Search Results (6,213)

The reactive transport of hexavalent chromium (Cr(VI)) in anthropogenically disturbed sites (e.g., mine waste rock dumps, chromium salt industrial sites) is critically influenced by physico-chemical heterogeneity, yet the interplay between physical and chemical heterogeneities remains poorly understood. This study employed a series of experiments and numerical modeling to investigate the transport of Cr(VI), focusing on the implications of physical heterogeneity—represented by preferential flow paths—and chemical heterogeneity—characterized by reductive mineral lenses. Key findings indicate that physical heterogeneity accelerates Cr(VI) breakthrough by 1.4 to 2.1 pore volumes (PV) relative to homogeneous columns. The presence of pyrite lenses delays breakthrough by 0.6–1.2 PV under neutral pH and 1.6–2.0 PV under acidic pH. At a flow rate of 3.0 m/day, the apparent sorption capacity decreases by ~62.5% compared to 0.3 m/day, indicating that physical advection largely suppresses chemical retention under high-flux conditions. The above results demonstrate that physical heterogeneity governs flow paths and advection rates, whereas chemical heterogeneity impedes transport through heterogeneous adsorption and reduction in Cr(VI) to Cr(III) along these pathways. Furthermore, the presence of preferential paths leads to greater spatial variability, which subsequently influences the interaction dynamics between Cr(VI) and reactive minerals in the aqueous environment. The dominance shifts between physical/chemical controls based on flow rates and pH. At higher flow rates, the influence of physical heterogeneity becomes more pronounced, diminishing chemical reactions due to insufficient residence time of Cr(VI). Conversely, a lower pH environment enhances pyrite dissolution, which decouples the dependency on physical heterogeneity by promoting homogeneous reactions. Further evidence was obtained through X-ray photoelectron spectroscopy (XPS) analysis. The experimental observations are complemented by TOUGHREACT-based reactive transport simulations, which further reveal that the apparent dominance shifts arise from competing timescales between advection and surface reaction. The insights gained from the study emphasize the necessity of integrating both physical and chemical spatial variability in risk assessments, transport modeling, and designing targeted remediation strategies. Full article

Background/Objectives: Drug resistance is a major challenge in cancer therapy, and mitochondria contribute to this process by controlling both metabolic adaptability and cell survival signaling. Mitophagy, the selective lysosomal removal of dysfunctional mitochondria, has been implicated in therapy resistance, yet its role in sunitinib-resistant renal cancer remains poorly defined. Methods: In this study, acquired sunitinib resistance was established in ACHN renal cancer cells through eight months of stepwise dose escalation. Initial selection conditions were determined using CCK-8 viability and crystal violet colony assays in parental ACHN cells, whereas sustained proliferation under continuous sunitinib exposure was used as the operational criterion for the resistant phenotype. Resistant and parental sensitive cells were treated with 25 µM and 50 µM succinic acid, alone or in combination with sunitinib. Gene expression of BNIP3, NIX, FUNDC1, LC3, PINK1, Parkin, PGAM5, SRC, LONP1, and ATP5F1A was measured by RT-qPCR, and BNIP3 and NIX protein levels were assessed by ELISA. Results: Resistant cells showed significant upregulation of receptor-mediated mitophagy components BNIP3, NIX and FUNDC1 (p < 0.05), with no significant change in LC3, alongside suppression of PINK1, Parkin, and mitochondrial homeostasis-associated genes LONP1, PGAM5, and ATP5F1A (p < 0.05). Succinic acid predominantly reduced BNIP3 and NIX protein levels in both cell lines and suppressed BNIP3, NIX, and LC3 mRNA expression in resistant cells. In contrast, the sunitinib + 50 µM succinic acid combination selectively increased PARKIN, PGAM5, LONP1, and ATP5F1A expression in resistant cells (2.49- to 5.98-fold; p < 0.005), a pattern not observed in parental cells. Conclusions: These findings indicate that sunitinib resistance in ACHN cells is associated with upregulated transcription of receptor-mediated mitophagy components and downregulated transcription of PINK1/Parkin pathway genes, and that exogenous succinic acid selectively upregulates PARKIN and other mitochondrial homeostasis-related gene expression in resistant, but not parental, cells. Full article

High carbonate alkalinity (CA) is a major constraint on shrimp culture in saline–alkaline waters. The hepatopancreas is central to shrimp immunity and metabolic regulation. Litopenaeus vannamei underwent a 7-day exposure period to 5 mmol/L CA, followed by a subsequent 7-day recovery phase after removal of the stressor. The physiological regulatory mechanism of the hepatopancreas during CA stress and recovery was investigated by integrating multiple biological levels including histomorphology, antioxidant and immune indices, energy metabolism, and metabolite profiles. Results showed that CA stress induced structural changes in the hepatopancreas and triggered stress responses. Specifically, a significant upregulation was observed in genes involved in antioxidation (romo1, nrf2, gpx, hsp70), apoptosis (casp-9, casp-3), endoplasmic reticulum (ER) stress (ire1, xbp1), immune defense (alf, crus, pen-3, lys, propo), and detoxification (cyp450). CA stress also increased osmoregulatory genes (ccp, nhe, ca, aqp, vatp, nka-β, nka-α), whereas clc and tip4 were suppressed. CA stress reduced the levels of energy-metabolism-related biochemical indicators, including glucose (GLU), pyruvic acid (PYR), lactic acid (LAC) and triglycerides (TG), while markedly inducing the expression of genes involved in carbohydrate metabolism (ldh, pdh, hk, pk), lipid metabolism (ampk, srebp, fas), the tricarboxylic acid (TCA) cycle (mdh, cs, idh, odh, sdh, fh), and the electron transport chain (ETC) (ndh, cytc, coi, cco, atph). Moreover, the hepatopancreatic metabolic profile was remodeled, especially “phenylalanine, tyrosine and tryptophan biosynthesis” and the metabolism of β-alanine, arachidonic acid, linoleic acid, and sphingolipids being substantially altered during both the stress and recovery phases. Several functional metabolites linked to stress responses were further pinpointed. Following stress relief, some physiological parameters partially recovered, yet overall function failed to return to normal. Collectively, CA stress compromised hepatopancreatic homeostasis by damaging morphological integrity, eliciting stress and immune responses, and perturbing energy metabolism and metabolite homeostasis; these adverse effects were not readily reversible in the short term. Full article

Acute and chronic inflammation underlies the pathogenesis of numerous diseases, including autoimmune disorders, atherosclerosis, infections, and cancer. Although non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids are widely used to control inflammation, their clinical utility is limited by adverse effects such as gastrointestinal toxicity and immunosuppression. Specialized pro-resolving mediators (SPMs), a family of endogenous lipid mediators derived from omega-3 fatty acids, have emerged as promising therapeutics because they actively promote the resolution of inflammation without suppressing host immunity. However, their clinical translation is hindered by poor chemical stability, rapid metabolic degradation, and short circulation half-lives. To overcome these limitations, a variety of delivery platforms—including liposomes, extracellular vesicles, PLGA nanoparticles, and hydrogels—have been developed to improve SPM stability, pharmacokinetics, and therapeutic efficacy. This review summarizes the cellular targets of SPMs, current delivery challenges, and emerging strategies for cell- and tissue-specific SPM delivery. We also discuss future opportunities for targeted SPM therapies in the treatment of inflammatory diseases and cancer. Full article

The fate of heavy metals in agricultural soils is governed by organo-mineral–microbial interactions, which predictive models often fail to capture. The competitive sorption mechanisms of Cd(II) and Cu(II) on montmorillonite/kaolinite composites (Mont/Kao) functionalized with humic acid (HA) and Pseudomonas putida (P. p), a model system representative of contaminated agricultural soils, were investigated. Batch experiments, XRD, FTIR, and thermodynamic analysis reveal that metal retention is a non-additive function of competing interfacial processes. Bacterial biomass dominated sorption, accounting for >50% of total metal uptake, with capacity ranked as: P. p > Mont/Kao-P. p > Mont/Kao-HA-P. p > Mont/Kao-HA > Mont/Kao. Humic acid exerts a dual, concentration-dependent role: Low levels enhanced adsorption via mineral dispersion, while high levels induced surface masking, suppressing bacterial binding sites. Competition was highly asymmetric: Cd(II) reduced Cu(II) maximum adsorption capacity by 75.5% in the Mont/Kao-HA system by preferentially occupying montmorillonite interlayer sites, whereas Cu(II) inhibited Cd(II) below pH 6. Single-metal sorption was characterized by positive ΔS° (32.96–58.89 J·mol⁻¹·K⁻¹), indicative of inner-sphere complexation, while negative ΔS° under competitive conditions signals a transition to outer-sphere complexation. This work provides mechanistic insights into site masking, competitive displacement, and ternary cation bridging controlling metal immobilization in organo-mineral assemblages. Full article

Effective iron removal from highly acidic leachates without neutralizer addition is a long-standing challenge in hydrometallurgy. For Cu-Co-bearing pyrite cinder, we demonstrate that a cyclic leaching process achieves this outcome. Operating entirely without neutralizers, the process consumed 96% of residual acid, enriched Cu and Co 4.76- and 3.88-fold, and removed 48.2% of iron, all while maintaining pH below 1.5 across four closed-loop cycles. Thermodynamic analysis reveals that Fe³⁺-${\mathrm{SO}}_4^{2-}$ complexation suppresses free Fe³⁺ to approximately 10⁻⁸ mol/L, ruling out conventional hydrolytic precipitation and directing precipitation towards schwertmannite-type basic ferric sulfate (Fe₈O₈(OH)₆SO₄). The formation of this sulfate-bearing Fe precipitate is consistent with the thermodynamic analysis, the iron mass balance, and a 176% increase in solid-phase sulfur. This neutralizer-free strategy offers a sustainable paradigm for recovering critical metals from iron-rich secondary resources. Full article

The lipoxygenase–hydroperoxide lyase (LOX-HPL) pathway is responsible for the biosynthesis of green leaf volatiles and traumatic acid (TA) in plants; however, the feedback regulatory role of TA in tea plant remains poorly understood. Here, we applied a gradient of exogenous TA concentrations (10⁻⁸–10⁻⁴ M) to both pre- and post-harvest tea leaves, and systematically determined fatty acid precursors, key enzyme activities, and structural gene genes in the LOX-HPL pathway. Moderate TA treatment (10⁻⁷ M) markedly enhanced the activities of LOX and ADH in post-harvest leaves, while concurrently upregulating multiple upstream CsLOX genes. Higher TA concentrations suppressed both enzyme activities and gene transcription. In pre-harvest leaves, the optimal concentration shifted to 10⁻⁶ M for gene upregulation. Higher TA concentrations (≥10⁻⁶ M post-harvest, ≥10⁻⁵ M pre-harvest) consistently suppressed both enzyme activities and gene transcription. Optimal TA treatment also markedly reduced ALA accumulation, indicating feedback inhibition on precursor pools. TA mediates feedback regulation of the LOX-HPL pathway, with its regulatory effect influenced by TA concentration and tissue type, providing a potential strategy for modulating fatty acid-derived flavor quality in tea production. Full article

Breast cancer cells exhibit a reversed pH gradient and metabolic plasticity that promote proliferation, invasion, and resistance to therapy. Natural products such as chlorogenic acid (CGA) and cinnamaldehyde (CA) have shown emerging anticancer potential. However, their effects on intracellular pH and metabolic transport systems remain undefined. Therefore, the aim of this study was to characterize these parameters in breast cancer and non-tumorigenic breast cells. This study evaluated the physiochemical properties of CGA and CA using LC–MS, under pH conditions (pH 1.2, 7.4, and 9.0) mimicking the gastrointestinal track (GIT). Additionally, LC–MS-based human liver microsome (HLM) assays with NADPH were used to evaluate susceptibility to CYP-mediated metabolism to evaluate first-pass metabolic stability. Intracellular uptake kinetics were quantified at multiple time points using LC–MS. Following CGA:CA treatment, intracellular pH (pH_i) was measured in cancerous MDA-MB-231 and non-tumorigenic MCF-10A breast cell lines using SNARF-1 targeted ratio-metric fluorescence approach. Expression of OATP1B1, GLUT1, and MCT1 were analyzed by Western and immunofluorescence respectively, to assess potential cellular uptake of CGA:CA through OATP1B1 and their effects on glucose uptake and lactate and proton transport. Physiochemical results demonstrated that the compounds ranged from fully stable (pH 1.2 and 7.4) to completely unstable (pH 9.0). HLM incubation indicated no CYP-mediated hepatic metabolism. Treatment results showed that there was rapid intracellular uptake of CGA and CA in cancer cells and that CGA:CA lowered pH_i in both MDA-MB-231 and MCF-7 cells, while pH_i remained mostly unchanged in MCF-10A cells. Protein analysis revealed that CGA:CA treatment downregulated GLUT1 and MCT1 expression in cancer cells, suggesting impaired glycolytic activity and lactate shuttling. OATP1B1 expression was significantly suppressed in cancer cells, suggesting feedback inhibition of the solute carrier protein. Collectively, these findings indicate that CGA and CA exhibit favorable biochemical stability and disrupt intracellular pH regulation and metabolic transporter expression in breast cancer cells. Importantly, normal cells are not significantly affected. Thus, CGA:CA demonstrates therapeutic potential for breast cancer through pH_i and metabolic modulation. Full article

Sporophyte propagation in medicinal ferns is influenced by explant type, owing to their distinctive two-phase life cycle: haloid gametophyte and sporophyte. However, few studies have systematically investigated sporophyte proliferation using different explants. This study established an efficient in vitro propagation system for the medicinal fern Drynaria roosii using two types of explants: with green globules (A) and without them (B). An L₉(3⁴) orthogonal design tested 6-benzylaminopurine (6-BA), 1-naphthaleneacetic acid (NAA), and 2,4-dichlorophenoxyacetic acid (2,4-D) on direct sporophyte regeneration. Results showed that sporophytes regenerated directly without a callus phase. For explant A, 6-BA was the dominant factor, with optimal proliferation at 3.00 mg/L 6-BA + 1.50 mg/L NAA + 0.05 mg/L 2,4-D. Explant B was less hormone-responsive but achieved a higher proliferation coefficient (116.50) under lower hormone levels. Endogenous hormone profiling revealed that increasing 6-BA triggered a biphasic cytokinin response, suppressed auxins, and elevated GA₉ in explant A, while most hormones in explant B were significantly lower. Transcriptomic GO enrichment highlighted differentially expressed genes involved in the chloroplast envelope, thylakoid membrane, and photosynthesis, indicating that membrane remodeling and photosynthetic reorganization underpin sporophyte dedifferentiation and redifferentiation. We propose that 6-BA modulates proliferation through a biphasic cytokinin response, auxin suppression, and GA₉ induction, coupled with transcriptomic reprogramming of the chloroplast envelope and thylakoid membrane components. Full article

Background: Seed dormancy is crucial for plant survival and agricultural productivity, yet its molecular mechanisms, particularly the role of maternal effects, remain poorly understood. Methods: In this study, we applied a SWATH-based, label-free, quantitative shotgun proteomic mass spectrometry approach to investigate the temporal dynamics of dormancy establishment in Xanthium strumarium, a wild plant with two seeds in one burr that, despite sharing the same genetic and environmental conditions, exhibit distinct dormancy states. Results: Our data show that dormant seeds undergo coordinated metabolic suppression, marked by a decrease in energy metabolism, cell cycle arrest, and auxin signaling, explaining their smaller size. Simultaneously, dormant seeds exhibit metabolic re-prioritization towards fatty acid desaturation, cell wall modification, and an active epigenetic program stabilized by dormancy-promoting factors alongside a transcriptionally quiescent state in early–mid development. However, in the late developmental stage, molecular signaling pathways showed a recalibration distinguished by changes in seed metabolism (such as carbon–nitrogen reallocation, sulfur assimilation, and GABA production), hormonal fluctuations, and epigenetic regulation. Notably, previously reported high DOG1 transcript abundance, together with the absence of detectable DOG1 protein in the proteomic dataset, suggests that post-transcriptional mechanisms may contribute to DOG1 regulation. Conclusions: Based on these findings and the available literature, we propose a framework whereby dormancy establishment occurs in two phases: an early DOG1-mediated priming phase followed by a temperature-sensitive plasticity phase during seed maturation. Full article

Immunotherapy can reduce treatment-related side effects but shows limited efficacy in “cold tumors,” whose immunosuppressive tumor immune microenvironment is characterized by abundant M2 macrophages and poor T cell infiltration. Because biopsy-based qualitative assessment of the tumor microenvironment is invasive and conventional imaging lacks functional information, this study aimed to develop an M2 macrophage-targeted theranostic agent enabling non-invasive photoacoustic (PA) imaging and pH-triggered cytotoxicity. A pullulan-based nanogel conjugated with mannose and near-infrared dye (IR-820) was further functionalized with the pH-responsive doxorubicin (DOX) prodrug, Aldoxorubicin, to develop Pullulan-mannose-IR820-Aldoxorubicin (PMID) nanogel. PMID was successfully synthesized, and the resulting self-assembled nanogels (<100 nm) exhibited a highly negative ζ-potential, near-infrared absorption peaks at 780 and 850 nm, and PA contrast comparable to IR-820 at 850 nm excitation. Dialysis studies demonstrated suppressed drug release at neutral pH (~20%) but accelerated release under acidic conditions, reaching ~80% within 48 h at pH 5.5, consistent with hydrazone hydrolysis and supporting tumor/lysosome-activated delivery. In RAW264.7 macrophages, PMID nanogel showed preferential uptake by M2-poralized versus M1-polarized macrophages, outperforming non-mannosylated PID nanogel and IR-820, and produced the strongest PA signal in M2 macrophage pellets. PMID nanogel also induced the highest concentration-dependent cytotoxicity in M2 macrophages, and microscopy indicated lysosomal accumulation of the nanogel with partial nuclear localization of released DOX. These findings support the use of PMID nanogel as M2 macrophage-targeted PA contrast agents and pH-responsive drug carriers with the potential to deplete immunosuppressive macrophages, modulate cold tumor microenvironments, and improve precision cancer theranostics. Full article

Bacterial decomposition of sweat produces odors affecting close-fitting garment comfort. This study selected five polyester filament types: coffee carbon polyester filament (CC-PET), bamboo charcoal polyester filament (BC-PET), oyster shell polyester filament (OS-PET), graphene polyester filament (GR-PET), and conventional polyester filament (C-PET). These four yarns exemplify three mainstream deodorizing mechanisms: BC-PET relies on physical adsorption through its porous structure; CC-PET combines adsorption with antibacterial moisture management to suppress odor at the source; GR-PET and OS-PET inhibit bacteria via reactive radicals from oxygen-containing groups and calcium oxide, respectively. Three structures were tested: weft flat knit, 1 × 1 rib, and 1 + 3 false rib. 1 + 1 rib and 1 + 3 false rib differ markedly in elasticity, thickness, and hand. Plain jersey is smooth, soft, and breathable with good extensibility. 1 + 1 rib delivers superior transverse elasticity and dimensional stability. 1 + 3 false rib is loftier and stiffer with enhanced shape retention and thermal insulation. Fifteen specimens were knitted on a seamless circular machine and evaluated using ammonia adsorption rate and acetic acid adsorption rate. Results show that fiber type significantly influences deodorizing performance, with the graphene polyester filament with the 1 + 3 false rib structure achieving the best adsorption for both gases. This provides a theoretical foundation for deodorizing functional fabric development. Full article

Acute myocardial infarction (AMI) is a leading cause of death worldwide, characterised by systemic inflammation and metabolic disorders. Tetrahydropalmatine (THP) and berberine (BBR) are major alkaloids derived from Corydalis yanhusuo and Coptis chinensis, respectively, both of which have been shown to be cardioprotective; however, whether their mechanisms differ remains unclear. In this study, we systematically compared THP and BBR in treating AMI using integrated spatial metabolomics (AFADESI-MSI), untargeted metabolomics, lipidomics, and molecular biology. The results showed that both compounds improved cardiac function, reduced fibrosis, and suppressed inflammation. Multi-omics revealed that although both regulate glycerophospholipid metabolism, their pathway preferences and functional roles diverge: THP primarily affects linoleic acid and acetylcholine metabolism with a greater propensity to restore membrane structural integrity, whereas BBR targets ether phospholipids and sphingolipids with preferential anti-inflammatory lipid modulation. At the enzymatic level, both downregulated CHKα, PEMT, ChAT, and PDHA1. A key difference is that THP uniquely upregulated acetylcholinesterase (AChE) mRNA expression, an effect absent with BBR. Spatial metabolomics directly visualised that both compounds reverse the accumulation of pro-inflammatory lysophosphatidylcholines (LPCs) and restore structural phosphatidylcholines (PCs) in the infarct region, thereby re-establishing regional lipid homeostasis. To our knowledge, this is the first integrated multi-omics comparison to suggest shared and distinct mechanisms of THP and BBR in AMI. Notably, the differential regulation of AChE, as visualised by spatial omics, may serve as a molecular basis for understanding their distinct therapeutic features, although further validation at the protein and enzymatic activity levels is warranted. Full article

Pseudomonas syringae pv. actinidiae (Psa) is the most destructive pathogen of kiwifruit, and the absence of curative measures makes the management of Psa-induced kiwifruit bacterial canker (KBC) particularly challenging. Elettaria cardamomum produces an essential oil (CAR) rich in bioactive compounds with demonstrated potential to act directly against Psa, but its mechanisms of action remain insufficiently explored. Here, we investigated CAR’s mode of action in plants with established mild KBC symptoms, and assessed its potential as a plant elicitor. In the in planta assay, CAR application (0.1% w/v, applied 7 days after inoculation) reduced KBC symptoms, with the strongest effect observed 14 days after treatment (DAT). However, CAR did not significantly affect oxidative stress biomarkers, antioxidant system, pigments and primary metabolism, or the expression of target genes related to systemic acquired resistance or salicylic acid and jasmonic acid pathways. For instance, Psa inoculation significantly upregulated PR1 (≈5.4-fold) and PR5 (≈4.3–5.5-fold), irrespective of CAR application. Complementary in vitro assays revealed a transient, phase-dependent antimicrobial activity of CAR: although the effect disappeared by 32 h in liquid-phase assay and no inhibition was observed under vapor-phase exposure, a strong reduction in Psa viable cells (79.7%) was observed after 8 h exposure in the liquid phase. This study demonstrates that CAR exerts a direct, albeit transient, antibacterial effect against Psa, conferring curative activity when applied to plants with mild KBC symptoms. Consequently, repeated applications may be required to maintain disease suppression, as CAR does not appear to induce a sustained preventive defense response in the host. Full article

Gene delivery to target cells is required for bioengineering or medical/agricultural applications. However, the hydrophobicity of the cell membrane always makes it resistant to polar nucleic acids. This physicochemical barrier is usually overcome by a nano-formulation to hide the polarity. This study evaluated a specific formulation called star polycation (SPc) regarding its efficacy in DNA/RNA delivery to insect cells. The delivery efficiency of the SPc formulation was assessed by transient expression of green fluorescence protein (GFP) in Sf9 cells, in which SPc formulation significantly enhanced the gene expression compared with an unformulated vector. In vivo transient expression (IVTE) was performed by injection of the expression construct with the SPc formulation into larvae of S. exigua. Fluorescence was detected in all four tissues, namely, epidermis, midgut, hemocyte, and fat body, where the SPc formulation enhanced the expression in most tissues except epidermis. Under this IVTE condition, an additional injection of SPc-formulated dsRNA specific to GFP suppressed the gene expression significantly more than the unformulated vector. The enhanced RNA interference (RNAi) efficiency caused by the SPc formulation was confirmed against four endogenous genes of S. exigua, namely, Snf7, PSMB5, vATPase, and α-tubulin, by either injection or feeding of dsRNA. These RNAi treatments were lethal to S. exigua, in which dsRNA specific to vATPase formulated with SPc resulted in almost 80% mortality through oral delivery. A similar oral toxicity by SPc-formulated dsRNA was demonstrated in another lepidopteran Plutella xylostella. The oral delivery of dsRNA was applied to control sucking insects such as aphids and thrips by spraying SPc-formulated dsRNA onto plant surfaces. The sprayed dsRNA labeled with Cy3 fluorescence was detected in the internal tissues of plant leaves, in which the penetration of dsRNA into the plant tissues was further accelerated by SPc formulation. The SPc formulation of dsRNA specific to vATPase was effective at killing the sucking insects by spraying on plant surfaces. These results suggest the application of an SPc formulation to deliver DNA/RNA to insect cells. Full article