Savoring Belief, Resilience, and Meaning in Life as Pathways to Happiness: A Sequential Mediation Analysis among Taiwanese University Students.

In recent decades, scholarly interest has grown in the psychological components of happiness. Savoring belief, or the capacity to attend to, appreciate, and enhance the positive experiences in one's life, along with resilience and meaning in life, have emerged as significant predictors of enhanced happiness among diverse populations. This research examined the interrelationships among savoring belief, resilience, meaning in life, and happiness. A sample of 561 students from 75 universities in Taiwan, comprising 361 female and 200 male participants with an average age of 20.88 years, participated in an online survey. The study employed various instruments, including the Savoring Belief Inventory, the Subjective Happiness Scale, the Brief Resilience Scale, and the Meaning in Life Questionnaire. These instruments were translated into Traditional Chinese using a back-translation method and subsequently validated for accuracy by specialists in the field. Analysis of the data using Hayes' PROCESS Model 6 revealed several key insights: (1) savoring belief positively influenced happiness, resilience, and meaning in life with resilience further enhancing happiness and meaning in life; (2) resilience served as a significant mediator in the relationship between savoring belief and happiness; (3) meaning in life significantly mediated the relationship between savoring belief and happiness; (4) a sequential mediation model illustrated the mediating effects of resilience and meaning in life on the relationship between savoring belief and happiness. This study illustrates that, much like a garden requires water, sunlight, and care to flourish, our happiness is cultivated through enhancing our ability to savor the good moments, rebound from challenges, and find deep significance in our lives. We can significantly boost well-being by fostering these qualities-savoring belief, resilience, and a sense of meaning. These findings are particularly relevant for educators, highlighting the critical need to develop these traits in students to promote greater happiness and fulfillment in their lives. Discussions included theoretical implications, educational implications, and avenues for future research.

Development of amine-sensitive intelligent film with MIL-100(Fe) as function filler based on anthocyanins/pectin for monitoring chilled meat freshness.

To enhance the amine-sensitivity of intelligent films for accurate monitoring of chilled meat freshness, different additions (0, 1, 2, 3 wt%) of MIL-100(Fe) were incorporated into the matrix composed of anthocyanins (ANs) and pectin (P). Results indicated that the tensile strength, thermal stability, barrier performance and absorption capacity of the films with MIL-100(Fe) were improved significantly (p < 0.05). Especially, the film with 2 % MIL-100(Fe) exhibited the best performance due to its compact structure and the highest crystallinity. Additionally, adsorption isotherms of the films with MIL-100(Fe) were fitted on the Langmuir and the Freundlich isotherm, and adsorption kinetics were fitted on the pseudo-second-order model and Elovich model, respectively (R2 > 0.96), suggesting a combined mechanism of chemisorption and intraparticle diffusion. Besides, when the films were exposed in ammonia environment, they changed color from purple to blue-violet, finally to green. Ultimately, film with 2 % MIL-100(Fe) was used to monitor the chilled meat freshness, as expected, similar color variation was observed at three stages of meat freshness (fresh, sub-fresh, and spoiled), which enabled the accurate differentiation of meat freshness. Thus, films with MIL-100(Fe) demonstrated the potential to be amine-sensitive intelligent packaging for monitoring chilled meat freshness in real time.

Zhilining Formula alleviates DSS-induced colitis through suppressing inflammation and gut barrier dysfunction via the AHR/NF-κBp65 axis.

BACKGROUND: Repairing the intestinal mucosal barrier and reducing persistent inflammation is the key strategies for the treatment of ulcerative colitis (UC). Zhilining Formula (ZLN), composed of Andrographis herba (AH), Sophorae flavescentis radix (SFA), and Aucklandia radix (AR), is a well-tried formula for the clinical treatment of enteritis and dysentery in China, and its mechanism has not been clarified. PURPOSE: This study aims to investigate the effect of ZLN on UC and elucidate its underlying mechanism via metabolomics analysis and experimental verification. METHODS: The effect of ZLN on UC was evaluated in a 3.5 % dextran sulfate sodium (DSS)-induced mice model via the body weight, disease activity index (DAI), colon length, colonic histopathology, expression of inflammation factors, and intestinal barrier in mice. An UPLC-Q-TOF-MS/MS approach-based metabolomics analysis was performed to preliminary explore the mechanism of ZLN in colitis. Based on the results of metabolomics analysis, the expression of related protein or mRNA in AHR/NF-κBp65 axis was determined by qPCR and western blotting. Moreover, the potential interactions of active ingredients of ZLN with NF-κBp65 and AHR were investigated in vitro through using agonists and inhibitors of NF-κBp65 and AHR, respectively. RESULTS: ZLN alleviated body weight loss and colonic shortening in colitis mice, and down-regulated the DAI and histopathological score as well. ZLN also decreased the levels of inflammatory factors (MPO, IL-1ß, TNF-α and IL-18), protected goblet cell function and intestinal barrier in DSS-induced mice. Metabolomics results revealed that 36 metabolites that were significantly altered in mice after induction with DSS, which involved in 16 metabolic pathways, including biosynthesis of unsaturated fatty acid, phenylalanine metabolism, arachidonic acid (AA) metabolism, tryptophan (Trp) metabolism, retinol metabolism, and sphingolipid metabolism, etc. ZLN restored 26 different metabolites (DEMs) of them to normal-like levels, indicating ZLN regulated the AA metabolism and Trp-metabolism in UC mice, which hinted its potential pharmacological mechanism related to AHR/NF-κBp65 axis. We further confirmed that ZLN could restrain the activation of NF-κBp65 signaling pathway and then inhibit the expression of its mediated inflammatory cytokines, such as IL-1ß, TNF-α, COX-2 and IL17A. Moreover, ZLN increased nuclear translocation of AHR and IL22 expression, which is an important regulatory signal for intestinal mucosal barrier repaired. Finally, we elucidated in vitro that the active ingredients of ZLN exerted anti-colitis effects by activating AHR and simultaneously inhibiting NF-κBp65. CONCLUSION: ZLN relieved colitis by AHR/NF-κBp65 axis. This study highlighted the important role of AHR and NF-κBp65 in UC, and provided a theoretical basis for the application of ZLN.

Potential of using qFibrosis analysis to predict recurrent and survival outcome of patients with hepatocellular carcinoma after hepatic resection.

BACKGROUND: There remains a lack of studies addressing the stromal background and fibrosis features and its prognostic value in liver cancer. qFibrosis can identify, quantify and visualize the fibrosis features from biopsy samples. In this study, we aim to demonstrate the prognostic value of histological features by using qFibrosis analysis in liver cancer patients. METHODS: Liver specimen from 201 patients with hepatocellular carcinoma underwent curative resection were imaged and assessed using qFibrosis system, and generated a total of 33 and 156 collagen parameters from tumor part and non-tumor liver tissue, respectively. We used these collagen parameters on patients to build two combined indexes, RFS-index and OS-index, in order to differentiate patients with early recurrence and early death, respectively. The models were validated using leave-one-out method. RESULTS: Both combined indexes had significant prediction value of patients' outcome. The RFS-index of 0.52 well differentiates patients with early recurrence (p < 0.001), and the OS-index of 0.73 well differentiates patients with early death during follow-up (p = 0.02). CONCLUSIONS: Combined index calculated with qFibrosis from digital readout of fibrotic status of peri-tumor liver specimen in patients with HCC have prediction values for their disease and survival outcomes. These results demonstrated the potentials to transform histopathological features into quantifiable data that could be used to correlate with clinical outcome.

Plasma Cell-Free Adenomatous Polyposis Coli Gene Promoter Methylation as a Prognostic Biomarker for Hepatocellular Carcinoma.

INTRODUCTION: Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide. Lack of biomarkers for follow-up after treatment is a clinical challenge. DNA methylation has been proposed to be a potential biomarker in HCC. However, there is still lacking of evidence of its clinical use. This study aims to evaluate the value of using plasma Adenomatous Polyposis Coli promoter methylation level (APC-MET) as a potential biomarker in HCC treatment. METHOD: A total of 96 patients with HCC at BCLC stage B underwent local tumor ablation treatment were prospectively included in this study. APC-MET was examined from the plasma of each patient before and 1 months after treatment. The prediction value of APC-MET for survival outcome and disease status after treatment were analyzed, and adjusted with alpha-fetoprotein and protein induced by vitamin K absence-II using cox regression analysis. RESULTS: Univariate cox regression analysis showed preoperative APC-MET >0 (HR, 2.9, 95% CI 1.05－8.05, p=0.041) and postoperative APC-MET >0 (HR, 3.47, 95% CI 1.16－10.4, p=0.026) were both predictors of death, and preoperative APC-MET >0 was a predictor of disease progression after treatment (HR, 2.04, 95% CI 1.21－3.44, p=0.007). In multivariate models, pre-op APC-MET >0 was a significant predictor of disease progression after adjusting with other two traditional biomarkers (HR, 1.82, 95% CI 1.05－3.17, p=0.034). CONCLUSIONS: Hypermethylation of APC promoter appears to be a potential biomarker that could predict patient survival and disease progression outcome in patients with intermediate stage HCC after local ablation treatment.

Computed Tomography-Defined Sarcopenia in Outcomes of Patients with Unresectable Hepatocellular Carcinoma Undergoing Radioembolization: Assessment with Total Abdominal, Psoas, and Paraspinal Muscles.

Introduction: Sarcopenia is an adverse prognostic factor in patients with liver cirrhosis and hepatocellular carcinoma (HCC). Image-based sarcopenia assessment allows a standardized method to assess abdominal skeletal muscle. However, which is an index muscle for sarcopenia remains unclear. Therefore, we investigated whether sarcopenia defined according to different muscle groups with computed tomography (CT) scans can predict the prognosis of HCC after radioembolization. Methods: In this retrospective study, we analyzed patients who underwent radioembolization for unresectable HCC between January 2010 and December 2019. Before treatment, the total abdominal muscle (TAM), psoas muscle (PM), and paraspinal muscle (PS) areas were evaluated using a single CT slice at the third lumbar vertebra. In previous studies, sarcopenia was determined using the TAM, PM, and PS after stratifying by sex. Finally, we investigated each muscle-defined sarcopenia to decide whether or not it can serve as a prognostic factor for overall survival (OS). Results: We included 92 patients (74 men and 18 women). TAM, PM, and PS areas were significantly higher in the men than in the women (all p < 0.05). The patients with sarcopenia defined using PM, but not TAM and PS, exhibited significantly poorer OS than those without sarcopenia (median 15.3 vs. 23.8 months, p = 0.034, 0.821, and 0.341, respectively). After adjustment for clinical variables, such as body mass index, liver function, alpha-fetoprotein level, clinical staging, treatment response, and posttreatment curative therapy, PM-defined sarcopenia (hazard ratio: 1.899, 95% confidence interval: 1.087-3.315) remained an independent predictor for the poor OS. Conclusion: CT-assessed sarcopenia defined using PM was an independent prognostic factor for the poorer prognosis of unresectable HCC after radioembolization.

DNA Methylation Biomarkers as Prediction Tools for Therapeutic Response and Prognosis in Intermediate-Stage Hepatocellular Carcinoma.

INTRODUCTION: Alfa-fetoprotein (AFP), as the main serum tumor marker of hepatocellular carcinoma (HCC), is limited in terms of specificity and ability to predict outcomes. This study investigated the clinical utility of DNA methylation biomarkers to predict therapeutic responses and prognosis in intermediate-stage HCC. METHODS: This study enrolled 72 patients with intermediate-stage HCC who underwent locoregional therapy (LRT) between 2020 and 2021. The immediate therapeutic response and disease status during a two-year follow-up were recorded. Analysis was performed on 10 selected DNA methylation biomarkers via pyrosequencing analysis of plasma collected before and after LRT. RESULTS: Analysis was performed on 53 patients with complete responses and 19 patients with disease progression after LRT. The mean follow-up duration was 2.4 ± 0.6 years. A methylation prediction model for tumor response (MMTR) and a methylation prediction model for early progression (MMEP) were constructed. The area under the curve (AUC) for sensitivity and specificity of MMTR was 0.79 for complete response and 0.759 for overall survival. The corresponding AUCs for sensitivity and specificity of AFP and protein induced by vitamin K absence-II (PIVKA-II) were 0.717 and 0.708, respectively. Note that the MMTR index was the only significant predictor in multivariate analysis. The AUC for sensitivity and specificity of the MMEP in predicting early progression was 0.79. The corresponding AUCs for sensitivity and specificity of AFP and PIVKA-II were 0.758 and 0.714, respectively. Multivariate analysis revealed that platelet count, beyond up-to-7 criteria, and the MMEP index were strongly correlated with early tumor progression. Combining the indexes and serum markers further improved the predictive accuracy (AUC = 0.922). Multivariate analysis revealed the MMEP index was the only independent risk factor for overall survival. DISCUSSION/CONCLUSIONS: This study indicates that these methylation markers could potentially outperform current serum markers in terms of accuracy and reliability in assessing treatment response and predicting outcomes. Combining methylation markers and serum markers further improved predictive accuracy, indicating that a multi-marker approach may be more effective in clinical practice. These findings suggest that DNA methylation biomarkers may be a useful tool for managing intermediate-stage HCC patients and guiding personalized treatment, particularly for those who are at high risk for close surveillance or adjuvant treatment after LRT.

NiPd co-doped nitrogen-coordinated graphene as a high-efficiency electrocatalyst for oxygen reduction reactions: a first-principles determination.

High-energy-density fuel cells and metal-air batteries are difficult to commercialize on a large scale mainly because of the sluggish oxygen reduction reaction (ORR) at the cathode. Hence, the development of high-efficiency and low-cost electrocatalysts as Pt substitutes for the ORR is of significance for the mass applications of these devices. In this work, we thoroughly investigated the structural and catalytic properties of NiPd co-doped N-coordinated graphene (denoted as NiPdN6-G) as an ORR electrocatalyst by using density-functional theory (DFT) calculations. Our results show that NiPdN6-G is structurally and thermodynamically stable. Furthermore, we explored all the possible paths and intermediates of the ORR, and identified the preferable active sites and the most stable adsorption configurations of the intermediates and transition states. In general, there are 15 possible reaction paths, of which 8 paths have lower energy barriers than pure Pt, and the maximum energy barrier and overpotential of the ORR for the optimal path are only 0.14 eV and 0.37 V, respectively. This work demonstrates that NiPdN6-G should be a promising candidate for substituting Pt and Pt-based catalysts for the ORR in energy conversion and storage devices.

Versatile and Accessible Magnetic Diagnosis Platform with Different Types of Magnetic Particles for Liquid and Solid Biopsies.

The diagnosis of liquid and solid biopsies by different instruments makes the clinic loading difficult in many aspects. Given the compositions of magnetic particles (MPs) with diverse characterizations and the innovative acoustic type of vibration sample magnetometer (VSM), the versatile, accessible magnetic diagnosis platform was proposed to meet clinical demands, such as low loading for multiple biopsies. In liquid biopsies of alpha-fetoprotein (AFP) standard solutions and subject serums, molecular concentration was analyzed from saturation magnetization by the soft type of Fe3O4 MPs with AFP bioprobe coating. In the phantom mixture simulated as bounded MPs in tissue, the bounded MPs was evaluated from the area of the hysteresis loop by hard type of cobalt MPs without bio-probes coating. Not only a calibration curve was founded for many hepatic cell carcinoma stages, but also microscale images verified the Ms increase due to magnetic protein clusters, etc. Hence, its wide populations in clinics could be expected.

Optimization of nutrient utilization efficiency and productivity for algal cultures under light and dark cycles using genome-scale model process control.

Algal cultivations are strongly influenced by light and dark cycles. In this study, genome-scale metabolic models were applied to optimize nutrient supply during alternating light and dark cycles of Chlorella vulgaris. This approach lowered the glucose requirement by 75% and nitrate requirement by 23%, respectively, while maintaining high final biomass densities that were more than 80% of glucose-fed heterotrophic culture. Furthermore, by strictly controlling glucose feeding during the alternating cycles based on model-input, yields of biomass, lutein, and fatty acids per gram of glucose were more than threefold higher with cycling compared to heterotrophic cultivation. Next, the model was incorporated into open-loop and closed-loop control systems and compared with traditional fed-batch systems. Closed-loop systems which incorporated a feed-optimizing algorithm increased biomass yield on glucose more than twofold compared to standard fed-batch cultures for cycling cultures. Finally, the performance was compared to conventional proportional-integral-derivative (PID) controllers. Both simulation and experimental results exhibited superior performance for genome-scale model process control (GMPC) compared to traditional PID systems, reducing the overall measured value and setpoint error by 80% over 8 h. Overall, this approach provides researchers with the capability to enhance nutrient utilization and productivity of cell factories systematically by combining genome-scale models and controllers into an integrated platform with superior performance to conventional fed-batch and PID methodologies.

A Botanical Drug Extracted From Antrodia cinnamomea: A First-in-human Phase I Study in Healthy Volunteers.

LEAC-102 is an emerging drug extracted from the medicinal fungus Antrodia cinnamomea (AC), which is traditionally used to ameliorate fatigue and liver disorders arising from excessive alcohol consumption. AC has been used as a health product with an immunomodulatory function, but its anticancer effect has not been applied in clinical therapy as a drug. This first-in-human study examined the safety and tolerability of LEAC-102 as a new drug in healthy adults.This standard 3 + 3 dose-escalation study included 18 participants administered LEAC-102 at doses of 597.6, 1195.2, 1792.8, 2390.4, or 2988 mg/day for 1 month plus 7 days of safety follow-up. The maximum planned dose was 2988 mg. Dose-limiting toxicity (DLT) was monitored from the start of LEAC-102 administration up to the final visit. The dose of LEAC-102 was escalated to the subsequent cohort as long as there was no DLT in the previous cohort. Tolerability, clinical status, safety (by laboratory parameters), and adverse event occurrence were documented weekly during the treatment and 1 week after the conclusion of the treatment.All clinical biochemistry profiles were in the normal range, and no serious adverse effects were observed. The maximum tolerated dose of LEAC-102 was determined to be 2988 mg/day because one participant experienced urticaria. Additionally, our exploratory objectives revealed that LEAC-102 significantly elevated natural killer, natural killer T, and dendritic cells in a dose-dependent manner, activated effector T cells, and upregulated programmed cell death-1 expression.The outcomes suggested that LEAC-102 was well tolerated and safe in healthy adults and exhibited potential immunomodulatory function.Supplemental data for this article is available online at https://doi.org/10.1080/07315724.2022.2032868 .

Efficacy and safety of combined targeted therapy and immunotherapy versus targeted monotherapy in unresectable hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: Cancer therapy has evolved from non-specific cytotoxic agents to a selective, mechanism-based approach that includes targeted agents and immunotherapy. Although the response to targeted therapies for unresectable hepatocellular carcinoma (HCC) is acceptable with the improved survival, the high tumor recurrence rate and drug-related side effects continue to be problematic. Given that immune checkpoint inhibitor alone are not robust enough to improve survival in unresectable HCC, growing evidence supports the combination of targeted therapy and immunotherapy with synergistic effect. METHODS: Online databases including PubMed, EMBASE, Cochrane Library, and Web of Science were searched for the studies that compared targeted monotherapy with the combination therapy of targeted drug and checkpoint inhibitors in unresectable HCC patients. Eligibility criteria were the presence of at least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors (version 1.1) for unresectable HCC patients, an Eastern Cooperative Oncology Group performance status of 0-2, and a Child-Pugh score ≤ 7. Outcome measurements include overall survival (OS), progression-free survival (PFS), and treatment-related adverse event (TRAE). RESULTS: Three phase II/III randomized controlled trials were included in this study. The pooled results showed that combination therapy significantly improved survival than targeted monotherapy, in terms of OS (hazard ratio (HR) = 0.67; 95% confidence interval [CI]: 0.50-0.91) and PFS (HR = 0.58; 95% CI: 0.51-0.67), respectively. In the incidence of grade 3-5 TRAEs, the combination therapy was significantly higher than targeted monotherapy (odds ratio = 1.98; 95% CI: 1.13-3.48). CONCLUSION: For unresectable HCC, combined targeted drug and immunotherapy significantly improved survival compared with targeted monotherapy. However, the incidences of AEs of combinational therapy were higher than targeted monotherapy.

Clinical practice guidelines on image-guided thermal ablation of primary and metastatic lung tumors (2022 edition).

The main contents of the Clinical Practice Guidelines on Image-Guided Thermal Ablation (IGTA) of Primary and Metastatic Lung Tumors (2022 Edition) include the following: epidemiology of primary and metastatic lung tumors; the concepts of the IGTA and common technical features; procedures, indications, contraindications, outcomes evaluation, and related complications of IGTA on primary and metastatic lung tumors; and limitations and future development.

Enhancing SIRT1 Gene Expression Using Small Activating RNAs: A Novel Approach for Reversing Metabolic Syndrome.

Metabolic syndrome (MetS) is a pathological condition characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. Sirtuin 1 (SIRT1), a highly conserved histone deacetylase, is characterized as a key metabolic regulator and protector against aging-associated pathologies, including MetS. In this study, we investigate the therapeutic potential of activating SIRT1 using small activating RNAs (saRNA), thereby reducing inflammatory-like responses and re-establishing normal lipid metabolism. SIRT1 saRNA significantly increased SIRT1 messenger RNA (mRNA) and protein levels in both lipopolysaccharide-stimulated and nonstimulated macrophages. SIRT1 saRNA significantly decreased inflammatory-like responses, by reducing mRNA levels of key inflammatory cytokines, such as Tumor Necrosis Factor alpha, Interleukin 1 beta (IL-1ß), Interleukin 6 (IL-6), and chemokines Monocyte Chemoattractant Protein-1 and keratinocyte chemoattractant. SIRT1 overexpression also significantly reduced phosphorylation of nuclear factor-κB and c-Jun N-terminal kinase, both key signaling molecules for the inflammatory pathway. To investigate the therapeutic effect of SIRT1 upregulation, we treated a high-fat diet model with SIRT1 saRNA conjugated to a transferrin receptor aptamer for delivery to the liver and cellular internalization. Animals in the SIRT1 saRNA treatment arm demonstrated significantly decreased weight gain with a significant reduction in white adipose tissue, triglycerides, fasting glucose levels, and intracellular lipid accumulation. These suggest treatment-induced changes to lipid and glucose metabolism in the animals. The results of this study demonstrate that targeted activation of SIRT1 by saRNAs is a potential strategy to reverse MetS.

Thermally activated microstructural evolution of metallic heterophase nanoparticles: insights from molecular dynamics simulations.

A crystal phase is a key factor to determine the physical and chemical properties of crystalline materials. As a new class of nanoscale structures, heterophase nanoparticles, which assemble conventional and unconventional phases, exhibit exceptional properties in comparison with their single-phase counterparts. In this work, we explored the thermodynamic stability of Au, Co, and AuCo heterophase nanoparticles with fcc and hcp phases by using molecular dynamics simulations. These heterostructured nanoparticles were continuously heated to examine their thermally activated structural evolutions. Au and Co single-phase nanoparticles were also considered for comparison. The results show that the phase transition between fcc and hcp is absent in these heterophase nanoparticles despite the existence of an unconventional phase. Although the melting of Au and Co heterophase nanoparticles is homogeneous, AuCo heterophase nanoparticles show heterogeneous melting, i.e., the Au fcc domain firstly melts, followed by the melting of the Co hcp domain, exhibiting a typical two-stage melting characteristic and resulting in the existence of a solid-core/liquid-shell structure within a considerable temperature region. Furthermore, the mutual diffusion of atoms between fcc and hcp domains is observed in the Au and Co heterophase nanoparticles. However, the unidirectional diffusion from the Au domain to the Co domain is found in the AuCo heterophase nanoparticles prior to their overall melting. This study deepens the fundamental understanding of the thermodynamic evolution of metallic heterogeneous nanoparticles and provides mechanistic and quantitative guidance for the rational design and applications of nanoscale multiphase heterostructures.

Comparative Pharmacokinetics of Three Bioactive Diterpenoids of Rabdosia serra Extract in Normal and Con A-Induced Liver Injury Rats Using UPLC-MS/MS.

Rabdosia serra (Maxim.) Hara (R. serra), one of the source plants of "Xihuangcao", has been widely used as a Chinese folk herb with the concomitant function of both medicine and foodstuff for the prevention and treatment of liver disease. Diterpenoids were considered as the major bioactive components in R. serra, responsible for their effect on hepatoprotection in previous phytochemical and pharmacological studies, while few comparative pharmacokinetic studies have been conducted under the physiological and pathological conditions. To reveal the difference in the pharmacokinetics process of R. serra extract (RSE) in normal and Con A-induced liver injury rats, a rapid ultra-high-pressure liquid chromatography-tandem mass spectrometry method (total running time: 5 min) was established to simultaneously determine three bioactive diterpenoids (enmein, epinodosin, and isodocarpin) in rat plasma. The results showed significant differences in the pharmacokinetic properties of three analytes between the physiological and pathological states. Compared with normal rats, the AUC of the three analytes was remarkably higher in liver injury rats, while the Tmax, T1/2, and MRT were shortened. It indicated that RSE has higher exposure and quicker elimination in liver injury rats than that in normal rats. Our results suggested that the pharmacokinetics of hepatoprotective medications was affected by liver injury, which prospected to provide essential information for guiding the healthcare and clinical application of R. serra in pathological states.

Noninvasive assessment of liver function reserve with fluorescent dosimetry of indocyanine green.

Using in vivo multiphoton fluorescent dosimetry, we demonstrate that the clearance dynamics of Indocyanine Green (ICG) in the blood can quickly reveal liver function reserve. In normal rats, the ICG retention rate was below 10% at the 15-minute post-administration; While in the rat with severe hepatocellular carcinoma (HCC), the 15-minute retention rate is over 40% due to poor liver metabolism. With a 785 nm CW laser, the fluorescence dosimeter can evaluate the liver function reserve at a 1/10 clinical dosage of ICG without any blood sampling. In the future, this low-dosage ICG 15-minute retention dosimetry can be applied for the preoperative assessment of hepatectomy or timely perioperative examination.

A U-snake based deep learning network for right ventricle segmentation.

PURPOSE: Ventricular segmentation is of great importance for the heart condition monitoring. However, manual segmentation is time-consuming, cumbersome, and subjective. Many segmentation methods perform poorly due to the complex structure and uncertain shape of the right ventricle, so we combine deep learning to achieve automatic segmentation. METHOD: This paper proposed a method named U-Snake network which is based on the improvement of deep snake together with level set to segment the right ventricular in the MR images. U-snake aggregates the information of each receptive field which is learned by circular convolution of multiple dilation rates. At the same time, we also added dice loss functions and transferred the result of U-Snake to the level set so as to further enhance the effect of small object segmentation. Our method is tested on the test 1 and test 2 datasets in the right ventricular segmentation challenge (RVSC), which shows the effectiveness. RESULTS: The experiment showed that we have obtained good result in the RVSC. The highest segmentation accuracy on the right ventricular test set 2 reached a dice coefficient of 0.911, and the segmentation speed reached 5 fps. CONCLUSIONS: Our method, a new deep learning network named U-snake, has surpassed the previous excellent ventricular segmentation method based on mathematical theory and other classical deep learning methods, such as Residual U-net, Inception CNN, and Dilated CNN. However, it can only be used as an auxiliary tool instead of replacing the work of human beings.

Di-functional Cu2+-doped BiOCl photocatalyst for degradation of organic pollutant and inhibition of cyanobacterial growth.

Photocatalytic oxidation of contaminants in water has recently gained extensive attentions. In this study, Cu2+-doped BiOCl microsphere photocatalysts were prepared using solvothermal method. The effects of Cu2+ doping ratio on the morphological structures and photoelectric and photocatalytic properties of BiOCl were studied in detail. Results showed that Cu2+ doping affected the particle size of BiOCl microspheres. The introduction of Cu2+ ions gradually increased the light absorption range and decreased the electron recombination rate of photocatalysts as shown by ultraviolet-visible diffuse reflection and photoluminescence spectra. The best doping ratio was 0.25 Cu2+-BiOCl, showing the highest photocatalytic activity for rhodamine B (14.25 time higher than BiOCl) and a good inhibition of algal growth. The main reactants in the photocatalytic system were·OH and h+ (electron holes). Density functional theory (DFT) calculations further demonstrated that the doping of Cu2+ ions made the photogenerated carriers in BiOCl easier to generate and ensured the charge was transferred more rapidly. In conclusion, a novel high-efficiency multifunctional photocatalyst is proposed for the efficient organic pollutants removal and algae growth inhibition from water.

MTL-CEBPA Combined with Immunotherapy or RFA Enhances Immunological Anti-Tumor Response in Preclinical Models.

The transcription factor CEBPA is a master regulator of liver homeostasis, myeloid cell differentiation and is downregulated in several oncogenic diseases. MTL-CEBPA is a small activating RNA drug which upregulates gene expression of CEBPA for treatment of hepatocellular carcinoma (HCC). We investigate whether MTL-CEBPA has immune modulatory effects by combining MTL-CEBPA with an anti-PD-1 checkpoint inhibitor (CPI) and/or radiofrequency ablation (RFA) in two preclinical models. First, mice with two flanks of HCC tumors (BNL) were treated with combinations of RFA (right flank), anti-PD-1 or MTL-CEBPA. The reduction of the left flank tumors was most pronounced in the group treated with RFA+anti-PD1+MTL-CEBPA and 7/8 animals responded. This was the only group with a significant increase in CD8+ and CD49b+/CD45+ tumor infiltrating lymphocytes (TIL). Second, a combination of anti-PD-1+MTL-CEBPA was tested in a CT26 colon cancer model and this treatment significantly reduced tumor size, modulated the tumor immune microenvironment and increased TILs. These data suggest a clinical role for combination treatment with CPIs, RFA and MTL-CEBPA through synergistic priming of the immune tumor response, enabling RFA and CPIs to have a pronounced anti-tumor effect including activity in non-treated tumors in the case of RFA.