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To develop a radiomics model with enhanced diagnostic performance, reduced unnecessary fine needle aspiration biopsy (FNA) rate, and improved clinical net benefit for thyroid nodules. We conducted a retrospective study of 217 thyroid nodules. Lesions were divided into training (n = 152) and verification (n = 65) cohorts. Three radiomics scores were derived from B-mode ultrasound (B-US) and strain elastography (SE) images, alone and in combination. A radiomics nomogram was constructed by combining high-frequency ultrasonic features and the best-performing radiomics score. The area under the receiver operating characteristic curve (AUC), unnecessary FNA rate, and decision curve analysis (DCA) results for the nomogram were compared to those obtained with the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS) score and the combined TI-RADS + SE + contrast-enhanced ultrasound (CEUS) advanced clinical score. The three radiomics scores (B-US, SE, B-US + SE) achieved training AUCs of 0.753 (0.668–0.825), 0.761 (0.674–0.838), and 0.795 (0.715–0.871), and validation AUCs of 0.732 (0.579–0.867), 0.753 (0.609–0.892), and 0.752 (0.592–0.899) respectively. The AUC of the nomogram for the entire patient cohort was 0.909 (0.864–0.954), which was higher than that of the ACR TI-RADS score (P < 0.001) and equivalent to the TI-RADS+SE+CEUS score (P = 0.753). Similarly, the unnecessary FNA rate of the radiomics nomogram was significantly lower than that of the ACR TI-RADS score (P = 0.007) and equivalent to the TI-RADS+SE+CEUS score (P = 0.457). DCA also showed that the radiomics nomogram brought more net clinical benefit than the ACR TI-RADS score but was similar to that of the TI-RADS + SE + CEUS score. The radiomics nomogram developed in this study can be used as an objective, accurate, cost-effective, and noninvasive method for the characterization of thyroid nodules. [ABSTRACT FROM AUTHOR]

To evaluate glymphatic function changes and their relationships with clinical features in patients with metabolic dysfunction-associated fatty liver disease (MAFLD), thereby facilitating early intervention before this disease progresses to cirrhosis. A cross-sectional cohort of 46 pre-cirrhotic MAFLD patients and 30 age-, sex-, and education-matched controls was enrolled, with diffusion-tensor imaging (DTI) data, laboratory and neurocognitive scores collected. The DTI analysis along the perivascular space (DTI-ALPS) index was computed for qualifying glymphatic function. Generalized linear model and partial correlation analyses were applied to evaluate relationships between the ALPS index and clinical variables. MAFLD group exhibited a decreased ALPS index and increased diffusivity along the y-axis in the projection fiber compared to the controls. The altered ALPS index was associated with clock drawing test (CDT) score (3.931 [0.914, 6.947], P = 0.011) and was correlated with diastolic pressure level (r = −0.315, P = 0.033) in MAFLD group. The relationships of ALPS index with CDT score (6.263 [2.069, 10.458], P = 0.003) and diastolic pressure level (r = −0.518, P = 0.014) remained in the MAFLD with metabolic syndrome (MetS) group. Furthermore, the ALPS index was even associated with Auditory Verbal Learning Test-Immediate recall score (−23.853 [−45.417, −2.289], P = 0.030) in MAFLD with MetS group. MAFLD patients may have a glymphatic dysfunction prior to cirrhosis, and this alteration may be related to cognition and diastolic pressure. Glymphatic dysfunction has a more severe impact on cognition when MAFLD patient is accompanied by MetS. [ABSTRACT FROM AUTHOR]

Anxiety disorders are one of the most epidemic and chronic psychiatric disorders. An incomplete understanding of anxiety pathophysiology has limited the development of highly effective drugs against these disorders. GPR17 has been shown to be involved in multiple sclerosis and some acute brain injury disorders. However, no study has investigated the role of GPR17 in psychiatric disorders. In a well-established chronic restraint stress (CRS) mouse model, using a combination of pharmacological and molecular biology techniques, viral tracing, in vitro electrophysiology recordings, in vivo fiber photometry, chemogenetic manipulations and behavioral tests, we demonstrated that CRS induced anxiety-like behaviors and increased the expression of GPR17 in basolateral amygdala (BLA) glutamatergic neurons. Inhibition of GPR17 by cangrelor or knockdown of GPR17 by adeno-associated virus in BLA glutamatergic neurons effectively improved anxiety-like behaviors. Overexpression of GPR17 in BLA glutamatergic neurons increased the susceptibility to anxiety-like behaviors. What's more, BLA glutamatergic neuronal activity was required for anxiolytic-like effects of GPR17 antagonist and GPR17 modulated anxiety-like behaviors via BLA to ventral hippocampal CA1 glutamatergic projection. Our study finds for the first and highlights the new role of GPR17 in regulating anxiety-like behaviors and it might be a novel potential target for therapy of anxiety disorders. Downregulation of GPR17 in BLA glutamatergic neurons alleviates anxiety-like behaviors by inhibiting BLA glutamatergic neuronal excitability, reducing the release of glutamate, and weakening the glutamatergic projection from BLA to vCA1. [Display omitted] [ABSTRACT FROM AUTHOR]

In this study, we analyzed the transcriptome sequences of Kupffer cells exposed to simulated microgravity for 3 d and conducted biological experiments to determine how microgravity initiates apoptosis in Kupffer cells. Rotary cell culture system was used to construct a simulated microgravity model. GO and KEGG analyses were conducted using the DAVID database. GSEA was performed using the R language. The STRING database was used to conduct PPI analysis. qPCR was used to measure the IL1B, TNFA, CASP3 , CASP9, and BCL2L11 mRNA expressions. Western Blotting was performed to detect the level of proteins CASP3 and CASP 9. Flow cytometry was used to detect apoptosis and mitochondrial membrane cells. Transmission electron microscopy was used to detect changes in the ultrastructure of Kupffer cells. Transcriptome Sequencing indicated that simulated microgravity affected apoptosis and the inflammatory state of Kupffer cells. Simulated microgravity improved the CASP3 , CASP9, and BCL2L11 expressions in Kupffer cells. Annexin-V/ PI and JC-1 assays showed that simulated microgravity promoted apoptosis in Kupffer cells. Simulated microgravity causes M1 polarization in Kupffer cells. Our study found that simulated microgravity facilitated the apoptosis of Kupffer cells through the mitochondrial pathway and activated Kupffer cells into M1 polarization, which can secrete TNFA to promote apoptosis. [ABSTRACT FROM AUTHOR]

Malnutrition is prevalent among hospitalised patients, and increases the morbidity, mortality, and medical costs; yet nutritional assessments on admission are not routine. This study assessed the clinical and economic benefits of using an artificial intelligence (AI)-based rapid nutritional diagnostic system for routine nutritional screening of hospitalised patients. A nationwide multicentre randomised controlled trial was conducted at 11 centres in 10 provinces. Hospitalised patients were randomised to either receive an assessment using an AI-based rapid nutritional diagnostic system as part of routine care (experimental group), or not (control group). The overall medical resource costs were calculated for each participant and a decision-tree was generated based on an intention-to-treat analysis to analyse the cost-effectiveness of various treatment modalities. Subgroup analyses were performed according to clinical characteristics and a probabilistic sensitivity analysis was performed to evaluate the influence of parameter variations on the incremental cost-effectiveness ratio (ICER). In total, 5763 patients participated in the study, 2830 in the experimental arm and 2933 in the control arm. The experimental arm had a significantly higher cure rate than the control arm (23.24% versus 20.18%; p = 0.005). The experimental arm incurred an incremental cost of 276.52 CNY, leading to an additional 3.06 cures, yielding an ICER of 90.37 CNY. Sensitivity analysis revealed that the decision-tree model was relatively stable. The integration of the AI-based rapid nutritional diagnostic system into routine inpatient care substantially enhanced the cure rate among hospitalised patients and was cost-effective. NCT04776070 (https://clinicaltrials.gov/study/NCT04776070). [ABSTRACT FROM AUTHOR]

Two uncharacterized monoterpenoids (1 – 2) and six known analogues (3 – 8) were isolated from the fruit of Gardenia jasminoides. Their structures were determined by comprehensive spectroscopic data analysis, and the absolute configuration of 2 was elucidated by comparing the calculated electronic circular dichroism (ECD) spectrum with experimental ECD spectrum. Additionally, the results of preliminary activity evaluation indicated that these compounds showed slightly α -glucosidase inhibitory activity. [Display omitted] • Two undescribed monoterpenoids were isolated from the fruit of Gardenia jasminoides Ellis. • The isolated compounds were evaluated for their α-glucosidase inhibitory activity. [ABSTRACT FROM AUTHOR]

To develop an efficient machine-learning model using pituitary MRI radiomics and clinical data to differentiate growth hormone deficiency (GHD) from idiopathic short stature (ISS), making the diagnostic process more acceptable to patients and their families. A retrospective cohort of 297 GHD and 300 ISS children (4–12 years) were enrolled as training and validation cohorts (8:2 ratio). An external cohort from another institution (49 GHD and 51 ISS) was employed as the testing cohort. Radiomics features extracted from the anterior pituitary gland on sagittal T1-weighted image (1.5 T or 3.0 T) were used to develop a radiomics model after feature selection. Hematological biomarkers were selected to create a clinical model and combine with the optimal radiomics features to create a clinical-radiomics model. The area under the receive operating characteristic curve (AUC) and Delong test compared the diagnostic performance of the previously mentioned three models across different validation and testing cohorts. 17 radiomics features were selected for the radiomics model, and total protein, total cholesterol, free triiodothyronine, and triglyceride were utilized for the clinical model. In the training and validation cohorts, the diagnostic performance of the clinical-radiomics model (AUC = 0.820 and 0.801) was comparable to the radiomics model (AUC = 0.812 and 0.779, both P >0.05), both outperforming the clinical model (AUC = 0.575 and 0.593, P <0.001). In the testing cohort, the clinical-radiomics model exhibited the highest AUC of 0.762 than the clinical and radiomics model (AUC = 0.604 and 0.741, respectively, P <0.05). In addition, the clinical and radiomics models demonstrated similar diagnostic performance in the testing cohort (P >0.05). Integrating radiomics features from conventional pituitary MRI with clinical indicators offers a minimally invasive approach for identifying GHD and shows robustness in a multicenter setting. [ABSTRACT FROM AUTHOR]

To explore and externally validate habitat-based radiomics for preoperative prediction of epidermal growth factor receptor (EGFR) mutations in exon 19 and 21 from MRI imaging of non-small cell lung cancer (NSCLC)-originated brain metastasis (BM). A total of 170, 62 and 61 patients from center 1, center 2 and center 3, respectively were included. All patients underwent contrast-enhanced T1-weighted (T1CE) and T2-weighted (T2W) MRI scans. Radiomics features were extracted from the tumor active (TA) and peritumoral edema (PE) regions in each MRI slice. The most important features were selected by the least absolute shrinkage and selection operator regression to develop radiomics signatures based on TA (RS-TA), PE (RS-PE) and their combination (RS-Com). Receiver operating characteristic (ROC) curve analysis was performed to access performance of radiomics models for both internal and external validation cohorts. 10, four and six most predictive features were identified to be strongly associated with the EGFR mutation status, exon 19 and exon 21, respectively. The RSs derived from the PE region outperformed those from the TA region for predicting the EGFR mutation, exon 19 and exon 21. The RS-Coms generated the highest performance in the primary training (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.955 vs. 0.946 vs. 0.928), internal validation (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.879 vs. 0.819 vs. 0.882), external validation 1 (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.830 vs. 0.825 vs. 0.822), and external validation 2 (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.812 vs. 0.818 vs. 0.800) cohort. The developed habitat-based radiomics model can be used to accurately predict the EGFR mutation subtypes, which may potentially guide personalized treatments for NSCLC patients with BM. [ABSTRACT FROM AUTHOR]

Near-infrared-II (NIR-II) photothermal therapy is emerging as a cutting-edge modality for tumor ablation due to its good biosafety, high penetration ability and spatiotemporal controllability. Despite efforts, establishing a link between cellular metabolic regulation and photothermal performance is still promising in synergistic cancer therapy. Herein, we developed a core-shell semiconducting polymer@metal-phenolic network (SP@GFP) nanomotor by assembling diphenol-terminated cisplatin prodrug ligand (cPt-DA) and iron (III) (Fe3+) through metal coordination on SP particles in the presence of GOx and DSPE-PEG-cRGD, for NIR-II-propelled self-propulsion and synergistic cancer therapy. Remotely driving the SP@GFP nanomotor with an NIR-II laser through a thermophoresis mechanism would allow for in-depth penetration and accumulation. The synergistic photothermal effect and continuous Fe2+-mediated ROS generation of SP@GFP nanomotor could activate photothermal, chemotherapeutic effects and ferroptosis pathway for cancer cells through reshaping cellular metabolic pathways (HSP and GPX4). By combining the concepts of chemotherapeutic prodrugs, catalytic ROS generation, photothermal response and cellular metabolic regulation, the NIR-II laser-controlled core-shell SP@GFP nanomotor displayed improved outcomes for enhanced cancer therapy through synergistic oxidative stress-photothermo modulation. • A NIR-II-powered core-shell SP@GFP prodrug nanomotor was constructed through metal coordination assembly for enhanced cancer therapy; • NIR-II laser propelled the propulsion of SP@GFP nanomotor through thermophoresis mechanism for in depth penetration and accumulation. • Therapeutic outcomes were improved through synergistic modulating oxidative stress and photothermal performance. [Display omitted] [ABSTRACT FROM AUTHOR]

Intratumor microbes have attracted great attention in cancer research due to its influence on the tumorigenesis, progression and metastasis of cancer. However, the therapeutic strategies targeting intratumoral microbes are still in their infancy. Specific microorganisms, such as Fusobacterium nucleatum (F. nucleatum), are abundant in various cancer and always result in the CRC progression and chemotherapy resistance. Here, a combined anticancer and antibacterial therapeutic strategy is proposed to deliver antitumor drug to the tumors containing intratumor microbiota by the antibacerial polymeric drug carriers. We construct oral tellurium-containing drug carriers using a complex of tellurium-containing polycarbonate with cisplatin (PTE@CDDP). The results show that the particle size of the prepared nanoparticles could be maintained at about 105 nm in the digestive system environment, which is in line with the optimal particle size of oral nanomedicine. In vitro mechanism study indicates that the tellurium-containing polymers are highly effective in killing F.nucleatum through a membrane disruption mechanism. The pharmacokinetic experiments confirmed that PTE@CDDP has the potential function of enhancing the oral bioavailability of cisplatin. Both in vitro and in vivo studies show that PTE@CDDP could inhibit intratumor F.nucleatum and lead to a reduction in cell proliferation and inflammation in the tumor site. Together, the study identifies that the CDDP-loaded tellurium-containing nanoparticles have great potential for treating the F.nucleatum -promoted colorectal cancer (CRC) by combining intratumor microbiota modulation and chemotherapy. The synergistic therapeutic strategy provide new insight into treating various cancers combined with bacterial infection. The synthesized antibacterial polymer was first employed to remodel the intratumor microbes in tumor microenvironment (TME). Moreover, it was the first report of tellurium-containing polymers against F.nucleatum and employed for treatment of the CRC. A convenient oral dosage form of cisplatin (CDDP)-loaded tellurium-containing nanoparticles (PTE@CDDP) was adopted here, and the synergistic antibacterial/chemotherapy effect occurred. The PTE@CDDP could quickly and completely eliminate F.nucleatum in a safe dose. In the CRC model, PTE@CDDP effectively reversed the inflammation level and even restored the intestinal barrier damaged by F.nucleatum. The ultrasensitive ROS-responsiveness of PTE@CDDP triggered the fast oxidation and efficient drug release of CDDP and thus a highly efficient apoptosis of the tumors. Therefore, the tellurium-containing polymers are expected to serve as novel antibacterial agents in vivo and have great potential in the F.nucleatum -associated cancers. The achievements provided new insight into treating CRC and other cancers combined with bacterial infection. [Display omitted] [ABSTRACT FROM AUTHOR]

We aimed to evaluate the histopathological alterations in human salivary glands after radioactive iodine (RAI) treatment for thyroid diseases. We retrospectively selected patients with a history of RAI treatment for thyroid diseases from a database of patients who underwent surgery for oral and maxillofacial diseases and had specimens of salivary glands at Peking University School of Stomatology between December 2012 and July 2023. The patients' clinical records and histopathological slides of the salivary glands were carefully reviewed. Sixteen patients were included. Three symptomatic patients showed duct cell cytoplasmic vacuolization and increased numbers of disordered duct cell layers (3/3), severe duct stenosis and dilation (2/3), and exfoliated epithelial cells in the duct lumen (1/3). The glandular parenchyma showed severe acinar atrophy (2/2), fat content enhancement (2/2), and severe periductal fibrosis (3/3). Thirteen asymptomatic patients showed duct cell cytoplasmic vacuolization (5/13), acinar atrophy and increased fat content in the parenchyma (5/13), and periductal fibrosis (5/13). Main histopathologic changes in the salivary glands after RAI treatment for thyroid diseases are cytoplasmic vacuolization of duct cells, acinar atrophy, fat content enhancement, and periductal fibrosis. These changes were evident in symptomatic cases, and were also seen in some asymptomatic patients. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? Whether and how acupuncture change the hippocampal structure and function of SCD individuals? • What is the main finding of this study? Compared to sham acupuncture control, acupuncture improved the cognitive function of SCD individuals, increased hippocampal volume on the regional level and enhanced the structural and functional connectivity of hippocampus on the connective level. • What is the meaning of the finding? Our study provides empirical evidence demonstrating the cognitive benefits and multi-modal neurological mechanisms of acupuncture on SCD, attracting more attention to early cognitive intervention in the elderly. Converging evidence indicates that subjective cognitive decline (SCD) could be an early indicator of dementia. The hippocampus is the earliest affected region during the progression of cognitive impairment. However, little is known about whether and how acupuncture change the hippocampal structure and function of SCD individuals. Here, we used multi-modal MRI to reveal the mechanism of acupuncture in treating SCD. Seventy-two older participants were randomized into acupuncture or sham acupuncture group and treated for 12 weeks. At the end of the intervention, compared to sham acupuncture, participants with acupuncture treatment showed improvement in composite Z score from multi-domain neuropsychological tests, as well as increased hippocampal volume and functional connectivity. Moreover, the greater white matter integrity of the fornix, which is the major output tract of the hippocampus, was shown in the acupuncture group. These findings suggest that acupuncture may improve the cognitive function of SCD individuals, and increase hippocampal volume on the regional level and enhance the structural and functional connectivity of hippocampus on the connective level. [ABSTRACT FROM AUTHOR]

Since the global burden of chronic kidney disease (CKD) is rising rapidly, the study aimed to assess the association of cardiovascular health (CVH) metrics with all-cause and cardiovascular disease (CVD) mortality among individuals with CKD. The cohort study included 5834 participants with CKD from the National Health and Nutrition Examination Survey 1999–2018. A composite CVH score was calculated based on smoking status, physical activity, body mass index, blood pressure, total cholesterol, diet quality, and glucose control. Primary outcomes were all-cause and CVD mortality as of December 31, 2019. Multivariable-adjusted Cox proportional hazards models were used to estimate the association between CVH metrics and deaths in CKD patients. During a median follow-up of 7.2 years, 2178 all-cause deaths and 779 CVD deaths were documented. Compared to participants with ideal CVH, individuals with intermediate CVH exhibited a 46.0% increase in all-cause mortality (hazard ratio, 1.46; 95% confidence interval: 1.17, 1.83), while those with poor CVH demonstrated a 101.0% increase (2.01; 1.54, 2.62). For CVD mortality, individuals with intermediate CVH experienced a 56.0% increase (1.56; 1.02, 2.39), and those with poor CVH demonstrated a 143.0% increase (2.43; 1.51, 3.91). Linear trends were noted for the associations of CVH with both all-cause mortality (P for trend <0.001) and CVD mortality (P for trend = 0.02). Lower CVH levels were associated with higher all-cause and CVD mortality in individuals with CKD, which highlights the importance of maintaining good CVH in CKD patients. • Lower CVH levels were associated with higher all-cause and CVD mortality in individuals with CKD. • Maintaining a better CVH status is beneficial for reducing the risk of premature death in patients with chronic kidney disease. • The benefits of ideal cardiovascular health were particularly evident in younger participants and those at an early stage of CKD. [ABSTRACT FROM AUTHOR]

• A teach-back education program based on BCW was proven effective to mitigate the perioperative pain among patients with lung cancer. • It could also reduce the use of PCA and increase patients' satisfaction, demonstrating it as a cost-effective method in pain management. To assess the effect of a teach-back educational intervention using Behavior Change Wheel (BCW) framework on perioperative pain among patients with lung cancer. A prospective quasi-experimental study was conducted in 88 patients with lung cancer from a tertiary hospital in China. According to the order of admission, they were allocated to either control group or intervention group, with 44 patients in each group. Patients in the control group received routine nursing care, while patients in the intervention group were given a teach-back education program based on BCW framework. The visual analog scale (VAS) was adopted to evaluate patients' pain on the day of surgery (T0), 1 (T1), 2 (T2), and 3 (T3) days after surgery. We also recorded the use of patient-controlled analgesia (PCA), the length of hospital stay, and the degree of patients' satisfaction. Rest pain, pain when coughing, and pain during activity that patients in the intervention group experienced were significantly less severe than those in the control group on T0 and T1. The pain when coughing in the intervention group was also significantly milder on T2 and T3. In addition, the number of self-control time, use duration, and total dose of PCA were significantly lower in the intervention group. Moreover, patients' satisfaction of nursing service was significantly higher in the intervention group. A teach-back education program based on BCW framework was effective in pain management among the perioperative patients with lung cancer. This study demonstrates the application of teach-back method and the BCW in the development of patient education intervention to mitigate perioperative pain. [ABSTRACT FROM AUTHOR]

The chicken embryo chorioallantoic membrane (CAM) model has played a crucial role in various aspects of cancer research. The purpose of this study is to help researchers clarify the research direction and prospects of the CAM model. A bibliometric analysis was conducted on the top 100 most cited articles on use of the CAM model in tumour research, retrieved from the Web of Science Core Collection database. Tools such as Bibliometrix, VOSviewer, CiteSpace and Excel were utilized for the visualization network analysis. The 100 articles analysed were mainly from the USA, China and European countries such as Germany and France. Tumour research involving CAM model experiments demonstrated reliability and scientific rigor (average citation count = 156.2). The analysis of keywords, topics and subject areas revealed that the applications of this model ranged from the biological characteristics of tumours to molecular mechanisms and signaling pathways, to recent developments in nanotechnology and clinical applications. Additionally, nude mouse experiments have been more frequently performed in recent years. We conclude that the CAM model is efficient, simple and cost-effective, and has irreplaceable value in various aspects of cancer research. In the future, the CAM model can further contribute to nanotechnology research. [ABSTRACT FROM AUTHOR]

Apoptosis generates plenty of membrane-bound nanovesicles, the apoptotic vesicles (apoVs), which show promise for biomedical applications. The liver serves as a significant organ for apoptotic material removal. Whether and how the liver metabolizes apoptotic vesicular products and contributes to liver health and disease is unrecognized. apoVs were labeled and traced after intravenous infusion. Apoptosis-deficient mice by Fas mutant (Fas mut ) and Caspase-3 knockout (Casp3 −/− ) were used with apoV replenishment to evaluate the physiological apoV function. Combinations of morphologic, biochemical, cellular, and molecular assays were applied to assess the liver while hepatocyte analysis was performed. Partial hepatectomy and acetaminophen liver failure models were established to investigate liver regeneration and disease recovery. We discovered that the liver is a major metabolic organ of circulatory apoVs, in which apoVs undergo endocytosis by hepatocytes via a sugar recognition system. Moreover, apoVs play an indispensable role to counteract hepatocellular injury and liver impairment in apoptosis-deficient mice upon replenishment. Surprisingly, apoVs form a chimeric organelle complex with the hepatocyte Golgi apparatus through the soluble N -ethylmaleimide–sensitive factor attachment protein receptor machinery, which preserves Golgi integrity, promotes microtubule acetylation by regulating α-tubulin N -acetyltransferase 1, and consequently facilitates hepatocyte cytokinesis for liver recovery. The assembly of the apoV-Golgi complex is further revealed to contribute to liver homeostasis, regeneration, and protection against acute liver failure. These findings establish a previously unrecognized functional and mechanistic framework that apoptosis through vesicular metabolism safeguards liver homeostasis and regeneration, which holds promise for hepatic disease therapeutics. [Display omitted] Apoptotic vesicles assemble with the recipient hepatocyte Golgi apparatus to form an apoptotic vesicle-Golgi complex, which is indispensable for the maintenance of liver homeostasis and regeneration. [ABSTRACT FROM AUTHOR]

Human milk is the optimal diet for very preterm infants (VPIs), but it requires nutrient fortification to support growth. Bovine colostrum (BC), rich in intact proteins and bioactive components, could serve as a novel fortifier with potential benefits to VPIs gut health. To evaluate a possible effect of feeding BC on intestinal metabolism, the gut microbiota, and their interaction, we studied the fecal metabolome of VPIs in the first month of life, as compared with a conventional fortifier (CF, based on infant formula ingredients). Fecal samples were collected from VPIs recruited to the FortiColos trial (NCT03537365, BC, n = 107; CF, n = 112) before (FT0) and one (FT1) or two (FT2) weeks after start of fortification and analyzed using 1H NMR spectroscopy. Abundances of metabolites were compared between BC versus CF groups. Further, temporal changes in metabolite levels after start of fortification, as well as correlations with specific gut bacterial genera were explored. Infants in the BC group had higher levels of fecal acetoacetate, choline, methanol, uracil, creatine, creatinine, lysine and a lower leucine at both FT1 and FT2, relative to the CF group. Asparagine, tryptophan and phenylalanine levels were higher, and butyrate was lower in the BC group at FT1. At FT2, higher fecal succinate and lower isoleucine were found in the BC group. In addition, eight metabolites (asparagine, phenylalanine, tryptophan, lysine, creatinine, acetoacetate, methanol and uracil) had fortification-specific changes over time. Positive correlations were found between succinate and unclassified Enterobacteriaceae , butyrate and Clostridium , uracil and Staphylococcus, while negative correlation were found between uracil and unclassified Enterobacteriaceae members. Our study shows distinct fecal metabolome profiles in VPIs in the first weeks after fortification with BC versus CF. The fortification- and time-specific gut metabolite changes suggest that fortifiers influence luminal nutrient metabolism and microbiota activity in VPIs. Fortifier type for human milk affected gut health of VPIs via altered gut metabolite levels, interacting with microbiota in VPIs. [ABSTRACT FROM AUTHOR]

Epidemiological evidence on ultra-processed food (UPF) and cause-specific mortality remains limited and mixed. Molecular mechanisms underlying UPF intake and mortality remain unexplored. This study aimed to evaluate the associations between UPF consumption, metabolic signatures, and all-cause, premature, and cause-specific mortality. This study included 27670 participants (mean age 58.1 years) from the Malmö Diet and Cancer (MDC) cohort study. Consumption of UPF was assessed using a food frequency questionnaire and a 7-day food diary. In a subset of the MDC (n = 879), the associations of UPF with 991 plasma metabolites were investigated. An elastic net regression model was used to establish the metabolic signature of UPF. Cox proportional hazards regression model was used to determine the association between UPF intake, metabolic signature, and mortality risk. During a median follow-up of 23.3 years, a total of 11333 participants died. UPF intake showed a nonlinear positive association with all-cause mortality, with more pronounced associations found in females (P interaction = 0.044); in females, UPF was linked to a higher mortality risk in a linear manner, while the association was J-shaped in males. Each standard deviation (SD) increment in UPF intake was associated with an increased risk of premature mortality (HR, 1.06; 95 % CI, 1.03–1.09), cardiovascular disease (CVD) mortality (HR, 1.05; 95 % CI, 1.01–1.08) or respiratory disease mortality (HR, 1.08; 95 % CI, 1.01–1.15), but not cancer mortality. The metabolic signature for UPF consumption (with 93 metabolites) was positively associated with all-cause mortality risk (HR per 1 SD, 1.23; 95 % CI, 1.06–1.42). Our results suggest that higher UPF intake is associated with increased risk of all-cause, premature, CVD, and respiratory disease mortality, with the association varying across sex for all-cause mortality. The plasma metabolic signature of UPF showed a positive association with all-cause mortality. [ABSTRACT FROM AUTHOR]

Perineural invasion (PNI) is an important prognostic biomarker for prostate cancer (PCa). This study aimed to develop and validate a predictive model integrating biparametric MRI-based deep learning radiomics and clinical characteristics for the non-invasive prediction of PNI in patients with PCa. In this prospective study, 557 PCa patients who underwent preoperative MRI and radical prostatectomy were recruited and randomly divided into the training and the validation cohorts at a ratio of 7:3. Clinical model for predicting PNI was constructed by univariate and multivariate regression analyses on various clinical indicators, followed by logistic regression. Radiomics and deep learning methods were used to develop different MRI-based radiomics and deep learning models. Subsequently, the clinical, radiomics, and deep learning signatures were combined to develop the integrated deep learning-radiomics-clinical model (DLRC). The performance of the models was assessed by plotting the receiver operating characteristic (ROC) curves and precision–recall (PR) curves, as well as calculating the area under the ROC and PR curves (ROC-AUC and PR-AUC). The calibration curve and decision curve were used to evaluate the model's goodness of fit and clinical benefit. The DLRC model demonstrated the highest performance in both the training and the validation cohorts, with ROC-AUCs of 0.914 and 0.848, respectively, and PR-AUCs of 0.948 and 0.926, respectively. The DLRC model showed good calibration and clinical benefit in both cohorts. The DLRC model, which integrated clinical, radiomics, and deep learning signatures, can serve as a robust tool for predicting PNI in patients with PCa, thus aiding in developing effective treatment strategies. [ABSTRACT FROM AUTHOR]

To explore the value of splenic hemodynamic parameters from low-dose one-stop dual-energy and perfusion CT (LD-DE&PCT) in non-invasively predicting high-risk esophageal varices (HREV) in cirrhotic patients. We retrospectively analyzed cirrhotic patients diagnosed with esophageal varices (EV) through clinical, laboratory, imaging, and endoscopic examinations from September 2021 to December 2023 in our hospital. All patients underwent LD-DE&PCT to acquire splenic iodine concentration and perfusion parameters. Radiation dose was recorded. Patients were classified into non-HREV and HREV groups based on endoscopy. Univariate and multivariate logistic regression analysis were performed, and the prediction model for HREV was constructed. P < 0.05 was considered statistically significant. Univariate analysis revealed that significant differences were found in portal iodine concentration (PIC), blood flow (BF), permeability surface (PS), spleen volume (V-S), total iodine concentration (TIC), and total blood volume of the spleen (BV-S) between groups. TIC demonstrated the highest predictive value with an area under the curve (AUC) value of 0.87. Multivariate analysis showed that PIC, PS, and BV-S were independent risk factors for HREV. The logistic regression model for predicting HREV had an AUC of 0.93. The total radiation dose was 20.66 ± 4.07 mSv. Splenic hemodynamic parameters obtained from LD-DE&PCT can non-invasively and accurately assess the hemodynamic status of the spleen in cirrhotic patients with EV and predict the occurrence of HREV. Despite the retrospective study design and limited sample size of this study, these findings deserve further validation through prospective studies with larger cohorts. [ABSTRACT FROM AUTHOR]

T2-weighted imaging (T2WI) is an essential sequence for assessing the staging of bladder cancer. This study aimed to compare the image quality and diagnostic performance of three-dimensional (3D) and two-dimensional (2D) T2WI in diagnosing muscle invasion of bladder cancer using Vesical Imaging Reporting and Data System (VI-RADS). Between August 2022 and May 2023, 101 participants with bladder cancer underwent multiparametric MRI including 3D and 2D T2WI. Two radiologists independently reviewed 2D and 3D T2WI, evaluating image quality and muscle invasion based on VI-RADS scoring. The paired Wilcoxon signed-rank test assessed the differences between 2D and 3D T2WI. The areas under the receiver operating characteristic curve (AUCs) were utilized to compare the diagnostic performance. 3D T2WI demonstrated significantly superior overall image quality scores with less artifacts than 2D T2WI. Compared to 2D T2WI, 3D T2WI categories had significantly higher AUC for both readers (reader 1: 0.937 vs. 0.909, p =.02; reader 2: 0.923 vs.0.884, p =.04). The VI-RADS score of 3D MR protocol had higher accuracy than 2D MR protocol (reader 1: 0.931 vs. 0.921, p =.02; reader 2: 0.931 vs. 0.911, p =.02). However, there were no significant differences in AUC values of VI-RADS categories between 2D and 3D MR protocol (all p > 0.05). In assessing muscle invasion of bladder cancer, 3D T2WI exhibited superior overall image quality and diagnostic performance than 2D T2WI. However, 3D T2WI did not significantly improve the diagnostic performance of VI-RADS. [ABSTRACT FROM AUTHOR]

To validate the image quality of low-dose ultra-high-resolution (UHR) scanning mode of photon-counting detector CT (PCD-CT) for visceral artery computed tomography angiography (CTA). We prospectively enrolled 57 patients each in the full dose (FD) and low-dose (LD) protocols, respectively, to undergo abdominal CT scans using the UHR mode on a PCD-CT system (NAEOTOM Alpha), between April 2023 and September 2023. Both the FD data and LD data were then reconstructed into two series of images: (a) 0.2 mm slice thickness, reconstruction kernel Bv48, quantum iterative reconstruction (QIR) 4; (b)1 mm slice thickness, Bv40, QIR 3. The signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) of seven arteries were objectively measured. The image noise, vessel sharpness, overall quality, and visibility of nine arteries were subjectively assessed by three radiologists. The SNRs and CNRs of 0.2 mm reconstruction set was inferior to that of 1 mm reconstruction set (p < 0.001 for all the arteries and noise), however, the image quality of 0.2 mm reconstruction set was higher than that of 1 mm reconstruction set in qualitative evaluation especially for tiny arteries in Volume-rendered (VR) image (p < 0.001). The SNRs and CNRs were not significantly higher for FD group than LD group on the same slice thickness except for SNRs of common hepatic artery, splenic artery and bilateral renal arteries in 0.2 mm reconstruction set. In the comparison on image quality between normal weight and overweight patients within the same reconstruction set, the results showed that low-dose scan did not significantly impact the image quality in overweight patients. The ratings of visibility of nine visceral arteries were not significantly different among FD and LD at the same thickness reconstruction set except for superior mesenteric artery (p = 0.002 and 0.007 for 0.2 mm and 1 mm reconstruction set in axial image; p = 0.002 and 0.007 for 0.2 mm and 1 mm reconstruction set in coronal image, respectively) and left gastric artery (p = 0.002 and p < 0.001 for 0.2 mm and 1 mm reconstruction set in VR image, respectively). The low-dose UHR scanning mode of PCD-CT has proven to be adequate for the clinical evaluation of visceral arteries. Utilizing a reconstruction with a slice thickness of 0.2 mm could enhance arterial depiction, particularly for small vessels. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is highly heterogeneous, and accurate preoperative assessment of lymph node status remains challenging. We aimed to develop a multiparametric MRI-based model for predicting lymph node metastasis (LNM) in GC and to explore its prognostic implications. In this dual-center retrospective study, 479 GC patients undergoing preoperative multiparametric MRI before radical gastrectomy were enrolled. 1595 imaging features were extracted from T2-weighted imaging, apparent diffusion coefficient maps, and contrast-enhanced T1-weighted imaging (cT1WI), respectively. Feature selection steps, including the Boruta and Simulated Annealing algorithms, were conducted to identify key features. Different radiomics models (RMs) based on the single- and multiple-sequence were constructed. The performance of various RMs in predicting LNM was assessed in terms of discrimination, calibration, and clinical usefulness. Additionally, Kaplan-Meier survival curves were employed to estimate differences in disease-free survival (DFS) and overall survival (OS). The multi-sequence radiomics model (MRM) achieved area under the curves (AUCs) of 0.774 [95 % confidence interval (CI), 0.703–0.845], 0.721 (95 % CI, 0.593–0.850), and 0.720 (95 % CI, 0.639–0.801) in the training and two validation cohorts, respectively, outperforming the single-sequence RMs. Notably, the RM derived from cT1WI demonstrated superior performance compared to the other two single-sequence models. Furthermore, the proposed MRM exhibited a significant association with DFS and OS in GC patients (both P < 0.05). The multiparametric MRI-based radiomics model, derived from primary lesions, demonstrated moderate performance in predicting LNM and survival outcomes in patients with GC, which could provide valuable insights for personalized treatment strategies. [ABSTRACT FROM AUTHOR]

To investigate the potential of T1-weighted imaging (T1WI)-based hippocampal radiomics as imaging markers for the diagnosis of Alzheimer's disease (AD) and their efficacy in discriminating between mild cognitive impairment (MCI) and dementia in AD. A total of 126 AD patients underwent T1WI-based magnetic resonance imaging (MRI) examinations, along with 108 age-sex-matched healthy controls (HC). This was a retrospective, single-center study conducted from November 2021 to February 2023. AD patients were categorized into two groups based on disease progression and cognitive function: AD-MCI and dementia (AD-D). T1WI-based radiomics features of the bilateral hippocampi were extracted. To diagnose AD and differentiate between AD-MCI and AD-D, predictive models were developed using random forest (RF), logistic regression (LR), and support vector machine (SVM). We compared radiomics features between the AD and HC groups, as well as within the subgroups of AD-MCI and AD-D. Area under the curve (AUC), accuracy, sensitivity, and specificity were all used to assess model performance. Furthermore, correlations between radiomics features and Mini-Mental State Examination (MMSE) scores, tau protein phosphorylated at threonine 181 (P-tau-181), and amyloid β peptide1–42 (Aβ1–42) were analyzed. The RF model demonstrated superior performance in distinguishing AD from HC (AUC = 0.961, accuracy = 90.8%, sensitivity = 90.7%, specificity = 90.9%) and in identifying AD-MCI and AD-D (AUC = 0.875, accuracy = 80.7%, sensitivity = 87.2%, specificity = 73.2%) compared to the other models. Additionally, radiomics features were correlated with MMSE scores, P-tau-181, and Aβ1–42 levels in AD. T1WI-based hippocampal radiomics features are valuable for diagnosing AD and identifying AD-MCI and AD-D. [ABSTRACT FROM AUTHOR]

It is critical to predict early recurrence (ER) after percutaneous thermal ablation (PTA) for hepatocellular carcinoma (HCC). We aimed to develop and validate a delta-radiomics nomogram based on multi-phase contrast-enhanced magnetic resonance imaging (MRI) to preoperatively predict ER of HCC after PTA. We retrospectively enrolled 164 patients with HCC and divided them into training, temporal validation, and other-scanner validation cohorts (n = 110, 29, and 25, respectively). The volumes of interest of the intratumoral and/or peritumoral regions were delineated on preoperative multi-phase MR images. Original radiomics features were extracted from each phase, and delta-radiomics features were calculated. Logistic regression was used to train the corresponding radiomics models. The clinical and radiological characteristics were evaluated and combined to establish a clinical-radiological model. A fusion model comprising the best radiomics scores and clinical-radiological risk factors was constructed and presented as a nomogram. The performance of each model was evaluated and recurrence-free survival (RFS) was assessed. Child-Pugh grade B, high-risk tumor location, and an incomplete/absent tumor capsule were independent predictors of ER. The optimal radiomics model comprised 12 delta-radiomics features with areas under the curve (AUCs) of 0.834, 0.795, and 0.769 in the training, temporal validation, and other-scanner validation cohorts, respectively. The nomogram showed the best predictive performance with AUCs as 0.893, 0.854, and 0.827 in the three datasets. There was a statistically significant difference in RFS between the risk groups calculated using the delta-radiomics model and nomogram. The nomogram combined with the delta-radiomic score and clinical-radiological risk factors could non-invasively predict ER of HCC after PTA. [ABSTRACT FROM AUTHOR]

Given the risk of infection through face-touching behaviors, investigators have called for more research into the development of interventions to reduce the frequency of face-touching. The current study aims to test the effectiveness of messages on reducing face-touching behaviors. Nine different messages that highlighted the risk of face-touching were developed. Study 1, an online survey-experiment with a national sample of US adults (N = 998), examined message-, risk perceptions, and face-touching-related behavioral intentions. The most promising messages identified in study 1 were then tested in study 2, a follow-up behavioral observation study with a class of undergraduate students. Students' face-touching behaviors were observed during a 4-week period when intervention versus control messages were displayed in the classroom. Four messages performed better in study 1, 2 of which were selected to test the actual message effectiveness in study 2. Study 2 results showed that on average, students touched their faces less frequently when a "Don't touch your face" message was present, although such decrease was not statistically significant. Having reminder messages of "Don't touch your face" in public spaces hold the potential to be a low-cost, effective strategy to reduce face-touching behaviors. [ABSTRACT FROM AUTHOR]

To explore the optimal plan for the timing of indwelling gastric tube placement in oral and maxillofacial malignant tumor patients. A prospective randomized controlled trial. 80 patients with oral and maxillofacial tumor were selected, and 40 patients were Pre-operative group. The remaining 40 patients were the control group, called Postoperative group. The body weight and hospital stay of the two groups were observed before and after surgery. Blood samples were taken before surgery and 1, 3 and 7 days after surgery to detect hemoglobin and plasma albumin. The number of postoperative hospitalization days in the pre-operative group was significantly lower than that in the post-operative group; postoperative hemoglobin and plasma albumins were lower in both groups compared with the preoperative level. Preoperative nasogastric tube ensured early postoperative administration of gastrointestinal nutrition, promoted postoperative plasma albumin recovery, and shortened the days of hospitalization. [ABSTRACT FROM AUTHOR]

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Five previously undescribed chromane-type meroditerpenoids, sargasilols J–N (1 – 5), were isolated from an EtOAc-soluble extract of the brown alga Sargassum siliquastrum collected in the China Sea. The chemical structures of these meroditerpenoids were determined by extensive spectroscopic analyses, including 1D/2D NMR, ECD, and HR-ESI-MS data. Compound 3 exhibited potent anti-neuroinflammatory activity against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV-2 microglia cells, with an IC 50 value of 9.9 μ M. [Display omitted] • Five previously undescribed chromane meroditerpenoids, sargasilols J–N (1 – 5), were isolated from the brown alga Sargassum siliquastrum. • Their chemical structures were established extensive spectroscopic analyses, including 1D and 2D NMR, ECD, and HR-ESI-MS data. • All compounds were evaluated for their anti-neuroinflammatory activities. [ABSTRACT FROM AUTHOR]

Childhood cancer survivors (CCS) are at increased risk for keratinocyte carcinomas (KC) however, the long-term incidence of single and multiple KC is not well established. Identify risk factors and quantify KC cumulative incidence and multiple-incidence burden in CCS. KC were identified among Childhood Cancer Survivor Study participants, a cohort of 5-year cancer survivors diagnosed <21 years of age between 1970 and 1999 in North America. Cumulative incidence was estimated and multivariable models assessed relative rates of KC associated with survivor and treatment characteristics. Among 25,658 participants, 1446 developed 5363 KC (93.5% basal cell carcinoma, 6.7% squamous cell carcinoma; mean age 37.0 years (range 7.3-67.4), mean latency 25.7 years; 95.3% White and 88.4% with radiotherapy). Mean lesion count was 3.7 with 26.1% experiencing ≥4. Radiotherapy imparted a 4.5-fold increase in the rate of any KC and 9.4-fold increase in the rate of ≥4 KC. Allogeneic and autologous hematopoietic cell transplant were associated with a 3.4- and 2.3-fold increased rate of KC, respectively. Participant self-reporting of some data including race without skin phototype and past medical history may have impacted analysis. The burden of KC in CCS remains high, but predictable risk factors should guide screening. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the impact of ultra-processed food (UPF) on type 2 diabetes (T2D), cardiovascular disease (CVD), hypertension, and cardiometabolic multimorbidity (CMM), and to explore the role of genetic susceptibility in these associations. 90 631 participants from the UK Biobank were included (collected between 2006 and 2010). The outcomes assessed included T2D, CVD, hypertension and CMM. The Cox proportional hazards model was used to evaluate their associations and the potential modification by genetic risk, which was estimated using the polygenic risk score (PRS). Participants with high UPF consumption had a higher risk of T2D, CVD, and CMM, with the adjusted hazard ratio (HR) of 1.36 (95 % confidence interval [CI]: 1.15, 1.61), 1.13 (95%CI: 1.03, 1.23), and 1.14 (95%CI: 1.05, 1.24), respectively. Those with high UPF consumption and high PRS for T2D, CVD, and hypertension had the highest risk of T2D (HR: 4.01; 95%CI: 2.83, 5.69), CVD (HR: 2.18; 95%CI: 1.86, 2.56), and hypertension (HR: 1.79; 95%CI: 1.61, 1.99), respectively. In participants with one cardiometabolic disease (CMD), those with high UPF consumption and high PRS T2D or PRS CVD had the highest risk of developing CMM. A significant additive interaction was observed between PRS T2D and UPF consumption on the risk of T2D. Our study underscored the importance of identifying individuals with high UPF consumption for targeted dietary interventions to mitigate the risk of CMDs and CMM, particularly among those with a high genetic risk of CMDs. • Higher UPF consumption was associated with a higher risk of T2D, CVD, and CMM. • High UPF consumption and high T2D-PRS were associated with a higher risk of T2D. • Limiting UPF consumption is essential for primary and secondary prevention of CMDs. [ABSTRACT FROM AUTHOR]

Excessive subendothelial retention of oxidized low-density lipoprotein (oxLDL) and subsequent oxLDL engulfment by macrophages leads to the formation of foam cells and the development of atherosclerosis. Our previous study showed that the plasma level of sialic acid-binding immunoglobulin-like lectin 5 (Siglec-5) was a novel biomarker for the prognosis of atherosclerosis in diabetic patients. However, the role and underlying mechanisms of Siglec-5 in atherosclerosis have not been elucidated. The interaction between oxLDL and Siglec-5 was detected by fluorescence colocalization and coimmunoprecipitation. The effect of oxLDL on Siglec-5 expression was detected in endothelial cells and macrophages, and the effect of Siglec-5 on oxLDL transcytosis and uptake was investigated. Siglec-5 was overexpressed in mice using recombinant adeno-associated virus vector serotype 9 (rAAV9-Siglec-5) to evaluate the effect of Siglec-5 on oxLDL uptake and atherogenesis in vivo. In addition, the effects of Siglec-5 antibodies and soluble Siglec-5 proteins on oxLDL transcytosis and uptake and their role in atherogenesis were investigated in vivo and in vitro. We found that oxLDL interacted with Siglec-5 and that oxLDL stimulated the expression of Siglec-5. Siglec-5 promotes the transcytosis and uptake of oxLDL, while both anti-Siglec-5 antibodies and soluble Siglec-5 protein attenuated oxLDL transcytosis and uptake. Interestingly, overexpression of Siglec-5 by recombinant adeno-associated viral vector serotype 9 (rAAV9-Siglec-5) promoted the retention of oxLDL in the aorta of C57BL/6 mice. Moreover, overexpression of Siglec-5 significantly accelerated the formation of atherosclerotic lesions in Apoe−/− mice. Moreover, both anti-Siglec-5 antibodies and soluble Siglec-5 protein significantly alleviated the retention of oxLDL in the aorta of rAAV9-Siglec-5-transfected C57BL/6 mice and the formation of atherosclerotic plaques in rAAV9-Siglec-5-transfected Apoe−/− mice. Our results suggested that Siglec-5 was a novel receptor that mediated oxLDL transcytosis and promoted the formation of foam cells. Interventions that inhibit the interaction between oxLDL and Siglec-5, including anti-Siglec-5 antibody or soluble Siglec-5 protein treatment, may provide novel therapeutic strategies in treating atherosclerosis. [ABSTRACT FROM AUTHOR]

Effective self-management after total knee arthroplasty (TKA) not only improves patients' knee pain and physical function but also improves quality of life. However, there is no assessment tool that can be targeted to evaluate the self-management level of patients after TKA. This study aimed to develop and validate a scale to specifically assess the level of self-management in patients after TKA. The study was conducted in 2 steps: (1) instrument development and (2) psychological tests (n = 428). For the instrument development portion, scale items were generated through a literature review and semi-structured interviews, then reviewed and revised by a panel of experts, and assessed for content validity and pilot testing. For the psychometric tests component, items were analyzed using corrected item-total scale correlations, the critical ratio method, and Cronbach's α. Construct validity was evaluated using exploratory factor analysis and validation factor analysis. Criterion correlation validity was checked by calculating Pearson's correlation coefficient using the Arthritis Self-Efficacy Scale-8 and the scale developed in this study. Internal consistency reliability was evaluated using Cronbach's α and fold-half reliability, and retest reliability was assessed using intragroup correlation coefficients. The Patient Self-Management Scale after Total Knee Arthroplasty (PSMS-TKA) comprises 4 factors and 23 items that assess daily behavior management, disease information management, psychosocial management, and exercise rehabilitation management. Exploratory factor analysis and validation factor analysis yielded a stable 4-factor model for the 23 items. The PSMS-TKA demonstrated good criterion-related validity when using the Arthritis Self-Efficacy-8 as a criterion. The Cronbach's α of the PSMS-TKA was 0.903, the split-half reliability was 0.934, and the test-retest reliability correlation coefficient was 0.887 (P <.01); thus, the reliability of the scale is good. The PSMS-TKA developed in this study has good validity and reliability and can be used to assess the level of self-management in patients after TKA. The scale helps healthcare professionals understand the level of self-management of patients undergoing TKA. [ABSTRACT FROM AUTHOR]

[Display omitted] • Mafic dikes of Emeishan Large Igneous Province are discovered in Yidun Terrane. • This proves that Yidun Terrane was part of Yangtze Craton in the Permian. • Yidun Terrane is a new exploration frontier for magmatic Fe-Ti-V oxide deposits. Due to the lack of paleomagnetic data and paleoclimatic records, the paleocontinental belonging of the Yidun terrane in northeastern Tibet plateau is debated. In this paper, we use the distribution of the Emeishan large igneous province (ELIP) to put the issue to rest. The ELIP is the product of mantle plume activity, which took place at 260 ± 3 Ma in the western margin of the Yangtze craton. The Yangtze craton is the northern part of the South China paleocontinental block. Our new discovery of four mafic dikes in the Yidun terrane with ages and chemistry like the ELIP strongly supports a new interpretation that this terrane was an integral part of the Yangtze craton during the ELIP magmatic event. Baddeleyites from these mafic dikes yield the U–Pb ages of 257.1 ± 4.8, 259.8 ± 8.5, 260.2 ± 4.5 and 261.5 ± 6.8 Ma for each of these dikes, which are similar to the zircon U-Pb ages of the mafic–ultramafic intrusions of the ELIP within the Yangtze craton. The Yidun mafic dikes and some high-Ti basalts of the ELIP within the Yangtze craton have similar Sr-Nd isotope compositions and mantle-normalized incompatible trace element distribution patterns, indicating similar mantle source compositions. Mixing calculation using Sr-Nd isotope compositions shows that the parental magmas for the Yidun mafic dikes experienced only 2–3 % crustal contamination. Partial melting modelling shows that the primary magmas for the Yidun mafic dikes were produced by 5–6 % mantle partial melting at the depths > 85 km below surface, consistent with mantle plume-related magmatism in a continental setting. The Yidun terrane is a new exploration frontier for magmatic Fe-Ti-V oxide deposits that are present elsewhere in the ELIP. [ABSTRACT FROM AUTHOR]

To study the multilevel coupled vibration of a naval gun under the foundation motion excitation of the ship, a mechanical-electrical-hydraulic coupled dynamic model of the naval gun including the follow-up systems' influence was established. The subprogram for calculating the ship foundation motion was written by the harmonic superposition method, and the motion in the 3 and 5-scale sea waves was reconstructed, respectively. Based on the multidisciplinary simulation, the transmission characteristics of the ship's foundation motion excitation along the naval gun and the influence of the tooth arc arrangement on the stabilization accuracy of the naval gun are analyzed. The results show that: the foundation motion excitation of the ship will aggravate the imbalance of the contact forces at the left and right trunnions of the cradle. A bilateral symmetrical arrangement scheme of the tooth arcs can reduce the contact forces' imbalance at the trunnions and reduce the adverse influence on the stabilization accuracy of the naval gun. The relevant research provides theoretical support and technical guidance for the structural design or verification of the naval gun. [ABSTRACT FROM AUTHOR]

In this paper, we present a novel approach based on Bayesian Expectation Maximization-Maximization (BEMM) to address this challenge. Unlike traditional optimization methods, which may struggle with high-dimensional and nonlinear optimization problems, BEMM offers a robust framework that combines the benefits of Bayesian inference with the flexibility of expectation maximization and maximization techniques. By iteratively updating parameter estimates based on observed data and maximizing the likelihood of the model, BEMM effectively navigates the solution space to converge on accurate estimates of the unspecified variables in Proton Exchange Membrane Fuel Cells (PEMFCs)models. Through extensive experimentation and comparison with other metaheuristic techniques, including Arithmetic Optimization Algorithm (AOA), Gravitational Search Algorithm (GSA), Flower Pollination Algorithm (FPA), and Biogeography-Based Optimization (BBO), we demonstrate the superior performance of our BEMM approach. Our results show that BEMM outperforms these alternative methods in terms of precision, convergence speed, and stability across various scenarios involving different numbers of unspecified variables. The implications of our findings are significant for both researchers and practitioners in the field of PEMFC modeling and optimization. By providing a more efficient and reliable method for estimating model parameters, our approach can facilitate more accurate predictions of PEMFC performance, leading to better-informed decision-making in the design, operation, and optimization of PEMFC systems. Furthermore, the robustness and versatility of BEMM make it well-suited for a wide range of optimization problems beyond PEMFC modeling, highlighting its potential impact across various domains of engineering and scientific research. In the sensitivity analysis, as the population size increases from 10 to 40, there is a significant improvement in solution quality by approximately 100 %. However, beyond a population size of 40, the marginal gains diminish, with only marginal improvements of less than 1 % observed despite further increases in population size up to 200. [ABSTRACT FROM AUTHOR]

Fructose is associated with colorectal cancer tumorigenesis and metastasis through ketohexokinase-mediated metabolism in the colorectal epithelium, yet its role in the tumor immune microenvironment remains largely unknown. Here, we show that a modest amount of fructose, without affecting obesity and associated complications, promotes colorectal cancer tumorigenesis and growth by suppressing the polarization of M1-like macrophages. Fructose inhibits M1-like macrophage polarization independently of fructose-mediated metabolism. Instead, it serves as a signal molecule to promote the interaction between hexokinase 2 and inositol 1,4,5-trisphophate receptor type 3, the predominant Ca2+ channel on the endoplasmic reticulum. The interaction reduces Ca2+ levels in cytosol and mitochondria, thereby suppressing the activation of mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 1 (STAT1) as well as NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation. Consequently, this impedes M1-like macrophage polarization. Our study highlights the critical role of fructose as a signaling molecule that impairs the polarization of M1-like macrophages for tumor growth. [Display omitted] • Fructose suppresses M1-like tumor-associated macrophage polarization • Fructose enhances the interaction between HK2 and ITPR3 in BMDMs • Fructose restrains inflammasome formation by regulating calcium flux • Macrophage GLUT5 expression positively relates to human colorectal cancer progression Yan et al. report that fructose promotes the progression of colorectal cancer by inhibiting M1-like tumor-associated macrophage polarization. Specifically, fructose functions as a signaling molecule, enhancing the interaction between HK2 and ITPR3, which disrupts intracellular calcium signaling, thereby impeding M1-like macrophage polarization. [ABSTRACT FROM AUTHOR]

G protein-coupled receptors (GPCRs) mediate most cellular responses to hormones, neurotransmitters, and environmental stimulants. However, whether GPCRs participate in tissue homeostasis through ferroptosis remains unclear. Here we identify that GPR56/ADGRG1 renders cells resistant to ferroptosis and deficiency of GPR56 exacerbates ferroptosis-mediated liver injury induced by doxorubicin (DOX) or ischemia-reperfusion (IR). Mechanistically, GPR56 decreases the abundance of phospholipids containing free polyunsaturated fatty acids (PUFAs) by promoting endocytosis-lysosomal degradation of CD36. By screening a panel of steroid hormones, we identified that 17α-hydroxypregnenolone (17-OH PREG) acts as an agonist of GPR56 to antagonize ferroptosis and efficiently attenuates liver injury before or after insult. Moreover, disease-associated GPR56 mutants were unresponsive to 17-OH PREG activation and insufficient to defend against ferroptosis. Together, our findings uncover that 17-OH PREG-GPR56 axis-mediated signal transduction works as a new anti-ferroptotic pathway to maintain liver homeostasis, providing novel insights into the potential therapy for liver injury. [Display omitted] • GPR56 is a potent ferroptosis suppressor • GPR56 remodels lipid metabolism to defend against ferroptosis via downregulating CD36 • Identification of 17-OH PREG as a potent agonist of GPR56 to inhibit ferroptosis • Targeting the GPR56-17-OH PREG-CD36 axis is beneficial for ferroptosis-induced liver injury Lin et al. found that adhesion GPCR family member GPR56 remodels CD36-mediated lipid metabolism to defend against ferroptosis. They also identified that 17-OH PREG acts as the endogenous agonist of GPR56 to suppress ferroptosis. Targeting the GPR56-17-OH PREG-CD36 axis efficiently alleviated ferroptosis-induced liver injury. [ABSTRACT FROM AUTHOR]

Asthma is a common chronic respiratory disease in childhood, requiring effective management strategies. This study aims to evaluate the effectiveness of a nurse-led WeChat Mini Program in managing asthma among children aged 6 to 11 years. This randomized controlled trial adhered to the CONSORT checklist and was conducted at a tertiary hospital in China from January 2023 to August 2023. One hundred and eight children with asthma were randomly assigned to two groups, and 81 children completed the 6-month follow-up. All participants received asthma management from specialist nurses, including routine treatments such as inhaled corticosteroids. The experimental group also utilized the WeChat Mini Program for asthma management. Both groups underwent follow-up assessments at 3 and 6 months post-enrollment, which included the Childhood Asthma Control Test (C-ACT), asthma control levels, frequency of exacerbations, and lung function. At 3 and 6 months, the experimental group showed significantly higher C-ACT scores and a lower exacerbation frequency compared to the control group (p < 0.05). While Peak Expiratory Flow improved, Forced Expiratory Volume in 1 Second Percentage Predicted (FEV1%) and FEV1/FVC did not change significantly. The WeChat Mini Program significantly improved asthma control and reduced exacerbations but did not substantially enhance all lung function parameters. Further research is required to confirm its long-term effects. Incorporating a specialist nurse-led digital management tool, such as the WeChat Mini Program, into standard pediatric asthma care may offer an effective management strategy. • WeChat Program Management improved asthma control and lung function in children. • Asthma specialist nurses played an essential role in the management of asthma. • Effective asthma management reduced the frequency of acute exacerbations. [ABSTRACT FROM AUTHOR]

To develop and validate a psychometrically sound self-reported Paternal involvement in Early InfAnCy ScalE (PEACE) for Asian fathers with infants aged 0–12 months old. This study comprised of three phases: (1) Pilot test among 100 fathers, (2) Exploring and confirming the PEACE's multidimensional structure using exploratory factor analysis (EFA) (n = 200 fathers) and confirmatory factor analysis (CFA) (n = 200 fathers), and (3) Assessing one-month test-retest reliability of PEACE among 30 fathers. Data was collected from August 2022 to August 2023. The EFA was conducted using principal axis factoring and varimax rotation. The CFA confirmed the factor structure via goodness-of-fit statistics. To assess the PEACE's concurrent validity, paternal involvement was measured using a previously validated paternal involvement scale. Convergent validity was established by examining correlations between PEACE and theoretically related measures of parenting self-efficacy, parent-child bonding, parenting satisfaction, and depression. Test-retest reliability was examined using the intra-class correlation coefficient. The EFA and CFA results supported the five-factor 25-item PEACE. The five subscales were: i) Providing Tangible Support, ii) Meeting Basic Needs, iii) Bonding with Baby, iv) Decision-Making for Baby, and v) Sense of Responsibility and Accomplishment. All subscales reported good internal consistency and weak to moderate one-month test-retest reliability. Correlation coefficients between the PEACE and other scales supported the concurrent and convergent validity of the PEACE. This study provided sufficient evidence to establish the initial reliability and validity of the five-factor 25-item PEACE. The PEACE could be used to quantitatively assess paternal involvement in infant care. • The initial reliability and validity of the 25-item PEACE has been established. • PEACE can be used to quantitatively assess paternal involvement in infant care. • Public awareness campaigns on paternal involvement for local communities are needed. • Clinicians (especially nurses) can encourage fathers' involvement in decision-making for children. [ABSTRACT FROM AUTHOR]

This study aimed to ascertain the inhibitory effect of ginsenoside Rg3 (Rg3) combined with 5-fluorouracil (5-FU) on 5-FU-resistant cells HCT116/5-FU and its molecular mechanism. The HCT116 cell line resistant to 5-FU (HCT116/5-FU) was established by repeated exposure to gradually increasing 5-FU concentrations. The effects of different concentrations of Rg3 and 5-FU on colorectal cancer (CRC) cell proliferation were evaluated, and suitable concentrations were screened for subsequent experiments. The treatment efficacy of Rg3 and 5-FU alone and in combination with CRC cell activity was observed, and the inhibitory effect of Rg3 and 5-FU on the Hedgehog pathway was verified. Finally, the effects of Rg3 and 5-Fu on in vivo tumor formation were evaluated in vivo. Rg3 enhanced the therapeutic efficacy of 5-FU in HCT116 cells by inducing apoptosis and suppressing cell activities and epithelial-mesenchymal transition (EMT), showing strong anti-tumor effects. Rg3 enhances the chemosensitivity of drug-resistant HCT116/5-FU cells to 5-FU. Additionally, the expression of Hedgehog pathway-relevant proteins (PTCH1, PTCH2, GLI1, and SHH) was increased in drug-resistant HCT116/5-FU cells, and Rg3 and 5-FU co-treatment downregulated the expression of PTCH1, PTCH2, GLI1, and SHH proteins in HCT116/5-FU cells. Rg3 reversed 5-FU resistance via by modulating the Hedgehog pathway. Rg3, in combination with 5-FU, repressed human CRC xenograft growth in nude mice, suppressed the expression of the proliferative nuclear factor KI67 in tumors, and promoted apoptosis. Rg3 enhances the anticancer effects of 5-FU in CRC cells that are sensitive and resistant to 5-FU, and its mechanism of action may be related to the inhibition of Hedgehog pathway activation. [ABSTRACT FROM AUTHOR]

Adherent invasive Escherichia coli (AIEC) are enriched in IBD (inflammatory bowel disease) patients, but the role and mechanism of AIEC in the intestinal epithelial barrier is poorly defined. We evaluated the role of the AIEC strain E. coli LF82 in vitro and investigated the role of Th17 in this process. After coincubation with AIEC, the epithelial barrier integrity was monitored by epithelial resistance measurements. The permeability of the barrier was evaluated by TEER (trans -epithelial electrical resistance) and mucosal-to-serosal flux rate. The presence of interepithelial tight junction proteins ZO-1 and Claudin-1 were determined by immunofluorescence and western blot analysis. Cytokines in the cell culture supernatant were assayed by enzyme-linked immunosorbent assay (ELISA). AIEC infection decreased TEER and increased the mucosal-to-serosal flux rate of Lucifer yellow in the intestinal barrier model in a time- and dose-dependent manner. AIEC infection decreased the expression and changed the distribution of ZO-1 and claudin-1. It also induced the secretion of cytokines such as TNF-α and IL-17. AIEC strain E. coli LF82 increased the permeability and disrupted the tight junctions of the intestinal epithelial barrier, revealing that AIEC plays an aggravative role in the inflammatory response. [ABSTRACT FROM AUTHOR]