Search Results (2,336)

Transient receptor potential melastatin 2 (TRPM2) channel is a Ca²⁺-permeable, redox-activated cardiac ion channel protective in ischemia–reperfusion, but whether it regulates atrial endocrine output under stress is unclear. Here, we investigated whether TRPM2 contributes to the atrial natriuretic peptide (ANP) response during β-adrenergic stimulation. We compared how male C57BL/6J wild-type (WT) and TRPM2 knockout (TRPM2^−/−) mice (8–12 weeks old) respond to β-adrenergic stress induced by isoproterenol (ISO) using echocardiography, histology, RT-PCR, electrophysiology, Ca²⁺ imaging, ELISA, and atrial RNA-seq. We detected abundant Trpm2 transcripts in WT atria and measured ADP-ribose (ADPr)-evoked currents and hydrogen peroxide (H₂O₂)-induced Ca²⁺ influx characteristic of TRPM2; these were absent in TRPM2^−/− cells. Under the ISO-induced hypertrophic model, TRPM2^−/− mice developed greater cardiac hypertrophy, fibrosis, and systolic dysfunction compared with WT mice. Atrial bulk RNA-seq showed significant induction of Nppa (ANP precursor gene) in WT + ISO, accompanied by higher circulating ANP; TRPM2^−/− + ISO showed blunted Nppa and ANP responses. ISO-treated TRPM2^−/− mice exhibited more blunt responses, in both Nppa transcripts and circulating ANP levels. Exogenous ANP attenuated ISO-induced dysfunction, hypertrophy, and fibrosis in TRPM2^−/− mice, suggesting that TRPM2 is needed for the cardioprotective endocrine response via ANP to control stress-induced β-adrenergic remodeling. Full article

The inhibition of low-position tillering in machine-transplanted seedlings affects rice yields. Paclobutrazol (PBZ) is a plant growth regulator that can improve seedling quality and promote low-position tillering in machine-transplanted seedlings. However, the physiological mechanisms underlying the promotion of tiller bud formation induced by exogenous PBZ via sucrose transport remain unclear. Thus, rice cultivar ‘Yongyou 12’ was used to analyze the effects of different seeding rates and the application of exogenous PBZ, gibberellin (GA₃), and water (control) on sucrose transport and metabolism as well as tiller bud development. Exogenous PBZ application combined with a low seeding rate significantly increased the number of tillers as well as seedling fullness (by 42.35%). Increases were also detected for the seedling cytokinin content, chlorophyll content (by 10.55%), and sucrose transport from leaves to the stem base. These changes were associated with the upregulated expression of sucrose transporter genes in leaves and the stem base, as well as increased activities of key sucrose-metabolizing enzymes in the stem base. Notably, the opposite trend was observed after exogenous GA₃ was applied or a high seeding rate was used. Hence, a low seeding rate combined with exogenous PBZ application is useful for controlling seedling height, promoting the formation of low-position tillering, facilitate sucrose translocation from leaves to the stem base, and increasing sucrose metabolism in the basal part of rice plants. These findings provide a theoretical basis for optimizing low-position tillering in machine-transplanted seedlings. Full article

Some organophosphorus compounds can induce delayed neurotoxicity, which is characterized by ataxia, also known as organophosphate-induced delayed neurotoxicity (OPIDN). The underlying mechanism of axonal degeneration and demyelination in OPIDN is still poorly understood, although progress on the studies has been made. Progesterone is an important sex hormone with a neuroprotective effect, and a decrease in progesterone level was observed in the hens with OPIDN. To investigate whether exogenous progesterone offers protective effects in OPIDN and to elucidate the underlying mechanisms, we conducted an investigation with adult hens, which is the typical model animal for OPIDN research. The hens were either administrated with a single dose of the classical OPIDN inducer tri-ortho-cresyl phosphate (TOCP) (750 mg/kg body weight, p.o.) or were pretreated with progesterone (2 mg/kg body weight/day, i.p.) prior to TOCP exposure. The results showed that TOCP exposure induced typical OPIDN signs in hens and caused demyelinating lesions in the sciatic nerves. The pretreatment of progesterone delayed and reduced TOCP-induced gait impairment scores and restored the decreased expression of S-100β in the sciatic nerves of TOCP-exposed hens. Moreover, progesterone alleviated the TOCP-induced demyelination of the sciatic nerves. These effects were accompanied by alterations in the protein levels of the ErbB2/p-Akt signaling pathway. These findings indicate that progesterone effectively attenuates TOCP-induced delayed neurotoxicity and protects against myelin damage. This protective effect may be associated with the suppression of TOCP-induced activation of the ErbB2/p-Akt pathway, accompanied by the restoration of S-100β expression. Full article

Increasingly frequent intense rainfall is increasing landslide occurrence and risk. In southern China in particular, steep slopes and thin residual soils produce frequent landslide events with pronounced spatial heterogeneity. Therefore, displacement prediction methods that function across sites and deformation regimes in similar settings are essential for early warning. Most existing approaches adopt a multistage pipeline that decomposes, predicts, and recombines, often leading to complex architectures with weak cross-domain transfer and limited adaptability. To address these limitations, we present CRAFormer, a causal role-aware Transformer guided by a dynamic-lag Bayesian network-style causal graph learned from historical observations. In our system, the discovered directed acyclic graph (DAG) partitions drivers into five causal roles and induces role-specific, non-anticipative masks for lightweight branch encoders, while a context-aware Top-2 gate sparsely fuses the branch outputs, yielding sample-wise attributions. To safely exploit exogenous rainfall forecasts, next-day rainfall is entered exclusively through an ICS tail with a leakage-free block mask, a non-negative readout, and a rainfall monotonicity regularizer. In this study, we curate two long-term GNSS datasets from Guangxi (LaMenTun and BaYiTun) that capture slow creep and step-like motions during extreme rainfall. Under identical inputs and a unified protocol, CRAFormer reduces the MAE and RMSE by 59–79% across stations relative to the strongest baseline, and it lowers magnitude errors near turning points and step events, demonstrating robust performance for two contrasting landslides within a shared regional setting. Ablations confirm the contributions of the DBN-style causal masks, the leakage-free ICS tail, and the monotonicity prior. These results highlight a practical path from causal discovery to forecast-compatible neural predictors for rainfall-induced landslides. Full article

Background: Cannabinoids (CBs) are FDA-approved for mitigating chemotherapy-induced side effects such as pain, nausea, and loss of appetite. Beyond palliative care, CBs exhibit anti-tumor properties in various cancers, including non-Hodgkin’s lymphoma (NHL). Previously, we demonstrated the cytotoxic effect of endogenous and exogenous cannabinoids on human and canine B- and T-cell-type NHL cell lines. The purpose of this study was to establish the cytotoxic effect of cannabinoids in combination with the components of CHOP and lomustine. This traditional NHL chemotherapy regimen comprises cyclophosphamide, doxorubicin, vincristine, and prednisolone. Methods: In this study, we studied three cannabinoids, one from each of the three major categories of cannabinoids (endocannabinoid AEA, phytocannabinoid CBD, and synthetic cannabinoid WIN-55 212 22). Each cannabinoid was selected based on potency, as determined in our previous experiments. For the combination, we used five NHL chemotherapy drugs. We analyzed the cytotoxicity of each drug alone and in combinations using canine malignant B-type NHL cell line 1771 and a colorimetric MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide) cell proliferation assay and combination index (CI) based on the Chou–Talalay method. Results: Our results demonstrate that the cytotoxic effects of all traditional NHL chemotherapy drugs are synergistically enhanced (interaction with CI < 1) by each of the three cannabinoids at sub-IC₅₀ concentrations. Conclusions: This work provides a proof of concept for using cannabinoids and traditional NHL drugs in combination to reduce the dose, and thereby potentially reducing the toxicity, of chemotherapeutic drugs and increasing the survival benefit in lymphoma clinical translation studies, offering a significant advancement in cancer treatment. Full article

The aim of this study was to evaluate the impact of fluoxetine, a widely used selective serotonin reuptake inhibitor, on two aquatic plants: Lemna minor and Spirodela polyrhiza. Additionally, the effect of exogenous serotonin on the level of fluoxetine-induced stress in duckweed will be studied. Increasing presence of antidepressants in surface waters poses ecological risks, and the duckweed species are ideal model organisms for ecotoxicological studies due to their rapid growth and ability to accumulate pollutants. For 14 days, plants were exposed to fluoxetine (0.001–150 mg L⁻¹), followed by a recovery phase in a drug-free medium or a medium supplemented with exogenous serotonin. We analysed morphological/physiological parameters (frond length and area, fresh and dry mass, hydration, stomatal size), the activity of antioxidant enzymes (catalase, ascorbate peroxidase, superoxide dismutase), cell viability, and the level of heat-shock proteins. The plants’ ability to remove fluoxetine from the medium was also assessed. High fluoxetine concentrations (50–150 mg L⁻¹) significantly reduced fresh mass (by 63–98% in L. minor and 56–97% in S. polyrhiza), frond area (by 21–48% in L. minor and 11–25% in S. polyrhiza), and cell viability (by 36–94% in L. minor and 49–94% in S. polyrhiza), and induced oxidative stress. Despite this, both species showed high regeneration potential after the stressor’s removal. Serotonin supplementation did not affect morphology but increased antioxidant enzyme activity, improved cell viability, and elevated heat-shock proteins levels. Crucially, serotonin significantly increased the efficiency of fluoxetine removal. The data can provide a basis for predicting fluoxetine removal efficiency in plants with different levels of endogenous serotonin. L. minor and S. polyrhiza exhibit substantial tolerance to fluoxetine, and antioxidative enzymes are sensitive markers of this stress. Full article

Root suckering is a key mode of clonal propagation in white poplar group, such as aspens (Populus section Leuce), enabling rapid vegetative spread, yet the molecular triggers remain elusive. Here, we developed a rapid protocol that produces abundant root suckers with the root cutting of white poplar (Populus davidiana × P. bolleana) roots in greenhouse. Anatomical analyses and daily resolution transcriptomes resolved three sequential developmental stages: primordium initiation (Days 0–1), SAM (shoot apical meristem) establishment (Days 1–4), and organ differentiation/growth (Days 4–6). Weighted gene co-expression network analysis revealed that auxin- and cytokinin-mediated signaling, integrated with nitrogen metabolism, orchestrates SAM formation and maintenance. Exogenous application of 0.5–1.0 mg L⁻¹ NAA suppressed sucker emergence by 48–60%, whereas inhibition of cytokinin biosynthesis with lovastatin reduced initiation by 60%. These data establish that auxin negatively regulates and cytokinin is indispensable for de novo shoot apical meristem establishment during poplar root-suckering, underscoring that a precise auxin–cytokinin balance governs the timing and extent of this developmental process. Cambial regulators WUSCHEL-Related Homeobox 4-1/2 (WOX4-1/2), together with core meristem regulators WUSCHEL (WUS) and SHOOT MERISTEMLESS (STM), were specifically induced during SAM establishment that underpin vascular integration between the nascent shoot and the parental root. These results uncover the molecular pathway controlling root suckering and provide potential targets for molecular breeding to either enhance or suppress root suckering in Populus. Full article

Circadian rhythm disruption induced by exposure to light—excessive in duration and intensity (dark deprivation)—and the impact of hepatotoxins are both significant risk factors for liver pathology. The purpose of this research was to evaluate the potentially synergistic effects of continuous lighting and carbon tetrachloride (CCl₄) toxicity on the structural and functional organization and daily (circadian) rhythmicity of the liver in rats, as well as to look at the corrective capability of exogenous melatonin under such influences. The experiment was conducted on 200 outbred 6-month-old Wistar rat males, which were distributed into five groups, including a control (normal light/dark cycle), dark deprivation (constant light), CCl₄ intoxication, and combined exposure to CCl₄ and dark deprivation with or without melatonin administration (0.3 mg/kg). Histological, immunohistochemical (Ki-67, Per2, and Bmal1), biochemical, and ELISA methods were used. Circadian rhythms were analyzed using cosinor. It was shown that dark deprivation and CCl₄ intoxication act synergistically, potentiating liver damage. The most severe necrosis (54.17 ± 9.13%), steatosis (57.85 ± 12.14%), and suppression of regenerative potential (decreased proportion of binucleated hepatocytes to 2.17 ± 0.21%) were observed in the group with combined exposure. This correlated with a substantial decline in melatonin content in blood plasma (7.85 ± 2.1 pg/mL) and a profound disruption in circadian rhythms. Administration of exogenous melatonin exerted pronounced hepatoprotective and chronotropic effects: it significantly reduced pathological changes (necrosis reduced to 16.35 ± 6.17%), stimulated regeneration (binucleated hepatocytes increased to 13.57 ± 0.81%), and restored the circadian rhythms of the studied parameters to levels close to those of the control. The key pathogenetic link in the potentiation of CCl₄ hepatotoxicity under dark deprivation is light-induced deficiency of endogenous melatonin. Exogenous melatonin demonstrated high efficacy in correcting both structural and functional damage and liver desynchronosis, confirming its therapeutic potential under conditions of combined exposure to chronodisruptors and toxins. Full article

Mine-induced surface subsidence threatens infrastructure and can trigger cascading geohazards, so accurate and computationally efficient monitoring and forecasting are essential for early warning. We integrate Persistent Scatterer InSAR (PS-InSAR) time series with a Bayesian-optimized CNN–LSTM designed for spatiotemporal prediction. The CNN extracts spatial deformation patterns, the LSTM models temporal dependence, and Bayesian optimization selects the architecture, training hyperparameters, and the most informative exogenous drivers. Groundwater level and backfilling intensity are encoded as multichannel inputs. Endpoint anchoring with affine calibration aligns the historical series and the forward projections. PS-InSAR indicates a maximum subsidence rate of 85.6 mm yr⁻¹, and the estimates are corroborated against nearby leveling benchmarks and FLAC^3D simulations. Cross-site comparisons show acceleration followed by deceleration after backfilling and groundwater recovery, which is consistent with geological engineering conditions. A symmetry-aware preprocessing step exploits axial regularities of the deformation field through mirroring augmentation and documents symmetry-breaking hotspots linked to geological heterogeneity. These choices improve generalization to shifted and oscillatory patterns in both the spatial CNN and the temporal LSTM branches. Short-term forecasts from the BO–CNN–LSTM indicate subsequent stabilization with localized rebound, highlighting its practical value for operational planning and risk mitigation. The framework combines automated hyperparameter search with physically consistent objectives, reduces manual tuning, enhances reproducibility and generalizability, and provides a transferable quantitative workflow for forecasting mine-induced deformation in complex goaf systems. Full article

This study explores the effects of exogenous SELENOV on cellular migration, viability, mitochondrial function, ROS production, and Ca²⁺ signaling in mouse fibroblast L-929 and testicular teratoma F-9 cells. In scratch assays, 50–100 µg/mL SELENOV significantly inhibited F-9 cell migration after 48 h, while in L-929 fibroblasts, only 100 µg/mL had a suppressive effect. Viability assays revealed strong cytotoxicity in F-9 cells. Critically, at a dose of 50 µg/mL (where the corresponding volume of solvent buffer alone was non-toxic), SELENOV reduced survival to 19%, triggering late apoptosis in 76% of cells, whereas in L-929 cells, comparable effects required 100 µg/mL. Mitochondrial depolarization (JC-1/Rhodamine-123 assays) was pronounced in F-9 cells even at 50 µg/mL, while L-929 cells responded only to 100 µg/mL. Similarly, 50 µg/mL SELENOV induced significant ROS overproduction in F-9 but not in L-929 cells, correlating with upregulated NOX1, NOX4, GPX3, and GPX4 expression. Ca²⁺ imaging showed dose-dependent [Ca²⁺]ᵢ elevation, with 50 µg/mL SELENOV inducing a sustained rise in F-9 cells, whereas L-929 cells required higher doses. Strikingly, 50 µg/mL SELENOV in F-9 cells downregulated BCL-2 and BCL-xL while upregulating pro-apoptotic BAX and PUMA, suggesting selective activation of intrinsic apoptosis. These results demonstrate that F-9 cancer cells are significantly more sensitive to SELENOV than normal fibroblasts, with 50 µg/mL sufficient to trigger mitochondrial dysfunction, oxidative stress, and apoptosis. The findings highlight SELENOV’s potential as a targeted anticancer agent, particularly for germ cell tumors. Full article

Objectives: Bone defects, resulting from many causes, represent a challenge in maxillofacial and orthopedic surgery. Regenerative medicine offers promising strategies by introducing exogenous materials to modify the tissue environment and modulate the body’s natural healing mechanisms. Dental pulp stem cells (DPSCs) are considered an effective source for tissue repair. Small molecules such as caffeic acid phenethyl ester (CAPE), although having promising effects in promoting bone regeneration, are characterized by low chemical stability, which impairs their clinical application. This study aimed to investigate the bone regenerative capability of four CAPE derivatives, recently synthesized in our laboratory and selected based on previous studies. Methods: DPSCs were induced to osteogenic differentiation in the presence of these compounds (0–5 μM), and cell viability, matrix deposition, alkaline phosphatase activity, and osteogenic marker gene expression were evaluated. In addition, bone biomaterials composed of a chitosan/agarose matrix reinforced with nanohydroxyapatite and enriched with these CAPE derivatives were fabricated and assessed for cytotoxicity and cell adhesion. Results: Two of the tested compounds effectively enhanced DPSC differentiation toward the osteogenic lineage. The fabricated bone biomaterials showed no cytotoxicity and supported cell adhesion. Furthermore, these compounds demonstrated stability under various conditions, confirming their suitability for incorporation into bone biomaterials. Conclusions: The tested CAPE derivatives exhibit promising osteoinductive properties and stability, offering a valid alternative to traditional therapeutic strategies in regenerative medicine. Full article

Drought is one of the most severe abiotic stresses limiting agricultural productivity and threatening global food security. As the central organelle responsible for photosynthesis and stress perception, the chloroplast is highly sensitive to drought, and its structural and functional stability directly determines plant adaptability. Recent studies have revealed that chloroplasts undergo pronounced ultrastructural alterations under drought stress, including thylakoid membrane shrinkage, disorganization of grana stacks, and accumulation of reactive oxygen species (ROS). Excessive ROS production causes oxidative damage to lipids, proteins, and nucleic acids, whereas moderate ROS levels act as retrograde signals to regulate nuclear gene expression. In parallel, calcium (Ca²⁺) oscillations and retrograde signaling pathways—such as those mediated by GENOMES UNCOUPLED PROTEIN1 (GUN), 3′-phosphoadenosine-5′-phosphate (PAP), and Methylerythritol cyclodiphosphate (MecPP)—integrate chloroplast-derived stress cues with nuclear responses. To counteract drought-induced damage, plants activate a series of antioxidant systems—both enzymatic (Superoxide Dismutase (SOD), Ascorbate Peroxidase (APX), Catalase (CAT)) and non-enzymatic (Ascorbic Acid (ASA), (Glutathione) GSH, tocopherols, carotenoids)—along with protective proteins such as fibrillins (FBNs) and WHIRLYs that stabilize thylakoid and membrane structures. In addition, autophagy and plastid degradation pathways selectively remove severely damaged chloroplasts to maintain cellular homeostasis. Exogenous substances, including melatonin, 5-aminolevulinic acid (ALA), and Zinc oxide (ZnO) nanoparticles, have also been shown to enhance chloroplast stability and antioxidant capacity under drought stress. In this review, we discuss the structural and functional changes in chloroplasts, signaling networks, and protective repair mechanisms under drought stress. Furthermore, we highlight future research prospects for enhancing plant stress resilience through multi-omics integration, application of functional regulators, and molecular design breeding. Full article

Aluminum (Al) toxicity is a key constraint on plant growth in acidic soils. To counteract Al stress, plants secrete organic acids such as malate from their roots to chelate Al³⁺, a process facilitated by Al-activated malate transporters (ALMTs). In this study, we identified 15 ALMT genes in the pumpkin (Cucurbita moschata) genome, which were phylogenetically classified into four subclades. Expression analysis revealed that several ALMTs, including CmaALMT5, CmaALMT6, and CmaALMT12, were upregulated in response to increasing Al concentrations. Exogenous application of polyamines (spermine, spermidine, and putrescine) alleviated Al-induced root growth inhibition, correlating with enhanced malate secretion. Notably, each polyamine differentially regulated specific ALMT genes: spermidine elevated the expression of CmaALMT1, CmaALMT6, CmaALMT13, and CmaALMT15; spermine induced CmaALMT1, CmaALMT2, CmaALMT3, CmaALMT11, and CmaALMT14; while putrescine significantly upregulated CmaALMT1, CmaALMT3, and CmaALMT4. These results suggest that polyamines may enhance Al tolerance in pumpkin through gene-specific transcriptional regulation of the ALMT family and promotion of root malate secretion, though further evidence is required. Full article

Genome modification of legumes, peas in particular, is accompanied by significant challenges. Establishing a reliable reporter system to identify tissue that expresses foreign DNA may help to optimize and develop transformation protocols for these species. The RUBY system, based on the synthesis of red betalain from tyrosine, offers a convenient solution for monitoring the efficiency of transgene introduction. To evaluate the effectiveness of RUBY application in pea tissue culture, we combined agrobacterial transformation with an in vitro cultivation system, inducing callus development. Transformed explants demonstrated RUBY pigmentation, but it disappeared during cultivation. We hypothesized that this issue is caused by tyrosine depletion. To check this suggestion, we tested whether tyrosine supplementation could maintain RUBY coloring. In the later stages, pigmentation still could not be preserved. However, our modified conditions increased the percent of colored shoot apex explants during the early cultivation stages. Thus, it is likely that some explants transformed with the RUBY cassette do not synthesize a sufficient amount of betalain due to the deficit of endogenous tyrosine. In this case, adding exogenous tyrosine would enhance betalain production and improve the detectability of tissues containing the RUBY cassette. These data can be used for the optimization of RUBY application conditions for peas and other species. Full article

MicroRNAs (miRNAs) are key posttranscriptional regulators of gene expression that influence cancer initiation, progression, and therapeutic response. While most studies have focused on endogenous miRNAs, emerging evidence has highlighted the role of plant-derived miRNAs as exogenous dietary regulators capable of cross-kingdom gene modulation. This review summarises current knowledge regarding plant-derived miRNAs and their ability to regulate human cancer-related genes. Experimental findings indicate that plant miRNAs can withstand gastrointestinal digestion, enter the circulation, and regulate the expression of oncogenes, tumour suppressors, long noncoding RNAs, and immune checkpoint molecules via canonical RNA-induced silencing mechanisms. Specific examples include miR-156a, miR-159a-3p, miR-166a, miR-167e-5p, miR-171, miR-395e, miR-2911, miR-4995 and miR-5754, which exhibit anticancer activities across various cancer types and modulate key signalling pathways in mammalian cells, highlighting their potential as cross-kingdom regulators with therapeutic relevance. In addition to these characterised miRNAs, certain plant groups, which are rich in bioactive compounds, remain unexplored as sources of functional miRNAs, representing a promising avenue for future research. Collectively, these studies underscore the ability of plant-derived miRNAs to modulate mammalian gene expression and suggest their potential as diet-based or synthetic therapeutic agents. Further investigations into their bioavailability, target specificity, and functional relevance could inform innovative strategies for cancer prevention, integrating nutritional, molecular biological, and therapeutic approaches. Full article