The relationship between mindfulness and cognitive reappraisal: the mediating role of emotional and interoceptive awareness.

Mindfulness and cognitive reappraisal have been recognized as two useful ways to regulate emotions. The former tends to cultivate an attitude of being open and accepting of emotional events; whereas the latter involves a top-down process of re-interpreting emotional events. However, it is unclear how mindfulness influences cognitive reappraisal. Hence, the current study mainly addressed this research issue by exploring the mediating role of emotional and interoceptive awareness. 372 participants were asked to report dispositional mindfulness, cognitive reappraisal, emotional awareness, and interoceptive awareness by means of corresponding questionnaires. First, we performed the Pearson Correlations among the four factors, then assessed the mediating role of emotional awareness and interoceptive awareness in the link between mindfulness and cognitive reappraisal in separated models. Last, we used structural equation modeling (SEM) to investigate the link when both emotional and interoceptive awareness acted as the mediating variables. Results showed that mindfulness was negatively correlated with cognitive reappraisal, emotional awareness, and interoceptive awareness; whereas emotional awareness, interoceptive awareness, and cognitive reappraisal were positively correlated with each other. Moreover, increased mindfulness had a significantly negative effect on cognitive reappraisal, by reducing emotional and interoceptive awareness separately or successively. Except for the No-worrying factor, the remaining seven factors of interoceptive awareness were significantly loaded onto the latent variable. The result reveals the negative relationship between mindfulness and cognitive reappraisal. This link is mediated by one's emotional awareness and interoceptive awareness independently or successively, which may reflect the intensity of externally-emotional reactivity that signify the need to regulate emotions by means of cognitive reappraisal.

Dizocilpine derivatives as neuroprotective NMDA receptor antagonists without psychomimetic side effects.

We aimed to prepare novel dibenzo [a,d][7]annulen derivatives that act on N-methyl-d-aspartate (NMDA) receptors with potential neuroprotective effects. Our approach involved modifying the tropane moiety of MK-801, a potent open-channel blocker known for its psychomimetic side effects, by introducing a seven-membered ring with substituted base moieties specifically to alleviate these undesirable effects. Our in silico analyses showed that these derivatives should have high gastrointestinal absorption and cross the blood-brain barrier (BBB). Our pharmacokinetic studies in rats supported this conclusion and confirmed the ability of leading compounds 3l and 6f to penetrate the BBB. Electrophysiological experiments showed that all compounds exhibited different inhibitory activity towards the two major NMDA receptor subtypes, GluN1/GluN2A and GluN1/GluN2B. Of the selected compounds intentionally differing in the inhibitory efficacy, 6f showed high relative inhibition (∼90 % for GluN1/GluN2A), while 3l showed moderate inhibition (∼50 %). An in vivo toxicity study determined that compounds 3l and 6f were safe at 10 mg/kg doses with no adverse effects. Behavioral studies demonstrated that these compounds did not induce hyperlocomotion or impair prepulse inhibition of startle response in rats. Neuroprotective assays using a model of NMDA-induced hippocampal neurodegeneration showed that compound 3l at a concentration of 30 µM significantly reduced hippocampal damage in rats. These results suggest that these novel dibenzo [a,d][7]annulen derivatives are promising candidates for developing NMDA receptor-targeted therapies with minimal psychotomimetic side effects.

AI for biofabrication.

Biofabrication is an advanced technology that holds great promise for constructing highly biomimeticin vitrothree-dimensional human organs. Such technology would help address the issues of immune rejection and organ donor shortage in organ transplantation, aiding doctors in formulating personalized treatments for clinical patients and replacing animal experiments. Biofabrication typically involves the interdisciplinary application of biology, materials science, mechanical engineering, and medicine to generate large amounts of data and correlations that require processing and analysis. Artificial intelligence (AI), with its excellent capabilities in big data processing and analysis, can play a crucial role in handling and processing interdisciplinary data and relationships and in better integrating and applying them in biofabrication. In recent years, the development of the semiconductor and integrated circuit industries has propelled the rapid advancement of computer processing power. An AI program can learn and iterate multiple times within a short period, thereby gaining strong automation capabilities for a specific research content or issue. To date, numerous AI programs have been applied to various processes around biofabrication, such as extracting biological information, designing and optimizing structures, intelligent cell sorting, optimizing biomaterials and processes, real-time monitoring and evaluation of models, accelerating the transformation and development of these technologies, and even changing traditional research patterns. This article reviews and summarizes the significant changes and advancements brought about by AI in biofabrication, and discusses its future application value and direction.

Developing Patient-Derived 3D-Bioprinting models of pancreatic cancer.

INTRODUCTION: Pancreatic cancer (PC) remains a challenging malignancy, and adjuvant chemotherapy is critical in improving patient survival post-surgery. However, the intrinsic heterogeneity of PC necessitates personalized treatment strategies, highlighting the need for reliable preclinical models. OBJECTIVES: This study aimed to develop novel patient-derived preclinical PC models using three-dimensional bioprinting (3DP) technology. METHODS: Patient-derived PC models were established using 3DP technology. Genomic and histological analyses were performed to characterize these models and compare them with corresponding patient tissues. Chemotherapeutic drug sensitivity tests were conducted on the PC 3DP models, and correlations with clinical outcomes were analyzed. RESULTS: The study successfully established PC 3DP models with a modeling success rate of 86.96%. These models preserved genomic and histological features consistent with patient tissues. Drug sensitivity testing revealed significant heterogeneity among PC 3DP models, mirroring clinical variability, and potential correlations with clinical outcomes. CONCLUSION: The PC 3DP models demonstrated their utility as reliable preclinical tools, retaining key genomic and histological characteristics. Importantly, drug sensitivity profiles in these models showed potential correlations with clinical outcomes, indicating their promise in customizing treatment strategies and predicting patient prognoses. Further validation with larger patient cohorts is warranted to confirm their potential clinical utility.

The clinical effect of gratitude extension-construction theory nursing program on bladder cancer patients with fear of cancer recurrence.

Objective: To explore the clinical effect of bladder cancer patients with Fear of Cancer Recurrence (FCR) after applying the gratitude extension construction theory nursing program. Methods: 168 patients with bladder cancer hospitalized in the Department of Urology from December 2021 to June 2023 in a hospital are study subjects. The experimental subjects are uniformly designed as an experimental group and a control group, with 52 participants in each group. The former receives routine nursing care, while the later receives nursing interventions based on gratitude extension construction theory. The baseline data, Quality of life Questionnaire-core 30, Quality of Life Questionnaire-non Invasive Bladder Cancer 24, Fear of Progression Questionnaire-Short Form, gratitude level questionnaire, Self-Rating Depression Scale, Self-rating Anxiety Scale, patient compliance behavior score, Overall Survival, and Progression-free Survival are evaluated. Results: The basic data revealed no statistical significance. The quality of life questionnaire-core 30 and quality of life questionnaire-noninvasive bladder cancer 24 was no significant difference before treatment and after treatment for 1 month. After 9 months, There was a significant difference in pre-treatment scores. The experimental group had no significant difference before and after treatment. For the overall survival rates, the two groups were 67.25% and 79.56%. The progression-free survival rates were 56.35% and 72.35%, respectively, with statistical difference. The compliance rates were 86.54% and 98.08%. The compliance rate of the experimental group exceeded the control group. After 3, 6, and 12 months, the gratitude level questionnaire score and the fear of progression questionnaire-short form in the experimental group were improved. After 3, 6, and 12 months, the control group had no statistically significant difference in the gratitude level questionnaire and the fear of progression questionnaire-short form scores. Compared with the control group, the scores on the gratitude level questionnaire and the fear of progression questionnaire-short form were significantly higher after 3, 6, and 12 months of intervention. Conclusion: After applying the gratitude extension construction theory nursing program, the FCR of bladder cancer patients is significantly reduced. The quality of life and compliance rate are significantly improved, and anxiety and depression are relieved.

Recessively Inherited Deficiency of Secreted WFDC2 (HE4) Causes Nasal Polyposis and Bronchiectasis.

Rationale: Bronchiectasis is a pathological dilatation of the bronchi in the respiratory airways associated with environmental or genetic causes (e.g., cystic fibrosis, primary ciliary dyskinesia, and primary immunodeficiency disorders), but most cases remain idiopathic. Objectives: To identify novel genetic defects in unsolved cases of bronchiectasis presenting with severe rhinosinusitis, nasal polyposis, and pulmonary Pseudomonas aeruginosa infection. Methods: DNA was analyzed by next-generation or targeted Sanger sequencing. RNA was analyzed by quantitative PCR and single-cell RNA sequencing. Patient-derived cells, cell cultures, and secretions (mucus, saliva, seminal fluid) were analyzed by Western blotting and immunofluorescence microscopy, and mucociliary activity was measured. Blood serum was analyzed by electrochemiluminescence immunoassay. Protein structure and proteomic analyses were used to assess the impact of a disease-causing founder variant. Measurements and Main Results: We identified biallelic pathogenic variants in WAP four-disulfide core domain 2 (WFDC2) in 11 individuals from 10 unrelated families originating from the United States, Europe, Asia, and Africa. Expression of WFDC2 was detected predominantly in secretory cells of control airway epithelium and also in submucosal glands. We demonstrate that WFDC2 is below the limit of detection in blood serum and hardly detectable in samples of saliva, seminal fluid, and airway surface liquid from WFDC2-deficient individuals. Computer simulations and deglycosylation assays indicate that the disease-causing founder variant p.Cys49Arg structurally hampers glycosylation and, thus, secretion of mature WFDC2. Conclusions: WFDC2 dysfunction defines a novel molecular etiology of bronchiectasis characterized by the deficiency of a secreted component of the airways. A commercially available blood test combined with genetic testing allows its diagnosis.

Impact of ERAS on Hysteromyomectomy: A Study on Anxiety, Depression, and Ovarian Function.

Objective: To analyze the application of the Enhanced Recovery After Surgery (ERAS) nursing mode in patients undergoing radical cystectomy with urinary diversion. Methods: A retrospective analysis was conducted on clinical data of 72 patients with bladder cancer who underwent "robot-assisted laparoscopic radical cystectomy + urinary diversion" in Nanjing University Medical College Affiliated Gulou Hospital between January 2021 and January 2023. All patients met the complete inclusion criteria. They were divided into a control group (n=35) and a observation group (n=37). Patients in the control group received routine rehabilitation nursing intervention, while patients in the study group received ERAS nursing mode intervention. The outcomes include time to first intake, time to first defecation, duration of enteral nutrition, duration of antibiotic use, duration of drainage tube placement, length of hospital stay, psychological status Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), quality of life (SF-36) scores, sexual function assessment Arizona Sexual Experience Scale (ASEX), International Index of Erectile Function-5 (IIEF-5), and occurrence of complications were compared between the two groups. Results: In the observation group, perioperative indicators, psychological status, quality of life, sexual function, and complication rates were notably improved compared to the control group (all P < .05). Conclusion: ERAS nursing mode intervention in bladder cancer patients exhibited significant effectiveness, enhancing postoperative recovery, reducing anxiety and depression, improving quality of life and sexual function, and lowering complication risks. These findings support the clinical merit and applicability of ERAS nursing in urinary diversion for bladder cancer patients.

3D Printing Cervical Implant Scaffolds Incorporated with Drug-Loaded Carboxylated Chitosan Microspheres for Long-Term Anti-HPV Protein Delivery.

As attempting personalized medicine, 3D-printed tissue engineering scaffolds are employed to combine with therapeutic proteins/peptides especially in the clinical treatment of infectious diseases, genetic diseases, and cancers. However, current drug-loading methods, such as immersion and encapsulation, usually lead to the burst release of the drugs. To address these issues, we proposed an integrated strategy toward the long-term controlled release of protein. In this study, patient-customized 3D scaffolds incorporated with drug-loaded microspheres were printed to realize the effective delivery of the anti-human papillomavirus (anti-HPV) protein after cervical conization in the treatment of cervical cancer. The 3D-printed scaffold could provide mechanical support to the defect site and ensure local release of the drug to avoid systemic administration. Meanwhile, microspheres serve as functional components to prevent the inactivation of proteins, as well as regulate their release period to meet the time requirement of different treatment courses. The research also utilized bovine serum albumin as a model protein to validate the feasibility of these scaffolds as a generic technology platform. The bioactivity of the released anti-HPV protein was validated using a pseudovirus model, which demonstrated that the microsphere encapsulation would not cause protein denaturation during the scaffold fabrication process. Besides, 3D-printed scaffolds incorporated with carboxylated chitosan microspheres were biocompatible and beneficial for cell attachment, which have been demonstrated by favorable cell viability and better coverage results for HeLa and HFF-1. This study highlights the great potential of scaffolds incorporated with microspheres to serve as tissue engineering candidate products with the function of effective protein delivery in a long-term controlled manner and personalized shapes for clinical trials.

Harnessing 3D in vitro systems to model immune responses to solid tumours: a step towards improving and creating personalized immunotherapies.

In vitro 3D models are advanced biological tools that have been established to overcome the shortcomings of oversimplified 2D cultures and mouse models. Various in vitro 3D immuno-oncology models have been developed to mimic and recapitulate the cancer-immunity cycle, evaluate immunotherapy regimens, and explore options for optimizing current immunotherapies, including for individual patient tumours. Here, we review recent developments in this field. We focus, first, on the limitations of existing immunotherapies for solid tumours, secondly, on how in vitro 3D immuno-oncology models are established using various technologies - including scaffolds, organoids, microfluidics and 3D bioprinting - and thirdly, on the applications of these 3D models for comprehending the cancer-immunity cycle as well as for assessing and improving immunotherapies for solid tumours.

Dynamic Characteristics of Asphalt Concrete as an Impervious Core in Embankment Dams under Varying Temperatures and Stress States.

To reveal the dynamic characteristics of asphalt core embankment dams (ACEDs), we carried out a dynamic triaxial experiment on hydraulic asphalt concrete (HAC) under different temperatures (T = 4 °C, 10 °C, 16 °C, and 22 °C) and stress states (Kc = 1.0, 1.2, 1.4, and 1.6; σ3 = 0.5, 0.6, 0.7, and 0.8 MPa). The results indicate that HAC's maximum dynamic elastic modulus increased with decreasing temperature, increasing principal stress ratio, and increasing confining pressure. However, the damping ratio showed the opposite trend. Moreover, in order to study the deformation capacity of HAC, 300 cyclic loads were applied to some specimens. At a temperature of 22 °C, the specimens had a tendency to deform axially, but not significantly. With a decrease in temperature, the axial deformation tendency of the specimen gradually weakened or even disappeared. However, a small number of cracks appeared in the aggregate and between the asphalt and the aggregate of the specimen. In order to quantify the dependence of dynamic parameters on temperature, the temperature influence factor of the maximum dynamic elastic modulus and the temperature sensing factor of the damping ratio were defined. The variation in the temperature influence factor of the maximum dynamic elastic modulus with temperature can be described by a logistic function. The temperature sensing factor of the damping ratio increased with an increasing principal stress ratio and peripheral pressure. Finally, maximum dynamic elastic modulus and damping ratio computational models for the interaction of temperatures and stress states were developed using the normalization method. Upon comparison, the dynamic parameters were observed to be very close to those listed in the literature, which verifies the applicability of the computational models of the maximum dynamic elastic modulus and damping ratio.

HIV-1 Subtype Diversity and Factors Affecting Drug Resistance among Patients with Virologic Failure in Antiretroviral Therapy in Hainan Province, China, 2014-2020.

Objective: This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance (HIVDR) in patients with ART failure from 2014 to 2020 in Hainan, China. Methods: A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan. We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences. Drug resistance mutations (DRMs) were analyzed using the Stanford University HIV Drug Resistance Database. Results: A total of 307 HIV-infected patients with ART failure were included, and 241 available pol sequences were obtained. Among 241 patients, CRF01_AE accounted for 68.88%, followed by CRF07_BC (17.00%) and eight other subtypes (14.12%). The overall prevalence of HIVDR was 61.41%, and the HIVDR against non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 59.75%, 45.64%, and 2.49%, respectively. Unemployed patients, hypoimmunity or opportunistic infections in individuals, and samples from 2017 to 2020 increased the odd ratios of HIVDR. Also, HIVDR was less likely to affect female patients. The common DRMs to NNRTIs were K103N (21.99%) and Y181C (20.33%), and M184V (28.21%) and K65R (19.09%) were the main DRMs against NRTIs. Conclusion: The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.

Spheroid on-demand printing and drug screening of endothelialized hepatocellular carcinoma model at different stages.

Hepatocellular carcinoma (HCC) poses a significant threat to human health and medical care. Its dynamic microenvironment and stages of development will influence the treatment strategies in clinics. Reconstructing tumor-microvascular interactions in different stages of the microenvironment is an urgent need forin vitrotumor pathology research and drug screening. However, the absence of tumor aggregates with paracancerous microvascular and staged tumor-endothelium interactions leads to bias in the antitumor drug responses. Herein, a spheroid-on-demand manipulation strategy was developed to construct staged endothelialized HCC models for drug screening. Pre-assembled HepG2 spheroids were directly printed by alternating viscous and inertial force jetting with high cell viability and integrity. A semi-open microfluidic chip was also designed to form a microvascular connections with high density, narrow diameter, and curved morphologies. According to the single or multiple lesions in stages Ⅰ or Ⅰ HCC, endothelialized HCC models from micrometer to millimeter scale with dense tumor cell aggregation and paracancerous endothelial distribution were successively constructed. A migrating stage Ⅰ HCC model was further constructed under TGF-ßtreatment, where the spheroids exhibited a more mesenchymal phenotype with a loose cell connection and spheroid dispersion. Finally, the stage ⅠHCC model showed stronger drug resistance compared to the stage Ⅰ model, while the stage III showed a more rapid response. The corresponding work provides a widely applicable method for the reproduction of tumor-microvascular interactions at different stages and holds great promise for the study of tumor migration, tumor-stromal cell interactions, and the development of anti-tumor therapeutic strategies.

Functional and Clinical Characterization of Variants of Uncertain Significance Identifies a Hotspot for Inactivating Missense Variants in RAD51C.

Pathogenic protein-truncating variants of RAD51C, which plays an integral role in promoting DNA damage repair, increase the risk of breast and ovarian cancer. A large number of RAD51C missense variants of uncertain significance (VUS) have been identified, but the effects of the majority of these variants on RAD51C function and cancer predisposition have not been established. Here, analysis of 173 missense variants by a homology-directed repair (HDR) assay in reconstituted RAD51C-/- cells identified 30 nonfunctional (deleterious) variants, including 18 in a hotspot within the ATP-binding region. The deleterious variants conferred sensitivity to cisplatin and olaparib and disrupted formation of RAD51C/XRCC3 and RAD51B/RAD51C/RAD51D/XRCC2 complexes. Computational analysis indicated the deleterious variant effects were consistent with structural effects on ATP-binding to RAD51C. A subset of the variants displayed similar effects on RAD51C activity in reconstituted human RAD51C-depleted cancer cells. Case-control association studies of deleterious variants in women with breast and ovarian cancer and noncancer controls showed associations with moderate breast cancer risk [OR, 3.92; 95% confidence interval (95% CI), 2.18-7.59] and high ovarian cancer risk (OR, 14.8; 95% CI, 7.71-30.36), similar to protein-truncating variants. This functional data supports the clinical classification of inactivating RAD51C missense variants as pathogenic or likely pathogenic, which may improve the clinical management of variant carriers. SIGNIFICANCE: Functional analysis of the impact of a large number of missense variants on RAD51C function provides insight into RAD51C activity and information for classification of the cancer relevance of RAD51C variants.

Reconstruction of tumor microenvironment viain vitrothree-dimensional models.

Recent advances in tumor microenvironment (TME) modeling as well as its applications to cancer therapy has brought various dramatical changes in multiple malignancies management. Understanding the mechanisms of response and resistance to cancer therapy requires a clear elucidation of the intricate interactions between TME cells, the surrounding stroma, and distant affected tissues or organs. To address this demand, various three-dimensional (3D) cell culture techniques have been developed in order to recapitulate and understand cancer biology over the past decade. This review summarizes some saliant progresses inin vitro3D TME modeling, including the cell-based, matrix-based, and vessel-based dynamic 3D modeling techniques and their applications in investigating tumor-stroma interactions and responses to cancer therapies. The review also discusses the limitations of current TME modeling approaches and proposes some new thoughts on the construction of more clinically relevant models.

A BAK subdomain that binds mitochondrial lipids selectively and releases cytochrome C.

How BAK and BAX induce mitochondrial outer membrane (MOM) permeabilization (MOMP) during apoptosis is incompletely understood. Here we have used molecular dynamics simulations, surface plasmon resonance, and assays for membrane permeabilization in vitro and in vivo to assess the structure and function of selected BAK subdomains and their derivatives. Results of these studies demonstrate that BAK helical regions α5 and α6 bind the MOM lipid cardiolipin. While individual peptides corresponding to these helical regions lack the full biological activity of BAK, tandem peptides corresponding to α4-α5, α5-α6, or α6-α7/8 can localize exogenous proteins to mitochondria, permeabilize liposomes composed of MOM lipids, and cause MOMP in the absence of the remainder of the BAK protein. Importantly, the ability of these tandem helices to induce MOMP under cell-free conditions is diminished by mutations that disrupt the U-shaped helix-turn-helix structure of the tandem peptides or decrease their lipid binding. Likewise, BAK-induced apoptosis in intact cells is diminished by CLS1 gene interruption, which decreases mitochondrial cardiolipin content, or by BAK mutations that disrupt the U-shaped tandem peptide structure or diminish lipid binding. Collectively, these results suggest that BAK structural rearrangements during apoptosis might mobilize helices involved in specific protein-lipid interactions that are critical for MOMP.

Overexpression of cholinergic receptor nicotinic gamma subunit inhibits proliferation and differentiation of bovine preadipocytes.

OBJECTIVE: Muscle acetylcholine receptors have five alpha subunits (α, ß, δ, ε, or γ), and cholinergic receptor nicotinic gamma subunit (CHRNG) is the γ subunit. It may also play an essential role in biological processes, including cell differentiation, growth, and survival, while the role of CHRNG has not been studied in the literature. Therefore, the purpose of this study is to clarify the effect of CHRNG on the proliferation and differentiation of bovine preadipocytes. METHODS: We constructed a CHRNG overexpression adenovirus vector and successfully overexpressed it on bovine preadipocytes. The effects of CHRNG on bovine preadipocyte proliferation were detected by Edu assay, cell counting Kit-8 (CCK-8), real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), Western blot and other techniques. We also performed oil red O, RT-qPCR, Western blot to explore its effect on the differentiation of preadipocytes. RESULTS: The results of Edu proliferation experiments showed that the number of EDU-positive cells in the overexpression group was significantly less. CCK-8 experiments found that the optical density values of the cells in the overexpression group were lower than those of the control group, the mRNA levels of proliferating cell nuclear antigen (PCNA), cyclin A2 (CCNA2), cyclin B1 (CCNB1), cyclin D2 (CCND2) decreased significantly after CHRNG gene overexpression, the mRNA levels of cyclin dependent kinase inhibitor 1A (CDKN1A) increased significantly, and the protein levels of PCNA, CCNB1, CCND2 decreased significantly. Overexpression of CHRNG inhibited the differentiation of bovine preadipocytes. The results of oil red O and triglyceride determination showed that the size and speed of lipid droplets accumulation in the overexpression group were significantly lower. The mRNA and protein levels of peroxisome proliferator activated receptor gamma (PPARγ), CCAAT enhancer binding protein alpha (CEBPα), fatty acid binding protein 4 (FABP4), fatty acid synthase (FASN) decreased significantly. CONCLUSION: Overexpression of CHRNG in bovine preadipocytes inhibits the proliferation and differentiation of bovine preadipocytes.

Bioprinting of a Hepatic Tissue Model Using Human-Induced Pluripotent Stem Cell-derived Hepatocytes for Drug-Induced Hepatotoxicity Evaluation.

Three-dimensional (3D) bioprinting technology is an effective method for exploring the biological functions of hepatocytes by building biomimetic 3D microenvironments. Various hepatic tissue models have been developed for disease modeling, drug screening, and tissue regeneration using 3D bioprinting technology. Human-induced pluripotent stem cells (hiPSCs) are a promising cell source for the generation of functional hepatocytes for bioprinting. In this study, we introduced hiPSC-derived hepatocytes (hiPSC-Heps) as mature hepatocytes for the bioprinting of a 3D hepatic tissue model. The 3D-printed (3DP) model facilitated the formation of hiPSC-Hep spheroids with higher viability and proliferation than the commonly used non-printed sandwich-cultured model. hiPSC-Heps in the 3DP model exhibited higher mRNA expression of liver-specific functions than those in the two-dimensional-cultured model. Moreover, enhanced secretion of liver function-related proteins, including α-1-antitrypsin, albumin, and blood urea nitrogen, was observed in the 3DP model. For the evaluation of acetaminophen-induced hepatotoxicity, the 3DP model exhibited a favorable drug response with upregulation of the drug metabolism-related gene cytochrome P450-1A2 (CYP1A2). Overall, the bioprinted hepatic tissue model showed great biofunctional and drug-responsive performance, which could be potentially applied in in vitro toxicological studies.

Advances in the pharmacological treatment of hepatic alveolar echinococcosis: From laboratory to clinic.

Hepatic alveolar echinococcosis (HAE) is a zoonotic parasitic disease caused by the larvae of Echinococcus multilocularis. Because of its characteristics of diffuse infiltration and growth similar to tumors, the disability rate and mortality rate are high among patients. Although surgery (including hepatectomy, liver transplantation, and autologous liver transplantation) is the first choice for the treatment of hepatic alveolar echinococcosis in clinic, drug treatment still plays an important and irreplaceable role in patients with end-stage echinococcosis, including patients with multiple organ metastasis, patients with inferior vena cava invasion, or patients with surgical contraindications, etc. However, Albendazole is the only recommended clinical drug which could exhibit a parasitostatic rather than a parasitocidal effect. Novel drugs are needed but few investment was made in the field because the rarity of the cases. Drug repurposing might be a solution. In this review, FDA-approved drugs that have a potential curative effect on hepatic alveolar echinococcosis in animal models are summarized. Further, nano drug delivery systems boosting the therapeutic effect on hepatic alveolar echinococcosis are also reviewed. Taken together, these might contribute to the development of novel strategy for advanced hepatic alveolar echinococcosis.

Effectiveness of interprofessional shared decision-making training: A mixed-method study.

OBJECTIVE: This study evaluated the learning effects and examined the participants' perceptions of an interprofessional shared decision-making (IP-SDM) training program. METHODS: This mixed-method study used a quasi-experimental pretest-posttest design in the quantitative phase and semi-structured interviews in the qualitative phase. The 6-week curriculum design, based on Kolb's experiential learning cycle, consisted of two simulated objective structured clinical examinations with standardized patients and blended teaching methods through various course modules. RESULTS: A total of 39 multidisciplinary healthcare personnel completed the 6-week training program, and 32 of them participated in qualitative interviews. The IP-SDM training program effectively improved the SDM process competency of the participants from the perspectives of the participants, standardized patients, and clinical teachers. The interviews illustrated how the curriculum design enhanced learning; the effectiveness results indicated improvements in learners' attitude, knowledge, skills, and teamwork. CONCLUSION: This IP-SDM training program improved multidisciplinary healthcare personnel's competency, self-efficacy, and intention to engage in IP-SDM. PRACTICE IMPLICATIONS: Applying Kolb's experiential learning cycle and blended teaching methods to develop and implement the IP-SDM training program can improve multidisciplinary healthcare personnel's knowledge, attitude, skills, and teamwork in IP-SDM.

Scalable Formation of Highly Viable and Functional Hepatocellular Carcinoma Spheroids in an Oxygen-Permeable Microwell Device for Anti-Tumor Drug Evaluation.

For high-throughput anti-cancer drug screening, microwell arrays may serve as an effective tool to generate uniform and scalable tumor spheroids. However, microwell arrays are commonly anchored in non-oxygen-permeable culture plates, leading to limited oxygen supply for avascular spheroids. Herein, a polydimethylsiloxane (PDMS)-based oxygen-permeable microwell device is introduced for generating highly viable and functional hepatocellular carcinoma (HCC) spheroids. The PDMS sheets at the bottom of the microwell device provide a high flux of oxygen like in vivo neighboring hepatic sinusoids. Owing to the better oxygen supply, the generated HepG2 spheroids are larger in size and exhibit higher viability and proliferation with less cell apoptosis and necrosis. These spheroids also exhibit lower levels of anaerobic cellular respiration and express higher levels of liver-related functions. In anti-cancer drug testing, spheroids cultured in PDMS plates show a significantly stronger resistance against doxorubicin because of the stronger stem-cell and multidrug resistance phenotype. Moreover, higher expression of vascular endothelial growth factor-A produces a stronger angiogenesis capability of the spheroids. Overall, compared to the spheroids cultured in conventional non-oxygen-permeable plates, these spheroids can be used as a more favorable model for early-stage HCCs and be applied in high-throughput anti-cancer drug screening.