Search Results (47,303)

Lichens have developed numerous adaptations to optimize their survival in various environmental conditions, largely by producing secondary compounds by the fungal partner. They often have antibiotic properties and are involved in protection against intensive UV radiation, pathogens, and herbivores. To contribute to the knowledge of the arsenal of secondary compounds in a crustose lichen species, we sequenced and assembled the genome of Toniniopsis dissimilis, an indicator of old-growth forests, using Oxford Nanopore Technologies (ONT, Oxford, UK) long reads. Our analyses focused on biosynthetic gene clusters (BGCs) and specifically on Type I Polyketide (T1PKS) genes involved in the biosynthesis of polyketides. We used the comparative genomic approach to compare the genome of T. dissimilis with six other members of the family Ramalinaceae and twenty additional lichen genomes from the database. With only six T1PKS genes, a comparatively low number of biosynthetic genes are present in the T. dissimilis genome; from those, two-thirds are putatively involved in melanin biosynthesis. The comparative analyses showed at least three potential pathways of melanin biosynthesis in T. dissimilis, namely via the formation of 1,3,6,8-tetrahydroxynaphthalene, naphthopyrone, or YWA1 putative precursors, which highlights its importance in T. dissimilis. In addition, we report the occurrence of genes encoding ribosomally synthesized and posttranslationally modified peptides (RiPPs) in lichens, with their highest number in T. dissimilis compared to other Ramalinaceae genomes. So far, no function has been assigned to RiPP-like proteins in lichens, which leaves potential for future research on this topic. Full article

The rational allocation of land resources is crucial to ensuring human well-being, livelihood, and survival. The study of Production-Living-Ecological Space (PLES) provides new perspectives on land resource allocation. However, few studies have assessed the feasibility of PLES optimization in ecological transition zones. For this study, using the composite functional space classification method, a classification and functional utility scoring system were constructed. Various methods, including dynamic attitude, transfer matrix, and spatial autocorrelation, were employed to characterize the evolution of the quantity and quality of PLES in the Hexi Corridor. Moreover, the mechanisms driving these changes were explored using a geodetector. Our findings revealed that: (1) The distribution of Production-Ecological Space (PES) is higher in the west and south and lower in the east and north. Production-Living Space (PLS) is scattered. Ecological-Production Space (EPS) is mostly distributed in the south or west, whereas Ecological Space (ES) is mainly located in the north and west of the Hexi Corridor. (2) From 1980 to 2020, the area of PES and PLS increased by 2037.84 km² and 673 km², respectively; the area of EPS was relatively stable, and the area of ES decreased by 2523.06 km². (3) The evolution of PLES quality indicated that the high functional utility area of PES and PLS was roughly the same as the expanded functional utility area, whereas the expanded functional utility area of EPS and ES is similar to the median functional utility area. (4) The spatiotemporal evolution of PLES is closely linked to natural, economic, and social factors. Full article

Neurotrophins, particularly brain-derived neurotrophic factor (BDNF), act as key regulators of neuronal development, survival, and plasticity. BDNF is necessary for neuronal and functional maintenance in the striatum and the substantia nigra, both structures involved in the pathogenesis of Parkinson’s Disease (PD). Depletion of BDNF leads to striatal degeneration and defects in the dendritic arborization of striatal neurons. Activation of tropomyosin receptor kinase B (TrkB) by BDNF is necessary for the induction of long-term potentiation (LTP), a form of synaptic plasticity, in the hippocampus and striatum. PD is characterized by the degeneration of nigrostriatal neurons and altered striatal plasticity has been implicated in the pathophysiology of PD motor symptoms, leading to imbalances in the basal ganglia motor pathways. Given its essential role in promoting neuronal survival and meditating synaptic plasticity in the motor system, BDNF might have an important impact on the pathophysiology of neurodegenerative diseases, such as PD. In this review, we focus on the role of BDNF in corticostriatal plasticity in movement disorders, including PD and dystonia. We discuss the mechanisms of how dopaminergic input modulates BDNF/TrkB signaling at corticostriatal synapses and the involvement of these mechanisms in neuronal function and synaptic plasticity. Evidence for alterations of BDNF and TrkB in PD patients and animal models are reviewed, and the potential of BDNF to act as a therapeutic agent is highlighted. Advancing our understanding of these mechanisms could pave the way toward innovative therapeutic strategies aiming at restoring neuroplasticity and enhancing motor function in these diseases. Full article

Acute myeloid leukemia (AML) has a poor survival rate for both pediatric and adult patients due to its frequent relapse. To elucidate the bioenergetic principle underlying AML relapse, we investigated the transcriptional regulation of mitochondrial–nuclear dual genomes responsible for metabolic plasticity in treatment-resistant blasts. Both the gain and loss of function results demonstrated that NFκB2, a noncanonical transcription factor (TF) of the NFκB (nuclear factor kappa-light-chain-enhancer of activated B cells) family, can control the expression of TFAM (mitochondrial transcription factor A), which is known to be essential for metabolic biogenesis. Furthermore, genetic tracking and promoter assays revealed that NFκB2 is in the mitochondria and can bind the specific “TTGGGGGGTG” region of the regulatory D-loop domain to activate the light-strand promoter (LSP) and heavy-strand promoter 1 (HSP1), promoters of the mitochondrial genome. Based on our discovery of NFκB2′s novel function of regulating mitochondrial–nuclear dual genomes, we explored a novel triplet therapy including inhibitors of NFκB2, tyrosine kinase, and mitochondrial ATP synthase that effectively eliminated primary AML blasts with mutations of the FMS-related receptor tyrosine kinase 3 (FLT3) and displayed minimum toxicity to control cells ex vivo. As such, effective treatments for AML must include strong inhibitory actions on the dual genomes mediating metabolic plasticity to improve leukemia prognosis. Full article

Introduction: One of the most important prognostic factors in non-small cell lung cancer (NSCLC), a condition with a high mortality rate, is the presence of mediastinal lymph node metastases alongside distant metastases. The aim of this study was to evaluate the prognostic value of selected parameters of N2 stage NSCLC with a special focus on lymph node ratio (LNR). Material: The study included 163 patients (61 women and 102 men) operated on due to NSCLC, postoperatively diagnosed as stage N2. The age of the patients ranged from 38 to 82 years (mean age: 62.4 years). The effects of the following factors on clinical data and survival rate were assessed: N1 stage, total number of all metastatic nodes, LNR and LNR N2 ratios, and the presence of skip, single- or multistation metastases. Results: Univariate analysis showed patient survival to be correlated with LNR and LNR N2 ratios, single/multistation metastases, and the number of nodes involved in metastasis. A multivariate model based on patient clinical data found nicotine dependence (p = 0.013), LNR > 0.26 (p = 0.004), and Charlson Comorbidity Index (CCI) value > 3 (p = 0.014) to be independent adverse prognostic factors in this group. Conclusions: LNR ratio is a significant cancer disease-derived independent prognostic factor for patients with postoperative N2 stage NSCLC. In addition, smoking and comorbidities also appear to have prognostic value. Full article

Dynamic climate changes pose a significant challenge for plants to cope with numerous abiotic and biotic stressors of increasing intensity. Plants have evolved a variety of biochemical and molecular defense mechanisms involved in overcoming stressful conditions. Under environmental stress, plants generate elevated amounts of reactive oxygen species (ROS) and, subsequently, modulate the activity of the antioxidative enzymes. In addition, an increase in the biosynthesis of important plant compounds such as anthocyanins, lignin, isoflavonoids, as well as a wide range of low molecular weight stress-related proteins (e.g., dehydrins, cyclotides, heat shock proteins and pathogenesis-related proteins), was evidenced. The induced expression of these proteins improves the survival rate of plants under unfavorable environmental stimuli and enhances their adaptation to sequentially interacting stressors. Importantly, the plant defense proteins may also have potential for use in medical applications and agriculture (e.g., biopesticides). Therefore, it is important to gain a more thorough understanding of the complex biological functions of the plant defense proteins. It will help to devise new cultivation strategies, including the development of genotypes characterized by better adaptations to adverse environmental conditions. The review presents the latest research findings on selected plant defense proteins. Full article

We consider two different time fractional telegrapher’s equations under stochastic resetting. Using the integral decomposition method, we found the probability density functions and the mean squared displacements. In the long-time limit, the system approaches non-equilibrium stationary states, while the mean squared displacement saturates due to the resetting mechanism. We also obtain the fractional telegraph process as a subordinated telegraph process by introducing operational time such that the physical time is considered as a Lévy stable process whose characteristic function is the Lévy stable distribution. We also analyzed the survival probability for the first-passage time problem and found the optimal resetting rate for which the corresponding mean first-passage time is minimal. Full article

Customer relationship management (CRM) has become increasingly important as a result of the pressure organizations are under to remain competitive. CRM has been and is widely promoted as essential to a company’s ability to survive. According to this study, CRM is more than just a computer program or software package. We believe that for organizations to use CRM effectively, it must be viewed from a strategic point of view. Therefore, this study focuses on the consequences of digital marketing on business performance, specifically, the consequences of customer relationship orientation and the use of CRM technologies as a support for analysis, data integration, and access on business performance. This study addresses a contemporary and relevant research problem that has national and international relevance. The research is based on quantitative methods to test hypotheses. Data were gathered from 73 organizations. The findings show the relationships between CRM and customer satisfaction, market effectiveness, and profitability. Customer relationship orientation positively affects customer satisfaction, market effectiveness, and market profitability. CRM technologies significantly improve business performance. This research contributes to the existing knowledge by shedding light on the complex relationships among CRM, customer relationship orientation, market effectiveness, market profitability, and customer satisfaction. Based on the research results, we provide practical recommendations for managers and decision makers. Full article

Epilepsy, a neurological disorder characterized by excessive neuronal activity and synchronized electrical discharges, ranks among the most prevalent global neurological conditions. Despite common use, antiepileptic drugs often result in adverse effects and lack effectiveness in controlling seizures in temporal lobe epilepsy (TLE) patients. Recent research explored the potential of occidentalin-1202, a peptide inspired by Polybia occidentalis venom, in safeguarding Wistar rats from chemically induced seizures. The present study evaluated the new analog from occidentalin-1202 named NOR-1202 using acute and chronic pilocarpine-induced models and an acute kainic acid (KA) male mice model. NOR-1202 was administered through the intracerebroventricular (i.c.v.), subcutaneous, or intraperitoneal routes, with stereotaxic procedures for the i.c.v. injection. In the acute pilocarpine-induced model, NOR-1202 (i.c.v.) protected against generalized seizures and mortality but lacked systemic antiepileptic activity. In the KA model, it did not prevent generalized seizures but improved survival. In the chronic TLE model, NOR-1202′s ED₅₀ did not differ significantly from the epileptic or healthy groups regarding time spent in spontaneous recurrent seizures during the five-day treatment. However, the NOR-1202 group exhibited more seizures than the healthy group on the second day of treatment. In summary, NOR-1202 exhibits antiepileptic effects against chemoconvulsant-induced seizures, but no effect was observed when administered systemically. Full article

As a euryhaline fish species that inhabits estuarine and coastal regions, the spotbanded scat (Selenotoca multifasciata) experiences growth influences during its larval stage due to variations in salinity. Here, we evaluated salinity required by early-stage spotbanded scat juveniles to achieve the highest growth performance, digestive enzyme activity, survival, and antioxidant capacity. We reared spotbanded scat juveniles (all 0.50 ± 0.05 g) in 0–35‰ salinity gradients for 50 days and recorded their survival rate every 10 days. After 50 experimental days, we measured morphological data, stomach and intestinal digestive enzyme activities, and liver antioxidant enzyme activities and malondialdehyde contents. In general, 5–15‰ salinity led to 100% survival. The 5‰ salinity group demonstrated the highest values for the following measures: final wet body weight; weight gain rate; specific growth rate; growth percentage; average daily gain; stomach amylase and lipase specific activities; and intestinal amylase, lipase, trypsin, and pepsin specific activities. However, stomach trypsin and pepsin activities did not demonstrate significant between-group differences (all p > 0.05). The 25‰ salinity group demonstrated the highest liver superoxide dismutase and glutathione peroxidase activities and malondialdehyde content. Finally, the 0‰ salinity group demonstrated the highest liver catalase activity. Thus, spotbanded scat juveniles demonstrate the highest survival rates, growth performance, and digestive enzyme activity at 5‰ salinity and the strongest oxidative stress responses at 25‰ salinity. Full article

The use of natural-origin biomaterials in bioengineering has led to innovative approaches in agroforestry. Bacterial cellulose (BC), sharing the same chemical formula as plant-origin cellulose (PC), exhibits significantly different biochemical properties, including a high degree of crystallinity and superior water retention capacity. Previous research showed that natural-origin glucose-based chitin enhanced plant growth in both herbaceous and non-herbaceous plants. In this study, we produced BC in the laboratory and investigated its effects on the substrate and on Solanum lycopersicum seedlings. Soil amended with BC increased root growth compared with untreated seedlings. Additionally, under limited irrigation conditions, BC increased global developmental parameters including fresh and dry weight, as well as total carbon and nitrogen content. Under non-irrigation conditions, BC contributed substantially to plant survival. RNA sequencing (Illumina^®) on BC-treated seedlings revealed that BC, despite its bacterial origin, did not stress the plants, confirming its innocuous nature, and it lightly induced genes related to root development and cell division as well as inhibition of stress responses and defense. The presence of BC in the organic substrate increased soil availability of phosphorus (P), iron (Fe), and potassium (K), correlating with enhanced nutrient uptake in plants. Our results demonstrate the potential of BC for improving soil nutrient availability and plant tolerance to low irrigation, making it valuable for agricultural and forestry purposes in the context of global warming. Full article

Background/Objectives: Understanding sex-based differences in cardiovascular outcomes is paramount to improving clinical outcomes. Surgery is an aggressive but effective therapy for ascending aortic aneurysm. We sought to determine if being a woman is a risk factor for long-term mortality after this surgery. We compared their life expectancy with a general population of the same age, sex, year, and region. Methods: We compared men and women undergoing AAA surgery at our institution from 2000 to 2019. After balancing the population with propensity score (PS) matching, we compared long-term mortality control with a Cox regression. We determined the RS using the Ederer II method and compared it to a healthy reference population of the same age, sex, and region. Results: From 2000 to 2019, 232 women and 506 men underwent ascending aortic aneurysm surgery. After a mean follow-up of 51.5 ± 34.5 months, sex was not an independent risk factor for long-term mortality in the multivariable analysis [HR: 0.68 (95% CI 0.43–1.07, p = 0.23)]. Matching by baseline characteristics, 196 pairs were analyzed with no differences regarding mortality in the Cox regression [HR: 1.11 (95% CI 0.65–1.9, p = 0.23)]. Men and women who survived the postoperative period presented a relative survival of 100.3% (95% CI 97.4–101%) and 100.3% (95% CI 98.9–101.1%), respectively, similar to the reference population without the disease. Conclusions: For patients undergoing AAA surgery, sex was not an independent predictor of mortality. Men and women who survived the postoperative period presented a similar life expectancy to that of the reference population (people free from the disease of the same age, sex, year, and region). Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that lacks effective treatment strategies to halt or delay its progression. The homeostasis of Ca²⁺ ions is crucial for ensuring optimal cellular functions and survival, especially for neuronal cells. In the context of PD, the systems regulating cellular Ca²⁺ are compromised, leading to Ca²⁺-dependent synaptic dysfunction, impaired neuronal plasticity, and ultimately, neuronal loss. Recent research efforts directed toward understanding the pathology of PD have yielded significant insights, particularly highlighting the close relationship between Ca²⁺ dysregulation, neuroinflammation, and neurodegeneration. However, the precise mechanisms driving the selective loss of dopaminergic neurons in PD remain elusive. The disruption of Ca²⁺ homeostasis is a key factor, engaging various neurodegenerative and neuroinflammatory pathways and affecting intracellular organelles that store Ca²⁺. Specifically, impaired functioning of mitochondria, lysosomes, and the endoplasmic reticulum (ER) in Ca²⁺ metabolism is believed to contribute to the disease’s pathophysiology. The Na+-Ca²⁺ exchanger (NCX) is considered an important key regulator of Ca²⁺ homeostasis in various cell types, including neurons, astrocytes, and microglia. Alterations in NCX activity are associated with neurodegenerative processes in different models of PD. In this review, we will explore the role of Ca²⁺ dysregulation and neuroinflammation as primary drivers of PD-related neurodegeneration, with an emphasis on the pivotal role of NCX in the pathology of PD. Consequently, NCXs and their interplay with intracellular organelles may emerge as potentially pivotal players in the mechanisms underlying PD neurodegeneration, providing a promising avenue for therapeutic intervention aimed at halting neurodegeneration. Full article

This 10-year retrospective cohort study at a single-center clinic in Germany aimed to analyze the outcomes of endometrial cancer patients and explore the impact of lymphovascular invasion (LV) on patient outcomes and disease-free survival (DFS). Identifying correlations among demographic data, tumor characteristics, treatment modalities, and survival outcomes could enhance patient management and improve survival rates. The study encompassed patients diagnosed and treated for endometrial cancer from January 2010 to December 2020. Clinical and pathological data were extracted from medical records for 311 patients, focusing on variables such as age, histological type, tumor grade, type of surgical treatment, and adjuvant therapies. Survival analysis was conducted using the Kaplan–Meier method and multivariate Cox proportional hazard models to identify factors independently associated with survival. The study demonstrated that lymphovascular invasion significantly impacted survival outcomes on Kaplan–Meier analysis (log-rank p-value = 0.0058). Patients with LV showed a marked decrease in DFS compared to those without LV invasion, with a median DFS of 3.2 years and a hazard ratio of 2.18 (95% CI: 1.56–3.04, p < 0.001). Furthermore, high-grade tumors and p53 positivity were strongly associated with reduced DFS, with hazard ratios of 1.93 (p = 0.001) and 2.11 (p < 0.001), respectively. Patients with distant metastasis exhibited the most significant decline in survival, with a hazard ratio of 5.56 (95% CI: 2.45–10.18, p < 0.001). Despite comprehensive surgical and adjuvant therapies, these high-risk factors dictated poorer outcomes. The presence of lymphovascular invasion, high-grade tumors, and genetic markers like MSI and p53 are pivotal in predicting the course of endometrial cancer. This study underscores the necessity for aggressive management strategies in patients exhibiting these high-risk features to potentially improve prognosis and survival outcomes. The findings advocate for enhanced therapeutic strategies tailored to the biological behavior of the tumor, thereby aiming to elevate the overall survival rates for women diagnosed with endometrial cancer. Full article

Background: This study aimed to assess the survival of implants placed in the maxillary tuberosity or in the pterygomaxillary region of the maxilla, based on a systematic review of the literature. Methods: An electronic search was undertaken in three databases. The cumulative survival rate (CSR) was calculated. The log-rank (Mantel–Cox) test was used to compare the survival distributions between some groups. Results: Thirty-eight studies were included, reporting 3446 implants (3053 pterygoid, 393 tuberosity) in 2245 patients, followed up for a mean ± SD of 61.0 ± 36.3 months (min–max, 1–144). A total of 208 pterygoid and 12 tuber implants failed, with a clear concentration of failures in the first year of follow-up and a 10-year CSR of 92.5% and 96.9%, respectively. The survival of pterygoid implants was lower than that of implants in the maxillary tuberosity (p = 0.006; log-rank test), and the survival of implants submitted to early/delayed loading was lower than that of immediately loaded implants (p < 0.001; log-rank test). Non-splinted implants presented higher failure rates. Few cases of intra- or postoperative complications were reported. Conclusions: Implants placed in the pterygoid process/maxillary tuberosity present a high 10-year CSR, although with lower survival for pterygoid in comparison to tuber implants. Pterygoid/tuber implants that are splinted with other implants may present higher survival rates than those that are not splinted. Full article