Search Results (317)

The use of multimodal data can effectively compensate for the lack of temporal resolution in streetscape imagery-based studies and achieve hourly refinement in the study of street walkability dynamics. Exploring the 24 h dynamic pattern of urban street walkability and its diurnal variation characteristics is a crucial step in understanding and responding to the accelerated urban metabolism. Aiming at the shortcomings of existing studies, which are mostly limited to static assessment or only at coarse time scales, this study integrates multimodal data such as streetscape images, remote sensing images of nighttime lights, and text-described crowd activity information and introduces a novel approach to enhance the simulation of pedestrian perception through a visual–textual multimodal deep learning model. A baseline model for dynamic assessment of walkability with street as a spatial unit and hour as a time granularity is generated. In order to deeply explore the dynamic regulation mechanism of street walkability under the influence of diurnal shift, the 24 h dynamic score of walkability is calculated, and the quantification system of walkability diurnal change characteristics is further proposed. The results of spatio-temporal cluster analysis and quantitative calculations show that the intensity of economic activities and pedestrian experience significantly shape the diurnal pattern of walkability, e.g., urban high-energy areas (e.g., along the riverside) show unique nocturnal activity characteristics and abnormal recovery speeds during the dawn transition. This study fills the gap in the study of hourly street dynamics at the micro-scale, and its multimodal assessment framework and dynamic quantitative index system provide important references for future urban spatial dynamics planning. Full article

Polypharmacology, the rational design of small molecules that act on multiple therapeutic targets, offers a transformative approach to overcome biological redundancy, network compensation, and drug resistance. This review outlines the scientific rationale for polypharmacology, highlighting its success across oncology, neurodegeneration, metabolic disorders, and infectious diseases. Emphasis is placed on how polypharmacological agents can synergize therapeutic effects, reduce adverse events, and improve patient compliance compared to combination therapies. We also explore how computational methods—spanning ligand-based modeling, structure-based docking, network pharmacology, and systems biology—enable target selection and multi-target ligand prediction. Recent advances in artificial intelligence (AI), particularly deep learning, reinforcement learning, and generative models, have further accelerated the discovery and optimization of multi-target agents. These AI-driven platforms are capable of de novo design of dual and multi-target compounds, some of which have demonstrated biological efficacy in vitro. Finally, we discuss the integration of omics data, CRISPR functional screens, and pathway simulations in guiding multi-target design, as well as the challenges and limitations of current AI approaches. Looking ahead, AI-enabled polypharmacology is poised to become a cornerstone of next-generation drug discovery, with potential to deliver more effective therapies tailored to the complexity of human disease. Full article

Insect pests inflict significant agricultural and economic losses on crops globally. Chemical control refers to the use of agrochemicals, such as insecticides, herbicides, and fungicides, to manage pests and diseases. Chemical control is still the prioritized method, as insecticides are highly effective and toxic to insect pests. However, it reduces the quality of the environment, threatens human health, and causes serious 3R (reduce, reuse, and recycle) problems. Current advances in the mining of functional symbiotic bacteria resources provide the potential to assuage the use of insecticides while maintaining an acceptably low level of crop damage. Recent research on insect–microbe symbiosis has uncovered a mechanism labeled “detoxifying symbiosis”, where symbiotic microorganisms increase host insect resistance through the metabolism of toxins. In addition, the physiological compensation effect caused by insect resistance affects the ability of the host to regulate the community composition of symbiotic bacteria. This paper reviews the relationship between symbiotic bacteria, insects, and insecticide resistance, focusing on the effects of insecticide resistance on the composition of symbiotic bacteria and the role of symbiotic bacteria in the formation of resistance. The functional symbiotic bacteria resources and their mechanisms of action need to be further explored in the future so as to provide theoretical support for the development of pest control strategies based on microbial regulation. Full article

Gestational diabetes mellitus (GDM) occurs in approximately 9–25% of pregnancies and, if left undiagnosed or inadequately controlled, can lead to adverse outcomes for both the mother and the fetus, short and long term. GDM is characterized by glucose intolerance with onset or first recognition during pregnancy and is a multifactorial condition with a pathophysiology that remains incompletely understood. It is strongly associated with a chronic low-grade inflammatory state that contributes to insulin resistance, a hallmark of GDM pathogenesis. Among the fundamental pro-inflammatory cytokines implicated in this process, TNF-α and IL-6 play central roles. TNF-α is a cytokine primarily secreted by activated macrophages, as well as by adipocytes in the context of obesity. Many studies have shown that its levels are elevated in pregnant women with GDM compared to normoglycemic pregnant individuals. IL-6 is another pro-inflammatory cytokine secreted by immune cells, adipose tissue, and the placenta. It is found in higher concentrations in the maternal circulation during pregnancies complicated by GDM. Both TNF-α and IL-6 act synergistically to perpetuate a pro-inflammatory intrauterine environment. Their combined effects exacerbate insulin resistance and may impair pancreatic β-cell compensation during pregnancy, facilitating the onset of GDM in genetically or metabolically susceptible individuals. Recent research has identified various maternal serum biomarkers, such as TNF-α and IL-6, that may hold promise for the early detection of GDM. The aim of our study is to evaluate whether TNF-α and IL-6 can be used as diagnostic tools for the early diagnosis of GDM, allowing for timely intervention and reducing the risk of associated maternal and fetal complications. Full article

Understanding how thermal variability affects marine ectotherms is essential for predicting species resilience under climate change. We investigated the physiological responses of juvenile Nodipecten subnodosus (lion’s paw scallop), offspring of two genetically distinct populations (Bahía de Los Ángeles and Laguna Ojo de Liebre), reared under common garden conditions and exposed to three temperature regimes: constant, regular oscillation, and stochastic variability. After 15 days of exposure, scallops underwent an acute hyperthermia challenge. We measured metabolic rates, scope for growth (SFG), tissue biochemical composition, and oxidative stress markers (SOD, CAT, GPx, TBARS). No significant differences were detected between populations for most traits, suggesting that phenotypic plasticity predominates over evolutionary divergence in thermal responses. However, the temperature regime significantly influenced metabolic, biochemical and oxidative stress markers, indicating that scallops in variable conditions compensated through improved energy balance and food assimilation but also showed higher oxidative stress compared to the constant regime. Following acute hyperthermic exposure, energy demand escalated, compensatory mechanisms were impaired, and scallops attained a state of physiological maintenance and survival under stress, irrespective of their population or prior thermal regime exposure. Full article

Eryptosis is a programmed cellular death involving red blood cells (RBCs). It is a physiological mechanism that leads to the removal of defective erythrocytes, similarly to apoptosis. Its typical features are cell shrinkage, cell membrane blebbing, and membrane scrambling with the consequent exposure of the aminophospholipid phosphatidylserine on the outer surface of RBCs. Different mechanisms play a role in the pathogenesis of eryptosis, such as the increase in cytosolic calcium concentration, oxidative stress, inflammation, and uremic toxins. If erythrocyte synthesis does not compensate for the accelerated eryptosis, anemia may develop. Moreover, enhanced eryptosis contributes to the pathogenesis of different clinical diseases, such as diabetes, sepsis, metabolic syndrome, and uremia. In particular, in patients with chronic kidney disease (CKD), deficiencies of erythropoietin and iron may further reduce the lifespan of RBCs. In this review, we focused on eryptosis in CKD and end-stage renal disease on peritoneal dialysis (PD) and hemodialysis (HD). Full article

Liver cirrhosis is a complex condition characterized by oxidative stress, inflammation, and metabolic dysfunction, contributing to systemic complications and high mortality. High-density lipoprotein (HDL), particularly its small subclasses, is known for its antioxidant, anti-inflammatory, and cholesterol efflux capacities. This study examined changes in HDL subclass distribution and composition in cirrhosis and assessed their prognostic relevance for mortality. We analyzed HDL profiles using nuclear magnetic resonance spectroscopy in patients with compensated (n = 205) and decompensated (n = 158) cirrhosis, compared to healthy controls (n = 16). Across all HDL subclasses in cirrhotic patients, cholesterol content was decreased, and triglyceride levels were elevated. In particular, compensated cirrhosis was associated with a marked reduction in small and extra-small HDL particles, while large HDL levels remained unchanged. This reduction was even more pronounced in decompensated disease. Small HDL particle levels were inversely correlated with oxidative stress markers and liver dysfunction and independently predicted 12-month mortality in patients with compensated cirrhosis, even after adjusting for MELD score. In conclusion, our findings highlight a substantial depletion of small and extra-small HDL particles as a key feature of cirrhosis, linked to oxidative stress and mortality in the compensated stage. Full article

Harmful Raphidiopsis raciborskii blooms threaten aquatic ecosystems via toxin production, hypoxia induction, and biodiversity loss. To elucidate the synergistic regulatory mechanisms of Fe³⁺ and phosphorus (P) in cyanobacterial growth, we used a sterile pure culture system under laboratory conditions. We set different phosphorus sources (organic phosphorus and inorganic phosphorus) and low phosphorus concentration of R. raciborskii culture medium for culture, and set different Fe³⁺ addition amount to determine the basic growth index of cyanobacteria cells and the phosphorus content of different components. The results revealed that under conditions of sufficient inorganic phosphorus, there was a logarithmic relationship between ferric ammonium citrate (Fe³⁺) and the specific growth rate of R. raciborskii. Fe³⁺ > 2 mg/L enhanced IPS enrichment and biomass accumulation. However, in oligotrophic or mesotrophic environments with low inorganic phosphorus concentrations, the effect of Fe³⁺ on the growth of R. raciborskii contrasted with that observed in high-IP (eutrophic) environments, exhibiting a pattern of ‘low promotion and high inhibition’. Under organic phosphorus conditions, R. raciborskii converted phosphorus by increasing alkaline phosphatase activity (APA), but this metabolic compensation failed to restore physiological functions, resulting in growth suppression and enhanced cellular phosphorus reserves. Our results establish quantitative linkages between Fe³⁺-P co-limitation thresholds and algal adaptive responses, providing mechanistic insights for controlling bloom dynamics through targeted manipulation of Fe-P bioavailability. Full article

Emerging evidence links ferroptosis–mitochondrial dysregulation to depression pathogenesis through an oxidative stress–energy deficit–neuroinflammation cycle driven by iron overload. This study demonstrates that iron accumulation initiates ferroptosis via Fenton reaction-mediated lipid peroxidation, compromising neuronal membrane integrity and disabling the GPx4 antioxidant system. Concurrent mitochondrial complex I/IV dysfunction impairs ATP synthesis, creating an AMPK/mTOR signaling imbalance and calcium dyshomeostasis that synergistically impair synaptic plasticity. Bidirectional crosstalk emerges: lipid peroxidation derivatives oxidize mitochondrial cardiolipin, while mitochondrial ROS overproduction activates ACSL4 to amplify ferroptotic susceptibility, forming a self-reinforcing neurodegenerative loop. Prefrontal–hippocampal metabolomics reveal paradoxical metabolic reprogramming with glycolytic compensation suppressing mitochondrial biogenesis (via PGC-1α/TFAM downregulation), trapping neurons in bioenergetic crisis. Clinical data further show that microglial M1 polarization through cGAS-STING activation sustains neuroinflammation via IL-6/TNF-α release. We propose a “ferroptosis–mitochondrial fragmentation–metabolic maladaptation” triad as mechanistic subtyping criteria for depression. Preclinical validation shows that combinatorial therapy (iron chelators + SIRT3 agonists) rescues neuronal viability by restoring mitochondrial integrity and energy flux. This work shifts therapeutic paradigms from monoaminergic targets toward multimodal strategies addressing iron homeostasis, organelle dynamics, and metabolic vulnerability—a framework with significant implications for developing neuroprotective antidepressants. Full article

Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) are widely used for type 2 diabetes mellitus (T2DM), conferring cardiovascular and renal benefits with evidence supporting their role in metabolic-associated steatotic liver disease (MASLD), the fastest rising etiology for liver cirrhosis. Our study collects and synthesizes all available data on SGLT2I use in liver cirrhosis to summarize their potential benefits and risks. We systematically reviewed the literature on SGLT2I use in adults with cirrhosis, focusing on 6 outcome domains, including ascites reduction, disease progression, hemodynamics, acute kidney injury (AKI), electrolyte abnormalities, and infection risk. We identified 16 studies: compensated (n = 5), decompensated (n = 3), and refractory ascites (n = 8). All studies of decompensated cirrhosis (n = 11) reported ascites reduction. Most studies (7 of 9) indicated SGLT2Is slowed disease progression by reducing clinical decompensation (n = 4) or improving laboratory markers (n = 3). A minority of studies revealed safety concerns with 2 of 9 studies showing evidence of hemodynamic instability and acute kidney injury (AKI), 2 out of 13 for electrolyte abnormalities, and 2 out of 5 for infection risk. Current evidence strongly supports SGLT2Is for refractory ascites management and suggests potential benefits in slowing progression across cirrhosis severities. Longer-term prospective trials in patients with non-refractory decompensated cirrhosis and real-world safety data are essential to clarify and potentially expand the role of SGLT2Is in cirrhosis management. Full article

In recent years, copper pollution has gradually become one of the major problems of soil environmental pollution. Lignin plays an important role in plant resistance to biotic and abiotic stresses. CCoAOMT is a key enzyme in the lignin biosynthesis process. In this study, the CCoAOMT gene family members of Platycodon grandiflorus were identified by bioinformatics methods, and their basic characteristics and potential functions were analyzed. The results showed that five members of the PgCCoAOMT gene family were identified in P. grandiflorus, with protein lengths ranging from 246 to 635 amino acids, and were evenly distributed on four chromosomes. Phylogenetic analysis indicated that the PgCCoAOMT gene family was divided into two subclades, namely Clade1a, Clade1b, Clade1c, Clade1d, and Clade2. The cis-regulatory element analysis of the promoter revealed that the PgCCoAOMT members contained a large number of cis-regulatory elements responsive to stress, and conjecture PgCCoAOMT2, PgCCoAOMT4, and PgCCoAOMT5 were involved in the lignin synthesis. The qRT-PCR results showed that, within 5 days of copper stress treatment, except for the PgCCoAOMT4 gene, the other genes exhibited different expression levels. Furthermore, the expression levels of all five PgCCoAOMT genes increased significantly at 7 days of treatment. With the increase in the number of days of treatment, the content of lignin in the seedings of P. grandiflorus showed a trend of increasing first and then decreasing under copper stress. In general, in the copper stress treatment of 1–3 days, the transcriptional inhibition of PgCCoAOMT1 and PgCCoAOMT3 and the increase in lignin content contradicted each other, suggesting that there was post-translational activation or alternative metabolic pathways compensation. Meanwhile, in the 7-day treatment, the coordinated up-regulation of the genes was accompanied by the failure of lignin synthesis, which pointed to the core bottleneck of metabolic precursors depletion and enzyme activity inactivation caused by root damage. Research objective: This study reveals the expression level of the PgCCoAOMT gene in the seedings of P. grandiflorus under copper stress, providing a theoretical basis for elucidating the mechanism of P. grandiflorus response to copper stress and for subsequent improvement of root resistance in P. grandiflorus. Full article

Desert shrubs play an important role in the stability of arid and fragile desert ecosystems. However, despite their significant ecological importance, limited research has been performed on shrub drought tolerance strategies at the morphological, physiological, and molecular levels. Therefore, this study focused on the typical desert shrub, Calligonum leucocladum, and analyzed its morphology, physiology, and protein expression under two different habitats: moist low-salt and arid low-salt. The results indicate that drought stress inhibited the growth of C. leucocladum, leading to significant reductions in its plant height, base diameter, and crown width by 14.93%, 49.57%, and 48.49%, respectively. Drought stress triggered a 30% decline in stomatal conductance, whereas homeostasis was observed in net photosynthesis, intercellular CO₂, and transpiration. The soluble sugar content significantly increased by 13.43%, while the starch, soluble protein, and proline content significantly decreased by 20.32%, 10.67%, and 55.61%, respectively. In addition, under drought stress, membrane peroxidation products, reactive oxygen species metabolites, and antioxidant enzyme activities significantly increased. Weighted gene co-expression network analysis revealed 40 proteins that were significantly enriched in the photosynthesis and oxidative phosphorylation pathways through KEGG enrichment analysis. In addition, C. leucocladum maintains photosynthetic homeostasis by enhancing PSII repair (PsbE, PsbL, PsbH) and electron transfer chain efficiency (PetD, nad 2, nad 9), thereby compensating for the insufficient carbon dioxide supply caused by stomatal limitation. This study integrated multidimensional data from morphology, physiology, and proteomics to reveal that C. leucocladum drives a coupled network of photosynthesis, antioxidant, and carbon metabolism through chloroplast translation reprogramming. It maintains photosynthetic homeostasis and osmotic balance under a 30% decrease in stomatal conductance, elucidating the cross-scale regulatory strategy of desert shrubs adapting to extreme drought. Full article

Oxidative stress (OS) occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the body’s antioxidant defenses, causing damage to lipids, proteins, and DNA. In marine mammals, physiological adaptation to aquatic life conditions, such as prolonged and repeated dives resulting in cycles of hypoxia followed by reperfusion, is associated with increased production of ROS. This study examines the relationship between oxidative stress, muscular stress, and metabolic damage in the blood serum of eleven captive bottlenose dolphins (Tursiops truncatus), six males and five females. This relationship is investigated using oxidative stress markers (d-ROMs, OXY, and Oxidative Stress index, OSi) and biochemical parameter measurements, including glucose (GLU), aspartate aminotransferase (AST), creatine kinase (CK), and lactate dehydrogenase (LDH). Pearson’s sex correlation was performed, and males exhibited significantly higher pro-oxidant levels than females, suggesting a potential protective role of female hormones. Also, a positive correlation between pro-oxidants and antioxidants has been observed in relation to age, as older dolphins produced more ROS but also exhibited higher antioxidant capacity, likely to compensate for oxidative damage. Results show no significant correlation between biochemical parameters and oxidative stress markers. However, a moderately positive correlation between LDH and antioxidant (OXY) capacity was observed (r = 0.458), suggesting a possible association between tissue turnover and antioxidant defenses. The results indicate that the biochemical markers analyzed are not strong predictors of oxidative stress in bottlenose dolphins. However, the correlation between LDH and antioxidant capacity suggests that tissue turnover may affect antioxidant defenses. This is a preliminary study, and further research is needed to clarify these relationships in order to better understand physiological adaptations in dolphins and their implications for management, health, and welfare. Full article

Choroideremia is a rare X-linked recessive retinal disorder characterized by progressive vision loss caused by retinal degeneration resulting from mutations in the CHM gene, which encodes Rab escort protein 1 (REP-1). In humans and mice, the Rab escort protein (REP) family consists of two members, REP-1 and REP-2, with REP-2 hypothesized to compensate for REP-1 deficiency in tissues outside the eye in choroideremia. In this study, we conducted a systematic mutational analysis of the mouse orthologs of REP-1 and REP-2. Blood analyses revealed metabolic abnormalities in the mutant mice deficient for REP-1, resembling the systemic metabolic disturbances observed in individuals with choroideremia, such as altered lipid and hemoglobin metabolism. We also observed an elevation in systemic inflammatory biomarkers in these mutant mice. Interestingly, these systemic abnormalities emerged before retinal degeneration became detectable in REP-1-deficient mice. Transcriptomic analysis of retinas isolated from REP-1 deficient mice revealed enrichment of proinflammatory signaling pathways. These results suggest important similarities between choroideremia and some forms of retinitis pigmentosa. While engineered loss of REP-2 alone caused no detectable phenotypic changes, dual deficiency in REP-1 and REP-2 resulted in lethality under both in vivo and in vitro conditions. Our findings offer novel insights into REPs and deepen our understanding of choroideremia, which may contribute to the development of new treatments for this genetic condition. Full article

This study examined the differences in physiological, metabolic and running dynamics responses between level and inclined treadmill protocols and their implications for accurately determining training intensities. Twenty-three healthy, active adults (18 male and 5 female) from 25 to 59 years old (age: 42.7 years, height: 1.77 m, body mass: 71.9 kg, $V{O}_{2max}$: 54.3 mL·${\mathrm{kg}}^{-1}$·${\min }^{-1}$) completed both protocols. Physiological markers (gas exchange threshold (GET), respiratory compensation point (RCP), $V{O}_{2max}$), metabolic variables (HR, $V{O}_2$, $VC{O}_2$, RER, VE, speed) and running dynamic variables (running economy (RE), stride length (SL), ground contact time (GCT), cadence) were measured and matched for the external work rate at each stage. The data were analyzed using one-way repeated measures ANOVA with Tukey’s post hoc procedure. No significant differences were observed in the physiological markers for the inclined and flat protocols across all the intensities. However, the metabolic variables showed significant differences (p = 0.0333 to <0.0001) between the inclined and flat protocols at higher intensities. The RE was consistently improved in the flat protocol compared with the inclined protocol, with significant differences observed at the high-intensity stages (p = 0.0232 to <0.0001). While the physiological markers remained unaffected, metabolic responses and running kinematics differed significantly between the protocols. These results highlight that training intensity zones derived from inclined protocols may not be appropriate for flat terrain training, underlining the importance of testing specificity in athlete preparation. Full article