To identify the various profiles of social isolation among 18-59-year-old patients with cancer in Western China and examine their demographic, clinical, and cultural predictors. This cross-sectional s Show more
To identify the various profiles of social isolation among 18-59-year-old patients with cancer in Western China and examine their demographic, clinical, and cultural predictors. This cross-sectional study included 300 patients from a tertiary hospital who completed standardized assessments of social isolation (Social Avoidance Scale, UCLA Loneliness Scale) and family functioning. Latent Profile Analysis (LPA) was used to identify the subgroups, and multinomial logistic regression was used to analyze predictors of the profiles. Three distinct latent profiles were identified: "avoidance-dominant" (52.3%), which was characterized by high levels of social avoidance (12.52 ± 1.38) and low loneliness (30.87 ± 6.89), "loneliness-dominant" (27.0%), which was characterized by high levels of loneliness (53.15 ± 6.24) and low social avoidance (2.07 ± 1.38), and "balanced" (20.7%), which was characterized by balanced scores on both the measures. Individuals with fatigue, employment status, personality traits, and family dynamics significantly predicted profile membership ( Social isolation was heterogeneous among young and middle-aged patients with cancer. Fatigue significantly predicted distinct patterns of social isolation. Furthermore, exploratory findings indicated a potential role of religious beliefs in the avoidance-dominant profile; however, replication with larger samples is required. Family dynamics may buffer the risk of isolation in patients prone to avoidance, whereas those dominated by loneliness may lack such safeguards. Health care providers can implement tailored interventions to mitigate social isolation based on these varying profiles. Show less
Childhood cancer can disrupt family functioning, increase caregiver psychological distress, and impair caregiver quality of life. While family resilience is crucial for adaptation, most research has f Show more
Childhood cancer can disrupt family functioning, increase caregiver psychological distress, and impair caregiver quality of life. While family resilience is crucial for adaptation, most research has focused on individual-level factors, neglecting heterogeneity and multilevel influences on family resilience. Guided by the Social Ecological Model (SEM), this cross-sectional observational study used latent profile analysis (LPA) to identify distinct profiles of family resilience among caregivers of children with cancer and to explore factors associated with these profiles. Between July 2022 and March 2024, 292 caregivers were recruited. Family resilience was measured using the Family Resilience Assessment Scale. LPA was employed to identify resilience profiles, and binary logistic regression was used to explore influencing factors. Two latent profiles were identified: the Low Resources-Low Positivity profile (86%) and the High Internal Resilience profile (14%). The Low Resource-Low Positivity profile demonstrated generally lower scores, especially in utilizing social and economic resources and maintaining a positive outlook. The High Internal Resilience profile showed higher scores across all family resilience dimensions, particularly in communication/problem solving, positive outlook, and meaning-making, while the use of external social and economic resources remained relatively lower. Univariate analysis showed significant differences between profiles in residence, number of siblings, caregiver education, individual resilience, social support, caregivers' physical and psychological well-being and child communication (caregiver-reported). Binary logistic regression identified having more than one child (OR = 3.184, 95% CI: 1.437 ~ 7.057, P = 0.004) and higher individual resilience (OR = 1.095, 95% CI: 1.028 ~ 1.165, P = 0.005) as significant predictors of High Internal Resilience profile. This study identified two distinct family resilience profiles among caregivers of children with cancer. Limited use of social and economic resources was common, while caregiver resilience and having multiple children predicted higher family resilience. Interventions should enhance caregiver coping capacity, support one-child families through peer and family programs, and improve access to social support, flexible employment, and affordable care to strengthen family resilience. Not applicable. Show less
Lifestyle improvement may help reverse prediabetes. Indicators such as Life's Essential 8 (LE8) and biological aging measures (phenotypic age, cardiovascular biological age) partially reflect metaboli Show more
Lifestyle improvement may help reverse prediabetes. Indicators such as Life's Essential 8 (LE8) and biological aging measures (phenotypic age, cardiovascular biological age) partially reflect metabolic status in prediabetes, but their predictive value for cardiovascular mortality and stroke in this population remains unclear. We analyzed data from 74,678 White participants with prediabetes in the UK Biobank, defined by either HbA1c (5.7-6.4%) or fasting glucose (6.1-6.9 mmol/L). Follow-up continued until October 10, 2023. Cox regression was used to examine associations between LE8, phenotypic age (PhenoAge), cardiovascular biological age (CBA), and outcomes of cardiovascular (CVD) mortality and stroke. Restricted cubic spline (RCS) models identified biological age risk thresholds. Mediation analysis assessed whether proteins such as CST3, EFEMP1, FES, IGFBP2, IGFBP6, LPA, PCSK9, and TIMP1 mediated these effects. Over a median follow-up of 13.4 years, 2263 participants died from CVD causes. Each 1-year increase in CBA or PhenoAge was associated with a ~ 10% higher risk of CVD mortality (CBA aHR = 1.10; PhenoAge aHR = 1.09; both P < 0.001), while each 1-point increase in LE8 score was linked to a 3% lower risk (HR = 0.97, P < 0.001). The risk biological ages for these two indicators were also identified: PhenoAge ≥ 58.52 years and CBA ≥ 62.42 years. Similar trends were observed for stroke. Mediation analysis revealed that CST3, TIMP1, IGFBP2, and IGFBP6 contributed to the biological pathways between aging/lifestyle and CVD outcomes. The combined LE8 and PhenoAge model showed the strongest predictive performance for CVD mortality (AUC = 0.716) and stroke (AUC = 0.638) over 15 years. LE8 combined with phenotypic age provides prognostic value for CVD outcomes in prediabetes. These findings highlight the potential of lifestyle modification and delayed biological aging in reversing prediabetes and underscore comorbidity-related proteins as promising therapeutic targets. Show less
This study aimed to explore the career adaptability status of cardiovascular specialist nurses (CSNs) through latent profile analysis (LPA), identify distinct subgroups and their demographic features, Show more
This study aimed to explore the career adaptability status of cardiovascular specialist nurses (CSNs) through latent profile analysis (LPA), identify distinct subgroups and their demographic features, and determine factors influencing different adaptability categories. CSNs play a vital role in treating and rehabilitating patients with cardiovascular conditions. However, the existing literature offers limited insights into the career adaptability of CSNs in China. A multicenter, cross-sectional survey involving 659 Chinese CSNs was conducted. LPA was utilized to classify career adaptability profiles based on responses to the Career Adaptation Abilities Scale Short Form (CAAS-SF). Influencing factors were assessed using the Conditions of Work Effectiveness Questionnaire-II (CWEQ-II) and the General Self-Efficacy Scale (GSES). Differences among identified profiles were analyzed through ANOVA, chi-square tests, and multinomial logistic regression to explore relevant socio-demographic characteristics and influencing variables. A four-profile model provided the best fit, identifying groups labeled as “high adaptability” (Class 4, These findings provide evidence to assist nursing administrators in developing training programs to enhance CSNs’ career adaptability. The variables identified as associated with profile membership may enable more tailored training strategies. Show less
Colorectal cancer (CRC) constitutes a significant public health burden in both China and the United States of America (USA), with low physical activity (LPA) identified as a key modifiable risk factor Show more
Colorectal cancer (CRC) constitutes a significant public health burden in both China and the United States of America (USA), with low physical activity (LPA) identified as a key modifiable risk factor. This study aimed to characterize temporal trends in CRC burden attributable to LPA in these 2 nations from 1990 to 2021. Using data from the 2021 global burden of disease database, age and sex-specific disparities in CRC burden attributed to LPA were evaluated in both countries. Trend analyses of age-standardized mortality rates and age-standardized disability-adjusted life year rates were performed using joinpoint regression. Decomposition analysis was applied to disentangle contributions from demographic aging, population growth, and epidemiological transitions. The age-period-cohort model was employed to quantify the independent effects of age, period, and birth cohort. Bayesian age-period-cohort modeling was utilized to project future CRC burden attributed to LPA through 2036. In 2021, LPA-attributable CRC mortality cases in China reached 16,698 (95% uncertainty interval: 10,065-24,626), exhibiting a 191.16% increase from 1990. The number of disability-adjusted life years attributed to LPA totaled 3,20,464 (95% uncertainty interval: 1,92,275-4,74,070), reflecting a 149.67% rise over the same period. Conversely, the USA reported more moderate increases of 18.26% in LPA-attributable CRC deaths and 20.28% in disability-adjusted life years. The age-period-cohort model revealed that the disease burden in both countries is shifting towards younger age groups. Further analysis of each state in the USA revealed that in 2021, the burden on low-income groups was heavier. The Bayesian age-period-cohort model predicts that the burden of CRC caused by LPA in the 2 countries will show a significant upward trend by 2036. As the burden of CRC caused by LPA becomes increasingly severe in China and the USA, there is an urgent need to raise public awareness about how physical activity can help prevent CRC and for policymakers to create targeted public health policies to lower this disease burden. Show less
Given the lack of evidence, we cannot definitively determine the relationship between attachment networks and problematic mobile phone use, hindering effective intervention strategies. Therefore, a th Show more
Given the lack of evidence, we cannot definitively determine the relationship between attachment networks and problematic mobile phone use, hindering effective intervention strategies. Therefore, a three-wave longitudinal study was designed to explore the heterogeneity of parent-child attachment networks using latent profile analysis (LPA) and random intercept latent transition analysis (RI-LTA). Participants included 2116 adolescents (ages 14-21; 53.8% girls). Results identified five stable parent-child attachment network profiles, each showing moderate but decreasing stability. Notably, adolescents who were grouped into an attachment network characterized by secure maternal attachment but insecure paternal attachment, similar to those in attachment networks with both insecure maternal and paternal attachment, scored higher levels of problematic mobile phone use than those who were grouped into attachment networks with both secure maternal and paternal attachment. Our findings fill empirical gaps and provide strong evidence supporting attachment-based interventions to reduce problematic mobile phone use. Show less
To explore the stratification and identification of adrenal lipid-poor adenomas (LPAs), adrenal cysts (ACs), and adrenal ganglioneuromas (AGNs) from each other using contrast-enhanced computed tomogra Show more
To explore the stratification and identification of adrenal lipid-poor adenomas (LPAs), adrenal cysts (ACs), and adrenal ganglioneuromas (AGNs) from each other using contrast-enhanced computed tomography (CT). Pathologically confirmed, 348 patients were categorized into Model 1 (260 LPAs, 34 ACs), Model 2 (260 LPAs, 54 AGNs), and Model 3 (34 ACs, 54 AGNs). Statistical analyses were performed on the differences in the degree of enhancement in the arterial/venous phase (DEap/DEvp) (in HU) and the corresponding graded variables for the arterial/venous phase (GVap/GVvp). Models were evaluated via receiver operating characteristic (ROC) curves, calibration curves, and the Hosmer‒Lemeshow (HL) test. The values of the area under the curve (AUC) for DEap, DEvp, GVap, and GVvp in Models 1-3 were 0.996, 1.000, 0.993, and 0.999; 0.980, 0.978, 0.961, and 0.975; and 0.734, 0.892, 0.725, and 0.883, respectively. The p values of the HL test were 0.984, 1.000, and 0.113, respectively. The DEvp interval values (in HU) for the LPAs, ACs, and AGNs were [4.9, 190.2] HU, [-3.7, 4.2] HU, and [-4.8, 41.8] HU, respectively. The GVap and GVvp ranges for the LPAs, ACs, and AGNs were [1, 6], [0, 2], and [0, 2] and [1, 6], [0, 1], and [0, 5], respectively. DEvp enhanced discrimination in Models 1 and 3, whereas DEap performed better in Model 2. Lesions with DEvp < 4.5 HU are likely represent non-enhancing pathology (e.g., cysts). When both GVap and GVvp are 0, when both GVap and GVvp are [2, 6], and when GVap is [3, 6] and GVvp is 6, LPA, AC, and AGN are excluded. Not applicable. Show less
Although previous studies have demonstrated that lipoprotein(a) (Lp[a]) and body mass index (BMI) are associated with atrial fibrillation (AF), their joint effect on AF remains poorly understood. Our Show more
Although previous studies have demonstrated that lipoprotein(a) (Lp[a]) and body mass index (BMI) are associated with atrial fibrillation (AF), their joint effect on AF remains poorly understood. Our primary objective was to examine the combined influence of BMI and Lp(a) on AF occurrence. The study included 8886 patients, among whom 205 were diagnosed with persistent AF. The joint association of BMI and Lp(a) with AF was evaluated. A mediation Mendelian randomization (MR) analysis was also performed. In comparison with the individuals with a higher Lp(a) level (≥30 mg/dl) and BMI equal to or above 24 kg/m2, those with a lower Lp(a) level and BMI had the lowest prevalence of AF (odds ratio, 0.96; 95% CI, 0.95-0.97; P <0.001), especially at the age of 50-69 years, and the lowest risk of stroke (hazard ratio [HR], 0.28; 95% CI, 0.12-0.68; P = 0.004), heart failure (HF; HR, 0.24; 95% CI, 0.08-0.66; P = 0.006), and major adverse cardiovascular events (MACE; HR, 0.35; 95% CI, 0.18-0.66; P = 0.001). Mediation MR analysis highlighted the coexposure effects of Lp(a) levels and BMI on AF and their independent influence on AF development. Lower BMI and Lp(a) levels were associated with a reduced prevalence of AF as well as a lower risk of stroke, HF, and MACE. Mediation analysis showed that neither BMI nor Lp(a) mediated the effect of the other, suggesting that their contributions to AF risk operate through independent pathways. Show less
Calcific aortic valve stenosis (CAVS) can lead to cardiac adverse outcomes; however, currently, no effective pharmacological interventions are available to prevent or delay disease progression. Emergi Show more
Calcific aortic valve stenosis (CAVS) can lead to cardiac adverse outcomes; however, currently, no effective pharmacological interventions are available to prevent or delay disease progression. Emerging evidence has identified significant associations between CAVS and key biomarkers, including Lp(a) (lipoprotein [a]), low-density lipoprotein cholesterol, and PCSK9 (proprotein convertase subtilisin/kexin type 9). However, robust evidence from randomized controlled trials is still lacking to substantiate these associations. The EPISODE (Effect of PCSK9 Inhibitors on Calcific Aortic Valve Stenosis) trial is a prospective, evaluator-blinded, randomized controlled trial designed to assess the therapeutic efficacy of PCSK9 inhibitors in patients with CAVS. A total of 160 patients with mild-to-moderate or asymptomatic severe CAVS will be randomly assigned to receive either statin monotherapy or a combination of statins and PCSK9 inhibitors. Participants will undergo follow-up assessments at 3-month intervals for 24 months, including transthoracic ultrasonic cardiogram, computed tomography, and quality-of-life evaluations using the EuroQol-5 Dimension-3 Level questionnaire. The primary end point is the annualized change in peak aortic jet velocity, whereas secondary end points encompass changes in aortic valve area, calcification score, incidence of heart valve surgery, and quality of life. Safety end points include all-cause mortality and cardiovascular events. The trial aims to evaluate the efficacy of PCSK9 inhibitors in modulating disease progression, reducing adverse cardiovascular events, and improving clinical outcomes in patients with CAVS. The anticipated findings are expected to provide critical insights for developing novel therapeutic strategies for early intervention in CAVS. URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04968509. Show less
Liqin Yu, Manyu Sun, Harrison Hao Yang+2 more · 2025 · Inquiry : a journal of medical care organization, provision and financing · SAGE Publications · added 2026-04-24
This study examines how distinct Information and Communication Technology (ICT) engagement profiles impact life satisfaction among older adults, aiming to inform digital inclusion policies for aging p Show more
This study examines how distinct Information and Communication Technology (ICT) engagement profiles impact life satisfaction among older adults, aiming to inform digital inclusion policies for aging populations. Cross-sectional data from 717 older adults in Central China were analyzed using latent profile analysis (LPA) to identify distinct ICT engagement profiles, followed by multinomial logistic regression to examine predictors of profile membership. LPA identified 3 profiles: Quiescent (39.75%), Compliant (42.96%), and Active (17.29%) Users. Active Users reported significantly higher life satisfaction ( Show less
To explore the optimal row-ratio in mechanized hybrid rice seed production, a field experiment was conducted in 2024 at Qionglai and Mianzhu using 'Tiantai A' × 'Taihui 808'. Three row-ratio treatment Show more
To explore the optimal row-ratio in mechanized hybrid rice seed production, a field experiment was conducted in 2024 at Qionglai and Mianzhu using 'Tiantai A' × 'Taihui 808'. Three row-ratio treatments (H1: 18:6, H2: 24:6, and H3: 30:6) were tested using agricultural unmanned aerial vehicles (AUAVs) for pollination assistance. The results showed that row-ratio had little effect on sterile line flowering dynamics. The index of flowers meeting (IFM) was 0.71-0.72 at Qionglai and 0.81-0.86 at Mianzhu, with 11 to 12 days of flowering duration. As the row-ratio increased, total pollen quantity in the panicle layer and grain filling rate (GFR) decreased, while grain infection rate (GIR) increased. The responses of grain blighted rate (GBR), grain empty rate (GER), and fertilization success rate (FSR) to row-ratio varied between sites. Pollen density and GFR followed the pattern of near region (NR) > central region (CR) > far region (FR). Within the panicle, pollen density was generally highest in the upper panicle layer (UPL), followed by the middle (MPL) and lower (LPL) layers, with partial exceptions observed in the H2 and H3 treatments at Mianzhu. The vertical distribution of GFR varied by site: at Qionglai, it was apical parts of panicle (APP) > median parts (MPP) > basal parts (BPP), whereas at Mianzhu the order was MPP > APP > BPP. With wider row-ratios, yield per unit area (YUA) and GFR declined (H1 > H2 > H3), while 1,000-grain weight increased or decreased and then increased. Under H1, yields reached 2,107.50 kg ha Show less
This study aims to investigate the effect of fermented onion on Liangshan black sheep's growth performance, health, meat quality, and rumen metabolite profiles. A total of 80 four-month-old female Lia Show more
This study aims to investigate the effect of fermented onion on Liangshan black sheep's growth performance, health, meat quality, and rumen metabolite profiles. A total of 80 four-month-old female Liangshan black sheep were randomly divided into four groups of five replicate pens (four sheep per pen). Sheep were fed a basal diet supplemented with 0 (control), 10, 20% or 30% fermented onion. Compared to that of the control group, dietary supplementation with 20% fermented onion improved final body weight, ADG and ADFI; enhanced GPT and GOT activities and increased IgA, IgG, IgM, C3, and C4 levels; increased the levels of IL-4, IL-10, TGF- Show less
The current trial sought to assess the impact of fermented chicory root waste (FCRW) dietary administration on growth, lipid metabolism, chemical composition, and intestinal barrier pathway in common Show more
The current trial sought to assess the impact of fermented chicory root waste (FCRW) dietary administration on growth, lipid metabolism, chemical composition, and intestinal barrier pathway in common carp ( Show less
Phenotypic transformation of Schwann cells (SCs) plays a crucial role in nerve regeneration. Previous studies have demonstrated that Runx2 significantly influences the biological behavior of SCs. None Show more
Phenotypic transformation of Schwann cells (SCs) plays a crucial role in nerve regeneration. Previous studies have demonstrated that Runx2 significantly influences the biological behavior of SCs. Nonetheless, the regulatory mechanisms that govern its epigenetic regulation are not yet fully elucidated. To facilitate this investigation, an adenovirus for the overexpression of Runx2 was constructed. Healthy adult Sprague-Dawley rats, weighing between 100 and 150 g and irrespective of sex, were randomly selected for the study. After establishing a model of sciatic nerve crush injury, tissue samples were harvested for histological analysis at both 4 and 7 days post-injury. In vitro, an Runx2-overexpressing SC line was established. Thorough analysis of transcriptome data, coupled with CUT&Tag sequencing of histones and transcription factors in SCs following Runx2 overexpression, was conducted. Additionally, single-cell RNA sequencing data from GSE216665 were incorporated to elucidate the mechanistic role of Runx2. The findings were subsequently validated through dual-luciferase assays. Following nerve crush injury, Runx2-positive SCs were identified at the injury site. Through comprehensive multiomics analysis, we discovered that lipid metabolism was disrupted in Runx2-overexpressing SCs. Further investigation established a detailed super-silencer landscape in these cells, revealing that elevated Runx2 levels form a super-silencer within the transcriptional regulatory region of the Lpl gene, thereby downregulating Lpl expression. Runx2 can modulate the biological behavior of SCs by forming super-silencers that interfere with the expression of lipid metabolism genes, such as Lpl, thereby altering the metabolic capacity of SCs. Show less
In peripheral tissues, an endothelial cell (EC) protein, GPIHBP1, captures lipoprotein lipase (LPL) from the interstitial spaces and transports it to the capillary lumen. LPL mediates the margination Show more
In peripheral tissues, an endothelial cell (EC) protein, GPIHBP1, captures lipoprotein lipase (LPL) from the interstitial spaces and transports it to the capillary lumen. LPL mediates the margination of triglyceride-rich (TG-rich) lipoproteins (TRLs) along capillaries, allowing the lipolytic processing of TRLs to proceed. TRL-derived fatty acids are used for fuel in oxidative tissues or stored in adipose tissue. In mice, GPIHBP1 is absent from capillary ECs of the brain (which uses glucose for fuel); consequently, LPL and TRL margination are absent in mouse brain capillaries. However, because fatty acids were reported to play signaling roles in the brain, we hypothesized that LPL-mediated TRL processing might occur within specialized vascular beds within the central nervous system. Here, we show that GPIHBP1 is expressed in capillary ECs of human and mouse choroid plexus (ChP) and that GPIHBP1 transports LPL (produced by adjacent ChP cells) to the capillary lumen. The LPL in ChP capillaries mediates both TRL margination and processing. Intracapillary LPL and TRL margination are absent in the ChP of Gpihbp1-/- mice. GPIHBP1 expression, intracapillary LPL, and TRL margination were also observed in the median eminence and subfornical organ, circumventricular organs implicated in the regulation of food intake. Show less
IgM-related AL amyloidosis is a rare and distinct clinical entity, often associated with underlying lymphoproliferative disorders such as Waldenström's macroglobulinemia (WM) or lymphoplasmacytic lymp Show more
IgM-related AL amyloidosis is a rare and distinct clinical entity, often associated with underlying lymphoproliferative disorders such as Waldenström's macroglobulinemia (WM) or lymphoplasmacytic lymphoma (LPL). Unlike non-IgM AL amyloidosis, it exhibits unique organ involvement patterns and generally poorer prognosis. We report a 66-year-old woman diagnosed with WM complicated by systemic IgM-κ AL amyloidosis. She received combination chemotherapy with rituximab and bendamustine (BR), resulting in a reduction of serum IgM levels. Despite the hematologic improvement, her liver dysfunction rapidly progressed, and she died of hepatic failure just two months after diagnosis. Pathological autopsy revealed massive IgM-κ amyloid deposition in the liver and multiple organs, with no residual lymphoma in the bone marrow or lymph nodes. These findings suggest that extensive hepatic amyloid infiltration was already present at diagnosis, and that organ response could not be achieved despite hematologic improvement. This case highlights the aggressive nature of IgM-related AL amyloidosis and the critical importance of early detection, especially when liver dysfunction is observed. Current therapies targeting the underlying clone may not be sufficient in cases with advanced organ involvement, emphasizing the urgent need for novel strategies to facilitate amyloid clearance and protect organ function. Show less
Ruyun Gao, Ning Lou, Sheng Yang+7 more · 2025 · Clinical cancer research : an official journal of the American Association for Cancer Research · added 2026-04-24
Third-generation EGFR tyrosine kinase inhibitors (TKI) have revolutionized the treatment of EGFR-mutant non-small cell lung cancer (NSCLC). However, acquired resistance remains a significant challenge Show more
Third-generation EGFR tyrosine kinase inhibitors (TKI) have revolutionized the treatment of EGFR-mutant non-small cell lung cancer (NSCLC). However, acquired resistance remains a significant challenge. This study investigates the metabolic mechanisms driving third-generation EGFR-TKI resistance. We conducted plasma metabolomics analysis on 216 longitudinal samples from 186 patients with NSCLC enrolled in the clinical trial of rezivertinib (NCT03386955). Additionally, multiomics profiling of rezivertinib-resistant cell lines, functional in vitro experiments, and single-cell RNA sequencing analyses of 215 patients with NSCLC were integrated to reveal underlying mechanisms. Nonresponder patients exhibited elevated glycerophospholipids and dysregulated lysophospholipid (LPL) metabolism. Unsupervised clustering identified two patient subgroups, with cluster 1 (characterized by high LPL levels) associated with poorer survival (P = 0.022). A metabolite-based predictive model achieved robust performance [AUC: 0.7762 (training) and 0.7485 (test)]. Longitudinal analyses demonstrated LPLs and lysophosphatidic acid (LPA) accumulation during the resistance process. Integrated multiomics analyses highlighted epithelial-mesenchymal transition and glycerophospholipid reprogramming in rezivertinib-resistant cells. Functional assays confirmed that LPA promoted cell migration and invasion and attenuated the efficacy of third-generation EGFR-TKI, whereas disruption of the LPA-LPA receptor signaling axis reversed LPA-mediated resistance. Single-cell RNA sequencing identified an LPA-secreting malignant subset (cluster c4), characterized by enhanced epithelial-mesenchymal transition activation and extensive microenvironmental cross-talk through Wnt, TGF-β, and extracellular matrix signals. Our study highlights the pivotal role of LPA-mediated signaling and metabolic reprogramming in third-generation EGFR-TKI resistance. Targeting LPA production or its downstream pathways may offer novel therapeutic strategies to overcome resistance. This study provides critical metabolic insights for managing EGFR-mutant NSCLC. Show less
Breast cancer (BRCA) ranks among the most frequently diagnosed malignancies worldwide. Immune infiltration plays a critical role in tumor progression and therapeutic response. However, the precise mec Show more
Breast cancer (BRCA) ranks among the most frequently diagnosed malignancies worldwide. Immune infiltration plays a critical role in tumor progression and therapeutic response. However, the precise mechanisms underlying immune infiltration in BRCA remain incompletely understood. Machine learning (support vector machine-recursive feature elimination and least absolute shrinkage and selection operator regression) and weighted gene co-expression network were utilized to screen hub genes. An immune infiltration assessment was carried out via TIMER and CIBERSORT. The prognostic and survival of risk model and immune infiltration-associated hub genes were analyzed through Kaplan-Meier survival analysis, Cox regression, and ROC curve evaluation. Cell functional assays and xenograft models in vivo were utilized to examine lipoprotein lipase (LPL) function. The impact of LPL on macrophage polarization was evaluated using THP-1-derived macrophages and immunohistochemistry analysis of immune infiltration (CD4, CD8, and F4/80) in vivo. 10 hub immune regulators were identified in BRCA, which were associated with lipid metabolism. Hub genes and a prognostic risk model exhibited high predictive accuracy for BRCA patient survival and prognosis. Overexpression of LPL inhibited BRCA cell proliferation, migration, and invasion while promoting M1-like macrophage polarization. In vivo, LPL overexpression significantly suppressed tumor growth and enhanced immune cell infiltration, as indicated by the elevation of CD4 + and F4/80 + cells along with a decline in CD8 + macrophage abundance. This study identifies a novel lipid metabolism-related gene signature and demonstrates that LPL overexpression modulates macrophage polarization and inhibits BRCA progression. Show less
Fats have been widely applied in aquaculture to promote growth performance and substitute partial protein in fish feeds. However, excessive dietary fat levels induce metabolic disorders harming the he Show more
Fats have been widely applied in aquaculture to promote growth performance and substitute partial protein in fish feeds. However, excessive dietary fat levels induce metabolic disorders harming the health of cultured fish. Helminth infection in mammals was inversely correlated with metabolic syndrome, but its effect in aquatic animals is unknown yet. Here, we evaluated the impacts of Show less
Radiation therapy for malignant tumor patients often induces radiation enteritis (RE), a condition that impairs their quality of life. Currently, there is no standard treatment regimen available. In t Show more
Radiation therapy for malignant tumor patients often induces radiation enteritis (RE), a condition that impairs their quality of life. Currently, there is no standard treatment regimen available. In this study, we used lyophilized apoptotic vesicles (Lpl-apoVs) from umbilical cord mesenchymal stem cells to treat RE in a murine model. We show that enema administration of lyophilized apoVs can ameliorate intestinal damage in RE mice. Mechanistically, Lpl-apoVs were internalized by intestinal endothelial cells (IECs) to alleviate radiation-induced DNA damage. In addition, mitophagy was identified as a prerequisite for therapeutic efficacy, suggesting that rescue of DNA damage and restoration of mitochondrial quality are collaboratively to ameliorate RE diseased phenotypes. These findings indicate that enema administration of Lpl-apoVs is a novel strategy for RE therapy. [Image: see text] The online version contains supplementary material available at 10.1186/s12951-025-03592-8. Show less
Lanthanides-doped luminescent materials have gathered considerable attention due to their application potential in stress sensing, lighting and display, anti-counterfeiting technology and so forth. Ho Show more
Lanthanides-doped luminescent materials have gathered considerable attention due to their application potential in stress sensing, lighting and display, anti-counterfeiting technology and so forth. However, existing materials mainly cover the 380-1540 nm range, with slight extension to the UV region, impeding their applications in solar-blind imaging, background-free tracking, concealed communication, etc. To address this challenge, here we propose guidelines for far-UVC (200-230 nm) optical design. Accordingly, we achieve multi-stimulated far-UVC luminescence at ~222 nm in Pr Show less
This study was conducted to investigate the effects of replacing fish meal with either whole-fat or defatted krill powder on the growth, body color, immunity, and related gene expression of red-white Show more
This study was conducted to investigate the effects of replacing fish meal with either whole-fat or defatted krill powder on the growth, body color, immunity, and related gene expression of red-white koi carp. A total of 630 red-white koi carp with an initial body mass of 13.5 ± 0.05 g were randomly divided into seven groups with three replicates per group and 30 fish per replicate. The control group was fed a basic diet (C0). The other six diets were supplemented with different levels of whole krill meal or defatted krill meal as replacements (10% whole fat, 20% whole fat, 30% whole fat, 10% defatted, 20% defatted, and 30% defatted) in the experimental groups, named W10, W20, W30, D10, D20, and D30, respectively, for a total duration of 60 days. The growth, body color, immunity and gene expression indexes were measured in the koi after completion. The results indicate the following. (1) Compared with C0, the experimental groups of koi showed a significant increase in the specific growth rate (SGR) ( Show less
Egg weight is a primary economic trait in poultry breeding. Putian Black duck, an excellent local laying duck breed in Fujian Province, includes two different strains, black feather strain and white f Show more
Egg weight is a primary economic trait in poultry breeding. Putian Black duck, an excellent local laying duck breed in Fujian Province, includes two different strains, black feather strain and white feather strain. The white feather strain of Putian Black duck is also known as Putian White duck. Except for the different feather colors, these two strains differ in egg weight. In this study, whole-genome resequencing was conducted on Putian Black duck and Putian White duck to explore the differences in the genetic mechanism of egg weight. Show less
Invertebrates constitute the largest group of animals on Earth, accounting for approximately 97 % of all animal species. Although the heart of invertebrates could be a sensitive target for environment Show more
Invertebrates constitute the largest group of animals on Earth, accounting for approximately 97 % of all animal species. Although the heart of invertebrates could be a sensitive target for environmental pollution, potential cardiotoxicity for most contaminants has received little attention. In this study, perfluorooctanoic acid (PFOA) and thick-shell mussels (Mytilus coruscus) were used to investigate the effect of PFOA on cardiac performance and the potential underlying mechanisms. Heart beat monitoring demonstrated that four-week exposure to 0.5 and 5.0 μg/L of PFOA resulted in bradycardia and arrhythmia in thick-shell mussels. Moreover, considerably more triglyceride (TG) accumulation, higher lipoprotein lipase (LPL) and lipase (LPS) activities, and disruption of lipid metabolism-related genes were observed in the hearts of PFOA-exposed mussels. In addition, comparable adverse impacts were detected in mussels treated with proliferator-activated receptor gamma (PPARγ) agonist whereas the PFOA-induced effects were fully or partially alleviated by PPARγ antagonist. Furthermore, molecular docking and molecular dynamics simulation revealed a high binding affinity of PFOA to the PPARγ of 12 invertebrates, including thick-shell mussels. In general, our data suggest that PFOA may pose a severe threat to cardiac performance of invertebrate species by inserting into the binding pocket of PPARγ, and thereby causing cardiac lipid metabolism disorders. Show less
To clarify the anatomical characteristics of the lateral plantar ligament (LPL) of the transverse metatarsal arch (TMA) in the population of southwest Shandong Province, so as to complement the anatom Show more
To clarify the anatomical characteristics of the lateral plantar ligament (LPL) of the transverse metatarsal arch (TMA) in the population of southwest Shandong Province, so as to complement the anatomical structures of the midfoot and Lisfranc joint complexes. A total of 100 adult lower limbs were dissected and the types of LPL were divided according to their insertions, among them, 63 were (63%) and 37 were female (37%); 50 were on the left side (50%) and 50 were on the right side (50%). The fiber bundle length, origin width, insertion width, and thickness of the LPL were measured. (1) According to the insertions of the LPL, they were divided into: ① Type I, the LPL was inserted at the base of the second metatarsal (M2) in 47 cases; ② Type II, the LPL was inserted at the base of M2 and fused with tibialis posterior tendon (TPT) in 16 cases; ③ Type III, the LPL was absent in 16 cases; ④ Type IV, the LPL was inserted at TPT in 6 cases; ⑤ Type V, the LPL was inserted at the intermediate cuneiform (IC) in 1 case; ⑥ Type VI, bifid LPL with one bundle inserted at the base of M2, and the other bundle inserted at the medial cuneiform (MC) in 4 cases; ⑦ Type VII, two bundles of LPL inserted at the base of M2 in 8 cases; ⑧ Type VIII, the LPL consisted of 3 bundles; the distal, middle and proximal bundles was inserted at the base of M2, the TPT and the lateral side of navicular bone in 2 cases, respectively. (2) There was a statistical significance in the length of LPL between male (31.62 ± 3.83) mm and female (28.07 ± 3.46) mm (t=-3.050, P = 0.003). There was no statistical significance in the types of LPL between male and female (Z=-1.721, P > 0.05), and no statistical significance in the types between left and right sides (Z=-0.026, P > 0.05). According to our research, LPL originates from M5 and is divided into 8 types according to its insertion location, of which insertion at the base of M2 is the most common. In addition, we found that LPL has fibrous fusion with the long plantar ligament and the TPT, which may be involved in maintaining arch stability. The classification of LPL in this study is a supplement to the anatomical structure of the middle foot and Lisfranc joint complex, providing a new direction for the diagnosis and treatment of middle foot and arch injury in the future. Show less
The relationship between high-density lipoprotein (HDL) and atherosclerotic risk remains incompletely elucidated, potentially due to the inherent heterogeneity of HDL particles. Hypertriglyceridemia i Show more
The relationship between high-density lipoprotein (HDL) and atherosclerotic risk remains incompletely elucidated, potentially due to the inherent heterogeneity of HDL particles. Hypertriglyceridemia is associated with alterations in HDL composition. This study investigated the impact of elevated triglycerides (TG) on HDL and its association with coronary artery disease (CAD) risk using a large prospective cohort study and Mendelian randomization (MR). We found that elevated TG was associated with reduced HDL particle size, decreased concentrations of HDL components, and increased triglycerides in HDL (HDL-TG) (all P for trend < 0.001). The protective effects of HDL particle concentration and HDL cholesterol on CAD are attenuated with increasing serum TG levels. An independent and positive association between HDL-TG levels and incident CAD events (hazard ratio [HR] per 1 standard deviation increase: 1.066, 95% CI: 1.052-1.080, P < 0.001) was confirmed even after adjustment for established cardiovascular disease risk factors. MR analyses supported a causal role for HDL-TG in CAD development (inverse-variance weighted [IVW] method: odds ratios [ORs] of 1.120 (95% CI: 1.053-1.192, P < 0.001) and 1.141 (95% CI: 1.032-1.263, P = 0.010) for dataset groups 1 and 2, respectively). Drug-target MR analyses suggested a potential association between omega-3 fatty acids (OM3-FA) and lower HDL-TG levels, with LPL and DGAT2 as key pharmacological targets. Our findings suggest that elevated TG contributes to adverse alterations in HDL, elevating CAD risk. HDL-TG is an independent positive risk factor for CAD and a potential causal contributor to CAD development. OM3-FA supplementation may offer a therapeutic strategy for mitigating the CAD risk associated with elevated HDL-TG. Show less
Dysregulation of fatty acid uptake and triglyceride transport can induce excess triglyceride accumulation. We propose that rice protein might suppress fatty acid uptake and/or triglyceride transport. Show more
Dysregulation of fatty acid uptake and triglyceride transport can induce excess triglyceride accumulation. We propose that rice protein might suppress fatty acid uptake and/or triglyceride transport. To elucidate potential mechanisms, expressions of cluster determinant 36 (CD36), microsomal triglyceride transfer protein (MTP), fatty acid transport protein-2 (FATP-2), fatty acid-binding protein-1 (FABP-1), lipoprotein lipase (LPL) and Niemann-Pick C1-like 1 (NPC1L1) were investigated in growing and adult male Wistar rats fed with caseins and rice proteins under normal and oil-enriched dietary conditions. After two weeks of feeding, rice protein depressed the gene and protein expressions of CD36, MTP, FATP-2, FABP-1 and NPC1L1, whereas rice protein up-regulated those of LPL. As a result, rice protein significantly reduced the concentrations of triglyceride and fatty acid in the plasma and liver ( Show less
Fatty liver hemorrhage syndrome (FLHS) is the most common metabolic diseases in laying hens during the late-laying period, and it causes a significant economic burden on the poultry industry. The comp Show more
Fatty liver hemorrhage syndrome (FLHS) is the most common metabolic diseases in laying hens during the late-laying period, and it causes a significant economic burden on the poultry industry. The competing endogenous RNA plays crucial roles in the occurrence and development of fatty liver. Based on the previously constructed lncRNA-miRNA-mRNA networks, we selected the axis of ENSGALT00000079786-LPL-miR-143-5p for further study to elucidate its mechanistic role in development of fatty liver. In this study, we identified a novel highly conserved lncRNA (ENSGALT00000079786) in poultry, which we designated as lncRNA A2ml2 based on its chromosomal location. Fluorescent in situ hybridization (FISH) revealed that lncRNA A2ml2 was localized in both the nucleus and cytoplasm. Dual-luciferase reporter assay validated the targeted relationship between lncRNA A2ml2, miR-143-5p, and the LPL gene. To further analyze the lncRNA A2ml2 and miR-143-5p function, lncRNA A2ml2 overexpression vector was successfully constructed and transfected into Leghorn male hepatocellular (LMH) cells, which could remarkably inhibit cellular lipid deposition was detected by oil red staining (P < 0.01), the opposite occurred for miR-143-5p (P < 0.01). qPCR demonstrated an inverse correlation between miR-143-5p expression and lncRNA A2ml2 expression, and confirmed that miR-143-5p directly target lncRNA A2ml2. Similarly, we found an inverse correlation between expression of LPL and the expression of miR-143-5p. To further investigate the interactions among these three factors and their effects on cellular lipid metabolism, we assessed the expression levels of LPL by co-transfecting lncRNA A2ml2 with miR-143-5p mimic and miR-143-5p mimic binding site mutants. Co-transfection experiments showed that miR-143-5p diminished the promoting effect of lncRNA A2ml2 on LPL. Meanwhile, miR-143-5p has the capacity to mitigate the suppressive impact of lncRNA A2ml2 overexpression on lipid accumulation in LMH cells. The results revealed that lncRNA A2ml2 attenuated hepatic lipid accumulation through negatively regulating miR-143-5p and enhancing LPL expression in LMH cells. Our findings offer novel insights into ceRNA-mediated in FLHS and identify a novel lncRNA as a potential molecular biomarker. Show less
The gut microbiota influences host immunity and metabolism, and changes in its composition and function have been implicated in several non-communicable diseases. Here, comparing germ-free (GF) and sp Show more
The gut microbiota influences host immunity and metabolism, and changes in its composition and function have been implicated in several non-communicable diseases. Here, comparing germ-free (GF) and specific pathogen-free (SPF) mice using spatial transcriptomics, single-cell RNA sequencing, and targeted bile acid metabolomics across multiple organs, we systematically assessed how the gut microbiota's absence affected organ morphology, immune homeostasis, bile acid, and lipid metabolism. Through integrated analysis, we detect marked aberration in B, myeloid, and T/natural killer cells, altered mucosal zonation and nutrient uptake, and significant shifts in bile acid profiles in feces, liver, and circulation, with the alternate synthesis pathway predominant in GF mice and pronounced changes in bile acid enterohepatic circulation. Particularly, autophagy-driven lipid droplet breakdown in ileum epithelium and the liver's zinc finger and BTB domain-containing protein (ZBTB20)-Lipoprotein lipase (LPL) (ZBTB20-LPL) axis are key to plasma lipid homeostasis in GF mice. Our results unveil the complexity of microbiota-host interactions in the crosstalk between commensal gut bacteria and the host. Show less