Efficient Prodrug Activator Gene Therapy by Retroviral Replicating Vectors Prolongs Survival in an Immune-Competent Intracerebral Glioma Model.

Prodrug activator gene therapy mediated by murine leukemia virus (MLV)-based retroviral replicating vectors (RRV) was previously shown to be highly effective in killing glioma cells both in culture and in vivo. To avoid receptor interference and enable dual vector co-infection with MLV-RRV, we have developed another RRV based on gibbon ape leukemia virus (GALV) that also shows robust replicative spread in a wide variety of tumor cells. We evaluated the potential of GALV-based RRV as a cancer therapeutic agent by incorporating yeast cytosine deaminase (CD) and E. coli nitroreductase (NTR) prodrug activator genes into the vector. The expression of CD and NTR genes from GALV-RRV achieved highly efficient delivery of these prodrug activator genes to RG-2 glioma cells, resulting in enhanced cytotoxicity after administering their respective prodrugs 5-fluorocytosine and CB1954 in vitro. In an immune-competent intracerebral RG-2 glioma model, GALV-mediated CD and NTR gene therapy both significantly suppressed tumor growth with CB1954 administration after a single injection of vector supernatant. However, NTR showed greater potency than CD, with control animals receiving GALV-NTR vector alone (i.e., without CB1954 prodrug) showing extensive tumor growth with a median survival time of 17.5 days, while animals receiving GALV-NTR and CB1954 showed significantly prolonged survival with a median survival time of 30 days. In conclusion, GALV-RRV enabled high-efficiency gene transfer and persistent expression of NTR, resulting in efficient cell killing, suppression of tumor growth, and prolonged survival upon CB1954 administration. This validates the use of therapeutic strategies employing this prodrug activator gene to arm GALV-RRV, and opens the door to the possibility of future combination gene therapy with CD-armed MLV-RRV, as the latter vector is currently being evaluated in clinical trials

A Reinforcement Learning Badminton Environment for Simulating Player Tactics (Student Abstract)

Recent techniques for analyzing sports precisely has stimulated various approaches to improve player performance and fan engagement. However, existing approaches are only able to evaluate offline performance since testing in real-time matches requires exhaustive costs and cannot be replicated. To test in a safe and reproducible simulator, we focus on turn-based sports and introduce a badminton environment by simulating rallies with different angles of view and designing the states, actions, and training procedures. This benefits not only coaches and players by simulating past matches for tactic investigation, but also researchers from rapidly evaluating their novel algorithms.Comment: Accepted by AAAI 2023 Student Abstract, code is available at https://github.com/wywyWang/CoachAI-Projects/tree/main/Strategic%20Environmen

Functional Effects of let-7g Expression in Colon Cancer Metastasis.

MicroRNA regulation is crucial for gene expression and cell functions. It has been linked to tumorigenesis, development and metastasis in colorectal cancer (CRC). Recently, the let-7 family has been identified as a tumor suppressor in different types of cancers. However, the function of the let-7 family in CRC metastasis has not been fully investigated. Here, we focused on analyzing the role of let-7g in CRC. The Cancer Genome Atlas (TCGA) genomic datasets of CRC and detailed data from a Taiwanese CRC cohort were applied to study the expression pattern of let-7g. In addition, in vitro as well as in vivo studies have been performed to uncover the effects of let-7g on CRC. We found that the expression of let-7g was significantly lower in CRC specimens. Our results further supported the inhibitory effects of let-7g on CRC cell migration, invasion and extracellular calcium influx through store-operated calcium channels. We report a critical role for let-7g in the pathogenesis of CRC and suggest let-7g as a potential therapeutic target for CRC treatment

Isokinetic eccentric exercise can induce skeletal muscle injury within the physiologic excursion of muscle-tendon unit: a rabbit model

BACKGROUND AND PURPOSE: Intensive eccentric exercise can cause muscle damage. We simulated an animal model of isokinetic eccentric exercise by repetitively stretching stimulated triceps surae muscle-tendon units to determine if such exercise affects the mechanical properties of the unit within its physiologic excursion. METHODS: Biomechanical parameters of the muscle-tendon unit were monitored during isokinetic eccentric loading in 12 rabbits. In each animal, one limb (control group) was stretched until failure. The other limb (study group) was first subjected to isokinetic and eccentric cyclic loading at the rate of 10.0 cm/min to 112% (group I) or 120% (group II) of its initial length for 1 hour and then stretched to failure. Load-deformation curves and biomechanical parameters were compared between the study and control groups. RESULTS: When the muscle-tendon unit received eccentric cyclic loading to 112%, changes in all biomechanical parameters – except for the slope of the load-deformation curve – were not significant. In contrast, most parameters, including the slope of the load-deformation curve, peak load, deformation at peak load, total energy absorption, and energy absorption before peak load, significantly decreased after isokinetic eccentric cyclic loading to 120%. CONCLUSION: We found a threshold for eccentrically induced injury of the rabbit triceps surae muscle at between 12% and 20% strain, which is within the physiologic excursion of the muscle-tendon units. Our study provided evidence that eccentric exercise may induce changes in the biomechanical properties of skeletal muscles, even within the physiologic range of the excursion of the muscle-tendon unit

Isoflavones prevent bone loss following ovariectomy in young adult rats

Soy protein, a rich source of phytoestrogens, exhibit estrogen-type bioactivity. The purpose of this study was to determine if ingestion of isoflavones before ovariectomy can prevent bone loss following ovariectomy. Twenty-four nulliparous Wistar rats were randomly divided into four groups. In the normal diet groups, a sham operation was performed on Group A, while ovariectomy was performed on Group B. For Groups C and D, all rats were fed with an isoflavone-rich (25 mg/day) diet for one month, then bilateral ovariectomy were performed. In the rats in Group C, a normal diet was begun following the ovariectomy. The rats in Groups D continued to receive the isoflavone-rich diet for two additional months postoperatively. All rats were sacrificed 60 days after surgery. The weight of bone ash of the long bones and whole lumbar spine were determined. A histological study of cancellous bone was done and biochemical indices of skeletal metabolism were performed and analyzed. The markers of bone metabolism exhibited no significant changes. When compared with the sham-operated rats fed a normal diet, the bone mass of ovariectomized rats decreased significantly; pre-ovariectomy ingestion of an isoflavone-rich diet did not prevent bone loss. The bone mass of rats treated with an isoflavone-rich diet for three months was higher than controls two months after ovariectomy

Physicochemical properties of rainbow trout (Oncorhynchus mykiss) filet treated with high-voltage electrostatic field under different storage temperatures

The post-mortem rigid of farmed rainbow trout (Oncorhynchus mykiss) affects the texture of the meat and might even be risky for microorganisms, undermining the popularity of frozen filets among consumers. This study investigated the importance of different conditions (0°C, 4°C, and 25°C for 0–4 days) and physicochemical characteristics of rainbow trout filet storage on fish’s characteristics, freshness, quality, and shelf-life. Results showed that the fish easily underwent rigor mortis and resolution of rigor mortis when stored at 25°C. However, rigor mortis was more likely to occur under storage at 0°C than at 4°C [with 100 kV/m high voltage electrostatic fields (HVEF)] due to low-temperature stimulation, but resolution of rigor mortis began to appear after 24 h of storage at either temperature. The protein solubility and gel strength of fish stored at 25°C continued to decrease due to thermal denaturation, and those of fish stored at 4°C and 0°C also showed a decrease owing to rigor mortis and then an increase when rigor mortis disappeared. The K values increased rapidly at 25°C and reached 61% at 14 h. Under storage at 4°C and 0°C, the K values only slightly increased before resolution of rigor mortis. However, the K-values did not exceed 40% for 4 days post-resolution of rigor mortis. Differential Scanning Calorimetry analysis and tissue sectioning showed that protein denaturation and separation between muscle fibers persisted during storage at various temperatures, most notably at 25°C. It is important to note that storing at 0°C for 96 h did not result in any significant changes in the molecular protein composition. Moreover, the muscle tissue remained in excellent condition compared to storage at 25°C and 4°C. Additionally, there was no significant difference in the total viable count (TVC) and psychrophilic bacteria between storage at 0°C and 4°C, considered safe for food consumption. These promising findings are conveyed in a circular economy based on the food industry, particularly adequate raw materials, stable prices, measures to reduce food loss and waste, and contributing to developing efficient, diverse, and sustainable food processing systems

Nervous Necrosis Virus Replicates Following the Embryo Development and Dual Infection with Iridovirus at Juvenile Stage in Grouper

Infection of virus (such as nodavirus and iridovirus) and bacteria (such as Vibrio anguillarum) in farmed grouper has been widely reported and caused large economic losses to Taiwanese fish aquaculture industry since 1979. The multiplex assay was used to detect dual viral infection and showed that only nervous necrosis virus (NNV) can be detected till the end of experiments (100% mortality) once it appeared. In addition, iridovirus can be detected in a certain period of rearing. The results of real-time PCR and in situ PCR indicated that NNV, in fact, was not on the surface of the eggs but present in the embryo, which can continue to replicate during the embryo development. The virus may be vertically transmitted by packing into eggs during egg development (formation) or delivering into eggs by sperm during fertilization. The ozone treatment of eggs may fail to remove the virus, so a new strategy to prevent NNV is needed