Integrative Physiology Research Articles

The Role of Resveratrol in Aging and Senescence: A Focus on Molecular Mechanisms.

Resveratrol (Res), a polyphenol found in red wine, has been shown to decelerate aging, the progressive loss of physiological integrity and cellular senescence, characterized by the inability to progress through the cell cycle. No successful clinical trials have yet to be completed in humans on dose limitations. Yet, the potent anti-aging and anti-senescence efficacy of Res has been documented in several in vivo animal models. In this review, we highlight the molecular mechanisms of Res efficacy in antiaging disorders, such as diabetes, neurodegenerative disorders, eye diseases, and cardiovascular diseases.

The endocrine basis of the cardio-renal axis: New perspectives regarding corin.

The central role of natriuretic peptides (NPs) in the complex cardio-renal integrated physiology and organ failure has been revealed over the last four decades. Atrial natriuretic peptide (ANP), the oldest representative of the NPs family, is produced through conversion of proANP to the mature peptide by corin, a trans-membrane protease localized to the cardiac myocyte membrane. Similarly, brain natriuretic peptide (BNP) is generated by furin, which cleaves proBNP to BNP in myocytes. Though the components of NPs system, their synthesis and target organs are well established, understanding their role in the interplay between the heart and the kidney is steadily evolving. In this context, Feldman etal. (New England Journal of Medicine, 389, 1685) recently described patients with hypertension, cardiomyopathy, atrial arrhythmia and left atrial fibrosis, associated with a homozygous loss-of-function variant of the gene encoding corin (Cor-/-). Notably, reduced baseline urinary electrolyte and creatinine excretion have been observed in one of the studied patients. This renal excretory functional impairment could be attributed to the lack of cardiac-derived ANP in these patients, as implied by Feldman etal. Yet, in this mini-review we suggest that this aberrant renal manifestation may principally stem from lack of local ANP production at renal tissue, as corin is normally expressed in proximal tubules, Henle's loop and collecting ducts, with locally produced ANP provoking Na+ and water exertion. Collectively, it seems that beside the classic well-established cardio-renal axis, the renal NPs system functions as local endocrine machinery in the regulation of sodium excretion.

Interactions between developmental phenology, carbon movement, and storage constrain demography in the understory clonal herb Podophyllum peltatum L.

Little is known about how carbon integration and storage dynamics affect and are affected by demography in field populations. We sought to elucidate this link by examining dynamic patterns of carbon integration relative to the timing of demographically significant developmental decisions regarding shoot type determination in mayapple, Podophyllum peltatum, a clonal plant with large and persistent rhizomes. Individual rhizome systems growing in natural populations were fed 14CO2 either in late-April, early-May, or mid-June, then harvested at intervals throughout the current season and into the next. When distribution of label was examined we found that carbon fixed at different times in the growing season is used differently: April-fixed assimilate remained in the labeled shoot or was moved into the old rhizome, May-fixed assimilate was found predominantly in the old rhizome, while early-June fixed assimilate moved into the old rhizome and the extending new ramet. Movement of assimilate into the old rhizome appeared to have precedence over formation of additional new ramets. Despite significant within season changes in location of dominant sinks within rhizome systems, there was little redistribution of labeled assimilate: early fixed assimilate was not used to fuel later within season growth, however, assimilate was redistributed between seasons. Vegetative and sexual systems differed in the distribution only of April-fixed assimilate. This was observed even though early labeling occurred prior to anthesis. Sexual systems retained a greater proportion of assimilate in the stem than did vegetative ones, which exported more to the old rhizome. 14C-distribution patterns did not vary between systems differing in future demographic status suggesting that the developmental decision regarding shoot type is based on resources acquired in prior years. We explore the hypothesis that preformation and storage are functionally linked traits that permit plants to coordinate the developmental determination of structures differing in cost and demographic function with known resource status. We conclude that demography influences and is influenced by integrative physiology and that physiological restrictions on within season redistribution of assimilates constrain plants' capacities to respond to short-term environmental variation. Such constraints may affect plants' abilities to respond to rapid environmental change in the Anthropocene.

Dual therapy with phospholipase and metalloproteinase inhibitors from Sinonatrix annularis alleviated acute kidney and liver injury caused by multiple snake venoms

Snakebite envenomation often induces acute kidney injury (AKI) and acute liver injury (ALI), leading to augmented injuries and poor rehabilitation. Phospholipase A2 (PLA2) and metalloproteinase (SVMP) present in venom are responsible for the envenomation-associated events. In this study, mice envenomed with Deinagkistrodon acutus, Naja atra, or Agkistrodon halys pallas venom exhibited typical AKI and ALI symptoms, including significantly increased plasma levels of myoglobin, free hemoglobin, uric acid, aspartate aminotransferase, and alanine aminotransferase and upregulated expression of kidney NGAL and KIM-1. These effects were significantly inhibited when the mice were pretreated with natural inhibitors of PLA2 and SVMP isolated from Sinonatrix annularis (SaPLIγ and SaMPI). The inhibitors protected the physiological structural integrity of the renal tubules and glomeruli, alleviating inflammatory infiltration and diffuse hemorrhage in the liver. Furthermore, the dual therapy alleviated oxidative stress and apoptosis in the kidneys and liver by mitigating mitochondrial damage, thereby effectively reducing the lethal effect of snake venom in the inhibitor-treated mouse model. This study showed that dual therapy with inhibitors of metalloproteinase and phospholipase can effectively prevent ALI and AKI caused by snake bites. Our findings suggest that intrinsic inhibitors present in snakes are prospective therapeutic agents for multi-organ injuries caused by snake envenoming.

An integration of physiology, transcriptomics, and proteomics reveals carbon and nitrogen metabolism responses in alfalfa (Medicago sativa L.) exposed to titanium dioxide nanoparticles

Nanoparticle (NP) pollution has negative impacts and is a major global environmental problem. However, the molecular response of alfalfa (Medicago sativa L.) to titanium dioxide nanoparticles (TiO2 NPs) is limited. Herein, the dual effects of TiO2 NPs (0–1000 mg L−1) on carbon (C) and nitrogen (N) metabolisms in alfalfa were investigated. The results showed that 500 mg L−1 TiO2 NPs (Ti-500) had the highest phytotoxicity in the C/N metabolizing enzymes; and it significantly increased total soluble sugar, starch, sucrose, and sucrose‐phosphate synthase. Furthermore, obvious photosynthesis responses were found in alfalfa exposed to Ti-500. By contrast, 100 mg L−1 TiO2 NPs (Ti-100) enhanced N metabolizing enzymes. RNA-seq analyses showed 4265 and 2121 differentially expressed genes (DEGs) in Ti-100 and Ti-500, respectively. A total of 904 and 844 differentially expressed proteins (DEPs) were identified in Ti-100 and Ti-500, respectively. Through the physiological, transcriptional, and proteomic analyses, the DEGs and DEPs related to C/N metabolism, photosynthesis, chlorophyll synthesis, starch and sucrose metabolism, and C fixation in photosynthetic organisms were observed. Overall, TiO2 NPs at low doses improve photosynthesis and C/N regulation, but high doses can cause toxicity. It is valuable for the safe application of NPs in agriculture.

Restricting the level of the proteins essential for the regulation of the initiation step of replication extends the chronological lifespan and reproductive potential in budding yeast

Aging is defined as a progressive decline in physiological integrity, leading to impaired biological function, including fertility, and rising vulnerability to death. Disorders of DNA replication often lead to replication stress and are identified as factors influencing the aging rate. In this study, we aimed to reveal how the cells that lost strict control of the formation of crucial for replication initiation a pre-initiation complex impact the cells’ physiology and aging. As strains with the lower pre-IC control (lowPICC) we used, Saccharomyces cerevisiae heterozygous strains having only one functional copy of genes, encoding essential replication proteins such as Cdc6, Dbf4, Sld3, Sld7, Sld2, and Mcm10. The lowPICC strains exhibited a significant reduction in the respective genes’ mRNA levels, causing cell cycle aberrations and doubling time extensions. Additionally, the reduced expression of the lowPICC genes led to an aberrant DNA damage response, affected cellular and mitochondrial DNA content, extended the lifespan of post-mitotic cells, and increased the yeast’s reproductive potential. Importantly, we also demonstrated a strong negative correlation between the content of cellular macromolecules (RNA, proteins, lipids, polysaccharides) and aging. The data presented here will likely contribute to the future development of therapies for treating various human diseases.

Towards Sustainable Agriculture: Integrating Agronomic Practices, Environmental Physiology and Plant Nutrition

Sustainable agriculture aims to meet the growing global demand for food without compromising environmental integrity. This review paper explores the integration of agronomic practices, environmental physiology, and plant nutrition as pathways toward sustainable crop production. Intensive agricultural practices have led to significant problems such as soil degradation, loss of biodiversity, and environmental pollution. Recent advancements in plant physiology have enhanced our understanding of plant growth and response to biotic and abiotic stresses. Optimizing crop production in a sustainable manner depends on insights into key processes like photosynthesis, water use efficiency, and nutrient uptake. This review discusses the role of plant growth-promoting microorganisms (PGPMs) as biofertilizers, providing an alternative to harmful agrochemicals. PGPMs can improve soil health and promote plant growth when applied to soil, seeds, or plant surfaces, reducing reliance on synthetic fertilizers and pesticides. Additionally, nanotechnology in agriculture is examined, illustrating how nanomaterials (NMs) and nano-based fertilizers can enhance nutrient absorption and increase crop yields. Beyond these scientific approaches, there is an urgent need to implement novel agricultural practices that support sustainability. The world population is growing at a disquieting rate, placing tremendous pressure on natural resources. This threatens future generations' access to nutritious food and clean air. Innovative approaches like climate-smart agriculture, organic farming, biodynamic agriculture, sustainable intensification, and regenerative agriculture, along with practices such as integrated farming systems, precision agriculture, integrated nutrient management, and integrated pest management, have proven to safeguard agricultural sustainability. By integrating these innovative approaches and practices, it is possible to meet the increasing demands for food while preserving the environment.

Effects of Insulin and Metformin on Indomethacin-Induced Gastric Injury in Streptozotocin-Induced Diabetic and Non-Diabetic Rats

Diabetes is one of the major health issues globally. Diabetic gastropathy is a well-documented phenomenon. Current treatments for diabetes and its complications have proven to be unsatisfactory. Currently, standard insulin therapy alone is still not the best treatment for type 1 diabetes (T1D). Metformin, besides use in type 2 diabetes (T2D), might be considered for a treatment of T1D. This study analyzed the effects of insulin and metformin on the gastric injury caused by indomethacin in the streptozotocin (STZ)-induced diabetic (T1D) and control non-diabetic rats. STZ (60 mg/kg, i.p.) was administered once 2 weeks before indomethacin (IM, 35 mg/kg, s.c.) in rats. Control non-diabetic rats were injected with STZ vehicle. The development of diabetes was assessed by blood glucose levels, changes in the rats' body weight, and water consumption. Insulin (2 IU/kg, i.p.) and metformin (100 mg/kg, orally) were administered daily, separately to different groups of rats, starting from the 8th day after the administration of STZ, for 7 days. After the last administration of the drugs, the rats were fasted for 22 hours before IM administration. Four hours after IM administration, the rats were decapitated, the stomachs were removed to estimate the erosion area; the adrenal glands and thymus were removed to estimate their weight, and trunk blood was collected to test the corticosterone and glucose levels. During the first week after STZ administration characteristic signs of diabetes developed: increased blood glucose, increased water consumption, and slower body weight gain. A week after daily insulin administration (on the 14th day), the glucose level in diabetic rats was lower compared to the corresponding level on the 7th day (before insulin administration). At the same time, the glucose levels before (day 7) and after administration (day 14) of metformin did not differ significantly. The development of STZ-induced diabetes led to a pronounced worsening of the ulcerogenic effect of IM: the average area of erosions caused by IM was increased significantly compared to that in control non-diabetic rats. Administration of both insulin and metformin for 7 days prevented the ulcer-promoting effect of STZ. In addition, insulin, but not metformin, also had a gastroprotective effect in non-diabetic rats: it reduced the average area of IM-induced erosions. The development of STZ-induced diabetes was accompanied by the manifestation of signs of chronic stress: an increase in plasma corticosterone level, an increase in the relative weight of the adrenal glands, and a decrease in the relative weight of the thymus. Daily administration of insulin for 7 days, but not metformin, resulted in a decrease in corticosterone levels on day 14 in diabetic rats. In conclusion, both insulin and metformin effectively prevented the pronounced ulcer-promoting effect of STZ-induced diabetes on the gastric injury caused by indomethacin in rats. However, only insulin, but not metformin, also exerted gastroprotective effect against IM-induced injury in non-diabetic rats under our experimental conditions. Grant for the creation and development of the world-class scientific center "Pavlov Center “Integrative Physiology - to medicine, high-tech healthcare and technologies of stress resistance” and with financial support from the Ministry of Education and Science of the Russian Federation (No 075-15-2022-303 от 21.04.2022.). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Collaborative Critical Thinking Problem Sets Enhance Student Perceived Learning and Promote Student Practice Outside of the Classroom

Collaborative learning and peer-to-peer teaching activities can greatly enhance student learning and engagement in the classroom. This work evaluates the implementation of an additional required class period dedicated to collaborative problem solving activities. A two-semester integrative upper-level anatomy and physiology course (Human Anatomy and Physiology 1 and 2) was revised for the 2022-2023 academic year from a 2 x 75-minute weekly schedule to a 3 x 75-minute weekly schedule to facilitate an extra class period each Friday dedicated to graded collaborative critical thinking worksheets called Problem Sets. Two Friday Problem Set sessions were scheduled for each unit, resulting in an additional 150 minutes of faculty-student contact time per unit and 8 Problem Sets per semester, totalling 16 Problem Sets for the year-long course. Students were encouraged to work in groups on these questions which integrated the previous two class period’s content and additional previous course content, as applicable. Questions in each Problem Set targeted concepts at the Apply, Analyze, or Evaluate learning levels of the Modified Bloom's Taxonomy. Each student turned in their own answer page for an individual grade, serving as a formative assessment. The Problem Set worksheets also included three reflective questions asking the student to note which classmates they worked with, how well they felt they understood the material, and what they did outside of class to prepare for the Problem Set session. The cohort of students in this study was 14 students/semester. In 16/16 Problem Sets, 100% of the students responded to an open-ended question indicating that they completed the Problems Sets with classmates and identified their specific collaborators. In 13/16 Problem Sets, students’ responses to the multiple choice reflective question, “After completing these questions with my classmates I feel…”, 85% of the students responded “...like I understand the material better,” and the remaining 15% responded “...about the same.” In the other 3/16 Problem Sets, only 64% of the students responded “...like I understand the material better.” This indicates that some Problem Sets were more effective than others in assisting students with perceived learning and understanding of the content. Notably, as the semester progressed, students increased their response details to the open-ended question, “How do you prepare for these Friday sessions?”. At the beginning of the semester many students left the question blank or wrote “nothing”, but beginning with Problem Set 4 students started to list specific things they did outside of class to prepare for these sessions, such as “reviewing course notes” or “redrawing pathways and figures” or “completing practice problems in the textbook.” By Problem Set 7 more than 80% of students were sharing details on how they increased their study time outside of class to prepare for Problem Sets. These responses highlight the students’ increased utilization of metacognitive strategies that lead to success (i.e. spending more time outside of class preparing for in class activities) and the benefit of these activities on their learning and understanding of the course material. Collectively, these qualitative data support the continued use of Problem Sets in this integrative year-long anatomy and physiology course. none. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Assessments from the first year of an underrepresented undergraduate internship program

To enhance our service to a diverse student population our faculty created the INtegrative biology and Physiology Undergraduate Training (INPUT) program. This research focused initiative solicited applications from first- and second-year students undergraduates of our large, urban, land-grant university. Selection criteria included academic aptitude, self-reported socioeconomic and cultural challenges, interest in physiological research and letters of support. Six students were selected from our initial cadre of applicants. The students were matched with faculty research mentors and provided a paid research opportunity for the spring semester of 2023. At the end of the term, an assessment of the experience by both each student and mentor determined whether a second semester experience was offered by the department. All of our faculty mentors were favorably impressed by the progress made by their INPUT scholars and five of the six students requested and were granted a second semester research opportunity. The five INPUT students continued their mentored research in the areas of neurophysiology, skeletal muscle physiology, and adipose biology. The one outlier stated that while she enjoyed the experience and that it encouraged her to continue in research. She also found that her scientific passion was in chemistry rather than physiology and moved to a different program. Based on the overall positive outcomes a second semester opportunity was offered to the five students who expressed an interest in continuing their physiology-focused projects. The second term experiences were completed either during the summer or fall of 2023. We will encourage our initial group of INPUT scholars to serve as ambassadors for other underrepresented students who are interested in physiology research and use their end of experience assessments to help shape the future of our INPUT program. We will report on the opportunities discovered and the challenges faced in launching the INPUT program as well as the prospects for continued outreach. Our hope is that our experiences with INPUT will encourage others to attract, encourage and prepare a robust and representative group of young scientists and clinicians to enter the 21st century biomedical community. Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, MN 55455. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Engaging Alumni as Peer Mentors: Fostering Belonging and Forging Paths to Success

Peer mentoring positively impacts students’ learning experience. It not only improves their content knowledge in courses but also reduces stress and anxiety levels, while increasing participation and engagement within the academic community. The MS in Integrative Physiology (MSIP) - graduate peer mentoring (GPM) program at Benedictine University, launched in 2020 during the COVID19 pandemic, aids in student and mentor success. The MSIP program, started in 2017 with 18 students, now has a total of 187, with 30 students enrolled in 2023. The cohort-based learning model, small class sizes, personalized advising, and a well-designed curriculum benefit diverse students. The shift to online learning during the pandemic challenged connections crucial for student success. An alum of the program was hired as a peer mentor to assist with classroom management, facilitate breakout room discussions, and provide insights into professional school applications. The students and the GPM establish an environment conducive to learning through in-person and virtual interactions. The MSIP-GPM program equips students with crucial learning skills that are needed for future success. It is a win-win situation for mentors and mentees alike. Mentors develop communication, interpersonal, and leadership skills along with confidence and motivation. They also deepen their understanding and exposure to content knowledge during their glide year. Mentees receive practical advice, academic strategies, career insights, and new friendships. Intentional selection of GPMs from underrepresented communities and first-generation students fosters inclusivity, support and a sense of belonging — all essential for their success. Positive feedback after the first semester led to program continuation, with GPMs providing support and mentorship. Since 2020, 13 students served as GPMs. 54% are in professional programs, and 23% are in the interview process for admittance. Based on the success of GPMs in Physiology, peer mentors were introduced in Immunology and Medical Biochemistry in Fall 2023. Results from student surveys, interviews, performance-metrics in tests and GPM feedback demonstrated the program’s effectiveness and peer mentor success. Peer mentoring aids active learning, boosts confidence and success, particularly for first-generation and underrepresented students. JS, TPM and MN are supported by BenU COSH and NSSRP Funds, Benedictine University, Lisle, IL. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Increased mucous cell population and modulation of Bax/Bcl-2 factors characterize in vivo gastroprotective activity of Cissampelos owariensis in rats

The physiological integrity of the gastric mucosa is dependent on the balance between the mucosal protective and aggressive factors. Medicinal plants or their derivatives generally exhibit gastroprotective effect by promoting the protective factors against the aggressive factors of the gastric mucosa. The study was conducted to elucidate the gastroprotective mechanism of the methanol extract of C. owariensis (MECo) in rats. Twenty male Wistar rats were divided into four groups, which include control groups A and B – given distilled water – and treated groups C and D – animals given 100 and 300 mg/kg MECo respectively for 28 days. After the treatment period, gastric mucosal injury was induced for groups B-D by pyloric ligation method. The gastric tissue of animals was collected, processed for histology (haematoxylin and eosin technique), histochemistry (periodic acid-schiff technique) and immunohistochemical staining (for Bcl-2 & Bax proteins). The results of the gastric histomorphology showed prominent and widespread mucosal erosion in positive control group B compared to normal control group A, while treated groups C and D showed only mild or focal mucosal erosion. Furthermore, the histochemical results showed significant increase in mucous cell population in treated groups C and D compared to positive control group B. The immunostaining results showed significant up-regulation of anti-apoptotic Bcl-2 protein and down-regulation of pro-apoptotic Bax protein in the treated groups C and D compared to the control groups A and B. In conclusion, the findings of this study indicate that the increased mucous cell population and modulation of apoptotic signaling highlights the mechanism of gastroprotective activity of MECo.

Designing and testing an Integrated Study Strategy: Core Concepts in physiology and Mind Maps

This abstract shows the result of an innovative approach for learning physiology by combining two widely recognized methods: Core Concepts in physiology and Mind Maps. The objective is demonstrating the graphic product that visualize conceptual relationships holistically (mind map) combined with core concepts in cardiovascular physiology generated by a group of students enrolled to the integrative physiology course (2nd-year medical students, medical bachelor's degree, Professional Studies Faculty, Autonomous University of San Luis Potosí, México) during the semester august to December 2023. Methods: the curriculum content of cardiovascular physiology includes excitation-contraction coupling of the heart, the heart cycle, determinants of arterial pressure and peripheric vascular characteristics, including special circulations. The development of the mind map was according to the academic content of the course (4 weeks). The group of students worked with a training physiology teacher (including core concept training) for one 2-hour session per week (total= 4 sessions). The result is a mind map that includes the aspects of cardiovascular physiology addressed by the core concepts tool. Conclusion: Contemporary education faces increasing challenges in information retention and comprehension., and in this context, the integration of these two strategies emerges as a promising solution. This combination of learning tool is applicable in environments of low socioeconomical status because not involve doesn´t involve any monetary investments. Curricular Commission and the Academy or Clinical and Basic Sciences belonging to the bachelor´s degree of the Professional Studies Faculty, Autonomous University of San Luis Potosí, México. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Dissecting unique and common variance across body and brain health indicators using age prediction

AbstractAgeing is a heterogeneous multisystem process involving different rates of decline in physiological integrity across biological systems. The current study dissects the unique and common variance across body and brain health indicators and parses inter‐individual heterogeneity in the multisystem ageing process. Using machine‐learning regression models on the UK Biobank data set (N = 32,593, age range 44.6–82.3, mean age 64.1 years), we first estimated tissue‐specific brain age for white and gray matter based on diffusion and T1‐weighted magnetic resonance imaging (MRI) data, respectively. Next, bodily health traits, including cardiometabolic, anthropometric, and body composition measures of adipose and muscle tissue from bioimpedance and body MRI, were combined to predict ‘body age’. The results showed that the body age model demonstrated comparable age prediction accuracy to models trained solely on brain MRI data. The correlation between body age and brain age predictions was 0.62 for the T1 and 0.64 for the diffusion‐based model, indicating a degree of unique variance in brain and bodily ageing processes. Bayesian multilevel modelling carried out to quantify the associations between health traits and predicted age discrepancies showed that higher systolic blood pressure and higher muscle‐fat infiltration were related to older‐appearing body age compared to brain age. Conversely, higher hand‐grip strength and muscle volume were related to a younger‐appearing body age. Our findings corroborate the common notion of a close connection between somatic and brain health. However, they also suggest that health traits may differentially influence age predictions beyond what is captured by the brain imaging data, potentially contributing to heterogeneous ageing rates across biological systems and individuals.

Integration of transcriptome, gut microbiota, and physiology reveals toxic responses of the red claw crayfish (Cherax quadricarinatus) to imidacloprid

Imidacloprid enters the water environment through rainfall and causes harm to aquatic crustaceans. However, the potential chronic toxicity mechanism of imidacloprid in crayfish has not been comprehensively studied. In this study, red claw crayfish (Cherax quadricarinatus) were exposed to 11.76, 35.27, or 88.17 μg/L imidacloprid for 30 days, and changes in the physiology and biochemistry, gut microbiota, and transcriptome of C. quadricarinatus and the interaction between imidacloprid, gut microbiota, and genes were studied. Imidacloprid induced oxidative stress and decreased growth performance in crayfish. Imidacloprid exposure caused hepatopancreas damage and decreased serum immune enzyme activity. Hepatopancreatic and plasma acetylcholine decreased significantly in the 88.17 μg/L group. Imidacloprid reduced the diversity of the intestinal flora, increased the abundance of harmful flora, and disrupted the microbiota function. Transcriptomic analysis showed that the number of up-and-down-regulated differentially expressed genes (DEGs) increased significantly with increasing concentrations of imidacloprid. DEG enrichment analyses indicated that imidacloprid inhibits neurotransmitter transduction and immune responses and disrupts energy metabolic processes. Crayfish could alleviate imidacloprid stress by regulating antioxidant and detoxification-related genes. A high correlation was revealed between GST, HSPA1s, and HSP90 and the composition of gut microorganisms in crayfish under imidacloprid stress. This study highlights the negative effects and provides detailed sequencing data from transcriptome and gut microbiota to enhance our understanding of the molecular toxicity of imidacloprid in crustaceans.

Regulation of body temperature and blood pressure in women: Mechanisms and implications for heat illness risk.

Increasing global temperatures due to ongoing climate change phenomena have resulted in increased risk of exertional heat illness in otherwise healthy, young individuals who work or play in the heat. With increasing participation of women in athletic, military and industrial activities that involve exertion in the heat, there is a growing need to study female physiology in this context. Mechanisms controlling blood pressure and body temperature have substantial overlap in humans, largely due to autonomic mechanisms which contribute to both. Similarly, illnesses that result from excessive heat exposure can often be traced back to imbalances in one or more of these autonomic mechanisms. In recent years, there has been increased recognition of the importance of sex as a biological variable for basic and applied research in these areas. The goal of this paper is to present an update on the integrative physiology and pathophysiology of responses to heat stress in women (thermoregulation and blood pressure regulation). In this context, it is often the case that differences between sexes are presented as 'advantages' and 'disadvantages' of one sex over the other. In our opinion, this is an over-simplification of the physiology which ignores the nuances and complexities of the integrative physiology of responses to heat exposure and exercise, and their relevance for practical outcomes.

Epigenetics of hematopoietic stem cell aging.

The development of new antiaging medicines is of great interest to the current elderly and aging population. Aging of the hematopoietic system is attributed to the aging of hematopoietic stem cells (HSCs), and epigenetic alterations are the key effectors driving HSC aging. Understanding the epigenetics of HSC aging holds promise of providing new insights for combating HSC aging and age-related hematological malignancies. Aging is characterized by the progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. During aging, the HSCs undergo both quantitative and qualitative changes. These functional changes in HSCs cause dysregulated hematopoiesis, resulting in anemia, immune dysfunction, and an increased risk of hematological malignancies. Various cell-intrinsic and cell-extrinsic effectors influencing HSC aging have also been identified. Epigenetic alterations are one such mechanism. Cumulative epigenetic alterations in aged HSCs affect their fate, leading to aberrant self-renewal, differentiation, and function of aged HSCs. In turn, these factors provide an opportunity for aged HSCs to expand by modulating their self-renewal and differentiation balance, thereby contributing to the development of hematological malignancies.

Integrative physiology and transcriptome reveal salt-tolerance differences between two licorice species: Ion transport, Casparian strip formation and flavonoids biosynthesis

BackgroundGlycyrrhiza inflata Bat. and Glycyrrhiza uralensis Fisch. are both original plants of ‘Gan Cao’ in the Chinese Pharmacopoeia, and G. uralensis is currently the mainstream variety of licorice and has a long history of use in traditional Chinese medicine. Both of these species have shown some degree of tolerance to salinity, G. inflata exhibits higher salt tolerance than G. uralensis and can grow on saline meadow soils and crusty saline soils. However, the regulatory mechanism responsible for the differences in salt tolerance between different licorice species is unclear. Due to land area-related limitations, the excavation and cultivation of licorice varieties in saline-alkaline areas that both exhibit tolerance to salt and contain highly efficient active substances are needed. The systematic identification of the key genes and pathways associated with the differences in salt tolerance between these two licorice species will be beneficial for cultivating high-quality salt-tolerant licorice G. uralensis plant varieties and for the long-term development of the licorice industry. In this research, the differences in growth response indicators, ion accumulation, and transcription expression between the two licorice species were analyzed.ResultsThis research included a comprehensive comparison of growth response indicators, including biomass, malondialdehyde (MDA) levels, and total flavonoids content, between two distinct licorice species and an analysis of their ion content and transcriptome expression. In contrast to the result found for G. uralensis, the salt treatment of G. inflata ensured the stable accumulation of biomass and total flavonoids at 0.5 d, 15 d, and 30 d and the restriction of Na+ to the roots while allowing for more K+ and Ca2+ accumulation. Notably, despite the increase in the Na+ concentration in the roots, the MDA concentration remained low. Transcriptome analysis revealed that the regulatory effects of growth and ion transport on the two licorice species were strongly correlated with the following pathways and relevant DEGs: the TCA cycle, the pentose phosphate pathway, and the photosynthetic carbon fixation pathway involved in carbon metabolism; Casparian strip formation (lignin oxidation and translocation, suberin formation) in response to Na+; K+ and Ca2+ translocation, organic solute synthesis (arginine, polyamines, GABA) in response to osmotic stresses; and the biosynthesis of the nonenzymatic antioxidants carotenoids and flavonoids in response to antioxidant stress. Furthermore, the differential expression of the DEGs related to ABA signaling in hormone transduction and the regulation of transcription factors such as the HSF and GRAS families may be associated with the remarkable salt tolerance of G. inflata.ConclusionCompared with G. uralensis, G. inflata exhibits greater salt tolerance, which is primarily attributable to factors related to carbon metabolism, endodermal barrier formation and development, K+ and Ca2+ transport, biosynthesis of carotenoids and flavonoids, and regulation of signal transduction pathways and salt-responsive transcription factors. The formation of the Casparian strip, especially the transport and oxidation of lignin precursors, is likely the primary reason for the markedly higher amount of Na+ in the roots of G. inflata than in those of G. uralensis. The tendency of G. inflata to maintain low MDA levels in its roots under such conditions is closely related to the biosynthesis of flavonoids and carotenoids and the maintenance of the osmotic balance in roots by the absorption of more K+ and Ca2+ to meet growth needs. These findings may provide new insights for developing and cultivating G. uralensis plant species selected for cultivation in saline environments or soils managed through agronomic practices that involve the use of water with a high salt content.

Integrative leaf anatomy structure, physiology, and metabolome analyses revealed the response to drought stress in sainfoin at the seedling stage.

Sainfoin (Onobrychis viciaefolia) is a vital legume forage, and drought is the primary element impeding sainfoin growth. The anatomical structure, physiological indexes, and metabolites of the leaves of sainfoin seedlings with a drought-resistant line of P1 (DRL) and a drought-sensitive material of 2049 (DSM) were analyzed under drought (-1.0 MPa) with polyethylene glycol-6000 (PEG-6000). The leaf anatomy was studied by the paraffin section method. The related physiological indexes were measured by the hydroxylamine oxidation method, titanium sulfate colorimetric method, thiobarbituric acid method, acidic ninhydrin colorimetric method, and Coomassie brilliant blue method. The metabolomics analysis was composed of liquid chromatography tandem high-resolution mass spectrometry (LC-MS/MS). The results revealed that the thickness of the epidermis, palisade tissue, and sponge tissue of DRL were significantly greater than those of DSM. The leaves of DRL exhibited lower levels of superoxide anion (O2 •-) production rate, hydrogen peroxide (H2O2) content, and malondialdehyde (MDA) content compared with DSM, while proline (Pro) content and soluble protein (SP) content were significantly higher than those of DSM. A total of 391 differential metabolites were identified in two samples. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment showed that the primary differential metabolites were concentrated into the tyrosine metabolism; isoquinoline alkaloid biosynthesis; ubiquinone and other terpenoid quinone biosynthesis; neomycin, kanamycin, and gentamicin biosynthesis; and anthocyanin biosynthesis metabolic pathways. Compared with DSM, DRL had more complete anatomical structure, lower active oxygen content, and higher antioxidant level. The results improved our insights into the drought-resistant mechanisms in sainfoin.

Enhancing thermal comfort prediction in high-speed trains through machine learning and physiological signals integration

Heating, Ventilation, and Air Conditioning (HVAC) systems in high-speed trains (HST) are responsible for consuming approximately 70% of non-operational energy sources, yet they frequently fail to ensure provide adequate thermal comfort for the majority of passengers. Recent advancements in portable wearable sensors have opened up new possibilities for real-time detection of occupant thermal comfort status and timely feedback to the HVAC system. However, since occupant thermal comfort is subjective and cannot be directly measured, it is generally inferred from thermal environment parameters or physiological signals of occupants within the HST compartment. This paper presents a field test conducted to assess the thermal comfort of occupants within HST compartments. Leveraging physiological signals, including skin temperature, galvanic skin reaction, heart rate, and ambient temperature, we propose a Predicted Thermal Comfort (PTC) model for HST cabin occupants and establish an intelligent regulation model for the HVAC system. Nine input factors, comprising physiological signals, individual physiological characteristics, compartment seating, and ambient temperature, were formulated for the PTS model. In order to obtain an efficient and accurate PTC prediction model for HST cabin occupants, we compared the accuracy of different subsets of features trained by Machine Learning (ML) models of Random Forest, Decision Tree, Vector Machine and K-neighbourhood. We divided all the predicted feature values into four subsets, and did hyperparameter optimisation for each ML model. The HST compartment occupant PTC prediction model trained by Random Forest model obtained 90.4% Accuracy (F1 macro = 0.889). Subsequent sensitivity analyses of the best predictive models were then performed using SHapley Additive explanation (SHAP) and data-based sensitivity analysis (DSA) methods. The development of a more accurate and operationally efficient thermal comfort prediction model for HST occupants allows for precise and detailed feedback to the HVAC system. Consequently, the HVAC system can make the most appropriate and effective air supply adjustments, leading to improved satisfaction rates for HST occupant thermal comfort and the avoidance of energy wastage caused by inaccurate and untimely predictive feedback.