Metabolic Rate Research Articles

Effects of dietary flavonoids on the metabolism of vortioxetine and its potential mechanism.

Quercetin and apigenin are two common dietary flavonoids widely found in foods and fruits. Quercetin and apigenin can act as the inhibitors of CYP450 enzymes, which may affect the pharmacokinetics of clinical drugs. Vortioxetine (VOR), approved for marketing by the Food and Drug Administration (FDA) in 2013, is a novel clinical drug for treating major depressive disorder (MDD). This study aimed to evaluate the effects of quercetin and apigenin on the metabolism of VOR in in vivo and in vitro experiments. Firstly, 18 Sprague-Dawley rats were randomly divided into three groups: control group (VOR), group A (VOR + 30 mg/kg quercetin) and group B (VOR + 20 mg/kg apigenin). We collected the blood samples at different time points before and after the final oral administration of 2 mg/kg VOR. Subsequently, we further used rat liver microsomes (RLMs) to investigate the half-maximal inhibitory concentration (IC50) of the metabolism of vortioxetine. Finally, we evaluated the inhibitory mechanism of two dietary flavonoids on VOR metabolism in RLMs. In animal experiments, we found AUC (0-∞) (area under the curve from 0 to infinity) and CLz/F (clearance) to be obviously changed. Compared to controls, AUC (0-∞) of VOR in group A and group B was 2.22 and 3.54 times higher, respectively, while CLz/F of VOR in group A and group B was significantly decreased down to nearly two-fifth and one-third. In in vitro studies, the IC50 value of quercetin and apigenin in the metabolic rate of vortioxetine was 5.322 μM and 3.319 μM, respectively. Ki value of quercetin and apigenin was found to be 0.279 and 2.741, respectively, and the αKi value of quercetin and apigenin was 0.066 and 3.051 μM, respectively. Quercetin and apigenin exhibited inhibitory effects on the metabolism of vortioxetine in vivo and in vitro. Moreover, quercetin and apigenin non-competitively inhibited the metabolism of VOR in RLMs. Thus, we should pay more attention to the combination between these dietary flavonoids and VOR in the future clinical use.

Transcriptome analysis of large yellow croaker (Larimichthys crocea) at different growth rates.

The unsynchronized growth of the large yellow croaker (Larimichthys crocea), which impacts growth efficiency, poses a challenge for aquaculture practitioners. In our study, juvenile stocks of large yellow croaker were sorted by size after being cultured in offshore cages for 4 months. Subsequently, individuals from both the fast-growing (FG) and slow-growing (SG) groups were sampled for analysis. High-throughput RNA-Seq was employed to identify genes and pathways that are differentially expressed during varying growth rates, which could suggest potential physiological mechanisms that influence growth rate. Our transcriptome analysis identified 382 differentially expressed genes (DEGs), comprising 145 upregulated and 237 downregulated genes in comparison to the SG group. GO and KEGG enrichment analyses indicated that these DEGs are predominantly involved in signal transduction and biochemical metabolic pathways. Quantitative PCR (qPCR) results demonstrated that cat, fasn, idh1, pgd, fgf19, igf2, and fads2 exhibited higher expression levels, whereas gadd45b and gadd45g showed lower expression compared to the slow-growing group. In conclusion, the differential growth rates of large yellow croaker are intricately associated with cellular proliferation, metabolic rates of the organism, and immune regulation. These findings offer novel insights into the molecular mechanisms and regulatory aspects of growth in large yellow croaker and enhance our understanding of growth-related genes.

Coronary circulation enhances the aerobic performance of wild Pacific salmon.

Female Pacific salmon often experience higher mortality than males during their once-in-a-lifetime up-river spawning migration, particularly when exposed to secondary stressors (e.g. high temperatures). However, the underlying mechanisms remain unknown. One hypothesis is that female Pacific salmon hearts are more oxygen-limited than males and are less able to supply oxygen to the body's tissues during this demanding migration. Notably, female hearts have higher coronary blood flow, which could indicate a greater reliance on this oxygen source. Oxygen limitations can develop from naturally occurring coronary blockages (i.e., coronary arteriosclerosis) found in mature salmon hearts. If female hearts rely more heavily on coronary blood flow but experience similar arteriosclerosis levels as males, they will have disproportionately impaired aerobic performance. To test this hypothesis, we measured resting (RMR) and maximum metabolic rate (MMR), aerobic scope (AS) and acute upper thermal tolerance in coho salmon (Oncorhynchus kisutch) with an intact or artificially blocked coronary oxygen supply. We also assessed venous blood oxygen and chemistry (cortisol, ions, and metabolite concentrations) at different time intervals during recovery from exhaustive exercise. We found that coronary blockage impaired MMR, AS, and the partial pressure of oxygen in venous blood (PvO2) during exercise recovery but did not differ between sexes. Coronary ligation lowered acute upper thermal tolerance by 1.1°C. Though we did not find evidence of enhanced female reliance on coronary supply, our findings highlight the importance of coronary blood supply for mature wild salmon, where migration success may be linked to cardiac performance, particularly during warm water conditions.

Prosthetic Stiffness and Added Mass Affect Metabolic Power and Asymmetry in Female Runners with a Leg Amputation.

Similar to non-amputees, female athletes with unilateral transtibial amputation (TTA) using running-specific leg prostheses (RSPs) may have worse running economy and higher rates of running-related injury than male athletes. Optimizing RSP configuration for female athletes could improve running economy and minimize biomechanical asymmetry, which has been associated with running-related injury. Nine females with a TTA ran at 2.5 m/s while we measured metabolic rates and ground reaction forces. Subjects used an RSP with a manufacturer-recommended stiffness category, one category less stiff and two categories less stiff than recommended. Use of an RSP two categories less stiff resulted in 3.0% lower net metabolic power (p=0.04), 7.8% lower affected leg stiffness (p=6.01x10-4), increased contact time asymmetry (p=0.04), and decreased stance average vertical ground reaction force asymmetry (p=0.04) compared to a recommended stiffness category RSP. Lower RSP stiffness (kN/m) values were associated with lower net metabolic power (p=0.02), lower affected leg stiffness (p=1.36x10-4), longer affected leg contact time (p=1.46x10-4) and similar affected leg peak and stance-average vertical ground reaction force compared to higher RSP stiffness values. Subjects then used the RSP stiffness category that elicited the lowest net metabolic power with 100 g, 200 g and 300 g added distally. We found no significant effects of added mass on net metabolic power, biomechanics, or asymmetry. These results suggest that female runners with a TTA could decrease metabolic power during running while minimizing biomechanical asymmetries, which have been associated with running-related injury using an RSP two categories less stiff than manufacturer recommended.

Time-restricted feeding reveals a role for neural respiratory clocks in optimizing daily ventilatory-metabolic coupling in mice.

The master circadian clock, located in the suprachiasmatic nuclei (SCN), organizes the daily rhythm in minute ventilation (VE). However, the extent that the daily rhythm in VE is secondary to SCN-imposed O2 and CO2 cycles (i.e., metabolic rate), or driven by other clock mechanisms, remains unknown. Here, we experimentally shifted metabolic rate using time-restricted feeding (without affecting light-induced synchronization of the SCN) to determine the influence of metabolic rate in orchestrating the daily VE rhythm. Mice eating predominantly at night exhibited robust daily rhythms in O2 consumption (VO2), CO2 production (VCO2), and VE with similar peak times (~ZT18) that were consistent with SCN organization. However, feeding mice exclusively during the day separated the relative timing of metabolic and ventilatory rhythms, resulting in a ~8.5-hr advance in VCO2, and a disruption of the VE rhythm, suggesting opposing circadian and metabolic influences on VE. To determine if the molecular clock of cells involved in the neural control of breathing contribute to the daily VE rhythm, we examined VE in mice lacking BMAL1 in Phox2b-expressing respiratory cells (i.e., BKOP mice). The ventilatory and metabolic rhythms of predominantly night-fed BKOP mice did not differ from wild-type mice. However, in contrast to wild-type mice, exclusive day feeding of BKOP mice led to an unfettered daily VE rhythm with a peak time aligning closely with the daily VCO2 rhythm. Taken together, these results indicate that both daily VCO2 changes and intrinsic circadian time-keeping within Phox2b respiratory cells are predominant orchestrators of the daily rhythm in ventilation.

What if the upwelling weakens? Effects of rising temperature and nutrient depletion on coastal assemblages.

Surface temperature of the oceans has increased globally over the past decades. In coastal areas influenced by eastern boundary upwelling systems (EBUS), winds push seawater offshore and deep, cold and nutrient-rich seawater rise towards the surface, partially buffering global warming. On the North coast of Portugal, the NW Iberian upwelling system allows extensive kelp forests to thrive in these "boreal-like" conditions, fostering highly diverse and productive communities. However, the warming of the upper layer of the ocean may weaken this upwelling, leading to higher sea surface temperature and lower nutrient input in the coastal areas. The effects of these changes on the structure and function of coastal ecosystems remain unexplored. The present study aimed to examine the combined effects of elevated temperature and nutrient depletion on semi-naturally structured assemblages. The eco-physiological responses investigated included growth, chlorophyll fluorescence and metabolic rates at the levels of individual species and whole assemblages. Our findings showed interactive effects of the combination of elevated temperature with nutrient depletion on the large canopy-forming species (i.e., kelp). As main contributor to community response, those effects drove the whole assemblage responses to significant losses in productivity levels. We also found an additive effect of elevated temperature and reduced nutrients on sub-canopy species (i.e., Chondrus crispus), while turfs were only affected by temperature. Our results suggest that under weakening upwelling scenarios, the ability of the macroalgal assemblages to maintain high productivity rates could be seriously affected and predict a shift in community composition with the loss of marine forests.

Interrelationship of Component Composition of the Body with Biological Age According to the <i>“Bio-Age”</i> Scale

A new method for estimating biological age (BA) on the Bio-age scale, which reflects the degree of its correspondence with respect to calendar age (CA), is presented. Anthropometric (body weight, systolic blood pressure, vital capacity, dynamometry of the right hand), biochemical (glucose and sugar levels in the blood) parameters were analyzed; body composition (percentage of active cell mass (ACM%), body fat mass (BFM%), total water (TW%), basal metabolism) in 972 people (427 men and 545 women) aged 18–70 years. An increase with age in the number of surveyed (especially among men) with BA CA was revealed. It was determined that an increase in the values of BFM%, a decrease in ACM% and TW% leads to an acceleration of the aging of the body. Dynamics of indicators of body components at the age stage of 18–70 years is characterized by a decrease in the values of ACM%, TW% and an increase in BFM%, and in the groups BA CA the negative dynamics is 2–3 times more intense. It is likely that the imbalance in the ratio of body components causes the development of numerous morphofunctional disorders. Therefore, in order to slow down the rate of aging of the organism, it is necessary to normalize the component composition of the body.

Lockbox enrichment facilitates manipulative and cognitive activities for mice

Background Due to the lack of complexity and variety of stimuli, conventional housing conditions of laboratory mice do not allow these animals to fully express their behavioral repertoire, including manipulative and cognitive activities. Therefore, we designed mechanical puzzles, so-called lockboxes, for mice that can be provided in their home cages. We investigated the impact of the lockbox enrichment on their phenotype and affective state when compared to conventional housing and super-environmental enrichment. Methods Young adult female C57BL/6JCrl mice were examined before and after 2-month exposure to the different types of enrichment in a phenotyping test battery, including tests for trait and state anxiety-related behavior, calorimetric measurements, body weight measurements, and the analysis of stress hormone metabolite concentrations as well as sequential problem-solving abilities. At the end of the study, adrenal gland weights were determined and pathohistological evaluation was performed. For all continuous variables, the relative variability was calculated. Results We demonstrated that lockbox enrichment decreased trait anxiety-related behavior compared to conventional housing in the Grid Exploratory Paradigm. In contrast, the different types of enrichment neither influenced state anxiety-related behavior in the Open Field and Elevated Plus Maze Test nor physiological variables (i.e., bodyweight, resting metabolic rate, stress hormone metabolite concentrations, and adrenal gland weights). Lockbox enrichment improved sequential problem-solving when compared to super-environmental enrichment. Regardless of the housing condition, the relative variability increased in most variables over time, although the coefficient of variation decreased for some variables, especially in animals with access to the lockbox enrichment. A pathohistological evaluation revealed no evidence of toxicopathological effects associated with the material from which the lockbox enrichment was made. Conclusions Overall, the lockbox enrichment revealed beneficial effects on the affective state and sequential problem-solving abilities of laboratory mice. The reproducibility was demonstrated not to be compromised by lockbox enrichment, similar to super-environmental enrichment.

A Transformative Approach for Breast Cancer Detection Using Physics-Informed Neural Network and Surface Temperature Data

Abstract Early detection is the most effective defense against breast cancer. Mammography is a well-established X-ray based technique that is used for annual or biennial screening of women above age of 40. Since the dense breast tissue sometimes obscures the cancer in an x-ray image, about 10% of screened women are recalled and undergo additional adjunctive modalities, such as ultrasound, digital breast tomosynthesis or magnetic resonance imaging (MRI). These modalities have drawbacks such as additional radiation dosage, overdiagnosis and high cost. A new concurrent multi-spectral imaging approach is recently presented to eliminate the high recall rates by utilizing the breast surface temperature data with an inverse physics-informed neural network algorithm. The multi-spectral imaging does not use any harmful radiations, such as x-rays, is contact-less and does not require breast compression. It has been validated in 23 patients and offers a cost-effective solution to provide improved detection capability of cancerous cells. It is estimated to reduce the recall rates significantly from the current 10%, with a corresponding reduction in the biopsies. This adjunctive approach builds on the strength of mammography and offers a safe adjunct by relying on the higher metabolic rates of cancer cells.

Efficacy and safety of ultrasound-guided thermal ablation of graves’ disease: a retrospective cohort study

BackgroundUltrasound-guided thermal ablation (TA) has emerged as a robust therapeutic approach for treating solid tumors in multiple organs, including the thyroid. Yet, its efficacy and safety profile in the management of Graves’ Disease (GD) remains to be definitively established.MethodsA retrospective study was conducted on 50 GD patients treated with TA between October 2017 and December 2021. Key metrics like thyroid volume, volume reduction rate (VRR), thyroid hormones, and basal metabolic rate (BMR) were evaluated using paired Wilcoxon tests.ResultsThe intervention of ultrasound-guided TA yielded a statistically significant diminution in total thyroid volume across all postoperative follow-up intervals—1, 3, 6, and 12 months—relative to pre-intervention baselines (p < 0.001). The median VRR observed at these time points were 17.5%, 26.5%, 34.4%, and 39.8%, respectively. Euthyroid status was corroborated in 96% of patients at the one-year follow-up milestone. Transient tachycardia and dysphonia were observed in three patients, while a solitary case of skin numbness was noted. Crucially, no instances of enduring injury to the recurrent laryngeal nerve (RLN) were documented.ConclusionsOur investigation substantiates ultrasound-guided TA as a pragmatic, well-tolerated, and safe therapeutic modality for GD. It effectively improves symptoms of hyperthyroidism, engenders a substantial reduction in thyroid volume, and restores thyroid hormone and BMR to physiological levels. Given its favorable safety profile, enhanced cosmetic outcomes, and minimally invasive nature, ultrasound-guided TA is a compelling alternative to thyroidectomy for GD patients.

Root-to-shoot signaling positively mediates source-sink relation in late growth stages in diploid and tetraploid wheat

Non-hydraulic root source signaling (nHRS) is a unique positive response to soil drying in the regulation of plant growth and development. However, it is unclear how the nHRS mediates the tradeoff between source and sink at the late growth stages and its adaptive mechanisms in primitive wheat. To address this issue, a root-splitting design was made by inserting solid partition in the middle of the pot culture to induce the occurrence of nHRS using four wheat cultivars (MO1 and MO4, diploid; DM22 and DM31, tetraploid) as materials. Three water treatments were designed as 1) both halves watered (CK), 2) holistic root system watered then droughted (FS), 3) one-half of the root system watered and half droughted (PS). FS and PS were designed to compare the role of the full root system and split root system to induce nHRS. Leaves samples were collected during booting and anthesis to compare the role of nHRS at both growth stages. The data indicated that under PS treatment, ABA concentration was significantly higher than FS and CK, demonstrating the induction of nHRS in split root design and nHRS decreased cytokinin (ZR) levels, particularly in the PS treatment. Soluble sugar and proline accumulation were higher in the anthesis stage as compared to the booting stage. POD activity was higher at anthesis, while CAT was higher at the booting stage. Increased ABA (nHRS) correlated with source-sink relationships and metabolic rate (i.e., leaf) connecting other stress signals. Biomass density showed superior resource acquisition and utilization capabilities in both FS and PS treatment as compared to CK in all plants. Our findings indicate that nHRS-induced alterations in phytohormones and their effect on source-sink relations were allied with the growth stages in primitive wheat.

Mitochondrial Protein-Coding Gene Expression in the Lizard Sphenomorphus incognitus (Squamata:Scincidae) Responding to Different Temperature Stresses.

In the context of global warming, the frequency of severe weather occurrences, such as unexpected cold spells and heat waves, will grow, as well as the intensity of these natural disasters. Lizards, as a large group of reptiles, are ectothermic. Their body temperatures are predominantly regulated by their environment and temperature variations directly impact their behavior and physiological activities. Frequent cold periods and heat waves can affect their biochemistry and physiology, and often their ability to maintain their body temperature. Mitochondria, as the center of energy metabolism, are crucial for maintaining body temperature, regulating metabolic rate, and preventing cellular oxidative damage. Here, we used RT-qPCR technology to investigate the expression patterns and their differences for the 13 mitochondrial PCGs in Sphenomorphus incognitus (Squamata:Scincidae), also known as the brown forest skink, under extreme temperature stress at 4 °C, 8 °C, 34 °C, and 38 °C for 24 h, compared to the control group at 25 °C. In southern China, for lizards, 4 °C is close to lethal, and 8 °C induces hibernation, while 34/38 °C is considered hot and environmentally realistic. Results showed that at a low temperature of 4 °C for 24 h, transcript levels of ATP8, ND1, ND4, COI, and ND4L significantly decreased, to values of 0.52 ± 0.08, 0.65 ± 0.04, 0.68 ± 0.10, 0.28 ± 0.02, and 0.35 ± 0.02, respectively, compared with controls. By contrast, transcript levels of COIII exhibited a significant increase, with a mean value of 1.86 ± 0.21. However, exposure to 8 °C for 24 h did not lead to an increase in transcript levels. Indeed, transcript levels of ATP6, ATP8, ND1, ND3, and ND4 were significantly downregulated, to 0.48 ± 0.11, 0.68 ± 0.07, 0.41 ± 0.08, 0.54 ± 0.10, and 0.52 ± 0.07, respectively, as compared with controls. Exposure to a hot environment of 34 °C for 24 h led to an increase in transcript levels of COI, COII, COIII, ND3, ND5, CYTB, and ATP6, with values that were 3.3 ± 0.24, 2.0 ± 0.2, 2.70 ± 1.06, 1.57 ± 0,08, 1.47 ± 0.13, 1.39 ± 0.56, and 1.86 ± 0.12, respectively, over controls. By contrast, ND4L exhibited a significant decrease (to 0.31 ± 0.01) compared with controls. When exposed to 38 °C, the transcript levels of the 13 PCGs significantly increased, ranging from a 2.04 ± 0.23 increase in ND1 to a 6.30 ± 0.96 rise in ND6. Under two different levels of cold and heat stress, the expression patterns of mitochondrial genes in S. incognitus vary, possibly associated with different strategies employed by this species in response to low and high temperatures, allowing for rapid compensatory adjustments in mitochondrial electron transport chain proteins in response to temperature changes. Furthermore, this underscores once again the significant role of mitochondrial function in determining thermal plasticity in reptiles.

Rearing and Experimental Uses of Daphnia: Controlling Animal Nutrition and Assessing Lifespan and Life-History Traits.

Caloric restriction has been found to extend the lifespan of many organisms including mammals and other vertebrates. With lifespans exceeding months to years, age-related experiments involving fish and mammals can be overtly costly, both in terms of time and funding. The freshwater crustacean, Daphnia, has a relatively short lifespan (∼50 to 100 days), which makes it a cost-effective alternative animal model for longevity and aging studies. Besides age-specific mortality, there are a suite of physiological responses connected to "healthspan" that can be tracked as these animals age including growth, reproduction, and metabolic rates. These responses can be complemented by assessment of molecular and cellular processes connected to aging and health. Lifespan and metabolism of this model organism is responsive to long studied modulators of aging, such as rearing temperature and nutritional manipulation, but also pharmacological agents that target aging, e.g., rapamycin, which adds to its usefulness as a model organism. Here we describe how to culture Daphnia for aging experiments including maintaining laboratory populations of Daphnia mothers, growing algal food, and manipulating nutrition of these animals. In addition, we provide methods for tracking common physiological and longevity responses of Daphnia. This protocol provides researchers planning to use this model organism with methods to establish and maintain Daphnia populations and to standardize their experimental approaches. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Culturing algae for Daphnia food Basic Protocol 2: General methods for culturing Daphnia Basic Protocol 3: Standardizing and controlling nutrition for experimental Daphnia Basic Protocol 4: Monitoring Daphnia lifespan Basic Protocol 5: Evaluating Daphnia health: Heart rate and respiration, body mass and growth rates, and reproduction.

Impacts of caffeine on fathead minnow behaviour and physiology

Pollution from regularly used substances such as pharmaceuticals, cleaning agents, and even food and beverages is an increasing problem in the environment. Caffeine, a commonly ingested stimulant, is one such contaminant that has been detected in aquatic environments worldwide. Yet, little is known about how ecologically relevant concentrations of caffeine influence the morphology, behaviour, and physiology of exposed organisms. To address this knowledge gap, we exposed fathead minnow (Pimephales promelas) to three caffeine treatments: a freshwater control (nominal: 0 ng/L), a low (nominal: 1,000 ng/L) and high environmentally relevant dose (nominal: 10,000 ng/L), for 35 days. We tested the learning abilities, anxiety, metabolic rates, and morphological features of exposed vs. control fish. Caffeine exposure did not affect the ability of fish to learn but did influence anxiety levels. Over the course of repeated anxiety testing, unexposed control fish visited a black square more often while fish exposed to low levels of caffeine did not, potentially indicating that these fish remained in a more anxious state. While caffeine did not impact metabolism, fish growth, or body size, it was associated with lower liver investment—although this response was only observed in our low caffeine treatment. Overall, our results suggest that even relatively low concentrations of caffeine may impact the liver size and anxiety of exposed fish, but further research is needed to assess how extended exposure to caffeine impacts fitness. Given the increase in anthropogenic contaminants in aquatic environments, it is important that we continue to investigate their effects on the organisms exposed to them.

Bigger isn't always better: Challenging assumptions about the associations between diapause, body weight, and overwintering survival.

During the winter, animals face limited food availability. Many animals enter dormancy to reduce their winter energy expenditure. Most insects spend the winter in diapause, a state of programmed dormancy. It is often assumed that diapausing insects need nutrient stores to fuel their many months of basal metabolism and must grow heavier than their non-diapause-programmed counterparts. However, the extent to which food limitation affects body weight during overwintering preparation as well as the likelihood and duration of diapause remainsunclear. We limited the duration of the feeding period and thus the total quantity of food available to diapause-destined larvae of the pupal-diapausing flesh fly, Sarcophaga crassipalpis, to test how food limitation affects body weight in the context of diapause programming. We also tested the extent to which food deprivation and body weight affect the likelihood and duration of diapause. We hypothesized that diapause-destined larvae grow more quickly and pupariate at a heavier body weight than non-diapause larvae. We also hypothesized that body weight is more dramatically reduced by food limitations when a larva is programmed for diapause. Finally, we hypothesized that larvae with lighter body weight (i.e., food limited) are less likely to enter pupal diapause and also stay in diapause for a shorter duration than heavier, well-fed, individuals. Contrary to our hypotheses that diapausing insects are heavier than their non-diapausing counterparts, we found diapausing pupae weighed less than non-diapausing pupae, especially when larvae received limited food. We found light pupae did not abort their diapause program. In both diapausing and non-diapausing pupae, body weight was positively correlated with simulated winter survival. However, above a weight threshold, body weight no longer affected simulated winter survival in diapausing pupae. Contrary to our predictions and the general consensus in much of the diapause literature, we also found that lighter pupae stayed in diapause longer than heavier pupae. Overall, our results challenge the precept that body weight and diapause are positively associated. The relationship between body weight and diapause is complex and may be affected by the availability of food before and after winter, the availability of high-quality overwintering sites, and the life history of a particular insect.

Are there sex differences in the variability of fasting metabolism?

There is evidence across species and across many traits that males display greater between-individual variance. In contrast, (premenopausal) females display large within-individual variance in sex hormone concentrations, which can increase within-individual variance in many other parameters. The latter may contribute to the lower representation of females in metabolic research. This study is a pooled secondary analysis of data from 7 crossover studies to investigate the between-individual and the within-individual variance in fasting plasma metabolites, resting metabolic rate (RMR) and body mass. Females demonstrated higher within-individual variability of plasma 17β-estradiol (CV 15±15 % for males vs 38±34 % for females, p<0.001) and progesterone concentrations (CV 13±11 % for males vs 52±51 % for females, p<0.001) but there were no meaningful differences in the variability of plasma glucose (CV 4±3 % for males vs 5 ± 5 % for females), insulin, lactate, triglycerides (CV 15±9 % for males vs 15 ± 10 % for females), and non-esterified fatty acid concentrations, nor in RMR and body mass (CV 0.43±0.34 % for males vs for 0.42±0.33 % females; p>0.05 for all outcomes). Males displayed higher between-individual variance in RMR compared to females (SD 224 kcal×day-1 for males vs 151 kcal×day-1 for females). In conclusion, these data do not provide evidence that females show greater within-individual variability in many fasting metabolic variables, RMR or body mass compared to males. We conclude that including females in metabolic research is unlikely to introduce greater within-individual variance when using the recruitment and control procedures described in these studies.

Genomic and Phenotypic Adaptations of Rattus tanezumi to Cold Limit Its Further Northward Expansion and Range Overlap with R. norvegicus.

Global climate change has led to shifts in the distribution ranges of many terrestrial species, promoting their migration from lower altitudes or latitudes to higher ones. Meanwhile, successful invaders have developed genetic adaptations enabling the colonization of new environments. Over the past 40 years, Rattus tanezumi (RT) has expanded into northern China (Northwest and North China) from its southern origins. We studied the cold adaptation of RT and its potential for northward expansion by comparing it with sympatric Rattus norvegicus (RN), which is well adapted to cold regions. Through population genomic analysis, we revealed that the invading RT rats have split into three distinct populations: the North, Northwest, and Tibetan populations. The first two populations exhibited high genetic diversity, while the latter population showed remarkably low genetic diversity. These rats have developed various genetic adaptations to cold, arid, hypoxic, and high-UV conditions. Cold acclimation tests revealed divergent thermoregulation between RT and RN. Specifically, RT exhibited higher brown adipose tissue activity and metabolic rates than did RN. Transcriptome analysis highlighted changes in genes regulating triglyceride catabolic processes in RT, including Apoa1 and Apoa4, which were upregulated, under selection and associated with local adaptation. In contrast, RN showed changes in carbohydrate metabolism genes. Despite the cold adaptation of RT, we observed genotypic and phenotypic constraints that may limit its ability to cope with severe low temperatures farther north. Consequently, it is less likely that RT rats will invade and overlap with RN rats in farther northern regions.

Unveiling the relationship between the UGT2B gene family and neoadjuvant treatment response in patients with HER2-positive breast cancer.

e12651 Background: Achieving a pathological complete response (pCR) following neoadjuvant treatment (NAT) in HER2-positive tumors significantly enhances patient survival, resulting in a remarkable 92% reduction in mortality risk. However, it is crucial to identify biomarkers capable of predicting the NAT response, moving towards more personalized medicine. This approach would enable the identification of patients likely to respond to specific therapies, thereby facilitating the implementation of targeted treatment strategies. Our study aims to identify potential molecular biomarkers predictive of NAT response through a comprehensive analysis of differential gene expression in tissue samples from patients with HER2-positive, hormone receptor (HR)-negative breast cancer. Methods: Total RNA was extracted from FFPE tissue samples from two independent cohorts of women diagnosed with localized or locally advanced HER2-positive, HR-negative breast cancer. These patients underwent NAT in several hospitals in Andalusia, Spain. Standard chemotherapy, including taxanes and/or anthracyclines, and targeted anti-HER2 treatment such as trastuzumab and pertuzumab were administered. The patients were stratified into responders (R), achieving pCR, and non-responders (nR). In a discovery cohort (n=20), RNA hybridization using Clariom D microarray was conducted to discern differentially expressed transcripts between R and nR. Subsequently, gene expression patterns, and related pathways involved in NAT response, were analyzed using Transcriptome Analysis Console (TAC). The selected transcripts then underwent validation through quantitative PCR (qPCR) in an independent cohort (n=40). The area under the receiver operating characteristic (ROC) curve was used to evaluate the sensitivity and specificity of the genes as predictive biomarkers. Results: Microarray analysis of the discovery cohort, revealed 954 differentially expressed transcripts between R and nR, following criteria of fold change greater than 1.5 or less than -1.5 and a p-value below 0.05. Among these, 643 were upregulated, while 311 were downregulated in nR compared to R. Bioinformatic analysis and a comprehensive literature review guided the selection of genes UGT2B10, UGT2B11, UGT2B15, UGT2B17, and UGT2B28 for further investigation. Subsequent qPCR analysis in the validation cohort, demonstrated the overexpression of these genes in non-responders, with statistical significance achieved only for UGT2B15. Conclusions: The UGT2B family genes encode enzymes involved in glucuronidation and metabolic pathways associated with drug detoxification and elimination. Our findings suggest that variations in the UGT2B15 expression may impact the metabolism rate of specific drugs, underscoring the necessity for additional research in this area.

Metabolic scaling of an invasive mussel depends on temperature and chemical cues from an invasive predator.

Metabolism drives various biological processes, potentially influencing the ecological success and evolutionary fitness of species. Understanding diverse metabolic rates is fundamental in biology. Mechanisms underlying adaptation to factors like temperature and predation pressure remain unclear. Our study explored the role of temperature and predation pressure in shaping the metabolic scaling of an invasive mussel species (Brachidontes pharaonis). Specifically, we performed laboratory-based experiments to assess the effects of phenotypic plasticity on the metabolic scaling by exposing the mussels to water conditions with and without predator cues from another invasive species (the blue crab, Callinectes sapidus) across various temperature regimes. We found that temperature effects on metabolic scaling of the invasive mussels are mediated by the presence of chemical cues of an invasive predator, the blue crab. Investigating temperature-predator interactions underscores the importance of studying the ecological effects of global warming. Our research advances our understanding of how environmental factors jointly impact physiological processes.

Prevalence and risk factors of sarcopenia in patients on maintenance hemodialysis: a retrospective cohort study

BackgroundThis study aimed to explore the prevalence and related risk factors of sarcopenia in patients on maintenance hemodialysis (MHD).MethodsThis cohort study enrolled 165 patients on MHD. The patients were divided into sarcopenia and non-sarcopenia groups based on the presence of sarcopenia or not. Sarcopenia was diagnosed according to the consensus of the Asian Sarcopenia Working Group that considers reduced muscle mass and decreased muscle strength (19). The muscle mass was measured using the multi-frequency bioelectrical impedance (Inbody260) and skeletal muscle index (SMI) was used: <7.0 kg/m2 (male); <5.7 kg/m2 (female) - with muscle mass reduction. The electronic grip dynamometer was used for measuring dominant handgrip strength (HGS) to reflect muscle strength. Male patients with HGS < 28 kg and female patients with HGS < 18 kg were considered with a decrease in muscle strength. The demographic characteristics, laboratory indexes, anthropometrical measurements, body compositions, and InBody score were compared between groups. The multivariate logistic regression was used to explore the risk factors for sarcopenia.ResultsOf the 165 patients on MHD, 36 had sarcopenia, and the prevalence was 21.82%. Patients in the sarcopenia group had higher ages and lower body mass index, serum albumin level, circumference of waist, hip, and biceps, handgrip strength, total water content, protein inorganic salt concentrations, skeletal muscle mass, basal metabolic rate, obesity degree, SMI, and body fat content. The multivariate logistic regression showed that age, waist circumference, handgrip strength, and InBody score were influencing factors for sarcopenia in patients on hemodialysis.ConclusionThe prevalence of sarcopenia was high in patients on MHD. Higher age, lower waist circumference, lower handgrip strength, and lower InBody score were independent risk factors for sarcopenia in such patients.