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Integrating biomedical electronic devices holds profound promise for advancements in healthcare and enhancing individuals' quality of life. However, the persistent challenges associated with the traditional batteries' limited lifespan and bulkiness hinder these devices' long-term functionality and consistent power supply. Here, we delve into the biology and material interfaces in self-powered medical devices by summarizing the intrinsic electric demands in humans, analyzing material and biological mechanisms for electricity generation and storage, and discussing the pathways toward self-chargeable powering. As a result, the current challenges in material designs and biological integrations emerged to shape the future directions in advancing self-powered medical devices. This paper calls on the community to integrate biology and material science to develop self-powering medical devices and improve their clinical prospects., (© 2025 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Alveolar bone resorption (ABR) is a key pathological manifestation in the development of apical periodontitis (AP) and contributes to the AP-associated tooth loss among AP patients in the clinic. However, the underlying mechanism of ABR development is largely unknown. Here we show, the total levels of N6-methyladenosine (m 6 A) were reduced in AP male rat alveolar bone tissues and BMDM-derived osteoclasts (OC), which was associated with the up-regulation of obesity-associated protein (FTO). Subsequently FTO-mediated hexokinase (HK1) demethylation modification enhancing glycolytic pathway that stabilizes receptor activator of NF-κB (RANK) protein via the deubiquitination activity of ubiquitin-specific protease 14 (USP14), which further promotes osteoclastogenesis to participate in the AP-related ABR development. Finally, Dac51 (an FTO inhibitor) and 2-DG (an HK1 inhibitor) both exhibit the inhibitory activity of osteoclastogenesis. Our current study reveals a molecular mechanism on osteoclastogenesis-related ABR and provides a therapeutic target of AP via modulating the FTO/HK1/USP14/RANK axis., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Sentinel lymph node biopsy (SLNB) has improved detection of low-volume node metastasis (LVNM) in endometrial cancer (EC), but its prognostic significance and the need for adjuvant therapy (AT) remain unclear. A comprehensive search was performed until August 31, 2024 in multiple databases and sources. From 21 studies, 65,228 apparent early-stage EC patients were identified: 370 with macrometastases (MAC), 526 with micrometastases (MM), 2,138 with isolated tumor cells (ITCs), and 62,194 with negative nodes. Findings indicated: 1) The MM group had a lower risk of recurrence or progression (R/P) than the MAC group (risk ratio [RR]=0.49; 95% confidence interval [CI]=0.31-0.78; p=0.002), higher risk than the negative nodes group (RR=2.07; 95% CI=1.59-2.68; p<0.001), and similar risk to the ITC group (RR=0.67; 95% CI=0.44-1.02; p=0.060). 2) The MM group had higher 3-year progression-free survival (PFS) (RR=1.36; 95% CI=1.21-1.52; p<0.001) and overall survival (OS) (RR=1.22; 95% CI=1.09-1.37; p<0.001) than the MAC group, similar to the ITC and negative nodes groups. 3) The ITC group had a lower R/P risk and higher 3-year PFS/OS than the MAC group, similar to the negative nodes group. 4) AT reduced the R/P risk in the MM group (RR=0.41; 95% CI=0.22-0.76; p=0.005) and increased 3-year OS in the ITC group (RR=1.06; 95% CI=1.04-1.08; p<0.001). Early-stage EC with LVNM had better prognostic outcomes than MAC, and AT may improve outcomes of LVNM patients. More evidence from prospective randomized controlled trials is needed to confirm these findings due to the inherent biases of retrospective studies. Trial Registration PROSPERO Identifier: CRD42022364536., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2025. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

A major characteristic of ovarian cancer (OC) is its unique route of metastasis via ascites. The immune microenvironment in ascites remains understudied, leaving the mechanism of ascites-mediated abdominal metastasis obscure. Here, a single-cell transcriptomic landscape of CD45 + immune cells across multiple anatomical sites is depicted, including primary tumors, metastatic lesions, and ascites, from patients diagnosed with high-grade serous ovarian carcinoma (HGSOC). A novel subset of perilipin 2 high (PLIN2 hi ) macrophages are identified that are enriched in ascites and positively correlated with OC progression, hence being designated as "ascites-associated macrophages (AAMs)". AAMs are lipid-loaded with overexpression of the lipid droplet protein PLIN2. Overexpression or suppression of PLIN2 can enhance or inhibit tumor cell migration, invasion, and vascular permeability in vitro, which is also confirmed in vivo. Mechanistically, it is demonstrated that PLIN2 boosts HIF1α/SPP1 signaling in macrophages, thereby exerting pro-tumor functions. Finally, a PLIN2-targeting liposome is designed to efficiently suppress ascites production and tumor metastasis. Taken together, this work provides a comprehensive characterization of the cancer-promoting function and lipid-rich property of ascites-enriched PLIN2 hi macrophages, establishes a link between lipid metabolism and hypoxia within the context of the ascites microenvironment, and elucidates the pivotal role of ascites in trans-coelomic metastasis of OC., (© 2025 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Purpose: To evaluate the clinical performance of expanded non-invasive prenatal testing (NIPT-plus) and compare its effectiveness in screening for chromosomal aneuploidies with that of NIPT., Methods: Screening results, confirmatory invasive testing results, and follow-up data from pregnant women who underwent either NIPT (6792 cases) or NIPT-Plus (5237 cases) testing at Luohe Central Hospital, China, from January 2019 to June 2023 were collected. The positive predictive value (PPV), sensitivity, specificity, and other indicators for different types of chromosomal abnormalities in NIPT/NIPT-plus screening were calculated. The willingness of pregnant women with various types of abnormalities to undergo confirmatory invasive testing and the proportion of pregnancy terminations were investigated., Results: The average number of unique reads in NIPT-plus samples was 5.26 times greater than that in NIPT samples. There was no significant difference in the PPV or positive rate between NIPT-plus and NIPT for screening chromosomal aneuploidies. Compared with the low-risk group, the high-risk group had a greater PPV; however, in the NIPT-plus group, there was no significant disparity in the PPV between the low-risk and high-risk groups. Compared with rare autosomal aneuploidies (RAAs), pregnant women had a higher rate of confirmatory invasive testing for common trisomies, sex chromosomal abnormalities (SCAs), and copy number variations (CNVs). However, the rate of pregnancy termination for common trisomies, RAAs, and CNVs was higher than that for SCAs., Conclusion: By enhancing sequencing data, NIPT-plus can effectively screen for CNVs as well as chromosomal aneuploidies. However, NIPT-plus does not have an advantage over standard NIPT in screening for chromosomal aneuploidies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study explores the effects of lipid oxidation products (LOPs), specifically CHP, t,t-DDE, and MDA, on the digestibility and structural integrity of myofibrillar proteins (MP) during processing. LOPs were first assessed by heating at 180 °C for 15 min, showing a significant reduction in digestibility in MDA-treated samples (65.40 %), followed by t,t-DDE (45.10 %) and CHP (13.07 %). MALDI-TOF MS analysis revealed decreased peptide abundance and lower average molecular weight in t,t-DDE- and MDA-treated samples. Notably, substantial decreases in α-helix content and increases in random coil structures were detected, particularly in MDA-treated samples. Assessments of surface hydrophobicity and thiol content underscored the detrimental impact of secondary LOPs on MP structure. Higher MDA concentrations led to a substantial reduction in intrinsic fluorescence intensity, along with an increase in Schiff base content. A PLS regression model demonstrated strong predictive capabilities for MP digestibility, highlighting the importance of optimizing meat processing parameters to minimize nutritional degradation., Competing Interests: Declaration of competing interest The authors declare no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Triglyceride-glucose (TyG) index has been found to be associated with female reproductive disorders, but its relationship with the risk of endometriosis is unknown. Therefore, the aim of this study was to investigate this relationship., Methods: We performed a two-sample mendelian randomization(MR) analysis to examine the causal effect of TyG index on endometriosis, and inverse variance weighting(IVW) was the main method of analysis. Then, we selected 1484 participants with endometriosis from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2006. Weighted multivariable-adjusted logistic regression and smoothed curve analysis were used to evaluate the correlation between the TyG index and endometriosis., Results: The results of MR analysis confirmed that higher TyG index was causally associated with the risk of endometriosis (OR=1.27, 95%CI: 1.05-1.54, P=0.01). In the cross-sectional study, subjects in the highest quartile of TyG index had the highest risk of incident endometriosis after adjusting for covariates(OR = 2.41, 95% CI:1.31-4.44, P for trend <0.01). The smoothed curve analysis also revealed a positive linear correlation between TyG index and endometriosis., Conclusion: Our study confirms that a higher TyG index is associated with an increased risk of endometriosis by MR analysis and cross-sectional study. These findings suggested that TyG index could serve as a biomarker in identifying individuals who may be at a higher risk for developing endometriosis. Further research is needed to explore the potential clinical implications of these findings and to elucidate the underlying mechanisms behind this observed relationship., 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 Xu, Zhuang, Cao and Yang.)

Aims: Endometriosis is a chronic inflammatory disease. The current treatment options in clinical practice mainly include hormonal therapy and surgical intervention. However, hormonal therapy is associated with serious side effects, and surgical treatment often leads to a high recurrence rate. Dandelion, a commonly used traditional Chinese medicine, has played a significant role in the treatment of endometriosis due to its notable efficacy and minimal side effects as a component of compound formulations. The purpose of this study is to investigate the molecular mechanisms of Taraxasterol, the main component of dandelion, in the treatment of endometriosis., Materials and Methods: This study employed network pharmacology to screen potential targets associated with Taraxasterol in the treatment of endometriosis. Subsequently, molecular docking was performed to preliminarily validate the core targets. Furthermore, GO and KEGG enrichment analyses were conducted to identify potential signaling pathways related to the treatment. The mechanisms underlying the therapeutic effects of Taraxasterol on endometriosis were further validated through in vitro cell experiments, including Western blotting, colony formation assays, scratch assays, and CCK-8 assays., Results: A total of 148 potential targets of Taraxasterol were selected through screening on a prediction website, along with 1180 disease targets and 71 overlapping targets. Subsequently, the overlapping targets were imported into the STRING database to construct a protein-protein interaction (PPI) network, which was visualized using Cytoscape 3.7. Ten key targets were identified from the network, and preliminary validation was performed through molecular docking of these ten targets. Additionally, GO and KEGG analyses were conducted on the overlapping targets, resulting in the identification of the top 10 enriched GO terms and the top 20 KEGG pathways, which were subsequently visualized. Finally, cellular experiments demonstrated that taraxasterol inhibits the proliferation and migration of ectopic endometrial cells through the PI3K/Akt/mTOR pathway, while promoting apoptosis., Conclusions: Our study investigated the potential mechanisms underlying the therapeutic effects of Taraxacum officinale (dandelion) on endometriosis. Through network pharmacology and in vitro cellular experiments, we revealed that Taraxasterol, a bioactive compound present in dandelion, can inhibit the proliferation and migration of endometrial ectopic cells and promote apoptosis through the PI3K/Akt/mTOR pathway., Competing Interests: Declaration of competing interest The authors disclose no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims/introduction: Diabetic foot ulcer (DFU) is a prevalent complication of diabetes characterized by heightened inflammation and impaired wound-healing processes. Interleukin-37 (IL-37) is a natural suppressor of innate inflammation. Here, we aim to investigate the potential of IL-37 in enhancing the healing process of diabetic wounds., Materials and Methods: The skin samples of DFU and non-diabetic patients during foot and ankle orthopedic surgery were collected. The IL-37 transgenic mice (IL-37Tg) were created using CRISPR/Cas-mediated genome engineering. Mice were administered streptozotocin (STZ, 150 mg/kg) to induce a diabetic model. After 4 weeks, an equidistant full-thickness excisional wound measuring 8 mm was created on the central back of each mouse and allowed to heal naturally. Body weight and blood glucose levels were measured weekly. The wound area was measured, and skin samples were collected on Day 10 for further Quantitative polymerase chain reaction (qPCR) and WB detection and RNA sequencing analysis., Results: The proinflammation cytokines such as TNF-α and IL-1β and the MAPK signaling pathway were significantly increased in the wound margin of DFU patients. Compared with diabetic mice, diabetic IL-37Tg mice showed a significantly accelerated healing process. The enriched signaling pathways in RNA sequencing included cytokine-cytokine receptor interaction, TNF signaling pathway, and NOD-like receptor signaling pathway. Through QPCR and WB detection, we found that IL-37 could inhibit the activated MAPK and NOD-like signaling pathway, reducing TNF-α, IL-1β, and NLRP3 expression in the diabetic wound., Conclusions: IL-37 promotes skin wound healing in diabetic mice, providing a new possible target for treating diabetic wounds., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background & Aims: Alcohol abuse is the most frequent precipitating factor of acute-on-chronic liver failure (ACLF). We aimed at developing an alcohol-induced ACLF model and dissecting its underlying molecular mechanisms., Methods: ACLF was triggered by a single alcohol binge (5 g/kg) in a bile duct ligation (BDL) liver fibrosis murine model. Liver, kidney, and brain tissues and behavior were assessed in mice. Livers from patients with sclerosing cholangitis with and without ACLF were also evaluated., Results: In advanced fibrosis induced by BDL, an alcohol binge induced features of ACLF, including significant liver damage, systemic inflammation (increased endotoxin and pro-inflammatory cytokines), and hepatocyte dysfunction compared with BDL alone. ACLF was associated with extrahepatic manifestations, including increased blood urea nitrogen and creatinine, impaired coagulation, and features of encephalopathy. We discovered significantly increased neutrophil count and neutrophil extracellular traps (NETs) in the liver, kidney, and brain in murine ACLF. Livers from ACLF mice showed increased pyroptosis (gasdermin D) and necroptosis (receptor-interacting protein kinase 3 [RIPK3]), when compared with BDL. In vitro, cell-free NETs were induced by alcohol and/or bile acids and triggered pyro-/necroptotic death in hepatocytes. NETosis, pyroptosis, and RIPK3 activation were validated in human livers with ACLF. Moreover, pharmacological inhibition of necroptosis with a RIPK3 inhibitor-ameliorated inflammation, NETs, and liver fibrosis, improving multi-organ ACLF pathophysiology., Conclusions: Our novel ACLF model triggered by alcohol binge mimics key features of pathophysiology and multi-organ impairment in human ACLF. Our results indicate that neutrophil infiltration and NETs contribute to hepatocyte cell death via pyroptosis and necroptosis in ACLF, identifying RIPK3 as a potential therapeutic target., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The emergence and dissemination of mcr-1-positive Escherichia coli (MCRPEC) represent a critical public health threat. Here, we conducted a prospective analysis of MCRPEC isolates from wastewater treatment plants (WWTPs), local residents' fecal (LRF), and international airplane waste (IAW) to investigate their genetic characteristics and transmission patterns circulating in human-environment domains. The MCRPEC prevalence was 2.43 % in WWTPs, 1.37 % in IAW and 0.69 % in LRF. MCRPEC showed substantial genetic diversity, encompassing 61 sequence types (primarily ST1011, ST101, and ST2705), 7 plasmid types (primarily IncI2), 8 phylogroups (primarily A and B1), 9 mcr-1-flanked lineages (primarily L5), 6 clusters (primarily C2 and C4), diverse serotypes, and 61.95 % transposon-containing strains. The mcr-1 gene co-existed with 46 antibiotic resistance genes (ARGs) and 19 virulence factor genes (VFGs). Notably, 6 IncI2 plasmids carried the bla CTX-M , IS1380, and mcr-1 genes. MCRPEC from WWTPs harbored a greater number of ARGs (56.95 ± 5.99) but fewer VFGs (15.03 ± 6.40) compared to those from human-associated sources (LRF and IAW). ST1011, ST2705, IncHI2, and L7 were prevalent in WWTP-derived MCRPEC, whereas IncX4 and L3 were more common in human-derived MCRPEC. Genetic features such as ST101, ST48, IncI2, L4, L5, C2, and C4 were simultaneously present in strains from LRF, IAW, and WWTPs. Core genetic analyses also showed genetically similar MCRPEC strains across various geographic locations. The findings underscore the extensive dissemination, strong environmental adaptation, and clonal transmission of MCRPEC across diverse reservoirs, reinforcing the urgent need for coordinated multisectoral surveillance of human and environment interfaces to effectively mitigate further transmission., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Accumulation of free α-globin is a critical factor in the pathogenesis of β-thalassemia. Autophagy plays a crucial role in clearing toxic free α-globin, thereby reducing disease severity. However, the impact of natural mutations in autophagy-related genes (ATGs) on the phenotypic variability of β-thalassemia remains unclear. In this study, we systematically investigated the relationship between variants in ATGs and disease phenotypes in a cohort of 1,022 patients with β-thalassemia, identifying four missense mutations in the autophagy and beclin 1 regulator 1 (AMBRA1) gene. Disruption of the Ambra1 gene in β-thalassemic mice was found to reduce autophagic clearance of α-globin in red blood cell precursors, exacerbating disease phenotypes. Functional characterization of the AMBRA1 gene and these mutations in patient-derived CD34+ cells, edited HUDEP-2 cells, and engineered HUDEP-2 β-thalassemic cells confirmed that AMBRA1 facilitates the autophagic clearance of free α-globin in human erythroid cells. Functional studies demonstrated that AMBRA1 missense mutants destabilize ULK1 protein, inhibit LC3 lipidation, and subsequently hinder autophagic flux, leading to increased α-globin deposition. Additionally, these mutations were associated with erythrotoxic effects in vitro, including increased intracellular reactive oxygen species levels, higher apoptosis rates, and impaired erythroid differentiation and maturation. This study sheds light on the molecular association between mutations in ATGs and the exacerbation of β-thalassemia, highlighting the potential role of the AMBRA1 gene as a promising diagnostic and therapeutic target for β-hemoglobinopathies., (Copyright © 2024 American Society of Hematology.)

Eccentric training has been proposed as a potential method for enhancing athletes' movement speed. However, a systematic review specifically examining the impact of eccentric training on movement speed in athletes has yet to be conducted. This paper aims to fill this gap by evaluating the effects of eccentric training on movement speed in athletes.A systematic search was carried out on May 15, 2024, in accordance with the PRISMA guidelines for systematic reviews and meta-analyses. The search was conducted across multiple databases, including Web of Science, EBSCOhost, PubMed, CNKI, and VIP, using keywords related to eccentric training, athletes, and movement speed. Out of 421 reviews screened, nine met the inclusion criteria. The quality of the studies was assessed using the PEDro scale, with an average score of 3.67 (range 3-4). The results indicated that short-distance sprint speed (n = 7) was the most affected by eccentric training interventions. Sport-specific movement speed (n = 3) and change of direction speed (COD) (n = 5) were also positively influenced, although to a lesser extent.In conclusion, eccentric training significantly enhances sport-specific movement speed and COD speed, with more moderate effects on short-distance sprinting. These findings suggest that eccentric training can be a valuable intervention for improving movement speed in athletes, especially for sports that involve rapid directional changes., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display&#95;record.php?ID=CRD42024547112, identifier CRD42024547112., 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 Zhang, Zhuang, Zhang and Sun.)

Background: Fibrosis is key in the development and progression of diabetic kidney disease (DKD). Baicalin (BA), wogonin (WGN), and wogonoside (WGS) have renoprotective effects. The mechanism of alleviation of DKD progression, by improving renal fibrosis, is unclear. This study aimed to investigate the mechanisms and effects of a Scutellaria baicalensis Georgi. (Lamiaceae) mixture (MIX, WGN:BA:WGS = 4:2:1) on DKD in a spontaneous DKD model., Methods: Male db/m mice were controls, and db/db mice were diabetes models. Both groups received daily oral gavage of normal saline. Treatment groups received daily oral gavage of BA or MIX (20 mg/kg) for 10 weeks. Biochemical indicators and kidney lesions were assessed. Fibrosis-related proteins were detected by immunoblotting, immunohistochemistry, and real-time fluorescence quantitative PCR., Results: MIX significantly reduced body weight (40.97 ± 1.43 vs. 42.26 ± 1.60), improved insulin sensitivity (63.70 ± 8.98 vs. 109.48 ± 0.69), lowered the renal hypertrophy index (19.81 ± 2.86 vs. 28.94 ± 0.256), and decreased blood urea nitrogen levels (7.57 ± 0.79 vs. 9.57 ± 0.38) and the urine protein/creatinine ratio (0.50 ± 0.06 vs. 0.80 ± 0.18). MIX also enhanced lipid profiles and renal function by improving renal tubular dilation, restoring renal structures, and reducing glomerulosclerosis, basal membrane thickening, and glycogen deposition. These effects were achieved by reducing the protein and gene expression of collagen II (Col-II), connective tissue growth factor, and collagen I (Col-I)., Conclusion: MIX inhibits the transforming growth factor-β/Smads signaling pathway, thus alleviating renal fibrosis, and can be used to develop a treatment for 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 Li, Zhuang, Fan, Wang, Yan, Guo, Zhang and Jiang.)

Objective: The aim of this study is to assess the latent profile types of marital adjustment in patients with breast cancer and to analyze the factors influencing these various profiles., Methods: Patients with breast cancer who visited the Breast Surgery Department from January to June 2023 were selected using convenience sampling. These patients were surveyed using a general data questionnaire, the Revised Dyadic Adjustment Scale (RDAS), the Interpersonal Reactivity Index-C (IRI-C), and the Emotional Regulation Self-Efficacy Scale (RESS). Latent profile analysis (LPA) was used to determine different types of marital adjustment among patients, and influencing factors for the various profiles were identified through univariate analysis and multivariate logistic regression analysis., Results: Marital adjustment in patients with breast cancer was categorized into three latent profiles: the "low marital adjustment-low cohesion group" (20.2%), the "midlevel marital adjustment group" (35.3%), and the "high marital adjustment-satisfaction group" (44.4%). The influencing factors included age, marital status, primary caregiver, type of surgical intervention, empathy, and emotional regulation self-efficacy ( P < 0.05)., Conclusion: The marital adjustment levels of patients with breast cancer exhibited significant heterogeneity. Medical staff can implement targeted interventions based on the distinct characteristics of each marital adjustment profile, thereby enhancing the marital adjustment of these patients., Competing Interests: The authors declare that they have no competing interests., (© 2024 Chen et al.)

Purpose: To propose an efficient, reproducible, and consistent transgenic technology based on plate centrifugation, which is particularly useful for polyethylenimine (PEI) transfection and lentiviral infection., Methods: We optimized multiple factors that could contribute to transfection efficiency, such as the dosage of the PEI or DNA, the working solution buffer used for diluting the PEI or DNA, the incubation time for the PEI/DNA complexes, and the transfection time., Results: Plate centrifugation led to a 5.46-fold increase in the transfection efficiency of PEI-based transfection while maintaining the cell survival rate. Moreover, the average copy number of viral genes in each genome increased 4.96-fold with plate centrifugation. Plate centrifugation alters the spatial arrangement of the PEI/DNA complexes or lentiviruses, increasing the chances of these complexes or viruses coming into contact with target cells, ultimately resulting in improved transfection or infection efficiency., Conclusions: We present a protocol based on plate centrifugation for transfection or lentiviral infection that is suitable for genetic modification of primary cells or stem cells., 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.)

To systematically characterize the loss of tissue integrity and organ dysfunction resulting from aging, we produced an in-depth spatial transcriptomic profile of nine tissues in male mice during aging. We showed that senescence-sensitive spots (SSSs) colocalized with elevated entropy in organizational structure and that the aggregation of immunoglobulin-expressing cells is a characteristic feature of the microenvironment surrounding SSSs. Immunoglobulin G (IgG) accumulated across the aged tissues in both male and female mice, and a similar phenomenon was observed in human tissues, suggesting the potential of the abnormal elevation of immunoglobulins as an evolutionarily conserved feature in aging. Furthermore, we observed that IgG could induce a pro-senescent state in macrophages and microglia, thereby exacerbating tissue aging, and that targeted reduction of IgG mitigated aging across various tissues in male mice. This study provides a high-resolution spatial depiction of aging and indicates the pivotal role of immunoglobulin-associated senescence during the aging process., Competing Interests: Declaration of interests Y.G., C.N., Y.S., Z.L., H.D., and F.W. are employees of BGI. J.C.I.B. and C.R.E. are employees of Altos Labs., (Copyright © 2024 Elsevier Inc. All rights reserved.)

To date, previous research has elucidated the impact of adult attachment type on marital relationships. However, the mechanisms underpinning the relationship between attachment type and marital adjustment in breast cancer patients remain unclear. In this study, a cohort of 272 breast cancer patients was surveyed using several instruments: the General Information Questionnaire, Revised Marital Adjustment Scale (RDAS), Adult Attachment Scale (AAS), Interpersonal Reactivity Indicator Scale (IRI), and Regulated Emotional Self-Efficacy Scale (RESS). We conducted moderated mediation analyses using the SPSS macro program PROCESS plug-in. Empathy was found to mediate the association between attachment type (attachment anxiety/attachment avoidance) and marital adjustment, with indirect effects of -0.141 (95% CI [-0.260, -0.063]) and 0.157 (95% CI [0.073,0.289]), respectively. Additionally, affect regulation self-efficacy was found to mediate the subsequent impact of attachment type (attachment anxiety/attachment avoidance) on marital adjustment via empathy, with moderated effects of 0.380 (95% CI [0.236, 0.525]) and 0.374 (95% CI [0.240, 0.509]), respectively. Consequently, the presence of insecure attachment in breast cancer patients appears to influence their empathy levels, thereby negatively impacting marital adjustment. Encouragingly, enhancing emotional regulation self-efficacy in patients holds the potential to mitigate these adverse effects. These findings contribute not only to a deeper theoretical understanding but also lay a solid foundation for practical interventions aimed at enhancing marital relationships among breast cancer patients.

Surface-enhanced Raman Scattering (SERS) has become a powerful spectroscopic technology for highly sensitive detection. However, SERS is still limited in the lab because it either requires complicated preparation or is limited to specific compounds, causing poor applicability for practical applications. Herein, a micro-macro SERS strategy, synergizing polymer-assisted printed process with paper-tip enrichment process, is proposed to fabricate highly sensitive paper cartridges for sensitive practical applications. The polymer-assisted printed process finely aggregates nanoparticles with a discrete degree of 1.77, and SERS results are matched with theoretical enhancement, indicating small cluster-dominated hotspots at the micro-scale and thus 41-fold SERS increase compared to other aggregation methods. The paper-tip enrichment process moves molecules in a fluid into small tips filled with plasmonic clusters, and molecular localization at hotspots is achieved by the simulation and optimization of fluidic velocity at the macro-scale, generating a 39.5-fold SERS sensibility increase in comparison with other flow methods. A highly sensitive paper cartridge contains a paper-tip and a 3D-printed cartridge, which is simple, easy-to-operate, and costs around 2 US dollars. With a detection limit of 10 -12  M for probe molecules, the application of real samples and multiple analytes achieves single-molecule level sensitivity and reliable repeatability with a 30-min standardized procedure. The micro-macro SERS strategy demonstrates its potential in practical applications that require point-of-care detection., 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. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We confirm that we have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing we confirm that we have followed the regulations of our institutions concerning intellectual property. We understand that the Corresponding Author is the sole contact for the Editorial process (including Editorial Manager and direct communications with the office). He/she is responsible for communicating with the other authors about progress, submissions of revisions and final approval of proofs. We confirm that we have provided a current, correct email address which is accessible by the Corresponding Author., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Adult severe caries (ASC) brings severe oral dysfunction and treatment difficulties to patients, and yet no clear pathogenic mechanism for it has been found. This study is focused on the composition of dental plaque microbiome profiles in order to identify disease-relevant species and to investigate into their interactions with the S. mutans . Samples of dental plaque were collected for metagenomic analysis. The acidification, aciduricity, oxidative stress tolerance, and gtf (glucosyltransferase) gene expression of S. mutans cocultured with V. parvula which was identified as ASC-related dominant bacterium. The biofilm formation and extracellular exopolysaccharide (EPS) synthesis of dual-strain were analyzed with scanning electron microscopy (SEM), crystal violet (CV) staining, live/dead bacterial staining, and confocal laser scanning microscopy (CLSM). Furthermore, rodent model experiments were performed to validate the in vivo cariogenicity of the dual-species biofilm. The most significantly abundant taxon found associated with ASC was V. parvula . In vitro experiments found that V. parvula can effectively promote S. mutans mature biofilm formation with enhanced acid resistance, hydrogen peroxide detoxicity, and biofilm virulence. Rodent model experiments revealed that V. parvula was incapable of causing disease on its own, but it significantly heightened the biofilm virulence of S. mutans when being co-infected and augmented the progression, quantity, and severity of dental caries. Our findings demonstrated that V. parvula may act as a synergistic pathobiont to modulate the metabolic activity, spatial structure, and pathogenicity of biofilms of S. mutans in the context of ASC.IMPORTANCEAdult severe caries (ASC), as a special type of acute caries, is rarely reported and its worthiness of further study is still in dispute. Yet studies on the etiology of severe caries in adults have not found a clear pathogenic mechanism for it. Knowledge of the oral microbiota is important for the treatment of dental caries. We discovered that the interaction between V. parvula and S. mutans augments the severity of dental caries in vivo , suggesting V. parvula may act as a synergistic pathobiont exacerbating biofilm virulence of S. mutans in ASC. Our findings may improve the understanding of ASC pathogenesis and are likely to provide a basis for planning appropriate therapeutic strategies., Competing Interests: The authors declare no conflict of interest.

Background: Endometriosis is a common cause of female reproductive problems, and vitamin intake may affect its incidence. Therefore, we further explored the association between multivitamin intake and endometriosis in a large population-based study., Methods: This study included 3351 participants from the National Health and Nutrition Examination Survey (NHANES) 1999-2006. The dietary intake of eight vitamins was calculated as the average of two 24-h recall interviews, and information on endometriosis was obtained through questionnaires that included gynecological history. Multiple logistic regression analysis was used to explore the relationship between multivitamin intake and endometriosis. Smoothed curve fitting analysis was employed to assess the dose-response relationship between vitamins and endometriosis. Finally, subgroup analysis and interaction tests were conducted to determine the association of covariates between vitamins and endometriosis., Results: In this large-scale cross-sectional study, multiple logistic regression analysis showed that the intake of vitamins A, B1, B2, B6, C and folate was negatively associated with the occurrence of endometriosis. The odds ratios associated with a per-SD increase were 0.836 (95%CI: 0.702, 0.997), 0.817 (95%CI: 0.702, 0.951), 0.860 (95%CI: 0.746, 0.991), 0.784 (95%CI: 0.669, 0.919), 0.845 (95%CI: 0.718, 0.994), and 0.772 (95%CI: 0.660, 0.903), respectively. Smoothed curve fitting analysis revealed that the intake of vitamins A, B1, B2, B6, C, and folate was negatively associated with the risk of endometriosis (P < 0.05). Vitamin E showed a saturating effect, with an optimal cutoff point at 13.18. Below this cutoff, the intake of vitamin E was negatively correlated with the risk of endometriosis (OR = 0.947, 95% CI: 0.906, 0.989), whereas above the cutoff, there was no significant correlation between vitamin E intake and the risk of endometriosis (OR = 1.001, 95% CI: 0.997, 1.005)., Conclusions: The results of this study indicate a significant linear negative correlation between the intake of vitamins A, B1, B2, B6, C, and folate, and the risk of endometriosis, and reveal a threshold effect for vitamin E intake on the risk of endometriosis. These findings could inform clinical dietary interventions and may support the development of preventive strategies for endometriosis, potentially aiding in its reduction., (© 2024. The Author(s).)

Controllable assembly of DNA nanostructure provides a powerful way for quantitative analysis of various targets including nucleic acid molecules. In this study, we have designed detachable DNA nanostructures at electrochemical sensing interface and constructed a ligation chain reaction (LCR) strategy for amplified detection of miRNA. A three-dimensional DNA triangular prism nanostructure is fabricated to provide suitable molecule recognition environment, which can be further regenerated for additional tests via convenient pH adjustment. Target triggered LCR is highly efficient and specific towards target miRNA. Under optimal experimental conditions, this approach enables ultrasensitive exploration in a wide linear range with a single-base resolution. Moreover, it shows excellent performances for the analysis of cell samples and clinical serum samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Alcohol use in metabolic dysfunction-associated steatohepatitis (MASH) is associated with an increased risk of fibrosis and liver-related death. Here, we aimed to identify a mechanism through which repeated alcohol binges exacerbate liver injury in a high fat-cholesterol-sugar diet (MASH diet)-induced model of MASH., Design: C57BL/6 mice received either chow or the MASH diet for 3 months with or without weekly alcohol binges. Neutrophil infiltration, neutrophil extracellular traps (NETs) and fibrosis were evaluated., Results: We found that alcohol binges in MASH increase liver injury and fibrosis. Liver transcriptomic profiling revealed differential expression of genes involved in extracellular matrix reorganisation, neutrophil activation and inflammation compared with alcohol or the MASH diet alone. Alcohol binges specifically increased NET formation in MASH livers in mice, and NETs were also increased in human livers with MASH plus alcohol use. We discovered that cell-free NETs are sensed via Nod-like receptor protein 3 (NLRP3). Furthermore, we show that cell-free NETs in vitro induce a profibrotic phenotype in hepatic stellate cells (HSCs) and proinflammatory monocytes. In vivo, neutrophil depletion using anti-Ly6G antibody or NET disruption with deoxyribonuclease treatment abrogated monocyte and HSC activation and ameliorated liver damage and fibrosis. In vivo, inhibition of NLRP3 using MCC950 or NLRP3 deficiency attenuated NET formation, liver injury and fibrosis in MASH plus alcohol diet-fed mice (graphical abstract)., Conclusion: Alcohol binges promote liver fibrosis via NET-induced activation of HSCs and monocytes in MASH. Our study highlights the potential of inhibition of NETs and/or NLRP3, as novel therapeutic strategies to combat the profibrotic effects of alcohol in MASH., Competing Interests: Competing interests: GS reports being a paid consult for Durect Corporation, Cyta Therapeutics, Generon, Terra Firma, Quest Diagnostics, Pandion Therapeutics, Surrozen, Merck, Novartis, Pfizer, Lab Corp, Intercept and Takeda. She has stock options in Glympse Bio, Satellite Bio and Ventyx., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Noninvasive preimplantation genetic testing (ni-PGT) is conducted by obtaining genetic information from embryos through the analysis of free DNA released by embryos in spent embryo culture medium or blastocoel fluid. Compared to conventional preimplantation genetic testing relying on trophectoderm biopsy, ni-PGT is characterized by its noninvasiveness. It has demonstrated early advancements in the detection of embryonic chromosomal aneuploidies and the diagnosis of monogenic diseases, showcasing considerable potential for clinical application. However, there are substantial controversies in the literature concerning the reliability of ni-PGT, the source of cell-free DNA, and maternal contamination. This paper elaborates on the principles, research advancements, effectiveness, and limitations of ni-PGT to provide a basis for clinical applications., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Nucleocytoplasmic large DNA viruses (NCLDVs; also called giant viruses), constituting the phylum Nucleocytoviricota, can infect a wide range of eukaryotes and exchange genetic material with not only their hosts but also prokaryotes and phages. A few NCLDVs were reported to encode genes conferring resistance to beta‑lactam, trimethoprim, or pyrimethamine, suggesting that they are potential vehicles for the transmission of antibiotic resistance genes (ARGs) in the biome. However, the incidence of ARGs across the phylum Nucleocytoviricota, their evolutionary characteristics, their dissemination potential, and their association with virulence factors remain unexplored. Here, we systematically investigated ARGs of 1416 NCLDV genomes including those of almost all currently available cultured isolates and high-quality metagenome-assembled genomes from diverse habitats across the globe. We reveal that 39.5% of them carry ARGs, which is approximately 37 times higher than that for phage genomes. A total of 12 ARG types are encoded by NCLDVs. Phylogenies of the three most abundant NCLDV-encoded ARGs hint that NCLDVs acquire ARGs from not only eukaryotes but also prokaryotes and phages. Two NCLDV-encoded trimethoprim resistance genes are demonstrated to confer trimethoprim resistance in Escherichia coli. The presence of ARGs in NCLDV genomes is significantly correlated with mobile genetic elements and virulence factors., (© 2024. The Author(s).)

The pathological role of interferon signaling is emerging in neuroinflammatory disorders, yet, the specific role of Interferon Regulatory Factor 3 (IRF3) in neuroinflammation remains poorly understood. Here, we show that global IRF3 deficiency delays TLR4-mediated signaling in microglia and attenuates the hallmark features of LPS-induced inflammation such as cytokine release, microglial reactivity, astrocyte activation, myeloid cell infiltration, and inflammasome activation. Moreover, expression of a constitutively active IRF3 (S388D/S390D: IRF3-2D) in microglia induces a transcriptional program reminiscent of the Activated Response Microglia and the expression of genes associated with Alzheimer's disease, notably apolipoprotein-e. Using bulk-RNAseq of IRF3-2D brain myeloid cells, we identified Z-DNA binding protein-1 (ZBP1) as a target of IRF3 that is relevant across various neuroinflammatory disorders. Lastly, we show IRF3 phosphorylation and IRF3-dependent ZBP1 induction in response to Aβ in primary microglia cultures. Together, our results identify IRF3 as an important regulator of LPS and Aβ -mediated neuroinflammatory responses and highlight IRF3 as a central regulator of disease-specific gene activation in different neuroinflammatory diseases., (© 2024. The Author(s).)

Background: Depression is increasingly recognized as a factor affecting infertility and the causal relationship between them remains controversial. The aim of this study was to explore the relationship between depression and infertility using Mendelian randomization (MR) and cross-sectional study, and to explore the potential mediating role of obesity., Methods: The cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) 2013-2018. Multivariable-adjusted logistic regression was used to assess the association between depression and infertility risk, and mediation analysis was to examine the mediating effect of obesity. Then, we performed MR analyses to investigate the causal effect of depression on infertility. Instrumental variables for depression were obtained from a genome-wide association meta-analysis (135,458 cases and 344,901 controls), and summary level data for infertility were obtained from the FinnGen database (6,481 cases and 68,969 controls)., Results: In the cross-sectional study, a total of 2,915 participants between the ages of 18 and 45 were included, of whom 389 were infertile. We observed that depression was strongly associated with an increased risk of infertility (OR=1.66, 95%CI: 1.19, 2.33), and this relationship remained significant in mild (OR=1.45, 95% CI: 1.09, 1.93), moderate (OR=1.89, 95% CI: 1.26, 2.84), and severe depression (OR=1.74, 95% CI: 1.02, 2.99). Mediation analysis showed that obesity mediated 7.15% and 15.91% of the relationship between depression and infertility for body mass index and waist circumference. Furthermore, depression significantly increased the risk of infertility in both the general obesity (OR=1.81, 95%CI=1.20-2.73, P<0.01) and abdominal obesity populations (OR=1.57, 95%CI=1.08-2.27, P=0.02) populations. In addition, the MR analysis also revealed a significant positive causal relationship between genetically predicted depression and infertility (OR=1.32, 95% CI: 1.03, 1.70)., Conclusion: Depression is associated with an increased risk of infertility, with obesity playing a significant mediating role. This study underscores the importance of incorporating mental health and weight management in infertility treatment strategies., 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, Zhuang, Cao and Yang.)

Severe alcohol-associated hepatitis (AH) is a life-threatening form of alcohol-associated liver disease. Liver neutrophil infiltration is a hallmark of AH, yet the effects of alcohol on neutrophil functions remain elusive. Identifying therapeutic targets to reduce neutrophil-mediated liver damage is essential. Bruton's tyrosine kinase (BTK) plays an important role in neutrophil development and function; however, the role of BTK in AH is unknown. Using RNA sequencing of circulating neutrophils, we found an increase in Btk expression ( P = 0.05) and phosphorylated BTK (pBTK) in patients with AH compared with healthy controls. In vitro, physiologically relevant doses of alcohol resulted in a rapid, TLR4-mediated induction of pBTK in neutrophils. In a preclinical model of AH, administration of a small-molecule BTK inhibitor (evobrutinib) or myeloid-specific Btk knockout decreased proinflammatory cytokines and attenuated neutrophil-mediated liver damage. We found that pBTK was essential for alcohol-induced bone marrow granulopoiesis and liver neutrophil infiltration. In vivo, BTK inhibition or myeloid-specific Btk knockout reduced granulopoiesis, circulating neutrophils, liver neutrophil infiltration, and liver damage in a mouse model of AH. Mechanistically, using liquid chromatography-tandem mass spectrometry, we identified CD84 as a kinase target of BTK, which is involved in granulopoiesis. In vitro, CD84 promoted alcohol-induced interleukin-1β and tumor necrosis factor-α in primary human neutrophils, which was inhibited by CD84-blocking antibody treatment. Our findings define the role of BTK and CD84 in regulating neutrophil inflammation and granulopoiesis, with potential therapeutic implications in AH.

Objectives: To develop and validate a radiomics nomogram combining radiomics features and clinical factors for preoperative evaluation of Ki-67 expression status and prognostic prediction in clear cell renal cell carcinoma (ccRCC)., Methods: Two medical centers of 185 ccRCC patients were included, and each of them formed a training group (n = 130) and a validation group (n = 55). The independent predictor of Ki-67 expression status was identified by univariate and multivariate regression, and radiomics features were extracted from the preoperative CT images. The maximum relevance minimum redundancy (mRMR) and the least absolute shrinkage and selection operator algorithm (LASSO) were used to identify the radiomics features that were most relevant for high Ki-67 expression. Subsequently, clinical model, radiomics signature (RS), and radiomics nomogram were established. The performance for prediction of Ki-67 expression status was validated using area under curve (AUC), calibration curve, Delong test, decision curve analysis (DCA). Prognostic prediction was assessed by survival curve and concordance index (C-index)., Results: Tumour size was the only independent predictor of Ki-67 expression status. Five radiomics features were finally identified to construct the RS (AUC: training group, 0.821; validation group, 0.799). The radiomics nomogram achieved a higher AUC (training group, 0.841; validation group, 0.814) and clinical net benefit. Besides, the radiomics nomogram provided a highest C-index (training group, 0.841; validation group, 0.820) in predicting prognosis for ccRCC patients., Conclusions: The radiomics nomogram can accurately predict the Ki-67 expression status and exhibit a great capacity for prognostic prediction in patients with ccRCC and may provide value for tailoring personalized treatment strategies and facilitating comprehensive clinical monitoring for ccRCC patients., (© 2024. The Author(s).)

Helicobacter pylori infection is characterized as progressive processes of bacterial persistence and chronic gastritis with features of infiltration of mononuclear cells more than granulocytes in gastric mucosa. Angiopoietin-like 4 (ANGPTL4) is considered a double-edged sword in inflammation-associated diseases, but its function and clinical relevance in H. pylori -associated pathology are unknown. Here, we demonstrate both pro-colonization and pro-inflammation roles of ANGPTL4 in H. pylori infection. Increased ANGPTL4 in the infected gastric mucosa was produced from gastric epithelial cells (GECs) synergistically induced by H. pylori and IL-17A in a cagA -dependent manner. Human gastric ANGPTL4 correlated with H. pylori colonization and the severity of gastritis, and mouse ANGPTL4 from non-bone marrow-derived cells promoted bacteria colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Il17a -/- , Angptl4 -/- , and Il17a -/- Angptl4 -/- mice. Mechanistically, ANGPTL4 bound to integrin αV (ITGAV) on GECs to suppress CXCL1 production by inhibiting ERK, leading to decreased gastric influx of neutrophils, thereby promoting H. pylori colonization; ANGPTL4 also bound to ITGAV on monocytes to promote CCL5 production by activating PI3K-AKT-NF-κB, resulting in increased gastric influx of regulatory CD4 + T cells (T regs ) via CCL5-CCR4-dependent migration. In turn, ANGPTL4 induced T reg proliferation by binding to ITGAV to activate PI3K-AKT-NF-κB, promoting H. pylori -associated gastritis. Overall, we propose a model in which ANGPTL4 collectively ensures H. pylori persistence and promotes gastritis. Efforts to inhibit ANGPTL4-associated pathway may prove valuable strategies in treating H. pylori infection., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Rui Xie et al.)

Purpose: Fatigue was a common symptom of non-alcoholic fatty liver disease (NAFLD), which seriously affected patients' quality of life. The aim of this study was to detect fatigue rate and to evaluate factors associated with fatigue in NAFLD patients., Patients and Methods: A cross-sectional study was carried out from the Huadong Sanatorium between April 2022 and May 2023, and 133 NAFLD patients were included in this study. They completed Fatigue Severity Scale to assess fatigue, the Hospital Anxiety and Depression Scale to estimate psychological status, and the Pittsburgh Sleep Quality Index for sleep quality. Data were analyzed by independent samples t -tests, χ2 tests and logistic regression models., Results: We found that 51.1% of NAFLD patients had fatigue. Exercise, anxiety, depression, subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disorders, daytime dysfunction and overall sleep quality were related to fatigue among NAFLD patients. Moreover, logistic regression models indicated anxiety, habitual sleep efficiency and sleep disorders as important predictors of fatigue., Conclusion: This was the first time to explore demographic, clinical, psychological and sleeping correlated factors for fatigue in Chinese NAFLD patients. Our study showed that more than half of NAFLD patients had fatigue, and anxiety, habitual sleep efficiency and sleep disorders were significantly associated with fatigue in NAFLD. The findings indicated that it was very necessary to pay more attention to fatigue of NAFLD patients, especially those with negative emotions and poor sleep quality by favorable intervention to relieve fatigue symptoms, so as to improve quality of life., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Du et al.)

The central nervous system (CNS) is a complicated neural network. The origin and evolution of functional neurons and glia cells remain unclear, as do the cellular alterations that occur during the course of cerebral disease rehabilitation. Lineage tracing is a valuable method for tracing specific cells and achieving a better understanding of the CNS. Recently, various technological breakthroughs have been made in lineage tracing, such as the application of various combinations of fluorescent reporters and advances in barcode technology. The development of lineage tracing has given us a deeper understanding of the normal physiology of the CNS, especially the pathological processes. In this review, we summarize these advances of lineage tracing and their applications in CNS. We focus on the use of lineage tracing techniques to elucidate the process CNS development and especially the mechanism of injury repair. Deep understanding of the central nervous system will help us to use existing technologies to diagnose and treat diseases., (© 2023. The Author(s).)

Introduction: Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder that influences structures of ectodermal origin, such as teeth, hair, and sweat glands. Compared with autosomal recessive and dominant modes of inheritance, the X-linked HED (XLHED) characterized by Hypodontia/Oligodontia teeth, Absent/sparse hair, Anhidrosis/hypohidrosis, and characteristic facial features, is the most frequent and its primary cause is the mutation of ectodysplasin A (EDA) gene. This research aimed to expound the clinical and molecular features of a Chinese male with XLHED and to summarize and compare several previous findings., Methods: Genomic DNA was obtained from the peripheral blood of the proband and his family members, then Sanger sequencing was used to perform a mutational analysis of EDA . Real-time quantitative PCR and Western blotting were used to detect EDA expression. The transcriptional activity of NF-κB was detected using a luciferase assay., Results: The probandwith XLHED was identified a novel EDA mutation, c.1119G>C(p.M373I), that affected the molecular analysis of transmembrane protein exon8 mutations, inherited from the mother. He showed a severe multiple-tooth loss, with over 20 permanent teeth missing and sparse hair and eyebrows, dry, thin, and itching skin. Furthermore, his sweating function was abnormal to a certain extent., Discussion: The functional study showed that this novel mutant led to a significant decrease in the EDA expression level and transcriptional activity of NF-κB. Our findings extend the range of EDA mutations in XLHED patients, which provides the basis and idea for further exploring the pathogenesis of XLHED., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Zhuang et al.)

Considering that heavy-metal contamination of seawater is getting worse, building a quick, accurate and portable device for detecting trace zinc in seawater in real time would be very beneficial. In this work, a microfluidic system was developed that includes a planar disc electrode, a micro-cavity for detection, an electrochemical workstation, a computer, a container for waste liquid reprocessing, an external pipeline and other components as well as a graphene/cerium oxide/nano-cerium oxide/Nafion composite membrane was used to modify the planar disc electrode (GR/CeO 2 /Nafion/Au) to investigate the electrochemical behaviour of Zn(II) using cyclic voltammetry, square-wave voltammetry and orthogonal test methods. Under optimal experimental conditions, the peak reaction current of Zn(II) showed a good linear relationship with the concentration of Zn(II) in the range of 1-900 μg/L with a correlation coefficient of 0.998, and the detection limit of the method was 0.87 μg/L. In addition, the microfluidic system had good stability, reproducibility and anti-interference. The system was used for determining zinc ions in real seawater samples, and the results were very similar to those of inductively coupled plasma-emission spectrometry, demonstrating the practicality of the system for the detection of trace zinc.

Background: The senescence marker protein 30 (SMP30) is a calcium-binding protein whose expression decreases with age, and is closely associated with hepatocellular carcinoma (HCC) development. The primary goal of this study was to examine the mechanistic effect of SMP30 on HCC migration and invasion., Methods: Bioinformatic and immunohistochemical approaches were used to examine the expression of SMP30 in HCC tissues and its relationship to patient survival. We investigated the effects of SMP30 expression on HCC cell proliferation, migration, invasion, and cell cycle dynamics. cDNA microarray technology was used to determine the gene expression profile of SK-Hep-1 cells following recombinant SMP30 overexpression to identify genes downstream of SMP30 that regulate HCC cell migration and invasion. We identified SMP30 interacting proteins by affinity purification-mass spectrometry (AP-MS) and co-immunoprecipitation/western blotting (COIP-WB)., Results: SMP30 expression was lower in HCC tissues compared with normal liver tissues, and its expression positively correlated with overall survival in HCC patients. Additionally, SMP30 overexpression effectively blocked the migratory and invasive properties of SK-Hep-1 cells, but did not affect either proliferation rates or cell cycle. cDNA microarray results confirmed that many of the differentially expressed genes identified are involved in the process of epithelial-mesenchymal transition (EMT). AP-MS and COIP-WB experiments confirmed that Rho-associated protein kinase 1 (ROCK1) interacts with SMP30 in SK-Hep-1 cells, and ROCK1 is known to intimately regulate the EMT process., Conclusion: SMP30 inhibits HCC metastasis by influencing the expression of EMT-related proteins after interacting with ROCK1., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

T cell receptor (TCR) signaling regulates important developmental transitions, partly through induction of the E protein antagonist, Id3. Although normal γδ T cell development depends on Id3, Id3 deficiency produces different phenotypes in distinct γδ T cell subsets. Here, we show that Id3 deficiency impairs development of the Vγ3 + subset, while markedly enhancing development of NKγδT cells expressing the invariant Vγ1Vδ6.3 TCR. These effects result from Id3 regulating both the generation of the Vγ1Vδ6.3 TCR and its capacity to support development. Indeed, the Trav15 segment, which encodes the Vδ6.3 TCR subunit, is directly bound by E proteins that control its expression. Once expressed, the Vγ1Vδ6.3 TCR specifies the innate-like NKγδT cell fate, even in progenitors beyond the normally permissive perinatal window, and this is enhanced by Id3-deficiency. These data indicate that the paradoxical behavior of NKγδT cells in Id3-deficient mice is determined by its stereotypic Vγ1Vδ6.3 TCR complex., (© 2024. The Author(s).)

Aim: Timbre in piano performance plays a critical role in enhancing musical expression. However, timbre control in current piano performance education relies mostly on descriptive characterization, which involves large variations of interpretation. The current study aimed to mitigate the limitations by identifying quantitative indices with adequate precision to characterize piano timbre., Methods: A total of 24 sounds of G6 were recorded from 3 grand pianos, by 2 performers, and with 4 repetitions. The sounds were processed and analyzed with audio software for the frequencies and volumes of harmonic series in the spectrum curves. Ten quantitative timbre indices were calculated. Precision validation with statistical gage R&R analysis was conducted to gage the repeatability (between repetitions) and reproducibility (between performers) of the indices. The resultant percentage study variation (%SV) of an index must be ≤10% to be considered acceptable for characterizing piano timbre with enough precision., Results: Out of the 10 indices, 4 indices had acceptable precision in characterizing piano timbre with %SV ≤10%, including the square sum of relative volume (4.40%), the frequency-weighted arithmetic mean of relative volume (4.29%), the sum of relative volume (3.11%), and the frequency-weighted sum of relative volume (2.09%). The novel indices identified in the current research will provide valuable tools to advance the measurement and communication of timbre and advance music performance education., 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 Zhuang and Yang.)

The facultative intracellular bacterium Listeria (L.) monocytogenes may cause severe diseases in humans and animals. The control of listeriosis/L. monocytogenes requires the concerted action of cells of the innate and adaptive immune systems. In this regard, cell-intrinsic immunity of infected cells, activated by the immune responses, is crucial for the control and elimination intracellular L. monocytogenes. Both the immune response against L. monocytogenes and cell intrinsic pathogen control are critically regulated by post-translational modifications exerted by the host ubiquitin system and ubiquitin-like modifiers (Ubls). In this review, we discuss our current understanding of the role of the ubiquitin system and Ubls in listeriosis, as well as future directions of research., 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 GmbH.. All rights reserved.)

Molecules-the elementary units of substances-are commonly considered the units of processing in olfactory perception, giving rise to undifferentiated odour objects invariant to environmental variations. By selectively perturbing the processing of chemical substructures with adaptation ('the psychologist's microelectrode') in a series of psychophysical and neuroimaging experiments (458 participants), we show that two perceptually distinct odorants sharing part of their structural features become significantly less discernible following adaptation to a third odorant containing their non-shared structural features, in manners independent of olfactory intensity, valence, quality or general olfactory adaptation. The effect is accompanied by reorganizations of ensemble activity patterns in the posterior piriform cortex that parallel subjective odour quality changes, in addition to substructure-based neural adaptations in the anterior piriform cortex and amygdala. Central representations of odour quality and the perceptual outcome thus embed submolecular structural information and are malleable by recent olfactory encounters., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The purpose of this research is to summarize the academic expertise of Professor Lu Zhizheng in the treatment of Chronic Atrophic Gastritis, and to explain his clinical reasoning and common prescriptions in the treatment of CAG., Methods: Professor Lu's outpatient cases of CAG from January 2008 to December 2021 were selected, and the PageRank algorithm was applied on the FangNet platform to analyze the usage frequencies of herbs, their four natures and five flavors according to Traditional Chinese Medicine, core herbs, and herb clustering patterns, with the goal of summarizing the distinguishing features of Professor Lu's academic and clinical approach to CAG. A total of 170 patients from 252 consultations were included in this study. The prescriptions involved a total of 239 herbs, which occurred a cumulative 4339 times. The herb natures were mainly warm, neutral, and slightly cold, and the herb flavors were predominantly sweet, bitter, and pungent. The channel tropism of the selected herbs primarily targeted the spleen, stomach, and lung meridians. Herb rank analysis showed that 34 herbs, including Gancao, Taizishen, Banxia, Huanglian, Shengjiang, Baizhu, Yiyiren, Maiya, Cangzhu, and Kuxingren, were the driver herbs used by Professor Lu for the treatment of CAG., Results: Herb-herb co-occurrence/exclusivity analysis revealed 10 sets of frequently used herb pairs; herb cluster analysis yielded 10 herb clusters. These results reflected the emphasis Professor Lu placed on protecting Qi and Yin while clearing damp-heat. Professor Lu Zhizheng utilized dialectics reinforced with flexible thinking in the treatment of CAG, and emphasized that identifying the pathogenesis and addressing the syndrome should be prioritized., Conclusions: The characteristic treatment strategy aimed to replenish Qi and nourish Yin, clear away damp-heat, and treat CAG patients comprehensively under the guidance of established principles.

The SPiForest, a new isolation-based approach to outlier detection, constructs iTrees on the space containing all attributes by probability density-based inverse sampling. Most existing iForest (iF)-based approaches can precisely and quickly detect outliers scattering around one or more normal clusters. However, the performance of these methods seriously decreases when facing outliers whose nature "few and different" disappears in subspace (e.g., anomalies surrounded by normal samples). To solve this problem, SPiForest is proposed, which is different from existing approaches. First, SPiForest uses the principal component analysis (PCA) to find principal components and estimate each component's probability density function (pdf). Second, SPiForest utilizes the inv-pdf, which is inversely proportional to the pdf estimated from the given dataset, to generate support points in the space containing all attributes. Third, the hyperplane decided by these support points is used to isolate the outliers in the space. Next, these steps are repeated to build an iTree. Finally, many iTrees construct a forest for outlier detection. SPiForest provides two benefits: 1) it isolates outliers with fewer hyperplanes, which significantly improves the accuracy and 2) it effectively detects the outliers whose nature "few and different" disappears in subspace. Comparative analyses and experiments show that the SPiForest achieves a significant improvement in terms of area under the curve (AUC) when compared with the state-of-the-art methods. Specifically, our method improves by at most 17.7% on AUC when compared to iF-based algorithms.

Binge drinking in obese patients positively correlates with accelerated liver damage and liver-related death. However, the underlying mechanism and the effect of alcohol use on the progression of metabolic-dysfunction-associated steatotic liver disease (MASLD) remain unexplored. Here, we show that short-term feeding of a metabolic-dysfunction-associated steatohepatitis (MASH) diet plus daily acute alcohol binges for three days induce liver injury and activation of the NLRP3 inflammasome. We identify that a MASH diet plus acute alcohol binges promote liver inflammation via increased infiltration of monocyte-derived macrophages, neutrophil recruitment, and NET release in the liver. Our results suggest that both monocyte-derived macrophages and neutrophils are activated via NLRP3, while the administration of MCC950, an NLRP3 inhibitor, dampens these effects.In this study, we reveal important intercellular communication between hepatocytes and neutrophils. We discover that the MASH diet plus alcohol induces IL-1β via NLRP3 activation and that IL-1β acts on hepatocytes and promotes the production of CXCL1 and LCN2. In turn, the increase in these neutrophils recruits chemokines and causes further infiltration and activation of neutrophils in the liver. In vivo administration of the NLRP3 inhibitor, MCC950, improves the early phase of MetALD by preventing liver damage, steatosis, inflammation, and immune cells recruitment.

Bryophyllum pinnatum (BP) is a medicinal plant used to treat many conditions when taken as a leaf juice, leaves in capsules, as an ethanolic extract, and as herbal tea. These preparations have been chemically analyzed except for decoctions derived from boiled green leaves. In preparation for a clinical trial to validate BP tea as a treatment for kidney stones, we used NMR and MS analyses to characterize the saturation kinetics of the release of metabolites. During boiling of the leaves, (a) the pH decreased to 4.8 within 14 min and then stabilized; (b) regarding organic acids, citric and malic acid were released with maximum release time (t max ) = 35 min; (c) for glycoflavonoids, quercetin 3-O-α-L-arabinopyranosyl-(1 → 2)-α-L-rhamnopyranoside (Q-3O-ArRh), myricetin 3-O-α-L-arabinopyranosyl-(1 → 2)-α-L-rhamnopyranoside (M-3O-ArRh), kappinatoside, myricitrin, and quercitrin were released with t max = 5-10 min; and (d) the total phenolic content (TPC) and the total antioxidant capacity (TAC) reached a t max at 55 min and 61 min, respectively. In summary, 24 g of leaves boiled in 250 mL of water for 61 min ensures a maximal release of key water-soluble metabolites, including organic acids and flavonoids. These metabolites are beneficial for treating kidney stones because they target oxidative stress and inflammation and inhibit stone formation.

Objectives: The rapid dissemination of the mcr-1 gene via plasmid-mediated transfer has raised concerns regarding the efficacy of colistin as a last-resort treatment for multidrug-resistant Gram-negative bacterial infections. Current mcr-1 gene detection methods mainly focus on cultured bacteria, which is a complex and time-consuming process requiring skilled personnel, making it unsuitable for field analysis., Methods: A rapid detection technique combining recombinase polymerase amplification with a lateral flow dipstick targeting uncultured clinical samples was developed., Results: This new method targeting the mcr-1 gene region (23 232-23 642 bp, no. KP347127.1) achieved a low detection limit of 10 copies/μL. The whole process was carried out with high specificity and was completed within 20 min. The evaluation assay was conducted using 45 human faecal samples; 16 strains yielded a 98% accuracy, closely matching antimicrobial susceptibility outcomes., Conclusions: The novel method integrates nucleic acid extraction, isothermal amplification, and a test assay, suggesting the potential for timely colistin resistance surveillance in frontline disease control and healthcare settings, supporting future prevention and clinical standardization efforts., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Loose deposit particles in drinking water distribution system commonly exist as mixtures of metal oxides, organic materials, bacteria, and extracellular secretions. In addition to their turbidity-causing effects, the hazards of such particles in drinking water are rarely recognized. In this study, we found that trace per- and polyfluoroalkyl substances (PFASs) could dramatically promote the formation of disinfection byproducts (DBPs) by triggering the release of particle-bound organic matter. Carboxylic PFASs have a greater ability to increase chloroacetic acid than sulfonic PFASs, and PFASs with longer chains have a greater ability to increase trichloromethane release than shorter-chain PFASs. Characterization by organic carbon and organic nitrogen detectors and Fourier transform ion cyclotron resonance mass spectrometry revealed that the released organic matter was mainly composed of proteins, carbohydrates, lignin, and condensed aromatic structures, which are the main precursors for the formation of DBPs, particularly highly toxic aromatic DBPs. After the release of organic matter, the particles exhibit a decrease in surface functional groups, an increase in surface roughness, and a decrease in particle size. The findings provide new insights into the risks of loose deposits and PFASs in drinking water, not only on PFASs per se but also on its effect of increasing toxic DBPs., 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 Ltd. All rights reserved.)

Ingenol diterpenoids continue to attract the attention for their extensive biological activity and novel structural features. To further explore this type of compound as anti-tumor agent, 13-oxyingenol dodecanoate (13-OD) was prepared by a standard chemical transformation from an Euphorbia kansui extract, and 29 derivatives were synthesized through parent 13-OD. Their inhibition activities against different types of cancer were screened and some derivatives showed superior anti-non-small cell lung cancer (NSCLC) cells cytotoxic potencies than oxaliplatin. In addition, TMBIM6 was identified as a crucial cellular target of 13-OD using ABPP target angling technique, and subsequently was verified by pull down, siRNA interference, BLI and CETSA assays. With modulating the function of TMBIM6 protein by 13-OD and its derivatives, Ca 2+ release function was affected, causing mitochondrial Ca 2+ overload, depolarisation of membrane potential. Remarkably, 13-OD, B6, A2, and A10-2 induced mitophagy and ferroptosis. In summary, our results reveal that 13-OD, B6, A2, and A10-2 holds great potential in developing anti-tumor agents for targeting TMBIM6., 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 Masson SAS. All rights reserved.)

In recent years, the visible light positioning field has experienced remarkable advancements. However, smartphones find it difficult to identify light-emitting diode (LED) and extract each LED's light signal intensity due to the low-frequency and uneven sampling of built-in ambient light sensors (ALS, which is a photodiode that measures ambient light in lux units). Thus, traditional visible light positioning systems cannot be directly applied to smartphones. In this Letter, we propose a single-light visible light positioning system using a non-modulated LED as an emitter, the built-in ALS as the receiver, and the inertial measurement unit of the smartphone to assist in measuring the smartphone's attitude. It only requires the user to turn the smartphone by a few angles in a stationary position to estimate its current three-dimensional (3D) spatial position. This method does not require modification of the existing lighting system and consumes less power than the camera-based visible light positioning (VLP) systems. We have built an experimental site measuring 5 m × 5 m × 2.2 m to evaluate the performance of the positioning system, and the preliminary results show that the proposed system achieves sub-meter-level positioning accuracy.