The establishment of diseased human whole organ model by normothermic machine perfusion technique: Principle of concept.

BACKGROUND: The global incidence of liver diseases is rising, yet there remains a dearth of precise research models to mimic these diseases. The use of normothermic machine perfusion (NMP) to study diseased livers recovered from liver transplantation (LT) recipients presents a promising avenue. Accordingly, we have developed a machine perfusion system tailored specifically for the human whole diseased livers and present our experience from the NMP of diseased livers. METHODS: Six diseased livers recovered from LT recipients with different diagnoses were collected. The diseased livers were connected to the machine perfusion system that circulated tailored perfusate, providing oxygen and nutrients. The pressure and flow of the system were recorded, and blood gas analysis and laboratory tests of perfusate and bile were examined to analyze the function of the diseased livers. Liver tissues before and after NMP were collected for histological analysis. RESULTS: Experiments showed that the system maintained the diseased livers in a physiological state, ensuring stable hemodynamics and a suitable partial pressure of oxygen and carbon dioxide. The results of blood gas analysis and laboratory tests demonstrated a restoration and sustenance of metabolism with minimal damage. Notably, a majority of the diseased livers exhibited bile production continuously, signifying their vivid functional integrity. The pathological characteristics remained stable before and after NMP. CONCLUSION: We successfully established the machine perfusion system tailored specifically for diseased human whole livers. Through the application of this system, we have developed a novel in vitro model that faithfully recapitulates the main features of human liver disease. This model holds immense promise as an advanced disease modeling platform, offering profound insights into liver diseases and potential implications for research and therapeutic development.

Association of chemotherapy dose intensity and age with outcomes in patients with Ewing's family sarcoma.

BACKGROUND: Ewing's family sarcoma (EFS) is an aggressive malignancy with a peak incidence in adolescents. Multimodal treatment involves surgery and/or radiotherapy, and chemotherapy typically with VDC/IE (vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide). There is a paucity of data for the treatment of adults, with protocols extrapolated from the pediatric setting. This study aimed to assess patterns of care, chemotherapy tolerability across age groups, and outcomes from four Australian sarcoma centers. METHODS: ANZSA ACCORD sarcoma database and medical records were used to identify and collect data of patients aged ≥ 10 years with EFS who received VDC/IE between 2010 and 2020. Survival outcomes were analyzed based on chemotherapy received dose intensity (RDI). Clinical predictors of RDI were explored using logistic regression. RESULTS: Of 146 patients with EFS, 76 received VDC/IE. The majority had localized disease (65%). Seventy-one percent completed scheduled chemotherapy, with some requiring dose reduction (29%), delay > 7 days (65%), or cycle omission (4%). Hematological toxicity was the main reason for dose reduction/delay. Fifty-seven percent patients achieved an acceptable RDI ≥85%. Compared to those aged 10-19, the odds ratio for acceptable RDI aged 40-59 was 0.20 (95% CI 0.04-0.86, p = 0.04). RDI was an independent prognostic factor for overall survival, after accounting for age, gender, Ewing's type, primary site, and stage (adjusted HR 0.25 [95% CI 0.10-0.63], p = 0.004). CONCLUSION: Survival outcomes in EFS were associated with chemotherapy RDI. Older adults more commonly required dose reduction or early cessation of treatment due to toxicity. VDC/IE chemotherapy should be carefully tailored in adults > 40 years.

Seminal Plasma ExLncRNA Pairs: Updating Perspectives in the Search for Testicular Spermatozoa Retrieval Biomarkers in Nonobstructive Azoospermia Patients with mTESE by WGCNA.

PURPOSE: This study aims to find candidates for testicular spermatozoa retrieval biomarkers among the seminal plasma exLncRNA pairs. MATERIALS AND METHODS: A set of exLncRNA pairs with the best potential biomarkers was selected and validated in 96 NOA samples. Weighted correlation network analysis (WGCNA) and Least Absolute Shrinkage and Selection Operator were used to identify possible biomarkers for these pairs (LASSO). These pairs' potential biomarkers were identified using receiver operating curves. Confusion matrices and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), FP, false-negative rates (FNR), and F1 scores are calculated. Through F1 scores, we selected the best threshold value. RESULTS: The relative differential expression of each pair in testicular spermatozoa retrieval (+) and testicular spermatozoa retrieval (-) men were validated. The six pairs displayed the best biomarker potential. Among them, CCDC37.DT-LOCI00505685 pair and LOC440934- LOCI01929088 (XR_001745218.1) pair showed the most significant potential and stability for detecting testicular spermatozoa retrieval in the selected and validated cohort. CONCLUSION: CCDC37.DT-LOCI00505685 pair and LOC440934- LOCI01929088 (XR_001745218.1) pair have the potential to become new molecular biomarkers that could help to select clinical strategies for microdissection testicular sperm extraction.

Amentoflavone inhibits colorectal cancer epithelial-mesenchymal transition via the miR-16-5p/HMGA2/ß-catenin pathway.

Background: Amentoflavone is a type of bioflavonoid that exists in many Chinese medicines and has anti-inflammatory, antioxidant, antiviral, and anticancer effects. However, the effect of amentoflavone on epithelial to mesenchymal transition (EMT) in human colorectal cancer (CRC) has not been studied. In this study, we aim to explore the effect of amentoflavone on EMT in CRC. Methods: The effects of long noncoding RNA (lncRNA) miR-16-5p on proliferation, migration, and invasion were determined by in vitro and in vivo experiments. A luciferase reporter assay was carried out to reveal the interaction between miR-16-5p and targeted genes. Reverse transcription polymerase chain reaction (RT-PCR) was used to evaluate the expression of miR-16-5p. A western blot assay was used to detect the expression of targeted genes in CRC cells. Results: The results showed that amentoflavone significantly inhibited CRC migration, invasion, and EMT by increasing miR-16-5p expression. Mechanistically, amentoflavone induced inactivation of the Wnt/ß-catenin pathway via miR-16-5p, directly targeting 3'-UTR of HMGA2 to suppress HMGA2 expression in CRC. Clinically, combined miR-16-5p and HMGA2 levels may serve as a predictor for poor prognosis in patients with CRC. Furthermore, an in vivo PDX model suggested that amentoflavone exhibited antitumor effects in vivo via the miR-16-5p/HMGA2/ß-catenin pathway. Conclusions: This is the first study to show that amentoflavone inhibits CRC EMT via the miR-16/HMGA2/ß-catenin pathway. Amentoflavone may be beneficial in treating CRC patients in the clinic.

Knowledge-sharing hostility, knowledge manipulation, and new product development performance.

New product development is an important driver of sustainable enterprise development. It is necessary to promote the knowledge sharing of heterogeneous individuals such as design, technology, market, and sociologists. This paper discusses the influence of negative individual knowledge management from the perspective of knowledge-sharing hostility and knowledge manipulation on the performance of new product development. To examine our hypotheses, we conducted a questionnaire survey of 438 employees in China. The results show that although knowledge manipulation contributes to individual innovation performance, it has an inverted U-shaped curve relationship with the team's product development performance. The hostility of knowledge sharing induces knowledge manipulation, which indirectly influences the performance of new product development. The coordination flexibility of R&D teams positively moderates the impact of knowledge manipulation on new product development. Implications and future research directions are discussed.

Correlations of Resource Bricolage and Exaptation With Low-Cost Breakthrough Innovations: Moderating Effect of Organizational Agility.

The mechanism influencing resource bricolage driving low-cost breakthrough innovations remains unclear. By introducing exaptation and organizational agility, this study creates a regulated mediation model, explores effects of resource bricolage on low-cost breakthrough innovations, and analyzes the moderating effect of organizational agility and mediation effect of exaptation. The results revealed that resource bricolage exerted a significant positive impact on low-cost breakthrough innovations, and exaptation played a mediation role between resource bricolage and low-cost breakthrough innovations. In addition, both marketing agility and operational agility positively regulated the correlation between resource bricolage and exaptation. Further research revealed that the mediation effect of exaptation was positively regulated by marketing agility and operational agility, respectively. Overall, this study enriches the discussion of the impact mechanism of breakthrough innovations by resource bricolage and provides valuable enlightenment for enterprises to implement innovation-driven development strategies in the context of economic transformation.

The Effects of Traditional Concepts on Personal Values Among University Students in China.

It is widely agreed that China is experiencing a substantial transition toward modernization. However, both business behavior and day-to-day life in China are still greatly influenced and regulated by the traditional culture that has been embedded in Chinese society for thousands of years. Therefore, when studying social phenomena in China, researchers must take the indigenous cultural context into account. Focusing on the young generation in China, the authors explore the relationships between the most fundamental traditional concepts and various value dimensions. Three hundred and thirty-two university students in Southeast China took part in the survey and data were analyzed with SPSS. The result might help both scholars and practitioners to better understand the contemporary Chinese culture. The discussion and implications are also offered.

Does Product Semantics Matter in Stimulating Impulse Buying Behavior for Internet Products?

Design-driven innovation has become the source of the third-dimensional innovation driving force behind technology and outside the market, aiming to explore breakthrough innovation in product semantics for Internet products. This research tries to define the concept of product semantics and construct a consumer purchase decision model for Internet products with product semantic perception as the antecedent variable. In addition, how product semantics could stimulate consumers' expected regret and impulse purchase for Internet products is explained. The research finds that product semantic perception significantly affects consumers' expected inaction regret, which promotes their impulse purchase intention for Internet products; and expected inaction regret partially mediates between product semantic perception and impulse purchase intention. Self-control ability of consumers negatively moderates the relationship between their expected inaction regret and impulsive purchase intention for Internet products. Thus, the "non-use function" design of product semantics can effectively meet and lead the spiritual and cultural needs in hedonistic Internet shopping for consumers.

New Sm-PMN-PT Ceramic-Based 2-D Array for Low-Intensity Ultrasound Therapy Application.

A two-dimensional (2-D) array with a small pitch (approximately 0.5λ in medium) can achieve complete 3-D control of ultrasound beams without grating lobes and enable the generation of multiple focal spots simultaneously, which is a desired tool for noninvasive therapy. However, the large electrical impedance of 2-D array elements owing to their small size results in a low energy transfer efficiency between a 2-D array and an electrical system, thereby limiting their practical applications. This article presents the development of a 1-MHz 256-element 2-D array ultrasonic transducer of low electrical impedance based on a new Sm-doped Pb(Mg1/3Nb2/3)O3-PbTiO3 (Sm-PMN-PT) piezoceramic with ultrahigh dielectric permittivity. The electrical impedance of the array element is decreased by 3.4 times as the Sm-PMN-PT replacing commercial PZT-5H. Consequently, the output acoustic pressure of the 2-D array made of Sm-PMN-PT ceramic is approximately twice that of the 2-D array made of PZT-5H ceramic under the same excitation conditions. Array elements are spaced at a 1.1-mm pitch ( 0.71λ in water), enabling a large steering range of the ultrasound beam. A multiple-target blood-brain barrier opening in vivo is demonstrated using the proposed 2-D array with electronic focusing and steering. The obtained results indicate that the 2-D array made of Sm-PMN-PT ceramic is promising for practical use in low-intensity ultrasound therapy applications.

Noninvasive Ultrasonic Neuromodulation in Freely Moving Mice.

Neuromodulation is a fundamental method for obtaining basic information about neuronal circuits for use in treatments for neurological and psychiatric disorders. Ultrasound stimulation has become a promising approach for noninvasively inducing neuromodulation in animals and humans. However, the previous investigations were subject to substantial limitations, due to most of them involving anesthetized and fixed small-animal models. Studies of awake and freely moving animals are needed, but the currently used ultrasound devices are too bulky to be applied to a freely moving animal. This study is the first time to design and fabricate a miniature and lightweight head-mounted ultrasound stimulator for inducing neuromodulation in freely moving mice. The main components of the stimulator include a miniature piezoelectric ceramic, a concave epoxy acoustic lens, and housing and connection components. The device was able to induce action potentials recorded in situ and evoke head-turning behaviors by stimulating the primary somatosensory cortex barrel field of the mouse. These findings indicate that the proposed method can be used to induce noninvasive neuromodulation in freely moving mice. This novel method could potentially lead to the application of ultrasonic neuromodulation in more-extensive neuroscience investigations.