Mucolipins: Intracellular TRPML1‐3 channels

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/116338/1/feb2s0014579310000281.pd

Forgetting before Learning: Utilizing Parametric Arithmetic for Knowledge Updating in Large Language Models

Recently Large Language Models (LLMs) have demonstrated their amazing text understanding and generation capabilities. However, even stronger LLMs may still learn incorrect knowledge from the training corpus, as well as some knowledge that is outdated over time. Direct secondary fine-tuning with data containing new knowledge may be ineffective in updating knowledge due to the conflict between old and new knowledge. In this paper, we propose a new paradigm for fine-tuning called F-Learning (Forgetting before Learning), which is based on parametric arithmetic to achieve forgetting of old knowledge and learning of new knowledge. Experimental results on two publicly available datasets demonstrate that our proposed F-Learning can obviously improve the knowledge updating performance of both full fine-tuning and LoRA fine-tuning. Moreover, we have also discovered that forgetting old knowledge by subtracting the parameters of LoRA can achieve a similar effect to subtracting the parameters of full fine-tuning, and sometimes even surpass it significantly.Comment: 8 pages, 2 figures, 2 table

Effect of Baicalin on inflammatory mediator levels and microcirculation disturbance in rats with severe acute pancreatitis

Objective: To investigate the effect of Bacailin on inflammatory mediator levels and microcirculation disturbance in severe acute pancreatitis (SAP) rats and explore its therapeutic mechanism on this disease. Methods: SAP model rats were randomly divided into model control group and Baicalin treated group, 45 rats in each group. The same number of normal rats were included in sham-operated group. These groups were further subdivided into 3 h, 6 h and 12 h subgroups, respectively (15 rats in each subgroup). At 3, 6 and 12 hours after operation, rats were killed to conduct the following experiments: (1) to examine the mortality rates of rats, the ascites volume and pancreatic pathological changes in each group; (2) to determine the contents of amylase, PLA~2~, TXB~2~, PGE~2~, PAF and IL-1[beta]; in blood as well as the changes in blood viscosity.Results: (1) Compared to model control group, treatment with Baicalin is able to improve the pathological damage of the pancreas, lower the contents of amylase and multiple inflammatory mediators in blood, decrease the amount of ascitic fluid and reduce the mortality rates of SAP rats; (2) at 3 hours after operation, the low-shear whole blood viscosity in Baicalin treated group was significantly lower than that in model control group;at 12 hours after operation, both the high-shear and low-shear whole blood viscosity in Baicalin treated group were also significantly lower than those in model control group.Conclusion: Baicalin, as a new drug, has good prospects in the treatment of SAP since it can exert therapeutic effects on this disease through inhibiting the production of inflammatory mediators, lowering blood viscosity, improving microcirculation and mitigating the pathological damage of the pancreas

Protective Effect of Calculus Bovis Sativus

Calculus Bovis Sativus (CBS) is a commonly used traditional Chinese medicine, which has been reported to exhibit antispasmodic, fever-reducing, anti-inflammatory, and gallbladder-repairing effects. The present study aims to investigate the protective effect of CBS on dextran sulphate sodium- (DSS-) induced ulcerative colitis (UC) in mice. C57BL/6 male mice were exposed to 5% DSS in drinking water. CBS was given orally at 50 and 150 mg/kg once per day for 7 days. Body weight, disease activity index (DAI), colon length, colonic myeloperoxidase (MPO) activity, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) and nitric oxide (NO) levels were measured. Administration of CBS significantly reserved these changes, decreased the MPO activity and MDA and NO level, and increased the SOD activity in the colon tissue. Histological observation suggested that CBS alleviated edema, mucosal damage, and inflammatory cells infiltration induced by DSS in the colon. Moreover, CBS significantly downregulated the mRNA expression of tumor necrosis factor-α (TNF-α), interleukin- (IL-) 1β and IL-6 in the colon tissue. Our data suggested that CBS exerted protective effect on DSS-induced UC partially through the antioxidant and anti-inflammatory activities