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Byline: Caner Simsir, C. Hakan Gur In this study, a mathematical framework based on finite element method (FEM) capable of predicting temperature history, evolution of phases and internal stresses during thermal treatment of metals and alloys was developed. The model was integrated into the commercial FEA software MSC.Marc[R] by user subroutines. The accuracy of the model was verified by simulating the quenching of eccentrically drilled steel cylinders. Simulation results were justified via SEM observations and XRD residual stress measurements.

Byline: Pinar Karpuz, Caner Simsir, C. Hakan Gur Severe plastic deformation methods are of great interest in industrial forming applications, as they give rise to significant refinement in microstructures and improvements in mechanical and physical properties. In the 'equal channel angular pressing (ECAP)', which is the most common method for production of ultrafine grained bulk samples, very high plastic strains are introduced into the bulk material without any change in cross section. In this study, the plastic deformation behaviour of the materials subjected to ECAP was analysed by modelling the process with Msc.Marc finite element software. Various numerical experiments were carried out for the die angles of 90°, 120° and 150°, different friction conditions, and different round corners. To simplify the problem, plane strain condition and an isothermal system was assumed. Auto-remeshing was applied when the strains reached to very large values. The numerical results are in good agreement with those of the theoretical studies and data in literature.

Byline: C. Hakan Gur, ibrahim Cam This study aims to characterise as-quenched and tempered steels by the Magnetic Barkhausen Noise method, and to contribute to optimisation of heat treatment processes. Identical austenitisation and quenching procedures were applied to SAE 1040 and SAE 4140 specimens to eliminate the effect of grain size. Samples were tempered at 200C and 600C for 2 hours. Microstructures were characterised by metallographic examinations and hardness measurements. Amplitude, position and frequency spectrum of signals were evaluated using a commercial system. As the tempering temperature increases, in contrast to the reduction in hardness, magnetic response increases due to the enhancement of domain wall displacement.

Byline: C. Hakan Gur, B. Orkun Tuncer The aim of the study is to investigate the effect of quenching and tempering on sound velocity of steels, and to contribute to the nondestructive control and optimisation of the quenching/tempering systems. Disk-shaped specimens were prepared from AISI/SAE 4140 and AISI/SAE 5140 steel bars. All specimens were austenised and quenched identically to eliminate the effect of grain size on sound velocity, and a constant tempering time was chosen. Microstructures of the samples were characterised by metallographic examinations and hardness measurements. The reference values were obtained for as-quenched and tempered structures by measuring sound velocities for both longitudinal and transversal waves. The sound velocity is lowest in the as-quenched martensite, and however, increases after tempering as a function of tempering temperature. The changes in sound velocity can be explained primarily by differences in the elastic modulus that is affected by the degree of lattice distortion and misorientation in the microstructure.

Abstract Background Type 1 Diabetes Mellitus (T1DM) is the autoimmune disorder of destruction of β cells of pancreas, creating insulin deficiency condition, which leads to hyperglycemia, polyuria, polydipsia, ketoacidosis, and other metabolic disorder especially in children. Different genetic aspects and environmental factors are involved in pathophysiology of the disease. About 20 genes are associated with this disease in which the most common is the different combination of haplotype DRB1‐DQA1‐DQB1 present at HLA gene. At HLA‐DQB1, there are some SNPs which are associated with T1DM. In T1DM, there are number of biochemical, serological parameters which show some abnormalities leading to some complications. Methods Samples were subjected to all biochemical and serological techniques to get the measurement of concentration of glucose, lipid profile (cholesterol, triglycerides, and HDL and LDL cholesterol), urea, creatinine, albumin, insulin, anti‐insulin antibodies, C‐peptides, and leptin. All these values were compared with controls values and statistical analysis was also done on these values. At molecular level, two primers set which were allele specific at HLA‐DQB1, were used to amplify the SNPs, homozygous and heterozygous conditions were stated. Results PCR results for the studied population showed that most of samples have heterozygous condition for these SNPs of this allele specific region on HLA‐DQB1. Very few of them have homozygous state for it. Even in the control sample have the same conditions. Conclusion In Pakistan, there is dire need of studies about SNPs and haplotypes related to HLA‐DQB1 which show association with T1DM.

Previous literature has confirmed that pesticides are posing serious threats to the lives of human beings and animals alike because of their use in agricultural crops. Pesticides have also increased pollution in aquatic and terrestrial environment. In this study, chlorpyriphos degrading bacterial strains were isolated from pesticide contaminated agricultural soils by the selective enrichment method. Bacterial isolates were biochemically characterized for the strain identification. The effect of different environmental factors on optimum growth was also checked. These factors included pH, temperature, and concentration of pesticide. Isolated strains were also ribotyped for identification. Metal resistance profiling was performed for different heavy metals, that is, ZnSO4.7H2O (Zinc sulphate), CdCl2.H2O (Cadmium chloride), CuSO4 (Copper sulphate), and K2CrO4 (Potassium chromate). It was found that strains NW3O and NW3T were sensitive to cadmium except NR2 and NR4, which were resistant at the concentration of 100 and 200 µg ml-1. NR4, NW4 and NW3G were resistant to chromium upto the concentration of 100 µg ml-1, while NR2, NW3O and NW3T tolerated 200 µgml-1 of the metal. All the strains were resistant to zinc at different concentrations. NR2 showed maximum resistance to copper by showing growth on all concentrations of the metal. Thin layer chromatography was performed for the detection of different intermediates formed during the degradation of chlorpyrifos. Minimum inhibitory concentration of pesticide was estimated in M9 medium containing chlorpyriphos. The current study resulted in the isolation of efficient chlorpyrifos degrading strains with a wide range of pH and temperature tolerance that can utilize chlorpyrifos upto 700mg/L during lab scale degradation tests (growth on chlorpyrifos supplemented minimal agar and broth).

Mercuric chloride (HgCl 2 ) is extremely toxic to both humans and animals. It could be absorbed via ingestion, inhalation, and skin contact. Exposure to HgCl 2 can cause severe health effects, including damages to the gastrointestinal, respiratory, and central nervous systems. The purpose of this work was to explore if carvacrol (CRV) could protect rats lungs from damage caused by HgCl 2 . Intraperitoneal injections of HgCl 2 at a dose of 1.23 mg/kg body weight were given either alone or in conjunction with oral CRV administration at doses of 25 and 50 mg/kg body weight for 7 days. The study included biochemical and histological techniques to examine the lung tissue's oxidative stress, apoptosis, inflammation, and autophagy processes. HgCl 2 -induced reductions in GSH levels and antioxidant enzymes (SOD, CAT, and GPx) activity were enhanced by CRV co-administration. Furthermore, MDA levels were lowered by CRV. The inflammatory mediators NF-κB, IκB, NLRP3, TNF-α, IL-1β, IL6, COX-2, and iNOS were all reduced by CRV. When exposed to HgCl 2 , the levels of apoptotic Bax, caspase-3, Apaf1, p53, caspase-6, and caspase-9 increased, but the levels of antiapoptotic Bcl-2 reduced after CRV treatment. CRV decreased levels of Beclin-1, LC3A, and LC3B, which in turn decreased HgCl 2 -induced autophagy damage. After HgCl 2 treatment, higher pathological damage was observed in terms of alveolar septal thickening, congestion, edema, and inflammatory cell infiltration compared to the control group while CRV ameliorated these effects. Consequently, by preventing HgCl 2 -induced increases in oxidative stress and the corresponding inflammation, autophagy, apoptosis, and disturbance of tissue integrity in lung tissues, CRV might be seen as a useful therapeutic alternative., (© 2024 The Author(s). Environmental Toxicology published by Wiley Periodicals LLC.)

Lead acetate (PbAc) is a compound that produces toxicity in many tissues after exposure. Sinapic acid (SNP) possesses many biological and pharmacological properties. This study aimed to investigate the efficacy of SNP on the toxicity of PbAc in lung tissue. PbAc was administered orally at 30 mg/kg and SNP at 5 or 10 mg/kg for 7 days. Biochemical, genetic, and histological methods were used to investigate inflammatory, apoptotic, endoplasmic reticulum stress, and oxidative stress damage levels in lung tissue. SNP administration induced PbAc-reduced antioxidant (GSH, SOD, CAT, and GPx) and expression of HO-1 in lung tissue. It also reduced MDA, induced by PbAc, and thus alleviated oxidative stress. SNP decreased the inflammatory markers NF-κB, TNF-α and IL-1β levels induced by PbAc in lung tissue and exhibited anti-inflammatory effect. PbAc increased apoptotic Bax, Apaf-1, and Caspase-3 mRNA transcription levels and decreased anti-apoptotic Bcl-2 in lung tissues. SNP decreased apoptotic damage by reversing this situation. On the other hand, SNP regulated these markers and brought them closer to the levels of the control group. PbAc caused prolonged ER stress by increasing the levels of ATF6, PERK, IRE1α, GRP78 and this activity was stopped and tended to retreat with SNP. After evaluating all the data, While PbAc caused toxic damage in lung tissue, SNP showed a protective effect by reducing this damage., (© 2024 The Authors. Environmental Toxicology published by Wiley Periodicals LLC.)

Successful immunotherapy relies on triggering complex responses involving T cell dynamics in tumors and the periphery. Characterizing these responses remains challenging using static human single-cell atlases or mouse models. To address this, we developed a framework for in vivo tracking of tumor-specific CD8 + T cells over time and at single-cell resolution. Our tools facilitate the modeling of gene program dynamics in the tumor microenvironment (TME) and the tumor-draining lymph node (tdLN). Using this approach, we characterize two modes of anti-programmed cell death protein 1 (PD-1) activity, decoupling induced differentiation of tumor-specific activated precursor cells from conventional type 1 dendritic cell (cDC1)-dependent proliferation and recruitment to the TME. We demonstrate that combining anti-PD-1 therapy with anti-4-1BB agonist enhances the recruitment and proliferation of activated precursors, resulting in tumor control. These data suggest that effective response to anti-PD-1 therapy is dependent on sufficient influx of activated precursor CD8 + cells to the TME and highlight the importance of understanding system-level dynamics in optimizing immunotherapies., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objectives: In the present study, the potential protective effects of zingerone (ZNG) against sciatic nerve damage caused by sodium arsenite (SA), a common environmental pollutant, were evaluated by various biochemical, molecular, and histological methods., Materials and Methods: In the study, SA and ZNG were given to 35 male Sprague Dawley rats for 14 days. At the end of the period, the sciatic nerve tissues were taken and the markers involved in oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis were analyzed., Results: The data obtained showed that SA decreased glutathione (GSH) levels and increased malondialdehyde (MDA) levels in the sciatic nerve tissue. However, it was determined that these markers approached the control group levels due to the anti-oxidant properties of ZNG. While SA triggered endoplasmic reticulum stress and apoptosis pathways, ZNG suppressed them. Moreover, SA up-regulated inflammatory markers such as nuclear factor kappa-B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1β), and neuronal nitric oxide synthases (nNOS) in the sciatic nerves and caused neuro-inflammation and inhibited cell survival by suppressing serine/threonine-protein kinase 2 (Akt2) and forkhead box protein O1 (FOXO1) genes. It has also been shown histopathologically that SA causes degeneration in the sciatic nerves. In contrast, ZNG suppressed neuro-inflammation, activated Akt2/FOXO1 signaling, and repaired histological irregularities., Conclusion: In general, SA caused oxidative stress, inflammation, ER stress, and apoptosis in the sciatic nerves of rats, causing damage to the tissues, however, ZNG suppressed these pathways and protected the sciatic nerves from the destructive effect of SA., Competing Interests: The authors declare no conflicts of interest.

Objectives: This study aimed to investigate the effects of zingerone (ZNG) treatment on testicular toxicity in rats induced by sodium arsenite (SA)., Materials and Methods: In the study, five groups were formed (n=7) and the experimental groups were designated as follows; Vehicle group, ZNG group, SA group, SA+ZNG 25 group, and SA+ZNG 50 group. While SA was administered orally to rats at 10 mg/kg/bw, ZNG was given to rats orally at 25 and 50 mg/kg/bw doses for 14 days., Results: As a result of the presented study, an increase was observed in the MDA contents of the testicular tissue of the rats administered SA, while significant decreases were observed in GSH levels, SOD, CAT, and GPx activities. The mRNA transcript levels of the pro-inflammatory genes NF-κB, TNF-α, IL-1β, and IL-6 were triggered after SA administration. Additionally, SA administration caused inflammation by increasing RAGE, NLRP3, and JAK-2/STAT3 gene expression. Moreover, endoplasmic reticulum (ER) stress occurred in the testicular tissues of SA-treated rats and thus ATF-6, PERK, IRE1, and GRP78 genes were up-regulated. SA caused apoptosis by up-regulating Bax and Caspase-3 expressions and inhibiting Bcl-2 expression in testicles. SA caused histological irregularities in the testicles, resulting in decreased sperm quality., Conclusion: ZNG treatment reduced SA-induced oxidative stress, ER stress, inflammation, apoptosis, and histological irregularities in the testicles while increasing sperm quality. As a result, it was observed that ZNG could alleviate the toxicity caused by SA in the testicles., Competing Interests: Authors declare that there are no conflicts of interest .

Cancer mortality primarily stems from metastatic recurrence, emphasizing the urgent need for developing effective metastasis-targeted immunotherapies. To better understand the cellular and molecular events shaping metastatic niches, we used a spontaneous breast cancer lung metastasis model to create a single-cell atlas spanning different metastatic stages and regions. We found that premetastatic lungs are infiltrated by inflammatory neutrophils and monocytes, followed by the accumulation of suppressive macrophages with the emergence of metastases. Spatial profiling revealed that metastasis-associated immune cells were present in the metastasis core, with the exception of TREM2+ regulatory macrophages uniquely enriched at the metastatic invasive margin, consistent across both murine models and human patient samples. These regulatory macrophages (Mreg) contribute to the formation of an immune-suppressive niche, cloaking tumor cells from immune surveillance. Our study provides a compendium of immune cell dynamics across metastatic stages and niches, informing the development of metastasis-targeting immunotherapies., Significance: Temporal and spatial single-cell analysis of metastasis stages revealed new players in modulating immune surveillance and suppression. Our study highlights distinct populations of TREM2 macrophages as modulators of the microenvironment in metastasis, and as the key immune determinant defining metastatic niches, pointing to myeloid checkpoints to improve therapeutic strategies. This article is featured in Selected Articles from This Issue, p. 2489., (©2023 American Association for Cancer Research.)

This study aimed to determine the potential protective effects of chrysin (CHR) on experimental cadmium (Cd)-induced lung toxicity in rats. To this end, rats were divided into five groups; Control, CHR, Cd, Cd + CHR25, Cd + CHR50. In the study, rats were treated with CHR (oral gavage, 25 mg/kg and 50 mg/kg) 30 min after giving Cd (oral gavage, 25 mg/kg) for 7 consecutive days. The effects of Cd and CHR treatments on oxidative stress, inflammatory response, ER stress, apoptosis and tissue damage in rat lung tissues were determined by biochemical and histological methods. Our results revealed that CHR therapy for Cd-administered rats could significantly reduce MDA levels in lung tissue while significantly increasing the activity of antioxidant enzymes (SOD, CAT, GPx) and GSH levels. CHR agent exerted antiinflammatory effect by lowering elevated levels of NF-κB, IL-1β IL-6, TNF-α, RAGE and NRLP3 in Cd-induced lung tissue. Moreover CHR down-regulated Cd-induced ER stress markers (PERK, IRE1, ATF6, CHOP, and GRP78) and apoptosis markers (Caspase-3, Bax) lung tissue. CHR up-regulated the Bcl-2 gene, an anti-apoptotic marker. Besides, CHR attenuated the side effects caused by Cd by modulating histopathological changes such as hemorrhage, inflammatory cell infiltration, thickening of the alveolar wall and collagen increase. Immunohistochemically, NF-κB and Caspase-3 expressions were intense in the Cd group, while these expressions were decreased in the Cd + CHR groups. These results suggest that CHR exhibits protective effects against Cd-induced lung toxicity in rats by ameliorating oxidative stress, inflammation, apoptosis, endoplasmic reticulum stress and histological changes., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)