Dense X Retrieval: What Retrieval Granularity Should We Use?

Dense retrieval has become a prominent method to obtain relevant context or world knowledge in open-domain NLP tasks. When we use a learned dense retriever on a retrieval corpus at inference time, an often-overlooked design choice is the retrieval unit in which the corpus is indexed, e.g. document, passage, or sentence. We discover that the retrieval unit choice significantly impacts the performance of both retrieval and downstream tasks. Distinct from the typical approach of using passages or sentences, we introduce a novel retrieval unit, proposition, for dense retrieval. Propositions are defined as atomic expressions within text, each encapsulating a distinct factoid and presented in a concise, self-contained natural language format. We conduct an empirical comparison of different retrieval granularity. Our results reveal that proposition-based retrieval significantly outperforms traditional passage or sentence-based methods in dense retrieval. Moreover, retrieval by proposition also enhances the performance of downstream QA tasks, since the retrieved texts are more condensed with question-relevant information, reducing the need for lengthy input tokens and minimizing the inclusion of extraneous, irrelevant information

Antitumor, Antiviral, and Anti-Inflammatory Efficacy of Essential Oils from Atractylodes macrocephala Koidz. Produced with Different Processing Methods

Atractylodes macrocephala Koidz. has been used as an invigorating spleen drug for eliminating dampness and phlegm in China. According to recent researches, different processing methods may affect the drug efficacy, so we collected A. macrocephala from the Zhejiang Province, produced with different processing methods, crude A. macrocephala (CA) and bran-processed A. macrocephala (BA), then analyzed its essential oils (EOs) by GC/MS. The results showed 34 components representing 98.44% of the total EOs of CA were identified, and 46 components representing 98.02% of the total EOs of BA were identified. Atractylone is the main component in A. macrocephala. Compared with CA, BA has 46 detected compounds, 28 of which were identical, and 6 undetected compounds. Pharmacodynamic results revealed that the EOs of CA and atractylone exhibited more effective anticancer activity in HepG2, MCG803, and HCT-116 cells than the EOs of BA; while the EOs of BA exhibited simple antiviral effect on viruses H3N2, both the EOs and atractylone show anti-inflammatory activity by inhibiting the lipopolysaccharide (LPS)-induced nitric oxide (NO) production in ANA-1 cells

Mechanism of Killing Effect of Thioridazine on Human Lung Cancer PC9 Cells

Background and objective Recent research shows thioridazine which is a kind of phenothiazine antipsychotic drugs can inhibit the proliferation of various tumor cells in vitro, but the role of thioridazine on lung cancer has not been reported. So we choose PC9 cell lines as the research object, the aim is to oberve the killing effect of thioridazine on PC9 cells and investigate its possible mechanism. Methods After being treated with different concentrations of thioridazine, the proliferation of PC9 cells was determined by methyl thiazolyltetrazolium (MTT) assay. Flow cytometry was used to measure the cell cycle distribution and apoptosis. The expressions of cell cycle-associated protein CyclinD1 and apoptosis-related proteins Caspase-3, Caspase-8, Caspase-9, Bcl-2, Bax and Bcl-xl were detected by Western blot. Results The proliferation of PC9 cells was significantly inhibited by thioridazine in a dose- and time-dependent manner. Flow cytometry showed that cell cycle was arrested in G0/G1 phase and the apoptotic rates were significantly increased with the increasing concentration of thioridazine. Compared with the control group, the differences were statistically significant (P<0.05). Western blot analysis showed that, compared with the control group, thioridazine reduced the expressions of CyclinD1, Bcl-2 and Bcl-xl (P<0.01) and increased the expression of Bax (P<0.01). In the mean time, thioridazine promoted the activities of Caspase-3, Caspase-8 and Caspase-9 (P<0.01). Conclusion The mechanism of thioridazine inhibiting the proliferation of PC9 cells may be related to stimulation of Caspase apoptotic pathway, down-regulation of CyclinD1, Bcl-2, Bcl-xl and up-regulation of Bax

FXR Regulates Intestinal Cancer Stem Cell Proliferation

Increased levels of intestinal bile acids (BAs) are a risk factor for colorectal cancer (CRC). Here, we show that the convergence of dietary factors (high-fat diet) and dysregulated WNT signaling (APC mutation) alters BA profiles to drive malignant transformations in Lgr5-expressing (Lgr5+) cancer stem cells and promote an adenoma-to-adenocarcinoma progression. Mechanistically, we show that BAs that antagonize intestinal farnesoid X receptor (FXR) function, including tauro-β-muricholic acid (T-βMCA) and deoxycholic acid (DCA), induce proliferation and DNA damage in Lgr5+ cells. Conversely, selective activation of intestinal FXR can restrict abnormal Lgr5+ cell growth and curtail CRC progression. This unexpected role for FXR in coordinating intestinal self-renewal with BA levels implicates FXR as a potential therapeutic target for CRC