LLaSM: Large Language and Speech Model

Multi-modal large language models have garnered significant interest recently. Though, most of the works focus on vision-language multi-modal models providing strong capabilities in following vision-and-language instructions. However, we claim that speech is also an important modality through which humans interact with the world. Hence, it is crucial for a general-purpose assistant to be able to follow multi-modal speech-and-language instructions. In this work, we propose Large Language and Speech Model (LLaSM). LLaSM is an end-to-end trained large multi-modal speech-language model with cross-modal conversational abilities, capable of following speech-and-language instructions. Our early experiments show that LLaSM demonstrates a more convenient and natural way for humans to interact with artificial intelligence. Specifically, we also release a large Speech Instruction Following dataset LLaSM-Audio-Instructions. Code and demo are available at https://github.com/LinkSoul-AI/LLaSM and https://huggingface.co/spaces/LinkSoul/LLaSM. The LLaSM-Audio-Instructions dataset is available at https://huggingface.co/datasets/LinkSoul/LLaSM-Audio-Instructions

Neuroprotective Effects of Ginsenoside-Rg1 Against Depression-Like Behaviors via Suppressing Glial Activation, Synaptic Deficits, and Neuronal Apoptosis in Rats

Depression is considered a neuropsychiatric disease associated with various neuronal changes within specific brain regions. We previously reported that ginsenoside-Rg1, a potential neuroprotective agent extracted from ginseng, significantly alleviated depressive-like disorders induced by chronic stress in rats. However, the mechanisms by which ginsenoside-Rg1 exerts its neuroprotective effects in depression remain largely uncharacterized. In the present study we confirm that ginsenoside-Rg1 significantly prevented the antidepressant-like effects in a rat model of chronic unpredictable mild stress (CUMS) and report on some of the underlying mechanisms associated with this effect. Specifically, we found that chronic pretreatment with ginsenoside-Rg1 prior to stress exposure significantly suppressed inflammatory pathway activity via alleviating the overexpression of proinflammatory cytokines and the activation of microglia and astrocytes. These effects were accompanied with an attenuation of dendritic spine and synaptic deficits as associated with an upregulation of synaptic-related proteins in the ventral medial prefrontal cortex (vmPFC). In addition, ginsenoside-Rg1 inhibited neuronal apoptosis induced by CUMS exposure, increased Bcl-2 expression and decreased cleaved Caspase-3 and Caspase-9 expression within the vmPFC region. Furthermore, ginsenoside-Rg1 could increase the nuclear factor erythroid 2-related factor (Nrf2) expression and inhibit p38 mitogen-activated protein kinase (p-p38 MAPK) and nuclear factor κB (NF-κB) p65 subunit activation within the vmPFC. Taken together, these results suggest that the neuroprotective effects of ginsenoside-Rg1, which may assume the antidepressant-like effect in this animal model of depression, appears to result from amelioration of a CUMS-dependent neuronal deterioration within the vmPFC. Moreover, they also provide support for the therapeutic potential of ginsenoside-Rg1 in the treatment of stress-related mental disorders

The Effect of Eight Thermal Protectants on the Survival Rate and the Viable Counts of Lactobacillus casei After Heat Treatment in Fermented Goat Milk

In order to improve the survival rate of probiotics and produce probiotic goat milk from fermented goat milk of Lactobacillus casei L61 by spray drying. Spray drying has been applied to large-scale industrial production of milk powder due to its high efficiency and low cost. However, high temperatures in spray drying can result in the loss of large numbers of probiotic.The purpose of this paper is to study the effects of eight thermal protectants including skim milk, sucrose, glucose, β-cyclodextrin, gelatin, maltodextrin, glycerol, trehalose on the survival rate and viable counts of L.casei L61 after heat treatment by the single factor experiment. All protective agents have a positive effect on increasing the survival rate of L.casei L61 (p<0.05). The results indicated that the survival rates of L.casei L61 were up to the maximum of 10.94%, 1.13%, 3.04%, 0.21%, 6.97%, 0.075, 4.71% and 0.29%, while the additions of skim milk, sucrose, glucose, β-cyclodextrin, gelatin, maltodextrin, glycerol, trehalose were 20mg/L, 10%, 7%, 15%, 1.5%, 3%, 8mL/L, 10%, respectively; the viable counts after heat treatment are 19.69, 0.81, 1.78, 0.455, 12.2, 0.12, 2.75, 0.435(×106CFU/mL), respectively. This paper provides technical a reference for the development of probiotic goat milk powder

Hippocampal CA1 βCaMKII mediates neuroinflammatory responses via COX-2/PGE2 signaling pathways in depression

Abstract Background Neuroinflammation has recently emerged as a critical risk factor in the pathophysiology of depression. However, the underlying molecular mechanisms and the development of novel therapeutic strategies as means to target these inflammatory pathways for use in the treatment of depression remain unresolved. In the present study, we aimed to investigate the molecular events of neuroinflammation as related to its induction of depression-like behaviors. Methods Chronic unpredictable mild stress (CUMS) or lipopolysaccharide (LPS) was used to induce depression-like behaviors in rats. The inflammatory factors and related proteins were verified by RT-PCR, immunoblotting, and immunofluorescence assay. In vivo intracerebral injection of adenovirus-associated virus (AAV) in rats was used to overexpress or block the function of the β form of the calcium/calmodulin-dependent protein kinase type II (βCaMKII). In vivo intracerebroventricular injection of SB203580 was used to block p38 mitogen-activated protein kinase (MAPK). Finally, the prostaglandin E2 (PGE2) concentration was verified by using enzyme-linked assay kit. Results The expression of cyclo-oxygenase (COX)-2, which is responsible for production of the pro-inflammatory factor PGE2 and thus glial activation, was increased in the CA1 hippocampus in a rat model of depression. Further, the βCaMKII in CA1 was significantly upregulated in depressed rats, while antidepressant treatment downregulated this kinase. Overexpression of βCaMKII via infusion of a constructed AAV-βCaMKII into the CA1 region resulted in phosphorylation of the p38 MAPK and the activating transcription factor 2 (ATF2). These effects were accompanied by an enhanced activity of the COX-2/PGE2 pathway and effectively induced core symptoms of depression. Conversely, knockdown of βCaMKII within the CA1 region reversed these inflammation-related biochemical parameters and significantly rescued depression symptoms. Conclusion These results demonstrate that βCaMKII can act as a critical regulator in depression via activating neuroinflammatory pathways within the CA1 region. Moreover, this study provides new perspectives on molecular targets and drug therapies for future investigation in the treatment of depression

Co-occurrence patterns and assembly processes of abundant and rare bacterioplankton in plain river network areas of eastern China

In the context of anthropogenic impacts on riverine ecosystems globally, understanding the response of bacterioplankton to anthropogenic stress is important for human and environmental health. Bacterioplankton communities are critical for maintaining ecosystem stability, but little is known about their co-occurrence networks and assembly processes in intense human-impacted plains river networks. By applying cooccurrence networks, variance partitioning, and null model analysis, we investigated the mechanisms of interaction and assembly of abundant (>1% relative abundance) and rare (<0.01%) taxa at 32 sites in river networks along an urbanization gradient (urban, suburban, and agricultural areas). Our results show that interactions between the bacterioplankton communities were more complex in urban areas than in other areas, and that environmental factors (primarily fluoride, nitrate nitrogen, and dissolved organic carbon) as well as spatial factors (i.e., Moran’s Eigenvector Maps) explained most of the variation in bacterioplankton communities. Abundant taxa showed stronger spatial turnover than rare taxa, indicating that spatial factors played a greater role in the assemblage of abundant taxa. Land use types, especially impervious surfaces, had a unique influence on rare taxa, but contributed less to community change than other factors. In addition, rare taxa were mainly influenced by deterministic processes, whereas abundant taxa were more influenced by stochastic processes, especially in agricultural areas. These findings suggest that the shares of abundant and rare taxa mediate disturbances in local environmental conditions in anthropogenic river network areas, while deterministic processes play a greater role in shaping bacterioplankton communities. Overall, our study provides important insights for environmental monitoring and management in areas of intense human activity, emphasizing the need to consider both abundant and rare taxa when assessing the impact of human activities on riverine ecosystems

ZIKV infection differentially affects the transcriptional profiles in HTR8 and U251 cells

The mechanism by which Zika virus (ZIKV) causes severe birth defects in pregnant women remains unclear. Cell tropisms in placenta and brain play a crucial role in ZIKV pathogenesis, leading to congenital Zika syndrome (CZS). To identify the host factors involved in ZIKV infection, we compared the transcriptional profiles of ZIKV-infected human first-trimester placental trophoblast cells HTR8/SVneo and a human glioblastoma astrocytoma cell line U251. Our results demonstrated that ZIKV exhibited lower rates of mRNA replication and protein expression in HTR8 than in U251 cells, while showing a higher release of infectious viral particles. However, a greater number of differentially expressed genes (DEGs) were found in ZIKV-infected U251 cells than in ZIKV-infected HTR8 cells. Several of these DEGs were enriched in distinct biological processes related to the characteristics of each cell type that may contribute to foetal damage. Both cell types exhibited activation of common interferons, inflammatory cytokines, and chemokine production upon ZIKV infection. Moreover, the neutralization of tumour necrosis factor-alpha (TNF-α) promoted ZIKV infection in both trophoblasts and glioblastoma astrocytoma cells. Overall, we identified multiple DEGs associated with ZIKV pathogenesis

Therapeutic targeting of the mevalonate-geranylgeranyl diphosphate pathway with statins overcomes chemotherapy resistance in small cell lung cancer

Ji and colleagues demonstrate that metabolic reprogramming in SCLC underlies chemotherapy resistance, resulting in an actionable dependency on the mevalonate pathway in tumor cells, which can be targeted using statins to revert chemoresistance. Small cell lung cancer (SCLC) lacks effective treatments to overcome chemoresistance. Here we established multiple human chemoresistant xenograft models through long-term intermittent chemotherapy, mimicking clinically relevant therapeutic settings. We show that chemoresistant SCLC undergoes metabolic reprogramming relying on the mevalonate (MVA)-geranylgeranyl diphosphate (GGPP) pathway, which can be targeted using clinically approved statins. Mechanistically, statins induce oxidative stress accumulation and apoptosis through the GGPP synthase 1 (GGPS1)-RAB7A-autophagy axis. Statin treatment overcomes both intrinsic and acquired SCLC chemoresistance in vivo across different SCLC PDX models bearing high GGPS1 levels. Moreover, we show that GGPS1 expression is negatively associated with survival in patients with SCLC. Finally, we demonstrate that combined statin and chemotherapy treatment resulted in durable responses in three patients with SCLC who relapsed from first-line chemotherapy. Collectively, these data uncover the MVA-GGPP pathway as a metabolic vulnerability in SCLC and identify statins as a potentially effective treatment to overcome chemoresistance