Niacin downregulates chemokine (c-c motif) ligand 2 (CCL2) expression and inhibits fat synthesis in rat liver cells

Purpose: To elucidate the role of chemokine (c-c motif) ligand 2 (CCL2) in fat metabolism in hepatocytes. Methods: Following partial hepatectomy, regenerated rat liver cells were isolated and cultured for 24 h were transfected with recombinant plasmid pEGFP-N1-CCL2 using liposomes. Niacin was added to the culture medium to inhibit fat synthesis. CCL2 expression was measured using western blot, while the expression of acly-coa synthetase long chain family 4 (ACSL4) and apolipoprotein E (ApoE) were assessed using real-time PCR. Results: At 12 h after transfection, GFP-positive rates in the pEGFP-N1 and pEGFP-N1-CCL2 transfection groups were 42.4 ± 5.6 % and 45.1 ± 3.5 %, respectively. Expression levels of CCL2 increased over time in pEGFP-N1 transfection group, pEGFP-N1-ccl2 transfection group, and niacin and pEGFP-N1-ccl2 transfection co-treatment group; however, CCL2 expression levels in the niacin and pEGFP-N1-ccl2 transfection co-treatment groups were similar to that of pEGFP-N1 transfection group, which were significantly lower than those of the pEGFP-N1-ccl2 transfection group. Expressionlevel trends of fat-related genes ACSL4 and ApoE were similar to that of CCL2. Conclusion: Niacin downregulates the expression of CCL2, thereby inhibiting lipid synthesis in liver cells. Keywords: Chemokine 2, Niacin, Hepatectomy, Lipid synthesis, Transfectio

PromptAgent: Strategic Planning with Language Models Enables Expert-level Prompt Optimization

Highly effective, task-specific prompts are often heavily engineered by experts to integrate detailed instructions and domain insights based on a deep understanding of both instincts of large language models (LLMs) and the intricacies of the target task. However, automating the generation of such expert-level prompts remains elusive. Existing prompt optimization methods tend to overlook the depth of domain knowledge and struggle to efficiently explore the vast space of expert-level prompts. Addressing this, we present PromptAgent, an optimization method that autonomously crafts prompts equivalent in quality to those handcrafted by experts. At its core, PromptAgent views prompt optimization as a strategic planning problem and employs a principled planning algorithm, rooted in Monte Carlo tree search, to strategically navigate the expert-level prompt space. Inspired by human-like trial-and-error exploration, PromptAgent induces precise expert-level insights and in-depth instructions by reflecting on model errors and generating constructive error feedback. Such a novel framework allows the agent to iteratively examine intermediate prompts (states), refine them based on error feedbacks (actions), simulate future rewards, and search for high-reward paths leading to expert prompts. We apply PromptAgent to 12 tasks spanning three practical domains: BIG-Bench Hard (BBH), as well as domain-specific and general NLP tasks, showing it significantly outperforms strong Chain-of-Thought and recent prompt optimization baselines. Extensive analyses emphasize its capability to craft expert-level, detailed, and domain-insightful prompts with great efficiency and generalizability.Comment: 34 pages, 10 figure

Antimicrobial Resistance in Non-typhoidal Salmonella from Retail Foods Collected in 2020 in China

Non-typhoidal Salmonella (NTS) is a major cause of human salmonellosis globally. Food animals are major NTS reservoirs. An increase in antimicrobial resistance (AMR) in foodborne NTS has led to clinical treatment failures. Here, to examine the prevalence and perform characterization of foodborne NTS with AMR in China, we tested the antimicrobial susceptibility of 1,256 NTS isolates cultured from retail foods in 2020 in China. The antimicrobial susceptibility of 26 antimicrobial agents representing 12 classes was evaluated with the broth-microdilution method; the presence of ten mcr genes was screened with multi-PCR. The complete closed genomes of mcr -gene-carrying isolates were generated by hybrid assembly through whole genome sequencing on both the PacBio and Illumina platforms. Genomic features and genetic environments of the mcr-1 gene were analysed. The overall drug resistance rate was 92.28%, and the multi-drug resistance (MDR) rate was 76.53%. A total of 341 AMR profiles were determined, and resistance was highest to nalidixic acid (63.38%). Among 887 NTS isolates with MDR, 232 showed co-resistance to cefotaxime and ciprofloxacin, and 25 were resistant to ten classes of antimicrobial agents. The resistance of NTS isolated from different regions varied. Isolates from raw chicken sources most frequently showed resistance. Four NTS carried the mcr-1 gene and represented four different serotypes. Four mcr-1 gene-bearing plasmids from the four Salmonella isolates were classified into two replicon types (IncI2 and IncHI2A). Two mcr-1 genes in IncI2 type plasmids were found to be located between a PAP2 family protein-encoding gene and a relaxase-encoding gene, whereas the other two mcr-1 gene structures in IncHI2A type plasmids showed variations in the presence of insertion sequences. Our data demonstrated severe AMR among foodborne NTS isolated from food in China, thus highlighting the importance of antimicrobial susceptibility surveillance to decrease the spread of AMR, particularly to critical drugs in human medicine

Ginsenosides on stem cells fate specification—a novel perspective

Recent studies have demonstrated that stem cells have attracted much attention due to their special abilities of proliferation, differentiation and self-renewal, and are of great significance in regenerative medicine and anti-aging research. Hence, finding natural medicines that intervene the fate specification of stem cells has become a priority. Ginsenosides, the key components of natural botanical ginseng, have been extensively studied for versatile effects, such as regulating stem cells function and resisting aging. This review aims to summarize recent progression regarding the impact of ginsenosides on the behavior of adult stem cells, particularly from the perspective of proliferation, differentiation and self-renewal

Preperitoneal pelvic balloon tamponade—an effective intervention to control pelvic injury hemorrhage in a swine model

Objective: This study aimed to estimate the effects of the volume of preperitoneal balloon (PPB) on arterial and venous hemorrhage in a swine pelvic fracture model.Methods: Twenty-four swine were randomized into 0-mL, 500-mL, 800-mL, and 1000-mL intra-hematoma PPB groups. They were subjected to open-book pelvic fracture and reproducible injuries in the external iliac artery and vein. The pelvic binder and IH-PPBs with different volumes of fluid were applied to control the active hemorrhage after arterial and venous injuries. The survival time and rate during 60-min observation and digital subtraction angiography (DSA) images were the primary endpoints in this study. Secondary endpoints included survival rate within 70 min, peritoneal pressure, hemodynamics, blood loss, infusion fluid, blood pH, and lactate concentration.Results: Our results indicated that the 800-mL and 1000-mL groups had a higher survival rate (0%, 50%, 100% and 100% for 0, 500, 800, and 1000-mL groups respectively; p < 0.0001) and longer survival time (13.83 ± 2.64, 24.50 ± 6.29, 55.00 ± 6.33, and 60.00 ± 0.00 min for 0, 500, 800, and 1,000 groups respectively; p < 0.0005) than the 0-mL or 500-mL groups during the 60 min observation. Contrastingly, survival rate and time were comparable between 800-mL and 1000-mL groups during the 60-min observation. The IH-PPB volume was associated with an increase in the pressure of the balloon and the preperitoneal pressure but had no effect on the bladder pressure. Lastly, the 1000-mL group had a higher mean arterial pressure and systemic vascular resistance than the 800-mL group.Conclusion: IH-PPB volume-dependently controls vascular bleeding after pelvic fracture in the swine model. IH-PPB with a volume of 800 mL and 1000 mL efficiently managed pelvic fracture-associated arterial and venous hemorrhage and enhanced survival time and rate in the swine model without evidences of visceral injury

Seizing the window of opportunity to mitigate the impact of climate change on the health of Chinese residents

The health threats posed by climate change in China are increasing rapidly. Each province faces different health risks. Without a timely and adequate response, climate change will impact lives and livelihoods at an accelerated rate and even prevent the achievement of the Healthy and Beautiful China initiatives. The 2021 China Report of the Lancet Countdown on Health and Climate Change is the first annual update of China’s Report of the Lancet Countdown. It comprehensively assesses the impact of climate change on the health of Chinese households and the measures China has taken. Invited by the Lancet committee, Tsinghua University led the writing of the report and cooperated with 25 relevant institutions in and outside of China. The report includes 25 indicators within five major areas (climate change impacts, exposures, and vulnerability; adaptation, planning, and resilience for health; mitigation actions and health co-benefits; economics and finance; and public and political engagement) and a policy brief. This 2021 China policy brief contains the most urgent and relevant indicators focusing on provincial data: The increasing health risks of climate change in China; mixed progress in responding to climate change. In 2020, the heatwave exposures per person in China increased by 4.51 d compared with the 1986–2005 average, resulting in an estimated 92% increase in heatwave-related deaths. The resulting economic cost of the estimated 14500 heatwave-related deaths in 2020 is US$176 million. Increased temperatures also caused a potential 31.5 billion h in lost work time in 2020, which is equivalent to 1.3% of the work hours of the total national workforce, with resulting economic losses estimated at 1.4% of China’s annual gross domestic product. For adaptation efforts, there has been steady progress in local adaptation planning and assessment in 2020, urban green space growth in 2020, and health emergency management in 2019. 12 of 30 provinces reported that they have completed, or were developing, provincial health adaptation plans. Urban green space, which is an important heat adaptation measure, has increased in 18 of 31 provinces in the past decade, and the capacity of China’s health emergency management increased in almost all provinces from 2018 to 2019. As a result of China’s persistent efforts to clean its energy structure and control air pollution, the premature deaths due to exposure to ambient particulate matter of 2.5 μm or less (PM2.5) and the resulting costs continue to decline. However, 98% of China’s cities still have annual average PM2.5 concentrations that are more than the WHO guideline standard of 10 μg/m3. It provides policymakers and the public with up-to-date information on China’s response to climate change and improvements in health outcomes and makes the following policy recommendations. (1) Promote systematic thinking in the related departments and strengthen multi-departmental cooperation. Sectors related to climate and development in China should incorporate health perspectives into their policymaking and actions, demonstrating WHO’s and President Xi Jinping’s so-called health-in-all-policies principle. (2) Include clear goals and timelines for climate-related health impact assessments and health adaptation plans at both the national and the regional levels in the National Climate Change Adaptation Strategy for 2035. (3) Strengthen China’s climate mitigation actions and ensure that health is included in China’s pathway to carbon neutrality. By promoting investments in zero-carbon technologies and reducing fossil fuel subsidies, the current rebounding trend in carbon emissions will be reversed and lead to a healthy, low-carbon future. (4) Increase awareness of the linkages between climate change and health at all levels. Health professionals, the academic community, and traditional and new media should raise the awareness of the public and policymakers on the important linkages between climate change and health.</p