Black Garlic Improves Heart Function in Patients With Coronary Heart Disease by Improving Circulating Antioxidant Levels

Background: Black garlic (BG) has many health-promoting properties.Objectives: We aimed to explore the clinical effects of BG on chronic heart failure (CHF) in patients with coronary heart disease (CHD).Design: The main components of BG were measured by gas chromatography–mass spectrometry (GC–MS) and its antioxidant properties were determined by the clearance rate of free radicals. One hundred twenty CHF patients caused by CHD were randomly and evenly assigned into BG group and placebo group (CG). The duration of treatment was 6 months. Cardiac function was measured according to the New York Heart Association (NYHA) functional classification system. The following parameters were measured, including walking distance, BNP precursor N-terminal (Nt-proBNP), left-ventricular ejection fraction (LVEF) value, and the scores of quality of life (QOL). The circulating antioxidant levels were compared between two groups.Results: There are 27 main compounds in BG with strong antioxidant properties. BG treatment improved cardiac function when compared with controls (P < 0.05). The QOL scores and LVEF values were higher in the BG group than in the CG group while the concentration of Nt-proBNP was lower in the BG group than in the CG group (P < 0.05). Circulating antioxidant levels were higher in the BG group than in the CG group. Antioxidant levels had positive relation with QOL and LVEF values, and negative relation with Nt-proBNP values.Conclusion: BG improves the QOL, Nt-proBNP, and LVEF in CHF patient with CHD by increasing antioxidant levels

Unveiling the Implicit Toxicity in Large Language Models

The open-endedness of large language models (LLMs) combined with their impressive capabilities may lead to new safety issues when being exploited for malicious use. While recent studies primarily focus on probing toxic outputs that can be easily detected with existing toxicity classifiers, we show that LLMs can generate diverse implicit toxic outputs that are exceptionally difficult to detect via simply zero-shot prompting. Moreover, we propose a reinforcement learning (RL) based attacking method to further induce the implicit toxicity in LLMs. Specifically, we optimize the language model with a reward that prefers implicit toxic outputs to explicit toxic and non-toxic ones. Experiments on five widely-adopted toxicity classifiers demonstrate that the attack success rate can be significantly improved through RL fine-tuning. For instance, the RL-finetuned LLaMA-13B model achieves an attack success rate of 90.04% on BAD and 62.85% on Davinci003. Our findings suggest that LLMs pose a significant threat in generating undetectable implicit toxic outputs. We further show that fine-tuning toxicity classifiers on the annotated examples from our attacking method can effectively enhance their ability to detect LLM-generated implicit toxic language. The code is publicly available at https://github.com/thu-coai/Implicit-Toxicity.Comment: EMNLP 2023 Main Conferenc

Antarctic Krill Oil Attenuates Oxidative Stress via the KEAP1-NRF2 Signaling in Patients with Coronary Heart Disease

Background. Antarctic krill oil (AKO) has strong antioxidant activities and is effective for alleviating coronary heart disease (CHD). Kelch-like ECH-associated protein 1-NF-E2-related factor 2 (KEAP1-NRF2) axis is a crucial antioxidant signaling pathway. Thus, AKO may exert its antioxidant effects on CHD patients via KEAP1-NRF2 signaling. Methods. AKO fatty acid (FA) profiles were analyzed by using gas chromatography (GC). One hundred CHD patients were divided into the intervention (IG, AKO) and control (CG, placebo) groups. Before and after 1, 2, and 3 months of intervention, we measured serum levels of reactive oxygen species (ROS), 8-hydroxy-2-deoxyguanosine (8-OHdG), nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH), and glutathione peroxidase (GPx), and KEAP1 and NRF2 levels in peripheral blood leukocytes (PBLs). Serum FAs were measured by GC at baseline and after 3-month intervention. Results. AKO contains rich eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which is more than 27% of total FA. The levels of EPA and DHA, KEAP1, and NRF2 in the IG group were higher than those in the CG group (p<0.05). Serum levels of ROS, 8-OHdG, NO, and MDA in the IG group were lower than those in the CG group, whereas the levels of SOD, GSH, and GPx in the IG group were higher than those in the CG group (p<0.05). Serum levels of saturated fatty acids (UFA) in the IG group were higher than those in the CG group, whereas reverse results were obtained for the levels of saturated fatty acids (SFA). Serum levels of EPA and DHA had a strong negative relationship with the level of ROS, whereas the ROS level had a strong negative relationship with the levels of KEAP1-NRF2. Conclusion. AKO increases antioxidant capacities of CHD patients via the KEAP1-NRF2 signaling in the PBL

Local Insolation Drives Afro-Asian Monsoon at Orbital-Scale in Holocene

Insolation changes play an important role in driving monsoon changes at orbital time scales. One key issue that has remained outstanding is whether the Asian monsoon is driven by local insolation from the Northern Hemisphere (NH) or remote insolation from the Southern Hemisphere (SH) at orbital band. Here, we perform a set of sensitivity experiments to quantify the impacts of local and remote insolation changes on the Afro-Asian summer monsoon at 11 ka BP relative to the present. We show that the Afro-Asian summer monsoon is overwhelmingly driven by the precession induced local insolation change in the tropical-subtropical NH. The insolation from NH high latitudes also affects the Afro-Asian summer monsoon. In contrast, the insolation from SH plays a negligible role. Our model experiments support the idea that the Afro-Asian summer monsoon are driven predominantly by the direct forcing of NH low latitudes summer insolation for the Holocene

Enterococcus faecalis Shields Porphyromonas gingivalis in Dual-Species Biofilm in Oxic Condition

Aim: To develop a reproducible biofilm model consisting of Enterococcus faecalis (E. faecalis) and Porphyromonas gingivalis (P. gingivalis) and to evaluate the interaction between the two bacterial species. Methodology: E. faecalis and P. gingivalis were grown in mono-culture, sequential, and co-culture models for 96 h in a 96-well polystyrene microtiter plate under both aerobic and anaerobic conditions separately. The viability of the two bacterial species in the biofilms was quantified by polymerase chain reaction (qPCR). Biofilm thickness and protein contents were measured using confocal laser scanning microscopy (CLSM). Two-way analysis of variance (ANOVA) was performed to analyze cell viability and biofilm thickness among different culture models cultivated under either aerobic or anaerobic conditions. The level of significance was set at p &lt; 0.05. Results: Different culture models tested did not show any significant difference between the viable cell counts of both E. faecalis and P. gingivalis cultivated under aerobic and anaerobic conditions (p &gt; 0.05). Biofilm was significantly thicker (p &lt; 0.05) in the co-culture models compared to the mono-culture and sequential models. Protein contents in the biofilms were more pronounced when both bacterial species were co-cultured under aerobic conditions. Conclusions: E. faecalis appeared to shield P. gingivalis and support its continued growth in oxic (aerobic) conditions. The co-culture model of E. faecalis and P. gingivalis produced a significantly thicker biofilm irrespective of the presence or absence of oxygen, while increased protein contents were only observed in the presence of oxygen

A Novel DNA Repair Gene Signature for Immune Checkpoint Inhibitor-Based Therapy in Gastric Cancer.

Gastric cancer is a heterogeneous group of diseases with only a fraction of patients responding to immunotherapy. The relationships between tumor DNA damage response, patient immune system and immunotherapy have recently attracted attention. Accumulating evidence suggests that DNA repair landscape is a significant factor in driving response to immune checkpoint blockade (ICB) therapy. In this study, to explore new prognostic and predictive biomarkers for gastric cancer patients who are sensitive and responsive to immunotherapies, we developed a novel 15-DNA repair gene signature (DRGS) and its related scoring system and evaluated the efficiency of the DRGS in discriminating different molecular and immune characteristics and therapeutic outcomes of patients with gastric adenocarcinoma, using publicly available datasets. The results demonstrated that DRGS high score patients showed significantly better therapeutic outcomes for ICB compared to DRGS low score patients (p &lt; 0.001). Integrated analysis of multi-omics data demonstrated that the patients with high DRGS score were characteristic of high levels of anti-tumor lymphocyte infiltration, tumor mutation burden (TMB) and PD-L1 expression, and these patients exhibited a longer overall survival, as compared to the low-score patients. Results obtained from HPA and IHC supported significant dysregulation of the genes in DRGS in gastric cancer tissues, and a positive correlation in protein expression between DRGS and PD-L1. Therefore, the DRGS scoring system may have implications in tailoring immunotherapy in gastric cancers. A preprint has previously been published (Yuan et al., 2021)

Antarctic Warming during Heinrich Stadial 1 in a Transient Isotope-Enabled Deglacial Simulation

Heinrich Stadial 1 (HS1) was the major climate event at the onset of the last deglaciation associated with rapid cooling in Greenland and lagged, slow warming in Antarctica. Although it is widely believed that temperature signals were triggered in the Northern Hemisphere and propagated southward associated with the Atlantic meridional overturning circulation (AMOC), understanding how these signals were able to cross the Antarctic Circumpolar Current (ACC) barrier and further warm up Antarctica has proven particularly challenging. In this study, we explore the physical processes that lead to the Antarctic warming during HS1 in a transient isotope-enabled deglacial simulation iTRACE, in which the interpolar phasing has been faithfully reproduced. We show that the increased meridional heat transport alone, first through the ocean and then through the atmosphere, can explain the Antarctic warming during the early stage of HS1 without notable changes in the strength and position of the Southern Hemisphere midlatitude westerlies. In particular, when a reduction of the AMOC causes ocean warming to the north of the ACC, increased southward ocean heat transport by mesoscale eddies is triggered by steeper isopycnals to warm up the ocean beyond the ACC, which further decreases the sea ice concentration and leads to more absorption of insolation. The increased atmospheric heat then releases to the Antarctic primarily by a strengthening zonal wavenumber-3 (ZW3) pattern. Sensitivity experiments further suggest that a similar to 4 degrees C warming caused by this mechanism superimposed on a comparable warming driven by the background atmospheric CO2 rise is able to explain the total simulated similar to 8 degrees C warming in the West Antarctica during HS1