phosphate and sphingomyelin were found to be downregulated. Time-course transcriptomic analysis suggests that degradation of sphingolipids by specific enzymes drives the progression of FK, involving phospholipid degradation, downregulation of TOR pathway, and activation of innate immune response. Consequently, epithelial cell function was inhibited and cell death increased. Importantly, restoring sphingolipid homeostasis by FTY-720 reversed the level of S1P and relieved the progression of FK., Conclusion: In summary, this study reveals that disruption of sphingolipid homeostasis promotes disease progression in FK. Furthermore, restoring sphingolipid homeostasis emerges as a promising strategy to mitigate the progression of FK., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ganoderma resinaceum is a traditional mushroom that contains natural products, including ergothioneine (EGT), which has powerful antioxidant properties in the human body. To increase EGT yield from G. resinaceum, the optimal carbon and nitrogen sources in the culture medium were determined as 20 g/L sucrose and 4 g/L NH4Cl, respectively. The fermentation conditions were then optimized using response surface methodology, with the highest EGT yield of approximately 4.10 mg/L achieved at an initial pH of 5.19, a culture medium volume of 118 mL, and a fermentation temperature of 26.90°C. After extraction, EGT was purified using Sephadex G-10, resulting in a purity of 43.72%. Both the crude and purified EGT extracts were evaluated for their inhibitory activity against xanthine oxidase in vitro, with positive results. These findings suggest the potential for developing edible fungi-derived medicines to treat gout, which could alleviate the side effects of traditional medicines.

Objectives: This study aimed to identify adverse lymph node (LN) features, specifically LN necrosis (LNN) and matted nodes (MNs), for the prediction of poor outcomes in stage IB nasopharyngeal carcinoma (NPC) patients according to the 9th edition of the AJCC/UICC staging system (TNM-9), with the ultimate goal of refining patient stratification and tailoring more individualized treatments., Materials: NPC patients classified as stage IB according to the TNM-9 staging system between January 2017 and December 2019 at our institution were candidates for this study. Baseline MRI assessments focusing on LNN and MNs were performed. Overall survival (OS), locoregional control (LRC), distant control (DC) and progression-free survival (PFS) were analyzed. Cox proportional hazards model analysis was used to identify prognostic factors., Results: Among the 318 patients included, 91 (28.6 %) presented with LNN, and 72 (22.6 %) presented with MNs. The presence of LNN and MNs was significantly correlated with inferior OS, DC and PFS. On the basis of these two nodal factors, patients were further categorized into low-risk (Group A, without LNN or MNs), intermediate-risk (Group B, with LNN or MNs), and high-risk (Group C, with both LNN and MNs) groups. As the number of adverse nodal features increased, the 5-year OS (Group A/B/C: 98.9 %/97.7 %/78.1 %, overall P < 0.001), DC (Group A/B/C: 99.5 %/94.2 %/78.3 %, overall P < 0.001), and PFS (Group A/B/C: 95.2 %/87.3 %/70.3 %, overall P < 0.001) decreased, whereas LRC (Group A/B/C: 96.8 %/92.9 %/91.4 %, overall P = 0.189) did not significantly differ., Conclusions: LNN and MNs are adverse LN features that significantly impact the prognosis of stage IB NPC patients. Stratifying patients into low-, intermediate-, and high-risk groups based on these factors provides a more nuanced understanding of prognosis and treatment needs for personalized care., 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.)

Background: Both rhabdomyosarcoma (RMS) and central retinal artery occlusion (CRAO) are rare medical diseases, and their simultaneous occurrence in the same patient is extraordinarily uncommon. This study presents a comprehensive overview of the clinical manifestations, diagnostic imaging results, and therapeutic interventions of a patient with both conditions., Case Summary: In this report, we present a 30-year-old male who presented with significant protrusion, pain and vision loss and was diagnosed with RMS in the orbit and sinus with CRAO. Following resection of the sinus and orbital mass and enucleation of the right eye, the patient experienced symptom improvement., Conclusion: This article provides an in-depth analysis of the patient's clinical manifestations, the tumor's anatomical origin, and the etiology of CRAO. The concurrent manifestation of both RMS and CRAO is exceedingly uncommon in clinical practice., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Aberrant elongation of proteins can lead to the activation of oncogenic signaling pathways, resulting in the dysregulation of oncogenic signaling pathways. Eukaryotic elongation factor 2 (eEF2) is an essential regulator of protein synthesis that precisely elongates nascent peptides in the protein elongation process. Although studies have linked aberrant eEF2 expression to various cancers, research has primarily focused on its structure, highlighting a need for deeper exploration into its molecular functions. In this review, recent advancements in the structure, guanosine triphosphatase (GTPase) activity, posttranslational modifications, regulatory factors, and inhibitors of eEF2 are summarized. These findings provide a comprehensive cognition on the critical role of eEF2 and its potential as a therapeutic target in cancer. Furthermore, this review highlights important unanswered questions that warrant investigation in future research., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Three species of the spider family Philodromidae are reported from the south of China. A new genus, Sinodromus gen. nov. , is described from Jiangxi, Fujian, and Hunan Provinces. It can be distinguished from other genera of Philodromidae by the tegular apophysis of the palp and the cymbial process, as well as by its uniquely striped abdomen. The type species, S.fujianensis sp. nov. , and a second species, S.perbrevis sp. nov. , are described and illustrated; these species occur in bamboo forests in hilly areas. Additionally, the female of Philodromusguiyang Long & Yu, 2022 is described for the first time from Jiangxi and Hunan Provinces. All species are illustrated with SEM micrographs, and their distributions are mapped., Competing Interests: The authors have declared that no competing interests exist., (Zhong-jing Wang, Yan-bin Yao, Zi-ying Tang, Wen-hui Li, Ke-ke Liu, Xiang Xu.)

Developing Ag-based surface-enhanced Raman spectroscopy (SERS) sensors for detecting Hg(II) has garnered significant research interest due to their unparalleled selectivity, which is brought by the specific Ag-Hg amalgamation reaction. However, existing sensors perform unsatisfactorily in the trace detection of Hg(II) because the low concentration of Hg(II) does not have the redox potential sufficient to amalgamate with Ag. To address this challenge, a plasmonic MOF SERS sensor is developed, nanoetched Ag@UiO-68-SMe, by integrating the enormous Raman enhancement effects of nanoetched Ag with the selective enrichment function of UiO-68-SMe into single entity. This sensor enables on-site readout of Hg(II) in various real-world samples with high selectivity and sensitivity (0.17 ppb) using a portable Raman spectrometer coupled with a homemade 3D print holder. Mechanistic studies reveal that the UiO-68-SMe selectively captures and concentrates trace amounts of Hg(II) through thiomethyl groups, significantly increasing their redox potential. The resultant higher oxidative capacity allows for the spontaneous Ag-Hg amalgamation, inducing a SERS turn-off response to Hg(II), which is otherwise thermodynamically prohibited. This work not only reports a powerful SERS sensor for monitoring trace levels of Hg(II) pollution but also offers a proof-of-concept demonstration of utilizing the enrichment capabilities of MOF to manipulate redox reaction., (© 2024 Wiley‐VCH GmbH.)

Background: Accurate assessment of pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer (BC) is crucial for mitigating chemotherapy-related toxicity in patients who do not respond to the treatment. Conventional ultrasound (US) has become a pivotal method for evaluating treatment response due to its cost-effectiveness, convenience, and absence of ionizing radiation. The objective of this study was to develop a model combining US and clinicopathological characteristics at baseline, as well as US features after one cycle of NAC, to predict the pCR to NAC in BC., Methods: This retrospective study included 74 patients with invasive BC who underwent NAC from January 2022 to December 2023. Data from US and clinicopathological characteristics before NAC (pre-NAC) and US features after one cycle of NAC were collected from all patients. Univariate and multivariate analyses were used to screen the factors independently associated with pCR and to develop the prediction model. Receiver operating characteristic (ROC) curve analysis was performed, and the area under the curve (AUC), sensitivity, and specificity were calculated to assess the predictive efficiency., Results: Four characteristics, including human epidermal growth factor receptor 2 (HER2)-positive [odds ratio (OR) 9.265; 95% confidence interval (CI): 1.617-53.095, P=0.012] and absence of posterior feature or posterior acoustic enhancement of the breast mass on the US pre-NAC (OR 9.435; 95% CI: 1.585-56.180, P=0.014), the maximum diameter reduction measured with the US (OR 1.081; 95% CI: 1.009-1.157, P=0.026), and the angular or spiculated margin of the breast lesion with the US after one cycle of NAC (OR 9.475; 95% CI: 1.247-71.969, P=0.030), were screened as independent predictors. The AUC, sensitivity, and specificity of the prediction model were 0.912, 90.0%, and 79.6%, respectively., Conclusions: US and clinicopathological characteristics at baseline and the US features after one cycle of NAC helped predict pCR for BC. The prediction model may enable early evaluation of the efficacy of treatment strategies and guide less invasive surgical options or personalized post-treatment plans., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-1268/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Atopic dermatitis is an inflammatory skin condition characterized by erythema, eruption, lichenification, and pruritus. Aged Camellia oleifera Abel oil, an effective empirical plant oil utilized by the Gannan Hakka people in China to alleviate the symptoms of atopic dermatitis. However, no scientific studies have been reported to prove whether this oil is truly effective. We conducted this study to confirm whether aged C. oleifera oil could alleviate the symptoms of 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis in mice. Differences in the thickness and weight of the right and left ears were measured. ELISA was used to determine the serum levels of the inflammatory factors IL-4, IgE, IFN-γ, and TNF-α. HE staining was performed to observe inflammatory cell infiltration in the mouse skin lesions. In addition, the metabolites of aged C. oleifera oils were analyzed, and molecular docking was used to assess the binding affinity of the major metabolites to filaggrin, a protein involved in skin barrier function. Animal studies showed that aged C. oleifera oil significantly improved the symptoms of atopic dermatitis. HE staining and measurement of inflammatory factor levels revealed similar results. A total of 41 metabolites were tentatively identified in the oil, with fatty acids emerging as the major metabolites. Molecular docking confirmed that the three most abundant fatty acids, i.e., oleic acid, n -hexadecanoic acid, and octadecanoic acid, bind well to filaggrin. Our results suggest that aged C. oleifera oils can be used to ameliorate the symptoms of atopic dermatitis. Fatty acids may be the major active metabolites responsible for the observed therapeutic effects by reducing transdermal water loss, increasing skin hydration, alleviating DNCB-induced skin barrier alterations, and eliminating itchy scratching caused by dry skin., 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 Ouyang, Yuan, Chen, Gan, Guo, Cai and Zhong.)

The aim of this experiment is to investigate the bioinspired diagnostic performance of color Doppler ultrasound (CDUS) and two-dimensional (2D) echocardiography (ECG) for fetal congenital heart disease (FCHD). The research subjects were 33 expectant mothers with a diagnosis of FCHD at Xiangyang No. 1 People's Hospital between January 2017 and January 2021. The accuracy, sensitivity, and specificity of the two detection techniques were computed to ascertain and compare the diagnostic efficiency after CDUS and ECG examinations of all pregnant women. According to the findings, the prenatal CDUS detection rate was 92.61% higher than the 2D ECG detection rate (64.32%). The CDUS had an accuracy of 93.94%, sensitivity of 93.55%, and specificity of 100%, detecting 29 true positives, 0 false positives, 2 false negatives, and 2 true negatives. At 84.85% accuracy, 88.89% sensitivity, and 80% specificity, the 2D ECG identified 16 true positives, 3 false positives, 2 false positives, and 12 true negatives. There was a statistically significant (P < 0.05) difference between the accuracy, sensitivity, and specificity of 2D ECG and CDUS. In summary, CDUS was more effective than 2D ECG in diagnosing prenatal FCHD, and it also had a lower rate of missed and incorrect diagnoses., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2024. Published by Elsevier Inc.)

Pancreatitis is a common gastrointestinal disorder that causes hospitalization with significant morbidity and mortality. The mechanistic pathophysiology of pancreatitis is complicated, limiting the discovery of pharmacological intervention methods. Here, we show that the administration of ATN-161, an antagonist of Integrin-α5, significantly mitigates the pathological condition of acute pancreatitis induced by caerulein. We find that CK19-positive pancreatic ductal cells align parallel to blood vessels in the pancreas. In the caerulein-induced acute pancreatitis model, the newly emergent CK19-positive cells are highly vascularized, with a significant increase in vascular density and endothelial cell number. Single-cell RNA sequencing analysis shows that ductal and endothelial cells are intimate interacting partners, suggesting the existence of a ductal-endothelial interface in the pancreas. Pancreatitis dramatically reduces the crosstalk in the ductal-endothelial interface but promotes the Spp-1/Integrin-α5 signaling. Blocking this signaling with ATN-161 significantly reduces acinar-to-ductal metaplasia, pathological angiogenesis, and restores other abnormal defects induced by caerulein. Our work reveals the therapeutic potential of ATN-161 as an uncharacterized pharmacological method to alleviate the symptoms of pancreatitis., Competing Interests: Conflict of interest The authors declare that no conflict of interest exists., (Copyright © 2024 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.)

Context: Plant microRNAs (miRNAs) present in Yishen Tongluo formula (YSTL, a traditional Chinese herbal medicine formula) are considered as potential therapeutic drugs for reducing the sperm DNA fragmentation index (DFI)., Objective: To study the effectiveness of plant miRNAs in YSTL for repairing mouse sperm DNA damage caused by benzo( a )pyrene (BaP)., Methods and Materials: Twenty-four male SPF ICR (CD1) mice were divided into control, BaP and YSTL groups. A BaP-induced (100 mg/kg) sperm DNA damage model was established in the BaP and YSTL groups, and the mice in the YSTL group were treated with YSTL (23.78 g/kg) for 8 weeks. Sperm DFI was determined via a sperm chromatin structure assay (SCSA). MicroRNAs in the testes of the mice were analysed via RNA-seq, and the top four plant miRNAs were screened, identified and overexpressed in GC cells. The effects of plant miRNAs on the viability and DNA integrity of GC cells exposed to benzo( a )pyrene diol epoxide (BPDE) (1 μM) were tested using CCK8 and comet assays., Results: Compared with that of the BaP group, the DFI of the YSTL group decreased (9.57% vs. 18.54%, F  = 18.645, p  = 0.0236). miR166-y, miR894-x, miR822-x and miR396-x were screened. The CCK8 and comet assays revealed that the DFI of the mimic group was significantly lower than that of the BPDE (IC 50 = 1.006 μM) group, with the most significant difference in the miR396-x group., Discussion and Conclusions: Plant miRNAs such as miR396-x can penetrate the blood-testis barrier through the digestive system to repair sperm DNA.

Peripheral inflammation is closely related to the pathogenesis of sickness behaviors and psychiatric disorders such as anxiety and depression. The circumventricular organs (CVOs) are important brain sites to perceive peripheral inflammatory signals, but few studies have reported their role in inflammation-induced anxiety or depression. Using a mouse model of lipopolysaccharide (LPS)-induced inflammation, we identified a previously unreported role of the subfornical organ (SFO), one of the CVOs, in combating inflammation-induced anxiety. LPS treatment induced anxiety-like and sickness behaviors in mice. Although both the SFO and the organum vasculosum of the lamina terminalis (a CVO) neurons were activated after LPS treatment, only manipulating SFO neurons modulated LPS-induced anxiety-like behaviors. Activating or inhibiting SFO neurons alleviated or aggravated LPS-induced anxiety-like behaviors. In addition, SFO exerted this effect through glutamatergic projections to the bed nucleus of the stria terminalis. Manipulating SFO neurons did not affect LPS-induced sickness behaviors. Thus, we uncovered an active role of SFO neurons in counteracting peripheral inflammation-induced anxiety.

Efficient and stable bifunctional oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) catalysts are urgently needed to unlock the full potential of zinc-air batteries (ZABs). High-valence oxides (HVOs) and high entropy oxides (HEOs) are suitable candidates for their optimal electronic structures and stability but suffer from demanding synthesis. Here, a low-cost fluorine-lodged high-valent high-entropy layered double hydroxide (HV-HE-LDH) (FeCoNi 2 F 4 (OH) 4 ) is conveniently prepared through multi-ions co-precipitation, where F - are firmly embedded into the individual hydroxide layers. Spectroscopic detections and theoretical simulations reveal high valent metal cations are obtained in FeCoNi 2 F 4 (OH) 4 , which enlarge the energy band overlap between metal 3d and O 2p, enhancing the electronic conductivity and charge transfer, thus affording high intrinsic OER catalytic activity. More importantly, the strengthened metal-oxygen (M-O) bonds and stable octahedral geometry (M-O(F) 6 ) in FeCoNi 2 F 4 (OH) 4 prevent structural reorganization, rendering long-term catalytic stability. Furthermore, an efficient three-phase reaction interface with fast oxygen transportation was constructed, significantly improving the ORR activity. ZABs assembled with FeCoNi 2 F 4 (OH) 4 @HCC (hydrophobic carbon cloth) cathodes deliver a top performance with high round-trip energy efficiency (61.3 % at 10 mA cm -2 ) and long-term stability (efficiency remains at 58.8 % after 1050 charge-discharge cycles)., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Due to their high computational efficiency, the coarse-grained water models are of particular importance for practical molecular simulations of gas hydrates. In these models, the mW model is successfully used to study many thermodynamics and dynamics of methane hydrate. Yet, despite several decades of intense research, the mW model is still found to overestimate the melting temperature of methane hydrate. We here employ the minimum mean squared error estimation to revisit the key parameter of the mW model, which determines the strength of the tetrahedral angle of the water system. Relying on the free energy calculations, we first estimate the chemical potentials of water in the liquid phase for temperatures at which methane hydrate forms. We then turn to the mean squared error to describe the chemical potential deviation between the mW model and the TIP4P/ice model (the latter could reproduce the experimental phase diagram of methane hydrate). By minimizing the mean squared error, we finally have an optimized parameter for the mW model. In this part, we also discuss the pressure effect on such reparameterization procedure. Moreover, relying on the direct coexistence method, the melting temperature determined using the reparameterized mW model is found to be consistent with the experimental data. This strategy provides a means to improve the coarse-grained model to match the experimental observations for temperatures in the range of interest., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background: The skin regulates body processes. When damaged, it is prone to breeding bacteria, causing inflammation and impeding wound healing. There is an urgent need for new dressings that can combat bacteria to aid in infectious wound repair., Methods: In this study, a curcumin-loaded nanocomposite hydrogel dressing (GelMA/AHA-Gel@Cur) with antibacterial properties and strong toughness was synthesized, designed to combine the modified gelatin-based hydrogel (GelMA/AHA) with curcumin-coated gelatin (Gel@Cur) nanoparticles to promote the healing of bacterial infection wounds. Under UV irradiation, methylacrylylated gelatin (GelMA) and aldehyaluronic acid (AHA) formed a composite network hydrogel through radical polymerization and Schiff base reaction. Meanwhile, the residual aldehyde group on the molecular chain of AHA securely locked Gel@Cur nanoparticles in the hydrogel network through Schiff base reaction., Results: The addition of Gel@Cur nanoparticles not only enhanced the hydrogel's mechanical strength but also facilitated a sustained, gradual release of curcumin, endowing the composite hydrogel with robust antimicrobial capabilities. In an animal model of infected wounds, the composite hydrogel significantly improved wound closure, healing, and vascularization compared to the control group. Hemocompatibility tests confirmed the hydrogel's safety, with a hemolysis ratio of just 0.45%. Histological evaluation following treatment with the composite hydrogel showed improved tissue architecture, increased collagen deposition, and regeneration of dermal gland structures., Conclusion: The GelMA/AHA-Gel@Cur composite hydrogel exhibits excellent mechanical properties, potent antimicrobial activity, and controlled drug release, along with superior cell and hemocompatibility. These characteristics make it a promising material for infected wound repair and a potential candidate for clinical skin regeneration applications., Competing Interests: The authors declare that they have no potential conflicts of interest regarding the research, authorship, and/or publication of this article., (© 2024 Fu et al.)

Epigenetic reprogramming plays a critical role in cancer progression of cancer, and N6-methyladenosine (m6A) is the most common RNA modification in eukaryotes. The purpose of this study was to explore the related modification mode of m6A regulator construction and evaluate the invasion and migration of thyroid cancer. Our results showed that m6A levels were significantly increased in papillary thyroid cancer (PTC) and anaplastic thyroid cancer (ATC) samples, which may have been induced by the down-regulation of demethylase fat mass and obesity-associated gene (FTO). Moreover, FTO inhibited PTC and ATC invasion and metastasis through the epithelial-to-mesenchymal transition (EMT) pathway in vivo and in vitro. Mechanistically, an m6A-mRNA epitranscriptomic microarray showed that Cadherin 12 (CDH12) is the key target gene mediated by FTO in an m6A-dependent manner. CDH12 promotes invasion and metastasis through the EMT pathway in thyroid cancer, both in vivo and in vitro. Furthermore, we found that insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is an important m6A reading protein, that regulates the stability of CDH12 mRNA and mediates EMT progression, thereby promoting the invasion and metastasis of PTC and ATC. Thus, FTO, IGF2BP2 and CDH12 may be effective therapeutic targets for PTC and ATC with significant invasion or distant metastasis. Schematic summary of FTO-IGF2BP2 axis in modulation of CDH12 mRNA m6A and upregulation of CDH12 expression in the invasion and metastasis of thyroid carcinoma., (© 2024. The Author(s).)

Overnutrition has gradually become the primary causative factor in nonalcoholic fatty liver disease (NAFLD). However, how nutritional signals are integrated to orchestrate the transcriptional programs important for NAFLD progression remains poorly understood. We identified hepatic BAF60b as a lipid-sensitive subunit of the switch/sucrose nonfermentable chromatin-remodeling complex that is negatively associated with liver steatosis in mice and humans. Hepatic BAF60b deficiency promotes high-fat diet (HFD)-induced liver steatosis in mice, whereas transgenic expression of BAF60b in the liver attenuates HFD-induced obesity and NAFLD, both accompanied by a marked regulation of peroxisome proliferator-activated receptor γ (PPARγ) expression. Mechanistically, through motif analysis of liver assay for transposase-accessible chromatin sequencing and multiple validation experiments, we identified C/EBPβ as the transcription factor that interacts with BAF60b to suppress Pparγ gene expression, thereby controlling hepatic lipid accumulation and NAFLD progression. This work identifies hepatic BAF60b as a negative regulator of liver steatosis through C/EBPβ-dependent chromatin remodeling., (© 2024 by the American Diabetes Association.)

In future regenerative medicine, far-infrared radiation (FIR) may be an essential component of optical therapy. Many studies have confirmed or validated the efficacy and safety of FIR in various diseases, benefiting from new insights into FIR mechanisms and the excellent performance of many applications. However, the lack of consensus on the biological effects and therapeutic parameters of FIR limits its practical applications in the clinic. In this review, the definition, characteristics, and underlying principles of the FIR are systematically illustrated. We outline the therapeutic parameters of FIR, including the wavelength range, power density, irradiation time, and distance. In addition, the biological effects, potential molecular mechanisms, and preclinical and clinical applications of FIR are discussed. Furthermore, the future development and applications of FIR are described in this review. By applying optimal therapeutic parameters, FIR can influence various cells, animal models, and patients, eliciting diverse underlying mechanisms and offering therapeutic potential for many diseases. FIR could represent a superior alternative with broad prospects for application in future regenerative medicine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In recent years, with the rapid development of omics technologies, researchers have shown that interactions between the intestinal flora and bile acids are closely related to the progression of diabetic kidney disease (DKD). By regulating bile acid metabolism and receptor expression, the intestinal flora affects host metabolism, impacts the immune system, and exacerbates kidney injury in DKD patients. To explore interactions among the gut flora, bile acids and DKD, as well as the related mechanisms, in depth, in this paper, we review the existing literature on correlations among the gut flora, bile acids and DKD. This review also summarizes the efficacy of bile acids and their receptors as well as traditional Chinese medicines in the treatment of DKD and highlights the unique advantages of bile acid receptors in DKD treatment. This paper is expected to reveal a new and important potential strategy for the clinical treatment of DKD., 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 Xu, Wang, Yang, Zhong and Chen.)

Membranous nephropathy (MN) is an autoimmune disease of the kidney glomerulus, which mainly leads to nephrotic syndrome. This study investigates the associations between air pollution and MN risk and from an epigenomic perspective. In this study, we examine the associations between genetically predicted deoxyribonucleic acid methylation related to air pollution and MN risk. The data of air pollution included particulate matter (PM) with a diameter of 2.5 µm or less (PM2.5), PM with a diameter between 2.5 and 10 µm (PM2.5-10), PM with a diameter of 10 µm or less (PM10), nitrogen dioxide, and nitrogen oxides. Inverse variance weighted method was used as the main analysis method, and weighted median model and Mendelian randomization-Egger methods were selected for quality control. To assess the reliability of the results of the analyses, heterogeneity test, horizontal pleiotropy test, and the leave-one-out method were applied. There was a causal relationship between nitrogen oxides and MN risk (P = .010). Other types of air pollution were found no statistical association with MN disease (PM2.5: P = .378; PM2.5-10: P = .111; PM10: P = .035; nitrogen dioxide: P = .094). There was no heterogeneity or pleiotropy in the results. Our study suggests the association between nitrogen oxides and membrane nephropathy (MN) risk from the genetic perspective. This provides a theoretical basis for the prevention of MN disease., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Gestational diabetes mellitus (GDM) is a complication of abnormal glucose tolerance during pregnancy, with incidence is on the rise. There are inconsistent results on the risks of GDM and it has not been reported in our region. The purpose of this study is to explore the risk factors of GDM., Methods: A total of 383 pregnant women were analyzed, including 67 (17.5%) pregnant women with GDM and 316 (82.5%) with normal glucose tolerance (NGT). The relationship of personal history, family history and reproductive history of pregnant women, the levels of alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), inflammatory markers in blood cell analysis at the first prenatal examination, and fetal ultrasound indices and the risk of GDM were analyzed., Results: The fetal biparietal diameter, head circumference, and femur length were negatively correlated with HCG level, but not inflammatory markers. The proportion of pregnant women aged ≥30 years old, body mass index (BMI) in early pregnancy≥24.0 kg/m 2 , history of polycystic ovary syndrome (PCOS), cesarean section, adverse pregnancy, and oral contraceptive use, and pregnant women who conceived through assisted reproduction in GDM group were higher than those in NGT group. Logistic regression analysis showed that age of pregnant woman ≥30 years old (≥30 vs <30 years old, odds ratio (OR): 2.142, 95% confidence interval (CI): 1.183-3.878, p =0.012), BMI≥24.0 kg/m 2 (≥24.0 kg/m 2 vs 18.5-23.9 kg/m 2 , OR: 1.887, 95% CI: 1.041-3.420, p =0.036), history of adverse pregnancy (yes vs no, OR: 1.969, 95% CI: 1.022-3.794, p =0.043), and history of oral contraceptive use (yes vs no, OR: 2.868, 95% CI: 1.046-7.863, p =0.041) were associated with GDM., Conclusion: Age of pregnant woman ≥30 years old, BMI≥24.0 kg/m 2 , history of adverse pregnancy and oral contraceptive use were independent risk factors for GDM., Competing Interests: The authors declare that they have no competing interests., (© 2024 Zhong et al.)

Recent observational studies have indicated that psychiatric disorders were associated with risk of bone mineral density (BMD) reduction. But the causal relationship between neuroticism and BMD remained unclear. By using public genome-wide association study data, a 2-sample bidirectional Mendelian randomization (MR) study was performed to investigate the causal relationship between neuroticism and BMD (heel BMD, forearm BMD, femoral neck BMD, lumbar spine BMD, and total body BMD). Inverse-variance weighted, weighted median, and MR-Egger were used to assess the causal effects. Multiple sensitivity analyses were conducted to assess the potential bias of the causal estimates. Multivariable MR analysis was used to assess the direct causal effects of neuroticism on BMD with adjustment of common risk factors of BMD reduction. Univariable MR analysis indicated that genetically predicted higher neuroticism was significantly associated with an increased risk of heel BMD reduction (inverse-variance weighted β = -0.039; se = 0.01; P = .0001; Bonferroni-corrected P = .0005) but not with other BMD (forearm BMD, femoral neck BMD, lumbar spine BMD, and total body BMD) potentially due to limited statistical power. The causal effects remained significant after accounting for the effects of body mass index, smoking, and drinking. Genetic proxy for higher neuroticism was significantly associated with an increased risk of heel BMD reduction. Further studies were warranted to elucidate the underlying biological mechanisms and explore the potential application in disease early screening and management., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Long COVID is a poorly understood condition characterized by persistent symptoms following the acute phase of COVID-19, including fatigue, cognitive impairment, and joint pain. Acupuncture, a key component of traditional Chinese medicine treatment, has shown potential in alleviating long COVID symptoms. However, the molecular mechanisms underlying its therapeutic effects remain largely unknown. In this study, we employed bioinformatics approaches to explore the potential molecular mechanisms of acupuncture's therapeutic effects on long COVID symptoms. We screened protein targets of active ingredients produced by the body after acupuncture and identified potential therapeutic targets of long COVID. Protein-protein interaction networks were constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to identify key targets and pathways. Our findings provide valuable insights into the potential molecular mechanisms of acupuncture's therapeutic effects on long COVID symptoms and may contribute to the development of targeted therapies for managing this challenging condition.

Schizophrenia (SCZ) is a severe neuropsychiatric disorder characterized by cognitive, affective, and social dysfunction, resulting in hallucinations, delusions, emotional blunting, and disordered thinking. In recent years, proteomics has been increasingly influential in SCZ research. Glycosylation, a key post-translational modification, can alter neuronal stability and normal signaling in the nervous system by affecting protein folding, stability, and cellular signaling. Recent research evidence suggests that abnormal glycosylation patterns exist in different brain regions in autopsy samples from SCZ patients, and that there are significant differences in various glycosylation modification types and glycosylation modifying enzymes. Therefore, this review explores the mechanisms of aberrant modifications of N-glycosylation, O-glycosylation, glycosyltransferases, and polysialic acid in the brains of SCZ patients, emphasizing their roles in neurotransmitter receptor function, synaptic plasticity, and neural adhesion. Additionally, the effects of antipsychotic drugs on glycosylation processes and the potential for glycosylation-targeted therapies are discussed. By integrating these findings, this review aims to provide a comprehensive perspective to further understand the role of aberrant glycosylation modifications in the pathophysiology of SCZ., 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 Feng, Sun, Dang, Liu, Liao, Yao, Zhang, Deng, Li, Zhao and Liu.)

Accumulation of advanced glycation end-products (AGEs) in the brain contributes significantly to cognitive impairment in patients with diabetes by disrupting the post-mitotic state of neuronal cells, thereby triggering ectopic cell cycle re-entry (CCR) and subsequent neuronal apoptosis. Cinnamaldehyde (CINA), a potential mitigator of cognitive impairment due to its blood glucose-lowering properties, warrants exploration for its role in counteracting diabetes-related neurological damage. In this study, we examined the neuroprotective effect of CINA on AGE-damaged SH-SY5Y human neuroblastoma cells differentiated in vitro. We investigated the impact of CINA on AGE-induced neuronal CCR and apoptosis, finding that it substantially suppressed aberrant DNA replication, precluded cells from entering the mitotic preparatory phase, and diminished apoptosis. Additionally, CINA inhibited the expression of eIF4E without altering S6K1 phosphorylation. These findings indicate that CINA safeguards neuronal cells from AGE-related damage by preventing abnormal CCR, preserving the post-mitotic state of neuronal cells, and reducing AGE-induced apoptosis, potentially through the inhibition of eIF4E-controlled cell proliferation. Our results highlight the prospective utility of CINA in managing diabetic neuropathy., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

This study established psycholinguistic norms in Cantonese for a set of 1286 colored pictures sourced from several picture databases, including 750 colored line drawings from MultiPic (Duñabeitia et al., 2018) and 536 photographs selected for McRae et al. (2005) concepts. The pictures underwent rigorous normalization processes. We provided picture characteristics including name and concept agreement, familiarity, visual complexity, and frequency of modal responses. Through correlational analyses, we observed strong interrelationships among these variables. We also compared the current Cantonese norming to other languages and demonstrated similarity and variations among different languages. Additionally, we embraced the multilingual diversity within the current sample, and found that higher Cantonese proficiency but lower non-native language proficiency were associated with better spoken picture naming. Last but not least, we validated the predictive power of normed variables calculated from typed responses to spoken picture naming, and the consistency between typed and spoken responses. The present norming provides a timely and valuable alternative for researchers in the field of psycholinguistics, especially those studying Cantonese production and lexical retrieval. All raw data, analysis scripts, and final norming results are available online as psycholinguistic norms for Cantonese in the following link at the Open Science Framework: https://osf.io/dz9j6/?view&#95;only=a452d8a56c92430b9dedf21ac26b1bc1 ., (© 2024. The Psychonomic Society, Inc.)

An optimum safety excision margin (EM) delineated by precise demarcation of field cancerization along with reliable biomarkers that enable predicting and timely evaluating patients' response to immunotherapy significantly impact effective management of melanoma. In this study, optimized biphasic "immunofluorescence staining integrated with fluorescence insitu hybridization" (iFISH) was conducted along the diagnosis-metastasis-treatment-cellular MRD axis to longitudinally co-detect a full spectrum of intact CD31 - aneuploid tumor cells (TCs), CD31 + aneuploid tumor endothelial cells (TECs), viable and necrotic circulating TCs (CTCs) and circulating TECs (CTECs) expressing PD-L1, Ki67, p16 and Vimentin in unsliced specimens of the resected primary tumor, EM, dissected sentinel lymph nodes (SLNs) and peripheral blood in an early-stage melanoma patient. Numerous PD-L1 + aneuploid TCs and TECs were detected at the conventional safety EM (2 cm), quantitatively indicating the existence of a field cancerized EM for the first time. Contrary to highly heterogeneous PD-L1 expression and degrees of Chr8 aneuploidy in TCs and TECs in the primary lesions as well as CTCs and CTECs in peripheral blood, almost all TCs and TECs in SLNs and EM were homogeneously PD-L1 + haploid cells. Dynamic monitoring and cellular MRD assessment revealed that, in contrast to PD-L1 + CTCs being responsive to the immune checkpoint inhibitor (ICI-anti-PD-1), multiploid (≥pentasomy 8) PD-L1 + and Ki67 + CTECs were respectively resistant to ICI-sensitized T cells. In therapeutically stressed lymphatic and hematogenous metastatic cascades, stratified phenotypic and karyotypic profiling of iFISH tissue and liquid biopsied TCs, TECs, CTCs and CTECs in future large-cohort studies will enable appropriate re-specification of the optimal safety EM and distribution mapping of in-depth characterized, subcategorized target cells to help illustrate their metastatic relevance, ultimately improving risk stratification and clinical intervention of tumor progression, metastases, therapy resistance and cancer relapse., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Protein L-isoaspartyl (D-aspartyl) methyltransferase (PIMT, gene name PCMT1) is an enzyme that repairs proteins with altered aspartate residues by methylation, restoring their normal structure and function. This study conducted a comprehensive analysis of PCMT1 in pan-cancer. The Cancer Genome Atlas, Human Protein Atlas website, and the Genotype-Tissue Expression were utilized in analysis of PCMT1 expression. We examined the association between PCMT1 expression and various factors, including gene modifications, DNA methylation, immune cell infiltration, immunological checkpoints, drug susceptibility, tumor mutation burden (TMB), and microsatellite instability (MSI). Enrichment analyses determined the potential biological roles and pathways involving PCMT1. Our focus then shifted to the role of PCMT1 in breast invasive carcinoma (BRCA). We found that PCMT1 expression was aberrant in many tumors and significantly influenced the prognosis across several cancer types. Gene alterations in PCMT1 predominantly involved deep deletions and amplifications. A negative correlation was observed between DNA methylation and PCMT1 expression across all studied cancer types except thyroid carcinoma PCMT1 exhibited positive correlations with common lymphoid progenitor and CD4(+) T helper 2 cells, whereas it was inversely correlated with central and effector memory T cells, memory CD8(+) T cells, and CD4(+) T helper 1 cells. In many cancer types, PCMT1 expression closely correlated with immunological checkpoint inhibitors, TMB, and MSI. It was also significantly linked to pathways involved in epithelial-mesenchymal transition (EMT), highlighting its role in cancer metastasis. PCMT1 emerged as a significant predictor of breast cancer progression. In vitro experiments demonstrated that reducing PCMT1 expression decreased BRCA cell migration and invasiveness. Additionally, animal studies confirmed that inhibition of PCMT1 slowed tumor growth., Competing Interests: None., (AJCR Copyright © 2024.)

Lung cancer is a predominant cause of cancer-related mortality worldwide, necessitating precise tumor segmentation of medical images for accurate diagnosis and treatment. However, the intrinsic complexity and variability of tumor morphology pose substantial challenges to segmentation tasks. To address this issue, we propose a multitask connected U-Net model with a teacher-student framework to enhance the effectiveness of lung tumor segmentation. The proposed model and framework integrate PET knowledge into the segmentation process, leveraging complementary information from both CT and PET modalities to improve segmentation performance. Additionally, we implemented a tumor area detection method to enhance tumor segmentation performance. In extensive experiments on four datasets, the average Dice coefficient of 0.56, obtained using our model, surpassed those of existing methods such as Segformer (0.51), Transformer (0.50), and UctransNet (0.43). These findings validate the efficacy of the proposed method in lung tumor segmentation tasks., 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 Zhou, Wu, Chen and Zhang.)

Corticosterone, an end product of the hypothalamic-pituitary-adrenal (HPA) axis, is a crucial stress hormone. A dysregulated HPA axis and corticosterone release play pivotal roles in the onset and persistence of symptoms of stress-related psychiatric disorders, such as anxiety. The intake of nutrients, probiotics, and prebiotic supplements decreases blood corticosterone levels. The dipeptide L-carnosine is composed of beta-alanine and L-histidine and is commercially available as a nutritional supplement for recovery from fatigue. L-carnosine is involved in stress-induced corticosterone responses and anxiety behaviors in rodents. Here, we assessed the effect of L-carnosine in CD157 knockout (KO) mice, a murine model of autism spectrum disorder (ASD). The uptake of L-carnosine suppressed the increase in plasma corticosterone levels in response to acute stress and attenuated anxiety-like behaviors in CD157 KO mice. These results suggest that L-carnosine supplementation may relieve anxiety by suppressing excessive stress responses in individuals with ASD.

Rationale: Pharmacological mechanism of Roxadustat in the treatment of renal anemia., Patient Concerns: To investigate the efficacy and safety of combined Roxadustat and erythropoiesis stimulator (ESA) treatment of renal anemia in hemodialysis patients with secondary hyperparathyroidism., Diagnoses: A retrospective analysis was conducted on hemodialysis patients with renal anemia and secondary hyperparathyroidism treated with ESAs alone, who were admitted to our hospital from March 2022 to December 2022., Interventions: The patients were treated with Roxadustat combined with ESAs for 3 months, during which oral iron supplementation was given, and the changes in Hb levels and laboratory-related indicators before and after the combined treatment were analyzed., Outcomes: The results showed that a total of 13 patients received combination therapy, with a significant increase in Hb compared to ESAs alone (t = -3.955, P = .002). The Hb qualification rate was 38.46%, and the ∆Hb response rate was 76.92%. The parathyroid hormone significantly decreased with a statistically significant difference (Z = -2.062b, P = .039). Hemoglobin (RBC), total iron binding capacity, and serum ferritin (male) were significantly increased compared to ESAs alone. Total cholesterol and low-density lipoprotein were significantly lower than ESAs alone. The differences in the changes in the above indicators were statistically significant (P < .05). There was no statistically significant difference in changes in other laboratory-related indicators (P > .05). No adverse reactions were observed during the combined treatment of 13 patients., Lessons Subsections: The combination of Roxadustat and ESAs can effectively improve renal anemia in hemodialysis patients with secondary hyperparathyroidism, as well as improve indicators of hyperparathyroidism and blood lipid levels with high levels of safety. This combined treatment thus provides a new and safe treatment method for these patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The authors aim to investigate the effect of music on hemodynamic fluctuations during induction of general anesthesia and reducing preoperative anxiety for women who underwent elective non-cardiac surgery., Methods: It is a multicenter, double-blind, randomized, parallel-group clinical trial. Patients were randomized 1:1 to either a Music Intervention group (MI) or a Control group (Control). The MI participants listened to their preferred music for more than 30 minutes in the waiting area. The State-Trait Anxiety Inventory (STAI) was used to measure anxiety levels in the groups, and hemodynamic parameters (Heart Rate [HR], Mean Arterial Pressure [MAP]) were continuously recorded before induction (T0), at loss of consciousness (T1), immediately before intubation (T2), and after intubation (T3). Intubation-related adverse events were also recorded. The primary outcome was the incidence of MAP changes more than 20 % above baseline during T0-T2., Results: A total of 164 patients were included in the final analyses. The incidence of MAP instability during T0-T2 was lower in the MI, and the 95 % Confidence Interval for the rate difference demonstrated the superiority of MI. HR instability was less frequent in MI participants both in T0-T2 and T2-T3. The overall incidence of preoperative anxiety was 53.7 % (88/164). After the music intervention, the mean score of STAI was significantly lower in the MI than in the Control, with a between-group difference of 8.01., Conclusions: Preoperative music intervention effectively prevented hemodynamic instability during anesthesia induction and significantly reduced preoperative anxiety in women undergoing elective non-cardiac surgery., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Ruthenium complexes are one of the most promising anticancer drugs and ferroptosis is a novel form of regulated cell death, the study on the effect of Ru complexes on ferroptosis is helpful to find more effective antitumor drugs. Here, the synthesis and characterization of two Ru complexes containing 8-hydroxylquinoline and triphenylphosphine as ligands, [Ru(L 1 ) (PPh 3 ) 2 Cl 2 ] (Ru-1), [Ru(L 2 ) (PPh 3 ) 2 Cl 2 ] (Ru-2), were reported. Complexes Ru-1 ∼ Ru-2 showed good anticancer activity in Hep-G2 cells. Researches indicated that complexes Ru-1 ∼ Ru-2 could be enriched and appear as red fluorescence in the mitochondria, arouse dysfunction of mitochondria, induce the accumulation of reactive oxygen species (ROS) and lipid peroxidation (LPO), while the morphology of nuclei and cell apoptosis had no significant change. Further experiments proved that GPX4 and Ferritin were down-regulated, which eventually triggered ferroptosis in Hep-G2 cells. Remarkably, Ru-1 showed high inhibitory activity against xenograft tumor growth in vivo (TGIR = 49%). This study shows that the complex Ru-1 could act as a novel drug candidate by triggering cell ferroptosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)