BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License

Dexamethasone ameliorates H₂S-induced acute lung injury by alleviating matrix metalloproteinase-2 and -9 expression.

Acute lung injury (ALI) is one of the fatal outcomes after exposure to high levels of hydrogen sulfide (H2S), and the matrix metalloproteinases (MMPs) especially MMP-2 and MMP-9 are believed to be involved in the development of ALI by degrading the extracellular matrix (ECM) of blood-air barrier. However, the roles of MMP-2 and MMP-9 in H2S-induced ALI and the mechanisms of dexamethasone (DXM) in treating ALI in clinical practice are still largely unknown. The present work was aimed to investigate the roles of MMP-2 and MMP-9 in H2S-induced ALI and the protective effects of DXM. In our study, SD rats were exposed to H2S to establish the ALI model and in parallel, A549 cells were incubated with NaHS (a H2S donor) to establish cell model. The lung HE staining, immunohistochemisty, electron microscope assay and wet/dry ratio were used to identify the ALI induced by H2S, then the MMP-2 and MMP-9 expression in both rats and A549 cells were detected. Our results revealed that MMP-2 and MMP-9 were obviously increased in both mRNA and protein level after H2S exposure, and they could be inhibited by MMP inhibitor doxycycline (DOX) in rat model. Moreover, DXM significantly ameliorated the symptoms of H2S-induced ALI including alveolar edema, infiltration of inflammatory cells and the protein leakage in BAFL via up-regulating glucocorticoid receptor(GR) to mediate the suppression of MMP-2 and MMP-9. Furthermore, the protective effects of DXM in vivo and vitro study could be partially blocked by co-treated with GR antagonist mifepristone (MIF). Our results, taken together, demonstrated that MMP-2 and MMP-9 were involved in the development of H2S-induced ALI and DXM exerted protective effects by alleviating the expression of MMP-2 and MMP-9. Therefore, MMP-2 and MMP-9 might represent novel pharmacological targets for the treatment of H2S and other hazard gases induced ALI

Effects of DXM on MMP-2 and MMP-9 mRNA expression.

<p>A/B, rats were pre-treated with DXM(2 mg/kg/day) and/or MIF(10 mg/kg/q12 h) for consecutive 3 days, then MMP-2 and MMP-9 mRNA expression were investigated 1 h after H₂S exposure. C/D, A549 cells were pre-treated with DXM(100 nM) and/or MIF(1 μM) for 24 h, then incubated with NaHS(500 μM) for 6 h to investigate MMP-2 and MMP-9 mRNA expression. MMP-2 or MMP-9/GAPDH mRNA ratios analyzed by using real-time PCR. Each bar represents the levels of MMP-2 and MMP-9 mRNA normalized to the level of GAPDH mRNA, shown as a percentage of the control value. Each data point represents mean±S.E. of mRNA levels from at least three separate experiments in which treatments were performed in triplicates. *Indicates significant difference (p<0.05) versus control group. # Indicates significant difference (p<0.05) versus DXM + H₂S/NaHS exposed group; & Indicates significant difference (p<0.05) between H₂S/NaHS + DXM + MIF and DXM + MIF treated group.</p

Groups of DOX.

<p>Groups of DOX.</p

Wet/dry ratio and protein content in BALF.

<p>A, wet/dry ratio; B, protein content in BALF. Mean values ± S.E. are presented from three independent experiments. * Indicates significant difference (p<0.05) versus control group. # Indicates significant difference (p<0.05) versus DXM + H₂S post 6 h group; & Indicates significant difference (p<0.05) between H₂S + DXM + MIF and DXM + MIF treated group.</p

Effects of H₂S on the lung W/D ratio.

<p>6₂S, and the W/D ratio was detected. * Indicates significant difference (p<0.05) when the values were compared to the control.</p

Effects of dexamethasone on MMP-2 and MMP-9 protein expression.

<p>A, rats pret-reated with DXM(2 mg/kg/day) and/or MIF(10 mg/kg/q12 h) for consecutive 3 days, then investigate MMP-2 and MMP-9 protein expression were investigated at the time point of 6 h after H₂S exposure. B, A549 cells were pre-treated with DXM(100 nM) and/or MIF(1 μM) for 24 h, then incubated with NaHS(500 μM) for 12 h and MMP-2 and MMP-9 protein expression were detected. Mean values ± S.E. are presented from three independent isolations and three independent samples. *Indicates significant difference (p<0.05) versus control group. # Indicates significant difference (p<0.05) versus DXM + H₂S/NaHS exposed group; & Indicates significant difference (p<0.05) between H₂S/NaHS + DXM + MIF and DXM + MIF treated group.</p

Groups of DXM and MIF.

<p>Groups of DXM and MIF.</p