Visible mould is widely used as a practical sorting cue in maize, but it remains unclear whether the visible lesion marks the boundary of mycotoxin contamination within an intact cob. This study examined mycotoxin attenuation, spatial heterogeneity, and co-occurrence in visibly mouldy white maize cobs, using measured distances from the visible mould margin. Cobs with visible mould (n = 35) were sampled for the study. For each cob, the visible mould margin was coded as 0 mm, and adjacent sections were collected at the 50% and 75% points along the measured distance from the lesion boundary to the distal cob tip, resulting in 98 cob-section observations. Mycotoxins, FUMs (FB1, FB2, FB3), deoxynivalenol (DON), zearalenone (ZEA), nivalenol (NIV) and AF (AFB1) were quantified by liquid chromatography tandem mass spectrometry. Samples with no detectable levels of mycotoxins were replaced with zero, and total FUMs were calculated (FB1 + FB2 + FB3). The visible mould margin accounted for the largest share of the measured toxin burden, accounting for 84.4% of total FUM, 89.4% of DON, 77.8% of ZEA, and 92.2% of NIV. Adjacent sections retained measurable residual mycotoxins, including 15.6% of total FUM, 10.6% of DON, 22.2% of ZEA, and 7.8% of NIV. In full-distance models, DON, ZEA, and NIV declined significantly with distance, whereas total FUM did not show significant monotonic attenuation. The AFB1 was detected in only three cob sections; these detections co-occurred with Fusarium-associated toxins. Co-occurrence analysis showed that adjacent sections frequently remained positive for multiple Fusarium-associated toxin groups, with the FUM + DON + ZEA profile persisting across measured-distance bands. These findings show that visible mould is a useful warning signal but not a reliable toxicological boundary. The results support cob-level rejection or segregation of visibly mouldy cobs before shelling, rather than lesion-level trimming, as a more defensible food-safety control measure.

Polystyrene microplastics (PS-MPs) are emerging environmental contaminants with increasing evidence of systemic toxicity; however, the mechanisms underlying their hepatic effects remain incompletely understood. The present study investigated the hepatotoxic effects of PS-MPs, focusing on hepatic bioaccumulation, mitochondrial homeostasis, inflammation, apoptosis, and liver functional impairment. Experimental animals were exposed to increasing concentrations of PS-MPs, after which liver tissues were subjected to GC-MS, biochemical, histopathological, and molecular analyses. GC-MS confirmed hepatic accumulation of PS-MPs predominantly in the higher exposure groups (20 and 40 μg), which were subsequently selected for mechanistic investigations. PS-MP exposure induced marked hepatic dysfunction, evidenced by elevated bilirubin, ALT, AST, and GGT levels together with significant reductions in total protein, albumin, and globulin concentrations. Histopathological examination revealed progressive hepatocellular degeneration, inflammatory infiltration, cytoplasmic vacuolation, and necrotic alterations. In parallel, inflammatory and apoptotic signaling were significantly activated, as demonstrated by increased NF-κB and caspase-3 levels. Mechanistically, PS-MPs were associated with transcriptional dysregulation of genes involved in mitochondrial homeostasis, including suppression of mitochondrial biogenesis markers (PGC-1α and TFAM), downregulation of mitochondrial fusion regulators (MFN2 and OPA1), increased DRP1 expression, and reduced PINK1 expression, suggesting altered mitophagy-related signaling. Principal Component Analysis further demonstrated clear separation between control and exposed groups, strongly associating PS-MP exposure with hepatic injury, transcriptional dysregulation of mitochondrial homeostasis-related genes, inflammation, and apoptosis. Collectively, these findings demonstrate that PS-MPs induce significant hepatotoxicity, accompanied by coordinated transcriptional dysregulation of mitochondrial homeostasis-related genes and activation of inflammatory and apoptotic pathways. These findings highlight the liver as a major target of microplastic toxicity and emphasize the need for further studies incorporating protein-level validation, functional mitochondrial assessments, and long-term exposure models to better understand the implications for human health.

Objective: To investigate the effects and mechanisms of polyvinyl alcohol/ionic liquid-tannic acid composite hydrogel (PIT) on wound healing of full-thickness skin defects in diabetic mice. Methods: This study was an experimental research involving grouped design and repeated measurements. An ionic hydrogel matrix crosslinked by polyvinyl alcohol-4-(1H)-vinylimidazole-1-methylene benzoic acid and oxidized hyaluronic acid was prepared, and tannic acid was loaded via Cu[2+] chelation to construct PIT. A 1,1-diphenyl-2-picrylhydrazyl (DPPH) solution was prepared and reacted respectively with tannic acid and PIT for 24 hours. An ultraviolet spectrophotometer was used to detect the DPPH radical scavenging rate. According to the random number table method (the same grouping method below), mouse macrophage RAW264.7 cells were divided into a phosphate buffered saline (PBS) group cultured with PBS, as well as a hydrogen peroxide group and a PIT group, in which cells were first treated with hydrogen peroxide for 12 hours and then respectively cultured under routine condition and with PIT. After 24 hours of culture, the fluorescent probe method was adopted to detect the intracellular reactive oxygen species (ROS) level. Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, methicillin-resistant Staphylococcus aureus (MRSA) BNCC 337371, and human umbilical vein endothelial cells (HUVECs) were collected and all divided into PBS group, tannic acid (TA) group, and PIT group, which were cultured with PBS, TA solution, and PIT, respectively. After 12 hours of bacterial culture, the plate counting method was used to count bacterial colonies; after 24 hours of cell culture, the tube formation assay was performed to measure the total tube length, the number of branching nodes, and the number of branches. The sample size of all the above experiments was 3. Eighteen 8-week-old male Kunming mice were selected and divided into PBS group, TA group, and PIT group (with 6 mice in each group) to establish a full-thickness skin defect wound model of diabetes (with one wound in each mouse). At post injury day (PID) 0 (immediately), the wounds of mice in PBS group, TA group, and PIT group were treated respectively with PBS, TA solution, and PIT by topical application, and then the dressings were changed daily. The wound healing status was observed at PID 0, 4, 8, and 12, and the wound healing rates at PID 4, 8, and 12 were calculated. At PID 12, wound tissue was harvested. Hematoxylin-eosin staining was performed to observe the status of wound re-epithelialization and to measure the thickness of newly formed epithelium. Masson staining was performed to observe the deposition of collagen fibers in wounds and to calculate the proportion of collagen fiber-positive area. Results: After 24 hours of reaction, the DPPH radical scavenging rate of PIT was significantly higher than that of TA (t=16.35, P<0.05). After 24 hours of culture, the ROS level of RAW264.7 cells in hydrogen peroxide group was significantly higher than that in PBS group (P<0.05), and the ROS level of RAW264.7 cells in PIT group was significantly lower than that in hydrogen peroxide group (P<0.05). After 12 hours of culture, the bacterial colony counts of Escherichia coli, Staphylococcus aureus, and MRSA in PIT group were significantly less than those in PBS group and TA group (P<0.05). After 24 hours of culture, compared with those in PBS group and TA group, the total tube length of HUVECs in PIT group was significantly increased (with P values both <0.05), and the number of branching nodes and the number of branches increased significantly (with P values all <0.05). From PID 0 to 12, the wounds of mice in all three groups healed gradually. At PID 4, 8, and 12, the wound healing rates of mice in PIT group were (31.6±2.0)%, (51.8±2.5)%, and (97.9±1.5)%, respectively, which were significantly higher than (18.6±0.6)%, (39.5±2.0)%, and (74.6±2.0)% in PBS group and (21.5±1.1)%, (40.7±0.8)%, and (85.3±2.1)% in TA group (P<0.05). At PID 12, the wound re-epithelialization of mice in PBS group was incomplete, and collagen fibers were sparsely distributed with disordered arrangement; the degree of wound re-epithelialization of mice in TA group was higher than that in PBS group, and collagen fibers were distributed in bundles with loose arrangement; the degree of wound re-epithelialization of mice in PIT group was higher than that in TA group, and collagen fibers were densely and orderly arranged in layers. At PID 12, compared with those in PBS group and TA group, the thickness of newly formed epithelium in wounds of mice in PIT group was significantly increased (with P values both <0.05), and the proportion of collagen fiber-positive area was significantly increased (with P values both <0.05). Conclusions: PIT significantly accelerates the wound healing of full-thickness skin defects in diabetic mice through multiple mechanisms driven by metal ion chelation including antibacterial, antioxidant, and pro-angiogenesis activities, thereby improving the quality of tissue repair.

Occupational exposure to polycyclic aromatic hydrocarbons (PAHs) or metal fumes in the workplace may be detrimental to male fertility. The present study compared sperm concentration, total motility, strict morphology and oxidative stress and SDF levels between 81 men, controls (n = 17) and workers from plastic industry workers (n = 18), steel EAF process (n = 15), waste incineration plants (n = 16) or aluminium factories smelting in the same plant for all workplaces involved in this cross-sectional research. In all treated groups, the sperm concentration, motility, normal morphology, acrosome integrity and membrane function dropped significantly compared with those in controls (p < 0.001). Elevated ROS, MDA and low SOD and CAT activities confirmed the presence of severe oxidoreductive imbalance, particularly in Aluminium and incineration workers. DNA breaks assayed by SCD and comet showed a clear positive exposure-response relationship with the highest OTM in aluminium workers. Network pharmacologic work showed that 67 shared targets were regulated by PAH exposure and male infertility. The hub gene analysis pointed at EGFR, ESR1, RELA, PTGS2, MMP2 and MMP9 as the core hub genes while KEGG enrichment suggested that the HIF-1 and TNF-related inflammatory pathway, along with the endocrine disruption side of stress activating signalling, was involved. Inflammatory signal activation and endocrine disturbance together seemed to end up with really severe damage to sperm DNA, and it also turned on a bunch of mechanisms through which these chemical carcinogens can exert effect. ROS and MDA were negatively correlated with motility as well as sperm concentration significantly (p < 0.05), whereas antioxidant enzymes showed a positive correlation. These findings show how PAH-related industrial poisoning disrupts important reproductive output through ROS-mediated genetic instability and suggest the relevance of protection measures in high-risk industries.

Microplastics (MPs), as widespread and increasingly prevalent environmental pollutants, pose a persistent threat to aquatic organisms and mammals, including humans. Sodium humate (HNa), a naturally derived humate salt that is widely available, low-cost, and has a favorable safety profile, exhibits multiple biological activities, including antimicrobial, anti-inflammatory, and antioxidant properties. This study was designed to evaluate whether HNa could protect against intestinal and hepatic injury caused by polystyrene microplastics (PS-MPs) exposure in mice and to clarify the involvement of the gut-liver axis. HNa intervention alleviated impairment of body weight gain and colonic pathological injury following PS-MPs exposure. HNa enhanced intestinal antioxidant capacity, suppressed pro-inflammatory mediator expression, and promoted anti-inflammatory factor expression. Furthermore, HNa upregulated the expression of mucins and adherens junction and tight junction proteins, thereby restoring intestinal barrier function and limiting endotoxin translocation. In the liver, HNa ameliorated histopathological lesions, improved biochemical injury markers, attenuated inflammatory responses, and suppressed excessive activation of the TLR4/NF-κB pathway. Collectively, HNa mitigated gut-liver axis injury following PS-MPs exposure in mice through coordinated protection of intestinal barrier integrity and attenuation of hepatic inflammatory signaling. This study provides the first experimental evidence that HNa mitigates PS-MPs toxicity by protecting the gut-liver axis, supporting its potential as a practical intervention strategy against MPs-related digestive system injury.

Despite cisplatin (CISP) is broadly employed in cancer therapy, its adverse effects, involving hepatotoxicity, restrict its clinical usage. Thus, this study was designed to explore the prospect of repurposing rupatadine (RUPA), a dual antagonist of histamine and platelet-activating factor (PAF), against CISP-evoked hepatotoxicity in rats. Rats were i.p. injected with CISP (6 mg/kg) for the induction of hepatotoxicity on the 8th day of the study in the presence and absence of RUPA in two dosages (3, 6 mg/kg) orally for 14 days. Different biochemical parameters and histopathological assessments, along with the mechanistic characterizations of the possible protective impact of the RUPA were conducted. Administration of CISP evoked hepatic histopathological modifications and raised serum liver enzyme levels and hepatic MDA content, PAF, and histamine levels, along with diminishing the serum albumin level, hepatic SOD activity, and GSH level. Moreover, CISP remarkably augmented the levels of HMGB1, TLR4, p-NF-κB p65, IL-6, TNF-α, IL-18, IL-1β, NLRP3, and cleaved caspase-1 proteins with an evident decline in the level of IL-10. On the contrary, pretreatment with either RUPA.3 or RUPA.6 dramatically ameliorated these alterations triggered by CISP injection. RUPA counteracts hepatotoxicity evoked by CISP in rats via its anti-oxidative as well as anti-inflammatory properties via repression of hepatic HMGB1/TLR4/NF-κB and thus restricts the activation of NLRP3/caspase-1 signaling cascade.

Service members are routinely deployed to geographical locations where arthropod-borne diseases are endemic. Force health protection relies on integrated vector management methods to reduce service member exposure to disease vectors. The United States Department of Defense relies heavily on personal protective measures that include proper uniform wear, on-skin application of topical repellents, and insecticidal treatment of working uniforms with permethrin. The objective of this study was to evaluate the effectiveness of topical N,N-diethyl-3-methylbenzamide (DEET) application, permethrin-treated U.S. Army Combat Uniforms (ACUs) with operational camouflage pattern, and their combination for protecting service members from the bite of Aedes aegypti (L.) mosquitoes in a semi-field environment. Volunteers wearing treated or untreated ACUs, with or without DEET on exposed skin, stood stationery in outdoor cages containing 100 unfed Ae. aegypti females. The data recorded included number of mosquito bites identified on the volunteer, the number of blood fed mosquitoes, and post-exposure mosquito mortality rates 24 hours following trials. Results demonstrated that properly worn ACUs prevented mosquito bites from occurring on covered body parts, even when untreated. However, bites were common on exposed skin when DEET was not applied. The combination of DEET and a properly worn uniform provided nearly 100% protection from bites. Permethrin-treated uniforms alone did not prevent mosquitoes from biting exposed skin but resulted in significant mosquito mortality 24 hours after exposure. These results show that the combination of proper uniform wear, uniform treatment, and use of topical repellent provides holistic protection including bite reduction and focal mortality of exposed mosquitoes.

Rickettsia helvetica is a spotted fever group rickettsia associated mainly with Ixodes ricinus and increasingly detected in European ticks. We describe two tick-bite-associated human cases in Serbia in May 2025. A 65-year-old woman (Case 1) developed pruritic erythematous lesions after two adult female I. ricinus attachments acquired in the Valjevo area. Rickettsia spp. DNA was detected in capillary blood from both lesions, and sequencing of the PCR amplicons identified R. helvetica, while whole blood was PCR-negative and serology did not show reproducible seroconversion. An 8-year-old girl (Case 2) developed a pruritic scalp papule/crust and occipital/cervical lymphadenopathy after an adult female Haemaphysalis punctata attachment in Petrovaradin forest. Rickettsia spp. DNA was detected in lesion capillary blood and whole blood; sequencing identified both as R. helvetica. Clinical signs resolved after doxycycline. These observations support lesion-focused molecular testing and integrated human-tick-environment surveillance for underdiagnosed spotted fever group rickettsioses in Serbia.

This study aimed to evaluate the general, hepatoprotective and renoprotective effects of amifostine (AMI) in rats treated with a large, single dose of doxorubicin (DOX), assessed at 7 and 56 days after administration. Rats were divided into six experimental groups: Control (0.9% NaCl intraperitoneally (ip)), amifostine (AMI300, 300 mg/kg (ip)), doxorubicin (DOX6, 6 mg/kg (ip)), doxorubicin (DOX10, 10 mg/kg (ip)), doxorubicin (DOX6, 6 mg/kg (ip)) + amifostine (AMI300, 300 mg/kg (ip) 30 min before DOX6), and doxorubicin (DOX10, 10 mg/kg (ip)) + amifostine (AMI300, 300 mg/kg (ip) 30 min before DOX10). Absolute liver and kidney weights were significantly increased in AMI300 + DOX6-treated animals compared to DOX6 only on day 56. In the group of DOX10-treated rats, AMI300 significantly prevented changes in the number of white blood cells during the four weeks after treatment. The severity of hepatic and renal injuries in the DOX6-treated groups was also significantly less in rats pretreated with AMI300 on day 56 (p < 0.01). Our results indicate that hepatic and renal protection significantly contribute to the successful use of AMI against DOX-induced subacute toxicity in rats.

The aim of this study was to examine the hepatoprotective activity of multicomponent mixtures of natural origin in the BALB/C mouse model (n = 59), with acute direct toxic liver injury (DTLI) induced by the administration of streptozotocin (STZ) (100 mg/kg) in combination with a high-fat and high-fructose diet (HFFD). The hepatoprotective activity of activated hydrolytic lignin (Bp-Cx-1), methanolic fraction of Bp-Cx-1 (Bp-Cx-M) and isoflavones from kudzu Pueraria lobata roots (IFL) were evaluated on molecular level using mass spectrometry (MS)-based omics technologies. Untargeted label-free DIA quantitation resulted in 7214 protein groups identification (FDR 1%) after filtering across 40 liver tissue extracts. All treatment groups were closer to the control samples on the liver proteomic landscape compared to the untreated DTLI group, with the best results shown for the Bp-Cx-M and IFL groups. In order to identify differences between specific groups, we applied the post hoc Dunn's test and used Hedges' g as the effect size metric, revealing 64 proteins that tended to return to their normal level after treatment. In-depth proteomic liver tissue analysis enabled us not only to reveal the main pathways such as inflammation and oxidative stress, which are in a good agreement with DTLI and non-alcoholic liver disease pathophysiology, but also to evaluate hepatoprotective activity of multicomponent mixtures of natural origin containing polyphenols and mostly associated with protein metabolism (e.g., PSMD7, HCFC1) and deubiquitination pathways (e.g., UCHL3). It is worth noting that the Bp-Cx-1 isolated methanol fraction (Bp-Cx-M) demonstrated a pronounced increased hepatoprotective activity compared to the parent material due to the enrichment with active components such as polyphenols. Consistent with the proteomic findings of restored ubiquitin-proteasome function, assessment by comet assay revealed that treatments with Bp-Cx-M and IFL significantly reduced DNA damage by 50% compared to the untreated DTLI group. The developed MS-based multi-omics approach may be implemented for the robust and high-throughput screening method during assessment of new hepatoprotective agents of synthetic or natural origin.

The treatment of advanced Parkinson's disease (PD) remains challenging, with few options to address motor fluctuations and dyskinesia simultaneously. Positive allosteric modulation of metabotropic glutamate 4 (mGlu4) receptors may be a therapeutic option that could alleviate both fluctuations and dyskinesia. mGlu4 receptors form hetero-dimers with metabotropic glutamate 2 (mGlu2) receptors, suggesting that additive anti-parkinsonian and antidyskinetic could be obtained upon dual mGlu2-mGlu4 positive allosteric modulation. Here, the mGlu2 positive allosteric modulator (PAM) LY-487,379 and the mGlu4 PAM ADX-88178 were administered, either alone or together, in combination with L-3,4-dihydroxyphenylalanine (L-DOPA), to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned marmosets, after which the severity of parkinsonism, dyskinesia and psychosis-like behaviours (PLBs) was assessed. We discovered that each of LY-487,379 and ADX-88178 enhanced the anti-parkinsonian action of L-DOPA and reduced dyskinesia severity when administered separately; when administered concurrently, the resulting anti-parkinsonian (P < 0.001) and anti-dyskinetic (P < 0.01) effects were greater than when both molecules were administered separately. LY-487,379, but not ADX-88178, alleviated L-DOPA-induced PLBs; when the two compounds were administered simultaneously, the resulting anti-psychotic benefit was greater than the effect achieved with LY-487,379 (P < 0.01). Our results indicate that dual mGlu2-mGlu4 positive allosteric modulation results in greater anti-parkinsonian and anti-dyskinetic effects than positive allosteric modulation of either target separately. In addition dual mGlu2-mGlu4 positive allosteric modulation enhances the anti-psychotic effect of selective mGlu2 positive allosteric modulation. Concurrent mGlu2-mGlu4 positive allosteric modulation represents a promising avenue for the treatment of complications in advanced PD.

Ochratoxin A (OTA) is a widespread nephrotoxic mycotoxin that contaminates cereal grains and feed, posing serious threats to animal health and food safety. Although curcumin has been reported to exert protective biological activities, it remains unclear whether its protection against OTA-induced renal epithelial injury is mediated by broad transcriptomic reversal or by selective regulation of key survival pathways. This study investigated the protective effect of curcumin against OTA-induced apoptosis in porcine renal epithelial (PK-15) cells and explored the underlying molecular mechanism using transcriptome sequencing combined with molecular validation. PK-15 cells were treated with 8 μg/mL OTA (approximately 19.8 μmol/L), 10 μmol/L curcumin, or their combination. Cell viability, LDH release, apoptotic morphology, mitochondrial membrane potential (ΔΨm), and apoptosis rate were assessed by CCK-8, LDH assay, Hoechst 33342 staining, JC-1 staining, and flow cytometry. Transcriptome sequencing was performed to identify global gene expression changes and key signaling pathways, followed by qRT-PCR and Western blot validation of apoptosis-related factors and the PI3K/AKT/mTOR pathway. OTA markedly reduced cell viability, increased LDH release, induced nuclear condensation and apoptotic body formation, and decreased ΔΨm. Transcriptome analysis revealed that OTA caused extensive transcriptional dysregulation (11,707 differentially expressed genes), whereas curcumin selectively modulated 498 genes, of which 380 overlapped with OTA-responsive genes. KEGG enrichment identified the PI3K-Akt signaling pathway as a key regulatory target. At the mRNA level, OTA upregulated Bax and Caspase-3 and downregulated Bcl-2; corresponding changes were observed at the protein level, and curcumin reversed these effects. Furthermore, OTA reduced the mRNA levels of PI3K, AKT, and mTOR and the protein abundance of PI3K, p-AKT, and mTOR, whereas curcumin partially restored these changes. In conclusion, curcumin alleviates OTA-induced mitochondrial apoptosis in PK-15 cells mainly by restoring PI3K/AKT/mTOR-associated survival signaling and Bcl-2/Bax/Caspase-3 balance rather than by broadly reversing the entire transcriptomic disturbance. These findings provide mechanistic insight into curcumin-mediated protection against OTA-induced renal epithelial toxicity.

Co-contamination of foods with multiple mycotoxins highlights the need for broad-spectrum detoxification enzymes. In this study, Klebsiella pneumoniae HNGD-HS06 was isolated from contaminated peanuts and degraded aflatoxin B1 (AFB1), zearalenone (ZEN), and alternariol (AOH) by 72.52%, 63.42%, and 76.17%, respectively. Genome-guided screening and heterologous expression identified two candidate proteins, HSFtsp and HSCueO. HSCueO shared only 28.08% sequence identity with CotA laccase, while HSFtsp has not previously been associated with mycotoxin degradation. HSFtsp degraded AFB1, ZEN, and AOH by up to 99.16%, 95.12%, and 94.72%, respectively, whereas HSCueO achieved 98.97%, 99.23%, and 99.74% degradation. Product analysis and zebrafish assays suggested that both enzymes transformed these toxins into less toxic products, while molecular docking supported potential enzyme-substrate interactions. Both enzymes retained detoxification activity in contaminated peanut, corn, and wheat flour, expanding enzyme resources for multimycotoxin control in foods.

Levodopa-induced dyskinesia remains one of the most prevalent and disabling complications in patients with Parkinson's disease receiving long-term levodopa therapy. Although levodopa-induced dyskinesia can substantially impair the quality of life, therapeutic strategies are often limited to levodopa dose adjustment, amantadine, or deep brain stimulation. These treatment options may be ineffective, poorly tolerated, or declined by some patients. We applied low-frequency deep repetitive transcranial magnetic stimulation over the supplementary motor area in two patients with Parkinson's disease and clinically significant levodopa-induced dyskinesia who had limited conventional treatment options. Both patients completed a 2-week protocol without medication changes and demonstrated short-term reductions in dyskinesia severity, as assessed using the Unified Dyskinesia Rating Scale and motor-complication measures. No serious adverse events occurred. These observations suggest that supplementary motor area-targeted deep repetitive transcranial magnetic stimulation is a feasible noninvasive neuromodulation approach for selected patients with levodopa-induced dyskinesia. However, this is a two-patient case report without sham stimulation or extended follow-up; therefore, the findings should be interpreted as preliminary and hypothesis-generating. Larger controlled studies with objective outcome measures and longer follow-up are needed to determine the efficacy, durability, and optimal stimulation parameters.