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Abstract Organoids as self-organized structure derived from stem cells can recapitulate the function of an organ in miniature form which have developed great potential for clinical translation, drug screening and personalized medicine. Nevertheless, the majority of patient-derived organoids (PDOs) are currently being cultured in the basement membrane matrices (BMMs), which are constrained by xenogeneic origin, batch-to-batch variability, cost, and complexity. Besides, organoid culture relies on biochemical signals provided by various growth factors in the composition of medium. We propose sodium alginate hydrogel scaffold in addition to the fibroblast conditioned medium (FCM)-enriched culture medium that is inexpensive and easily amenable to clinical applications for the culture of bladder cancer PDOs. PDOs grown in sodium alginate and FCM based medium have proliferation potential, growth rate, and gene expression that are similar to PDOs cultured in BME. According to the results, sodium alginate has substantial mechanical properties and reduces variance in early passage bladder tumor organoid cultures collected from patients. Furthermore, using FCM based medium as an alternative solution to eliminate some essential growth factors can be considered, especially for low-resource situation and develop cost effective tumor organoids.

Plant stresses caused by phytopathogenic bacteria are categorized into biotic stresses. The study aimed to perform a meta-analysis of A. thaliana transcriptomic data in response to infection by P. syringae and P. syringae pv. maculicola. The gene expression and transcription factors (TFs) of A. thaliana infected by the bacteria were investigated using published RNA-Seq data. Also, critical factors, including hub genes, protein-protein interaction (PPI), and micro RNAs (miRNAs), were analyzed. A total number of 22 biological pathways were significantly enriched with up-/down-regulated differentially expressed genes (DEGs) in the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Also, 39 TFs of A. thaliana were altered during the bacterial infection. Moreover, 5034 DEGs were significantly different from non-stressed plants, of which 2291 and 2743 DEGs were up- and down-regulated, respectively. The expression of genes related to stress response, cellular process, metabolic process, and stimulus response was up-regulated in the bacteria-infected plant. In contrast, the down-regulation of genes involved in the cellular and biosynthesis processes was observed. Regarding molecular function, 412 genes associated with kinase, catalase, and oxidoreductase activities were up-regulated in the bacteria-infected plants, while down-regulation of hydrolase and transferase activity genes was observed. The PPI network showed 107 nodes and 189 edges. The most important hubs genes included MYC2, WRKY40, WRKY33, and other genes. Moreover, the total number of 41 miRNA families was determined during the A. thaliana-bacterium interaction. Infection of A. thaliana by P. syringae and P. syringae pv. maculicola induced the expression of some stress-responsive genes and pathways among which some defense-related hub genes were identified. The results provide a clearer understanding of the strategies applied to program defense pathways in bacterial infection of A. thaliana.

Abstract Potatoes (Solanum tuberosum L.) are a significant food crop cultivated around the world. Caffeic acid (CA) can enhance plant growth by promoting antioxidant activity and stimulating root development, contributing to overall plant health and vigor. Cobalt sulfate (CoSO4) boosts plant growth by promoting nitrogen (N) fixation, healthier root development, and chlorophyll synthesis, enhancing photosynthesis and overall plant health. Nanoparticle-coated urea (NPCU) improves nutrient uptake, promoting plant growth efficiency and reducing environmental impact. This study investigates the effects of combining CA, CoSO4, and NPCU as amendments on potatoes with and without NPCU. Four treatments, control, 20 μM CA, 0.15 mg/L CoSO4, and 20 μM CA + 0.15 mg/L CoSO4 with and without NPCU, were applied in four replications using a completely randomized design. Results demonstrate that the combination of CA + CoSO4 with NPCU led to an increase in potato stem length (~ 6%), shoot dry weight (~ 15%), root dry weight (~ 9%), and leaf dry weight (~ 49%) compared to the control in nutrient stress. There was a significant rise in chlorophyll a (~ 27%), chlorophyll b (~ 37%), and total chlorophyll (~ 28%) over the control under nutrient stress also showed the potential of CA + CoSO4 with NPCU. In conclusion, the findings suggest that applying CA + CoSO4 with NPCU is a strategy for alleviating potato nutrient stress.

IntroductionAdrenergic receptors regulate metabolic, cardiovascular, and immunological functions in response to the sympathetic nervous system. The effect of β2-adrenergic receptor (AR) as a high expression receptor on different subpopulations of T cells is complex and varies depending on the type of ligand and context. While traditional β2-AR agonists generally suppress T cells, they potentially enhance IL-17A production by Th17 cells. The effects of pharmacological drugs that count as biased agonists of AR like nebivolol are not completely understood. We investigated the impact of nebivolol on human memory CD4+ T (Th1, Th2, Th17) cells and polarized naive Th17 cells, highlighting its potential for IL-17A suppression via a non-canonical β2-AR cell signaling pathway.MethodsThe effects of nebivolol were tested on healthy human peripheral blood mononuclear cells, purified memory Th cells, and polarized naive Th17 cells activated with anti-CD3/anti-CD28/anti-CD2 ImmunoCult reagent. IFN-γ, IL-4, and IL-17A, which are primarily derived from Th1, Th2, and Th17 cells, respectively, were quantified by ELISA and flow cytometry. IL-10 was measured by ELISA. Gene expression of RORC, ADRB1, ADRB2, and ADRB3 was evaluated by qPCR. The ADRB2 gene was knocked out in memory Th cells using CRISPR/Cas9. Protein expression of phosphorylated serine133-CREB and phosphorylated NF-κB p65 was assessed by Western blot. Proliferation was assessed by fluorescent dye loading and flow cytometry.ResultsNebivolol treatment decreased IL-17A and IFN-γ secretion by activated memory Th cells and elevated IL-4 levels. Nebivolol reduced the proportion of IL-17A+ Th cells and downregulated RORC expression. Unlike the β2-AR agonist terbutaline, nebivolol inhibited the shift of naive CD4+ T cells toward the Th17 phenotype. IL-10 and the proliferation index remained unchanged. Nebivolol-treated β2-knockout memory Th cells showed significant inhibition of β2-AR-mediated signaling, evidenced by the absence of IL-17A suppression compared to controls. Phosphorylation of the NF-κB p65 subunit was inhibited by nebivolol, but CREB phosphorylation was not changed, suggesting a selective transcriptional control.ConclusionsThe findings demonstrate that nebivolol acts through a β2-AR-mediated signaling pathway, as a distinctive anti-inflammatory agent capable of selectively shifting Th17 cells and suppressing the phosphorylation of NF-κB. This highlights nebivolol’s potential for therapeutic interventions in chronic autoimmune conditions with elevated IL-17A levels.

While met with initial and ground-breaking success targeting blood borne cancers, cellular immunotherapy remains significantly hindered in the context of solid tumors by the tumor microenvironment. Focused ultrasound, in conjunction with microbubbles, has found tremendous potential as a targeted and local drug/gene delivery technique for cancer therapy. The specific immunomodulating effects of this technique on immune cells, including T-cells, remain unexplored. Here, with freshly isolated human immune cells, we examine how focused ultrasound can viably modulate immune cell membrane permeability and influence the secretion of over 90 cytokines, chemokines and other analytes relevant to a potent immune response against cancer. We determine that microbubble-mediated focused ultrasound modulates the immune cell secretome in a time-dependent manner – ranging in ~0.1-3.6-fold changes in the concentration of a given cytokine compared to sham controls over 48 hours post-treatment (e.g. IL-1β, TNF-α, CX3CL1, CCL21). Further, we determine the general trend of a negative correlation between secreted cytokine concentration and viable ultrasound-assisted membrane permeability with negligible loss of cell viability. Taken together, the data presented here highlights the potential of microbubble-mediated focused ultrasound to viably enhance T-cell permeability and modulate key pro-immune pathways, offering a novel approach to augment targeted cellular therapies for solid tumors.

Considering the different side effects of the long-time conventional anti-rheumatic drugs prescribed for the treatment of rheumatoid arthritis, numerous studies have focused on herbal medicines to reduce inflammation in autoimmune diseases. Although the beneficial properties of evening primrose on rheumatoid arthritis have been determined, the results of the studies have not been systematically reported. The present review has investigated the effects of evening primrose on rheumatoid arthritis systematically. We searched the following electronic databases until March 2023: PubMed, the Cochrane Library, the China National Knowledge Infrastructure, Scopus, ProQuest, Google Scholar electronic databases, allied and complementary medicine database (AMED), and scientific information database (SID) databases for relevant studies. We excluded non-English articles and those not meeting our criteria. We chose all of the correlated original clinical, animal, and in vitro studies. Each article was assessed critically for the possible risk of bias. Thirteen articles were analyzed. Animal and in vitro research confirmed the desired effects of evening primrose on clinical, inflammatory, oxidative, and immunologic factors in rheumatoid arthritis. Also, the results of clinical studies showed the change and improvement of inflammatory and oxidative biomarkers in rheumatoid arthritis. Evening primrose could control rheumatoid arthritis in multiple ways such as decreasing inflammation, inhibiting oxidative stress, and modulating the immune system. This article provides convincing evidence to support the efficacy of evening primrose in rheumatoid arthritis and explains the significance of future clinical trials. Further large-scale high-quality randomized controlled trials (RCTs) assessing the efficacy of evening primrose on rheumatoid arthritis as a primary outcome variable are recommended.

Potassium (K+) transporters, particularly high-affinity K+ transporters (HKT), are crucial for plant growth and abiotic stress response. These transporters regulate Na+ and K+ balance in the cells to prevent sodium toxicity in plant tissues. Although HKT genes have been extensively studied in various crops, there is a deficiency in their characterization and understanding of their role in wheat, particularly regarding their involvement in adaptive response to environmental stresses like salinity. In this study, several bioinformatics tools including web-based platforms and software applications were employed to identify, characterize and localize HKTs genes within the wheat genome. A greenhouse trial was also conducted to investigate the mRNA expression levels of some of the significant salt-responsive genes in wheat seedlings grown under different concentrations of NaCl (0, 200, and 400 mM). Genome-wide analysis, resulted in identification of 35 TaHKTs that are unevenly distributed on ten chromosomes. The majority of these transporters are localized on plasma membrane. Analysis of promoter regions showed that most of the TaHKT genes have abundant cis-elements that involved in hormones and abiotic stress responses. Gene expression analysis indicated a significant upregulation of TaHKT6 and TaSOS1 genes were found in wheat seedlings treated with 400 mM NaCl. Expression levels of TaNHX1, TaNHX2 and TaTVP1 genes were also higher in 200 mM and 400 mM NaCl-treated plants when compared to non-stressed plants. Overall, the results provide further evidence for the role of the TaHKT in wheat's stress response to elevated salt levels and pave the way for further functional research in K+ transporters in plants.

Polyamines (PAs) are small molecules that exist in all living organisms. They play a crucial role in various physiological processes in plants, including growth, development and responses to stress. Cold stress is one of the major abiotic stresses that has a negative effect on the growth, development and productivity of plants. In the present study, exogenous PAs (Spd, Put and distilled water as control) were efficiently used in mitigating of stress effects in two contrasting wheats cultivars (‘Mihan’ and ‘Rakhshan’) grown under cold conditions. Shoot and root dry weight, chlorophyll, carotenoid, proline contents, catalase and ascorbate peroxidase activities were improved by PA application (10 mg L−1 foliar spray) in the cold-stressed plants. The gene expression analysis with RT-qPCR showed transcriptional variation of selected genes in response to cold condition and PAs. Under cold condition the expression levels of genes responsible for the synthesis (TaADC, TaSAMDC, TaSPDS) and catabolism (TaPAO11–7B TaPAO11–7D) increased in both cultivars, but at higher level in the tolerant one. These results reveal a significant role of PAs under cold acclimation in wheat leaves.

Abstract Background Monosodium glutamate (MSG) is a food ingredient that is increasingly used commercially. MSG leads to oxidative stress, consequently suppressing steroid hormone production that causes defects in male reproductive system. This study aimed to evaluate the effect of L-carnitine as an antioxidant on testicular damage in MSG-induced male rats. Methods Sixty adult male Spargue-Dawley rats were randomly divided into six groups of ten as follows: control (water), sham (normal saline), L-carnitine (200 mg/kg b.w), MSG (3 g/kg b.w), MSG + L-carnitine 100 (3 g/kg b.w of MSG and 100 mg/kg b.w of L-carnitine), and MSG + L-carnitine 200 (3 g/kg b.w of MSG and 200 mg/kg b.w of L-carnitine). The treatment was administered by oral gavage for six months. Serum levels of Malondialdehyde (MDA), Total Anti-oxidant Capacity (TAC), LH, FSH, testosterone, and mRNA expressions of Star, Cyp11a1, and Hsd17b3 genes, and histological and stereological changes were assessed. Results L-carnitine led to a significant decrease in the level of MDA and a significant rise in the serum levels of TAC, LH, FSH, and mRNA expression of Star and Cyp11a1 compared to the MSG group (p

Introdution: The aim of the present study was to investigate the efficacy of cognitive-behavioral therapy and hope therapy on quality of life, life expectancy, resiliency in patients with thalassemia who went to Bushehr Thalassemia Therapy Center in 2017. Methods: The study was experimental and census was used. It consisted of 21 patients with thalassemia in Bushehr province who were randomly divided into two experimental groups of cognitive-behavioral therapy and hope therapy and one control group. To conduct the research, World Health Organization Quality of Life Questionnaire, Life Expectancy Questionnaire by Schneider and Connor–Davidson Resilience Scale were used. All the patients completed the questionnaires before and after the intervention. In order to analyze data, analysis of covariance was performed. Results: In the therapy group, the majority of the patients were female, single and held a bachelor's degree. Similarly, in the control group, the highest proportion belonged to females and married patients, whereas a minority held a bachelor's degree. Compared with the control group, the findings of analysis of covariance revealed that both cognitive-behavioral therapy and hope therapy were significantly effective (p-value

Recently, food safety and cold chain food have been closely related to the epidemic. The party and the state have intensified efforts to solve food safety problems and prevent possible epidemic risks. China has issued a series of policies and plans to strengthen food safety supervision to improve the food safety policy system. To our knowledge, little work has studied policy problems of food safety with in-depth quantitative analysis for an extended period. In accordance with the different national policies and regulations for food safety, this paper fills the gap by analyzing the policies and comparing the central and local policies issued in China from 2007–2022. In addition, the Latent Dirichlet Allocation (LDA) topic model and K-Means clustering model are constructed to analyze the content of food safety policies and identify hot topics. Finally, a quantitative analysis of China’s food safety policies is made from four aspects: the number of policy release years, the distribution area, the range of action, and the affiliated institutions. The results show that: (a) there is a partial surge in food safety policies issued in 2007, 2011, and 2017; (b) the local food safety policy has a high inheritance to the central policy content, and the trends of annual publication number are highly consistent; (c) the innovation of different policy contents in the region have their own characteristics; (d) the proportion of compulsory and capacity policies is much more significant than that of other types of policies. This paper provides some novel insights into food safety policies.

چکیده زمینه و هدف: خروج از بیمارستان بدون اطلاع پزشک و پرسنل یا به عبارتی فرار از بیمارستان، یکی از چالش های بزگ نظام سلامت محسوب می شود چرا که می تواند باعث ایجاد هزینه های اقتصادی برای سیستم و زیان جانی برای بیمار گردد . هدف از این مطالعه بررسی عوامل موثر در فرار بیماران و بار مالی ناشی از آن در یکی از بیمارستان های عمومی شهر بوشهر می‌باشد. مواد و روش‌ها: این پژوهش یک مطالعه توصیفی- مقطعی است که در یکی از بیمارستان‌های شهر بوشهر انجام گرفته است. در این مطالعه، اطلاعات بیماران با روش سرشماری و با استفاده از یک چک لیست استخراج گردیده است. این چک لیست حاوی سئوالات دموگرافیک، بالینی و اقتصادی می‌باشد. تحلیل داده ها از آمار توصیفی در محیط نرم افزار spss نسخه 25 بهره گرفته شد. یافته‌ها: بنابر نتایج حاصل از آنالیزهای آماری نرخ فرار از بیمارستان0018/0 برآورد می‌شود. یعنی به طور میانگین، هر ماه 6 نفر از بیماران فرار کرده‌اند. زیان مالی وارد شده به بیمارستان شهدای خلیج فارس بوشهر بابت فرار بیماران در سالهای 1396 و 1397 بالغ بر ده میلیارد ریال بوده است که سهم بیمارانی که بیمه داشتند در آن بیشتر از افراد فاقد بیمه بوده است. نتیجه گیری: نرخ فرار در بیمارستان مورد پژوهش کم بود. با این حال به دلیل این که فرار علاوه بر زیان مالی قابل توجهی که به بیمارستان ها وارد می‌کند می‌تواند مشکلاتی را برای خود بیماران، خانواده‌‌‌‌هایشان و نیز جامعه ایجاد کند، لازم است تلاش ها در جهت کاهش وقوع این معضل توسط مدیران به کار گرفته شود.

Salinity stress is one of the major plant growth-limiting factors in agriculture. It causes ionic imbalance, thus decrease the growth and yield attributes of crops especially wheat. Seedling stage is considered as one of the most sensitive stages under salinity stress. Survival of seeds at seedling stage can overcome the adverse impacts of salinity stress to some extent. Selection of salt tolerant varieties in seedling stage is considered as an effective strategy. Hence, current study was conducted to examine the seed germination responses of four wheat varieties under different levels of salinity. The wheat varieties such as 'Rakhshan', 'Sirvan', 'Pishgam' and 'Heidari' were grown and four salinity levels of 0, 4, 8 and 12 dS/m were applied under completely randomized design. The varieties such as 'Sirvan', 'Rakhshan' and 'Heidari' showed significant response for germination compared to 'Pishgam' at 12 dS/m salinity. Furthermore, the variety 'Rakhshan' showed significantly higher germination rate (20.3%), higher root length (33.4%) and higher shoot length (84.3%) than 'Pishgam', 'Sirvan' and 'Sirvan' respectively. However, contrasting results were obtained for dry weight of seedlings where 12.2% increase was observed in 'Pishgam' over 'Rakhshan' at 12 dS/m salinity that might be due to higher capability to uptake of Na and Cl ions. In conclusion, 'Rakhshan' wheat variety proved to be the most salinity tolerant as it grew better under saline soil conditions. More investigations at field level are recommended to declare 'Rakhshan' as salinity tolerant cultivar.

Tabaristan was conquered during Al-Mansour (158-137 AH) after one and a half centuries of resistance to the Arabs. From then on Tabaristan was managed by Abbasid Governors. Our knowledge of the governors of the province is primarily based on historical sources and Arab-Tabaristan coins. Despite the information that is available from Abbasid governors in various sources, determining the precise timing of each and every one of them due to the inconsistency of written texts with numismatic evidences is a challenge for the researchers. The purpose of this research is to answer this question that what are the reasons of the difference between the information extracted from the sources and from the Abbasid coins in Tarbristan? To answer this question, a descriptive-analytical approach has been used. The results of the studies indicate that the political and social turmoil during this period, due to the dissatisfaction of the local people and Ispahbads in the region, as well as the administrative hierarchy of the Abbasids, led to the permanent dismissal and appointment of governors by the Abbasid Caliphs, which could be a reason for incomplete or sometimes mistaken reporting in historical texts. Therefore, coins can be considered as the most important resources and means for establishing the chronology of the rule of Abbasid governors. As the result of present study, in addition to finding an answer to the reasons for the heterogeneity in the chronology of the government of governors, a new and accurate list of the governors in Tabaristan is presented.

Amine oxidases (AOs) including copper containing amine oxidases (CuAOs) and FAD-dependent polyamine oxidases (PAOs) are associated with polyamine catabolism in the peroxisome, apoplast and cytoplasm and play an essential role in growth and developmental processes and response to biotic and abiotic stresses. Here, we identified PAO genes in common wheat (Triticum aestivum), T. urartu and Aegilops tauschii and reported the genome organization, evolutionary features and expression profiles of the wheat PAO genes (TaPAO). Expression analysis using publicly available RNASeq data showed that TaPAO genes are expressed redundantly in various tissues and developmental stages. A large percentage of TaPAOs respond significantly to abiotic stresses, especially temperature (i.e. heat and cold stress). Some TaPAOs were also involved in response to other stresses such as powdery mildew, stripe rust and Fusarium infection. Overall, TaPAOs may have various functions in stress tolerances responses, and play vital roles in different tissues and developmental stages. Our results provided a reference for further functional investigation of TaPAO proteins.

Equisetum telmateia (Equisetaceae) seems to have anti inflammatory and antioxidant properties. In the present study, the neuroprotective effects of organic and inorganic silica were investigated on spinal cord alpha motoneuron of rats after injury of sciatic nerve. After highly compression of sciatic nerve in 42 Wistar rats, the injured rats were divided into sham (n= 6) and two experimental groups which each were divided into 3 subgroups (n= 6). The first subgroups received 3, 6 or 9 injections (15 mg/kg/injection, ip) of horse tail extract and the second subgroups received 3, 6 or 9 injections (6 mg/kg/injection, ip) of sodium meta silicate, respectively. The first injection was made after sciatic nerve injury and the others by 72 hours intervals. After a month, the rats were sacrificed and their spinal cord lumber segment sampled, processed for histological preparation and analyzed stereologicaly (the dissector technique) for estimation of numerical density of alpha motoneurons. The results showed significant decrease in the numerical density of alpha motoneurons in shams (p< 0.05) and no significant differences between experimental and control groups. This may suggest the neuroprotective effects of silica on the survival of alpha motoneurons.