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Forest fires cause societal damage, including injuries, burns, and the development and exacerbation of cardiorespiratory diseases. One of the damaging factors of forest fires is carbonaceous particles heated up to high temperatures. These particles are carried from the forest fire front and can interact with human tissue. Three scenarios for the interaction of a heated carbonaceous particle with human tissue are considered. The first scenario involves particle impact on the skin. The second scenario involves particle impact on the nasopharyngeal mucosa. The third scenario involves the impact on the tissues of the upper airways. A two-dimensional mathematical statement is considered in the “carbonaceous particle–human tissue” system. Mathematically, the heat transfer process is described by non-stationary parabolic partial differential equations with corresponding initial and boundary conditions. The problem is solved using locally one-dimensional and finite-difference methods. Difference analogs of the differential equations are solved using the marching method. Temperature distributions for particles of varying sizes and initial heat contents were obtained. The software realization was implemented using the high-level Object Pascal programming language in the RAD Studio environment. Conclusions were drawn regarding the potential practical applications of the developed software in healthcare and environmental protection. Full article

Background and Objectives: Small lymphocytic lymphoma (SLL) represents the tissue-based manifestation of chronic lymphocytic leukemia (CLL). Despite their shared biological background, patients with SLL have been underrepresented in CLL-focused clinical trials, and data addressing the clinical behavior of pure nodal SLL remain scarce. The present study aimed to identify factors associated with time to first treatment (TTFT) and progression-only survival in patients with pure nodal SLL. Materials and Methods: In this prospective observational study, 46 patients with pure nodal SLL were included and followed for a median duration of approximately 5 years. Clinical, laboratory, histopathological, and TP53-related parameters were evaluated for their prognostic impact on TTFT and progression-only survival. Results: On univariable analysis, advanced-stage disease, hemoglobin < 10 g/dL, elevated serum β2M, elevated lactate dehydrogenase, del(17p), and aberrant p53 immunohistochemical expression were significantly associated with shorter TTFT and progression-only survival. Conclusions: Pure nodal SLL is a heterogeneous entity with a variable clinical course. Easily assessable clinical and biological parameters, including TP53 abnormalities, may help predict treatment requirement and disease progression, thereby contributing to better risk stratification and more individualized management. Kaplan–Meier analysis demonstrated significantly shorter time-to-first-treatment (TTFT) among patients with elevated β2M levels (≥3.5 mg/L), bulky lymphadenopathy (≥5 cm), and advanced-stage disease. Full article

In the context of global climate change, intensified salinity fluctuations driven by altered precipitation, extreme rainfall events, and typhoons have emerged as a major threat to coastal mollusk aquaculture. In this study, integrated physiological and transcriptomic analyses were performed to investigate the responses of Pacific abalone (DD, Haliotis discus hannai) and its hybrid (DF, H. discus hannai ♀ × H. fulgens ♂) to hypo- and hypersalinity stress. Two salinity breakpoints (BPS1 for hyposalinity, BPS2 for hypersalinity) were identified using heart rate monitoring to indicate the osmotic tolerance thresholds of the abalone. The BPS1 and BPS2 values did not differ significantly between the DD and DF groups. However, a subsequent 30-day culture trial confirmed that exposure to the salinity level corresponding to BPS1 significantly reduced growth and survival of both DD and DF groups. To explore the molecular mechanisms underlying these two salinity breakpoints in abalone, the transcriptomes of hemocytes and gill tissues were profiled under both stress conditions. Both hypo- and hypersalinity stress induced pronounced transcriptomic responses in abalone, accompanied by upregulated differentially expressed genes (DEGs) significantly enriched in pathways like TNF and NF-κB signaling, including genes like piap, diap2, birc7-a, birc2, and birc3. However, abalone exhibited more intense responses to hypersalinity stress, as reflected by a greater number of annotated differentially expressed genes (DEGs) and more complex transcriptional regulation. Overall, this study integrates physiological assessment based on heart rate monitoring, aquaculture trials, and transcriptomic analysis to advance our mechanistic understanding of osmotic stress adaptation in abalone, while laying a scientific foundation for the sustainable development of abalone aquaculture under global climate change. Full article

Background: Calonysterone (CAL) is a natural derivative of 20-hydroxyecdysone (20E) with enhanced bioactivity on skeletal muscle cells in vitro, but its in vivo physiological actions remain less well characterized. This study aimed to compare the effects of 20E and CAL on metabolic, muscular, and endocrine parameters in normal and obese male rats, with a particular focus on androgen balance. Methods: Male rats were treated with 20E or CAL under normal (ND) or high-fat, high-sugar dietary (HFHSD) conditions for 12 weeks. Body weight, food intake, skeletal and androgen-sensitive muscle mass, and testicular weight were measured. Testicular expression of androgen receptor (Ar) and aromatase (Cyp19a1) mRNA was assessed by RT-PCR. ELISA was used to determine the plasma corticosterone, testosterone and ERβ level in testes. Results: 20E and CAL prevented HFHSD-induced weight gain and skeletal muscle atrophy. CAL uniquely preserved testicular and levator ani muscle mass in obese rats. CAL increased the expression of Cyp19a1 and ERβ in testicles. Decreased Ar mRNA expression was regulated in 20E- and CAL-treated obese animals. While 20E treatment significantly reduced plasma testosterone levels in the normal diet group compared to controls, both 20E and CAL interventions elicited significant reductions in the obese group relative to both the ND and HFHSD groups. HFHSD-induced increase in plasma corticosterone levels was normalized by 20E or CAL treatment. Conclusions: 20E and CAL exhibit beneficial metabolic and anabolic effects by preventing HFHSD-induced obesity and consequential muscle atrophy. CAL counteracts obesity-induced testicular atrophy in terms of tissue mass. Based on our results, we hypothesized that CAL enhances testicular aromatase levels, which may lead to increased compensatory androgen receptor mRNA expression and increased ERβ levels. These complex, not yet fully understood results underscore the need for caution in the use of phytoecdysteroids as dietary supplements. Full article

Background: Osteochondral lesions of the talus (OLT) remain a challenging condition due to the limited regenerative potential of articular cartilage. Conventional bone marrow stimulation (BMS) techniques often result in fibrocartilage formation with inferior biomechanical properties. This study aimed to evaluate the safety and preliminary clinical efficacy of an arthroscopically assisted, single-stage injection of a heparin-conjugated fibrin hydrogel (HCFH) for OLT treatment. Methods: Twelve patients with symptomatic OLT underwent arthroscopic debridement, microfracturing, and HCFH injection containing autologous mesenchymal stromal cells (MSCs) and growth factors. Safety was assessed through systematic monitoring of adverse events (graded according to Common Terminology Criteria for Adverse Events criteria), wound healing, and serial laboratory inflammatory markers (leukocytes, erythrocyte sedimentation rate, C-reactive protein) during early and late follow-up. Clinical outcomes were evaluated using the Visual Analog Scale (VAS) and American Orthopedic Foot and Ankle Society score (AOFAS) preoperatively and at 6 and 12 months. Morphological assessment was performed using magnetic resonance imaging (MRI) with the modified Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scoring system, evaluated independently by two blinded musculoskeletal radiologists. Results: No serious adverse events (Grade III–IV) were observed during the 12-month follow-up. All adverse events were mild (Grade I) and self-limited. A transient postoperative elevation in inflammatory markers was observed, returning to clinically acceptable levels by day 14. Significant improvements were noted in pain (VAS decreased from 6.0 to 2.0) and ankle function (AOFAS increased from 70.0 to 90.6) (p < 0.001). MRI demonstrated progressive morphological improvement, with the MOCART score increasing from 34.16 ± 17.1 at 6 months to 75 ± 5.43 at 12 months (p < 0.001). This increase corresponded with imaging features consistent with tissue maturation over time. The favorable MOCART outcomes observed in this study may be explained by the regenerative properties of heparin-conjugated fibrin hydrogels; however, larger randomized controlled trials with longer follow-up are needed to confirm the durability of the regenerated tissue. Interobserver agreement was substantial to almost perfect for MOCART scoring (κ = 0.68–0.84), with perfect agreement observed for surface assessment, bony defect/overgrowth, and cysts. Conclusions: Within the limitations of this study, single-stage HCFH injection demonstrated an acceptable safety profile and favorable preliminary clinical and radiological outcomes at 12 months. These findings suggest potential regenerative capability; however, controlled studies with larger cohorts and longer follow-up are required to determine comparative efficacy and long-term durability. Full article

Polycyclic aromatic hydrocarbons (PAHs) are widespread, persistent pollutants that can be sequestered within human adipose tissue due to their lipophilic nature. While this accumulation poses toxicological risks depending on dose and individual susceptibility, the specific morphological impact of chronic PAH storage on tissue architecture remains poorly defined. Here, we performed a histopathological and morphometric analysis on human subcutaneous adipose tissue samples characterized by high pyrene levels. We evaluated tissue organization, collagen distribution, the presence of inflammatory, neural, and vascular alterations and adipocyte morphometry to assess the structural response to PAH sequestration. Despite high pyrene concentrations, PAH-positive tissues maintained preserved overall architecture with normal collagen distribution, absence of lymphocytic infiltration, low macrophages, unaltered nerve fiber patterns, without evidence of vascular remodeling. Morphometry revealed smaller adipocyte area in PAH-positive samples, although not statistically significant. Our experimental data indicate that high PAH accumulation does not necessarily induce subcutaneous adipose tissue remodeling, suggesting that biochemical or metabolic alterations might occur even in the absence of evident histological changes. Further studies, with a broadened cohort, are needed to define the threshold at which PAHs’ presence translates into permanent tissue damage. Full article

Saline–alkali stress is a widespread adversity that severely affects plant growth and productivity. Plant-specific NAC transcription factors (TFs) play a crucial role in various pathways associated with stress responses. However, the function of NAC proteins in conferring tolerance to abiotic stress, along with the underlying mechanisms in apple (Malus domestica), remains incompletely understood. In this study, we identified MdNAC17 from the transcriptome of apple leaves under saline–alkali stress. The overexpression of MdNAC17 in apple calli tissue and Malus hupehensis roots significantly improved resistance to saline–alkali stress by enhancing reactive oxygen species (ROS) scavenging. Transgenic apple plants exhibited higher photosynthetic capacity and antioxidant enzyme activity, as well as less membrane damage. In contrast, silencing MdNAC17 using virus-induced gene silencing (VIGS) technology resulted in the opposite phenotype. Furthermore, MdNAC17 is associated with changes in the transcriptional levels of genes involved in Na⁺/K⁺ homeostasis. Overall, our results demonstrate that MdNAC17 positively regulates saline–alkali tolerance in apple. Full article

The Popeye domain-containing protein 1 (Popdc1), also known as Bves, plays a crucial role in maintaining skeletal muscle homeostasis, with its variants leading to limb–girdle muscular dystrophy type R25. Skeletal muscles of patients with the homozygous missense variant of Bves exhibit impaired membrane trafficking, while skeletal muscle fibers in bves^S191F homozygous mutant zebrafish are significantly reduced and disorganized. However, the mechanism by which the absence of bves induces skeletal muscle atrophy remains unclear. In this study, we discovered a novel mechanism whereby bves deficiency drives skeletal muscle atrophy by disrupting mitochondrial structure and function. Our findings indicate that bves knockout leads to a significant decrease in zebrafish’s ability to swim, atrophy of skeletal muscle tissue, loss of cell membrane localization signals, and abnormalities in mitochondrial structure and function. After an 8-week intervention of regular aerobic exercise, the symptoms of skeletal muscle atrophy in bves knockout zebrafish were significantly alleviated, and the expression levels of genes and proteins related to mitochondrial were effectively rescued. These findings establish a connection between bves deficiency-induced disruption of mitochondrial structure and function and the onset and progression of skeletal muscle tissue atrophy symptoms, thereby laying a molecular foundation for exercise rehabilitation strategies in atrophic myopathy. Full article

In hemodialysis patients, Body Mass Index is insufficient in assessing their nutritional status due to the ‘obesity paradox’ and the association between body composition and inflammation. This study assessed the relationship between body composition, traditional inflammatory markers, the new NETosis indicators (neutrophil extracellular traps), and their association with 12-month mortality. The study included 99 maintenance hemodialysis (HD) patients. Their body composition was assessed using bioelectrical impedance analysis. Blood serum was tested for inflammatory markers (hs-CRP-high sensitive c-reactive protein, IL-6 interleukin-6, TNF-α tumor necrosis factor alfa, IL-1β interleukin-1 beta), NETosis markers (citrullinated histone CH3, myeloperoxidase -MPO, elastase), and nutritional status parameters (albumin, transferrin). No correlation between BMI -body mas index and inflammation was demonstrated. Higher adipose tissue, particularly visceral, was significantly positively correlated with IL-6 and hs-CRP levels, while muscle mass was negatively correlated with inflammation. Dialysis catheter use was associated with higher CH3 levels (NETosis indicator) and lower albumin concentrations. Low albumin levels and high TNF-α levels were independent predictors of death. Body composition, rather than BMI, is associated with the severity of inflammation. Visceral obesity is positively correlated with increased inflammation, while muscle mass shows an inverse association. Dialysis catheters are linked to higher NETosis markers and lower albumin levels, which are associated with a poorer prognosis. Full article

1-Deoxy-D-xylulose-5-phosphate synthase (DXS) serves as the initial rate-limiting enzyme in the methylerythritol phosphate (MEP) pathway, governing the biosynthesis of precursors for photosynthetic pigments and terpenoids. In this study, the LaDXS2-2 gene was cloned and functionally characterized in lavender (Lavandula angustifolia). The full-length coding sequence (CDS) of LaDXS2-2 spans 2178 base pairs, encoding a protein of 725 amino acids. Phylogenetic analysis revealed that LaDXS2-2 is most closely related to the DXS from Salvia miltiorrhiza. Expression profiling demonstrated that LaDXS2-2 was highly expressed in flower buds, and its transcript levels were significantly upregulated (p < 0.05) in response to ethephon, high light intensity, and low temperature, while exhibiting tissue-specific responses to gibberellin application. Subcellular localization assays confirmed LaDXS2-2 is targeted to the chloroplast. Heterologous overexpression of LaDXS2-2 in tobacco resulted in a marked increase in photosynthetic pigment content, enhanced the actual photochemical efficiency of photosystem II [Y(II)], and reduced non-photochemical quenching (NPQ). Integrated transcriptomic and metabolomic analyses further revealed that LaDXS2-2 overexpression activated the diterpenoid biosynthesis pathway and upregulated amino acid metabolism as well as the TCA cycle, while competitively suppressing phenylpropanoid and flavonoid biosynthesis pathways. These findings indicate that LaDXS2-2 not only enhances photosynthetic efficiency by promoting the synthesis of photosynthetic pigments but also suggests a potential role in influencing primary carbon and nitrogen metabolism, as inferred from transcriptomic and metabolomic data. This functionality may ultimately influence plant growth and metabolic homeostasis. Overall, this study provides a theoretical foundation for the synergistic improvement of photosynthetic efficiency and secondary metabolism in crops. Full article

Plants must continuously balance the trade-offs between growth and defense, a constraint that is exacerbated by biotic and abiotic stresses, particularly when they occur together. Ethylene (ET) serves as a central, integrative regulatory node controlling this by linking developmental programs to stress-responsive signaling networks. Advances at the molecular and systems levels have revealed that ET mediates the redistribution of metabolic resources via coordinated regulation of its synthesis, perception, and downstream signaling. The ETR (Ethylene Receptor)-CTR1 (Constitutive Triple Response 1)-EIN2 (Ethylene Insensitive 2)-EIN3(Ethylene Insensitive 3) signaling module lies at the core of this network, integrating multiple hormonal pathways. Through dynamic crosstalk with jasmonic acid (JA), salicylic acid (SA), abscisic acid (ABA), auxin (AUX), and gibberellins (GA), ET enables the fine-tuned coordination of growth inhibition, immune activation, and stress acclimation in response to environmental fluctuations. Processes such as induced systemic resistance, programmed cell death, and architectural plasticity further reinforce this regulatory framework, with ethylene-responsive transcription factors, including ERFs (ethylene responsive factor gene family) and WRKYs, acting as critical convergence points. Emerging insights into ACC (1-aminocyclopropane-1-carboxylic acid) -dependent signaling, chromatin remodeling, and tissue-specific regulation expand the functional scope of ET beyond traditional hormone paradigms. At the same time, the ability of pathogens to manipulate ET signaling underscores its dual role in both promoting immunity and facilitating susceptibility. By integrating molecular, physiological, and ecological perspectives, this review highlights ET as a central coordinator of plant stress resilience and growth optimization, providing a unifying framework for understanding how plants adapt to complex and dynamic environments. Full article

Severe acute pancreatitis (SAP) is a life-threatening inflammatory disorder characterized by high mortality and limited therapeutic options. Alginate oligosaccharide (AOS), a marine-derived bioactive polysaccharide, exhibits prebiotic, anti-inflammatory and antioxidant properties that are effective against various inflammatory diseases. In this study, a mouse model of SAP was established by intraperitoneal injection of cerulein (100 μg/kg) and lipopolysaccharide (5 mg/kg), and the mice were pretreated with AOS (200 mg/kg) by gavage for 4 consecutive weeks to explore the potential protective efficacy and underlying mechanisms. The results shown that AOS attenuated the severity of SAP, as evidenced by reduced serum amylase and lipase levels, as well as alleviated histopathological injury in both pancreatic and ileal tissues. AOS suppressed the overproduction of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) in serum, pancreas, and ileum at protein or mRNA levels. Moreover, AOS effectively diminished pancreatic and ileal inflammatory infiltration and oxidative stress in SAP mice, accompanied by inhibited the TLR4/MyD88/NF-κB pathway and activated the Nrf2/HO-1 antioxidant axis. Furthermore, AOS restored intestinal barrier integrity, as manifested by upregulated expression of tight junction proteins (claudin-1, occludin, ZO-1), reduced serum diamine oxidase, and decreased bacterial translocation from the gut to the pancreas. It was revealed by 16S rRNA sequencing that AOS ameliorated SAP-induced gut dysbiosis by restoring microbial diversity, normalizing the Firmicutes/Bacteroidetes ratio, enriching beneficial genera (Lactobacillus, Blautia), and enhancing cecal short-chain fatty acid (acetic, propionic, butyric acid) production. Collectively, our findings demonstrate that AOS exerts comprehensive protective effects against SAP through suppression of inflammatory signaling and oxidative stress, as well as restoring gut homeostasis. These results suggest that AOS may serve as a promising prebiotic-based nutritional strategy for the management of SAP. Full article

Background and Clinical Significance: Inflammatory myopericardial syndrome is an umbrella term recently introduced by the European Society of Cardiology, which encapsulates the overlap that exists in clinical practice between myocardial and pericardial disease. It has a heterogeneous aetiology and a broad spectrum of severity in terms of its clinical features. Toxoplasma gondii is a rare but recognised infectious cause of myopericarditis and is typically seen in immunocompromised individuals. Case Presentation: We present the case of a young, immunocompetent male, presenting with pleuritic chest pain following a recent flu-like illness. Investigations revealed an acute myocardial injury based on elevated troponin T levels, in the absence of ventricular dysfunction. Toxoplasma immunoserology was consistent with primary toxoplasma infection. The remainder of his viral panel was negative. There was prompt symptom improvement following commencement of treatment with colchicine and a non-steroidal anti-inflammatory agent. Cardiac magnetic resonance imaging post-discharge revealed findings consistent with prior myocarditis. Conclusions: This case is an example of the rare occurrence of toxoplasma myopericarditis in an immunocompetent individual. Cardiac MRI is an invaluable imaging modality used to evaluate myocardial function and tissue characteristics in patients presenting with inflammatory myopericardial syndrome. Full article

Objective: To evaluate the efficacy of NADPH oxidase 4 and miR-146a-5p in current treatment planning for ascending aortic aneurysms, independent of aortic diameter, and to develop protocols that will ensure the treatment of ascending aortic aneurysms, which pose a risk for aortic dissection, without complications. Methods: Patients who met the inclusion criteria and underwent surgery at Dr. Siyami Ersek Chest, Heart, and Vascular Surgery Training and Research Hospital for ascending aortic aneurysms and coronary artery disease between 2023 and 2024 were included in the study. This study was designed as a prospective study. Demographic, biochemical, radiological, and echocardiographic data were collected, and NOX4 mRNA and miR-146a-5p expressions were examined and compared in tissue samples. Results: The study was conducted on a total of 50 patients, with 25 patients in the aneurysm group and 25 patients in the control group. miR-146a-5p expression levels were found to be significantly decreased in the patient group compared to the control group (p = 0.001). When NOX4 mRNA expression levels were examined, no significant difference was found between the control and aneurysm groups. No correlation was found between NOX4 mRNA and miR-146a-5p levels (p = 0.764). When the relationship between ascending aorta diameter and both NOX4 mRNA and miR-146a-5p was examined, it was found that miR-146a-5p expression was negatively correlated with ascending aorta diameter (p = 0.036) and did not show a significant correlation with NOX4 mRNA levels (p = 0.318). A similar correlation was also found with ascending aorta length. The correlation of NOX4 mRNA and miR-146a-5p expression levels with age, gender, and ejection fraction was investigated separately. No significant correlation was found for all three variables. The optimum cut-off value to be used to separate the patient group from the control group using miR-146a-5p expression levels, as well as the sensitivity and specificity of miR-146a-5p expression levels when this cut-off value was used, was calculated using an ROC curve. Specificity for miR-146a-5p expression was found to be 88%, and sensitivity was found to be 66%. Conclusions: The study found promising results indicating that NOX4, shown to be a determinant of vascular oxidative stress, is not involved in the development of ascending aortic aneurysms; however, miR-146a-5p, which functions in the regulation of many inflammatory responses, including the regulation of NOX4 expression, may help prevent the development of ascending aortic aneurysms. Further studies aimed at elucidating the genetic and biochemical processes involved in aneurysm development suggest that miR-146a-5p could be a therapeutic target for preventing aneurysms. Full article

Immune checkpoint inhibitors (ICIs) show promise in cancer but have limited efficacy in ovarian cancer. This study compared combinations of the PD-1/PD-L1 inhibitor with anti-LAG-3, anti-TIM-3, or anti-CTLA-4 to identify the most effective regimen by assessing T-cell CD8/CD4 ratios and cytokine production. T cells isolated from ovarian cancer tissues (mean 3.8 × 10⁸ cells) were stimulated and treated with the PD-1/PD-L1 inhibitor alone or combined with anti-LAG-3, anti-TIM-3, or anti-CTLA-4. Flow cytometry measured CD8/CD4 expression; ELISAs quantified TNF-α, IL-6, and IFN-γ. Anti-PD-1 monotherapy produced no significant change in CD8/CD4 ratio (1.36 ± 0.43 vs. 1.41 ± 0.36) or cytokine levels. Combination therapy with PD-1/PD-L1 inhibitor + anti-CTLA-4 induced the largest increase in CD8/CD4 ratio (3.69 ± 1.33, p < 0.001) compared with PD-1/PD-L1 inhibitor alone; increases were smaller for PD-1/PD-L1 inhibitor + anti-LAG-3 (2.11 ± 0.63, p = 0.009) and PD-1/PD-L1 inhibitor + anti-TIM-3 (1.87 ± 0.48, p = 0.026). TNF-α rose significantly only with PD-1/PD-L1 inhibitor + anti-CTLA-4 (106.69 ± 45.42 pg/mL, p = 0.008), not with PD-1/PD-L1 inhibitor + anti-LAG-3 (72.46 ± 31.79 pg/mL, p = 0.231) or PD-1/PD-L1 inhibitor + anti-TIM-3 (82.06 ± 33.63 pg/mL, p = 0.074). IFN-γ increase was greater with PD-1/PD-L1 inhibitor + anti-CTLA-4 than with PD-1/PD-L1 inhibitor + anti-LAG-3 (p = 0.026). In conclusion, dual PD-1/PD-L1 and CTLA-4 blockade induced concomitant increases in T-cell CD8/CD4 proportions and cytokine levels compared to monotherapy or alternative ICI pairings. These descriptive ex vivo observations offer preliminary evidence of altered immune profiles, highlighting this combination as a candidate for further functional validation. Full article