Czech Academy of Sciences, Institute of Biotechnology

Osteosarcoma (OS) is one of the most malignant bone tumors in children and adolescents, but the molecular mechanisms of OS progression remain largely undefined. In this study, we demonstrate that Integrin subunit beta-like 1 (ITGBL1) is downregulated in OS tissues, and its downregulation correlates with poor prognosis in OS patients. Functional assays revealed that ITGBL1 inhibits OS cell growth, metastasis, and stemness, while promoting apoptosis. The in vitro and in vivo experiments further revealed that ITGBL1 activates endoplasmic reticulum (ER) stress by upregulating ROS, thereby triggering autophagy in OS cells. In addition, the downregulation of ITGBL1 in OS is partly attributed to the abnormal upregulation of HSP90AB1 (heat shock protein 90 alpha family class B1). Mechanistically, ITGBL1 interacts with HSP90AB1 which facilitates ITGBL1 degradation through K63-linked ubiquitination. Finally, through virtual screening and Co-IP, we identified ivermectin as a potent inhibitor of the HSP90AB1-ITGBL1 interaction, and treatment with ivermectin dramatically inhibited OS progression in vivo. In conclusion, we uncover a novel mechanism that promotes OS progression and identify a new candidate drug for the treatment of OS.

This study aims to evaluate the changes in the content of bioactive compounds and the antioxidant capacity of lotus (Nelumbo nucifera Gaertn.) leaf tea throughout the production process. The results show that leaf age significantly affects the accumulation of bioactive compounds, with mature leaves having the highest total polyphenol content and total flavonoid content. After processing, all tea samples showed increased antioxidant activity due to the heat process, helping to release bound phenolic compounds and inhibit the enzyme polyphenol oxidase. A 10% moisture reduction before fermentation resulted in the highest antioxidant activity (85%), while excessive moisture reduction (> 15%) decreased total polyphenol content and antioxidant activity. The best fermentation conditions were determined to be 40 °C for 5 h. Additionally, the best hot extraction conditions for the finished tea were 95 to 100 °C for 6 to 8 min, which allowed to obtain the highest phenolic content without causing thermal degradation.

Sperm quality in TGCT patients showed marked variability. Non-seminoma diagnosis appeared less detrimental than seminoma, yet BEP chemotherapy severely impaired sperm parameters, especially in non-seminoma cases. These results highlight the importance of individualized post-chemotherapy monitoring using standard semen analysis, cytometry-based qualitative assessments, and epigenetic profiling of histone modifications to optimize fertility preservation and guide optimal treatment strategies by andrologists.

Kinetoplastids, such as Trypanosoma brucei , are eukaryotes that likely separated from the main lineage at an exceptionally early point in evolution. Consequently, many aspects of kinetoplastid biology differ significantly from other eukaryotic model systems, including yeasts, plants, worms, flies, and mammals. As in many eukaryotes, the T. brucei genome contains repetitive elements at various chromosomal locations, including centromere- and telomere-associated repeats and interspersed retrotransposon elements. T. brucei also contains intermediate-sized and mini-chromosomes that harbour abundant 177 bp repeat arrays and 70 bp repeat elements implicated in Variable Surface Glycoprotein (VSG) gene switching. In many eukaryotes, repetitive elements are assembled in specialised chromatin such as heterochromatin; however, apart from centromere- and telomere-associated repeats, little is known about chromatin-associated proteins that decorate these and other repetitive elements in kinetoplastids. Here, we utilise affinity selection of synthetic TALE DNA binding proteins designed to target specific repeat elements to identify enriched proteins by proteomics. Validating the approach, a telomere repeat binding TelR-TALE identifies many proteins previously implicated in telomere function. Furthermore, the 70R-TALE designed to bind 70 bp repeats indicates that proteins involved in DNA repair are enriched on these elements that reside adjacent to VSG genes. Interestingly, the 177 bp repeat binding 177R-TALE enriches for many kinetochore proteins, suggesting that intermediate-sized and mini-chromosomes assemble kinetochores related in composition to those located on the main megabase chromosomes. This provides a first insight into the chromatin landscape of repetitive regions of the trypanosome genome with relevance for their mechanisms of chromosome integrity, immune evasion, and cell replication.

Abstract Background Enhanced soil salinity is a major constraint to rice production in the coastal regions of Bangladesh. Salinity stress impairs nutrient uptake and induces ionic toxicity and osmotic stress, while excessive use of chemical fertilizers degrades soil health and causes environmental pollution. A novel salt-tolerant endophytic fungus, Aspergillus welwitschiae Oc streb1, isolated from the halophytic wild rice Oryza coarctata, exhibited multiple plant growth–promoting traits under both non-saline and 900 mM salt-stress conditions in vitro. These findings suggest that Ocstreb1-based biofertilizer could serve as an eco-friendly and cost-effective alternative to enhance rice productivity under saline conditions. Methods In this experiment, the biofertilizer was prepared using fungal spores produced on wheat bran and subsequently mixed with talcum powder as a carrier. Field trials were conducted following a randomized complete block design (RCBD), incorporating different levels of chemical fertilizer application (0%, 80%, and 100% of the BRRI-recommended NPKSZn rates) in both biofertilizer-treated and untreated plants. Results Compared with the 100% chemical fertilizer treatment, the combined application of biofertilizer and 80% chemical fertilizer resulted in a comparable yield in Barguna and an increased yield of 196.6 kg ha⁻¹ in Satkhira. Profitability analysis showed that this treatment provided an additional economic benefit of USD 48–68 ha⁻¹ over the 100% chemical fertilizer treatment. Moreover, fumonisin B1 levels in grains from biofertilizer-treated plants were negligible. Conclusion In conclusion, commercial production of this Biofertilizer will pave the way for enhancing rice yield with less chemical fertilizer use and ensuring sustainable agricultural practice particularly in areas affected by salinity stress.

<title>Abstract</title> Wheat is the most important food crop worldwide with second rank next to maize in total production .It’s production has to be increased by 70% to feed the rocket shooting wold population by 2050.But the production of wheat was challenged by salinity stress and lead to loss of about 50% products. Improving the germination performance of bread wheat under salinity stress is the basic mechanism to solve the product loss and enhance breeding strategies in wheat. Hence, the present study aimed to identify salt tolerance genes and genomic loci related to germination performance under salinity stress in wheat, providing insights into salinity-responsive pathways and candidate genes to support future breeding strategies for improved salt tolerance at early developmental stages. To obtain this target Genome wide association study was performed on 154 Ethiopian bread wheat genotypes. Three groups of bread wheat were identified under salt stress as tolerant, moderate tolerant and sensitive. Based on this a total of 31 QTNs were revealed through GWAS analysis. Finally 10 functional genes were identified and annotated as functional genes to determine their effects on germination performance traits. Most of the genes were involved in transcription regulation, carbohydrate metabolism, immune response and cell cycle regulation and stress signalling. The germination trait based phenotyping of the genotypes, revealed QTNs and candidate genes, mechanism of action identified during annotation with respect to function increase the understanding for better germination performance of bread wheat under salt stress.

We report growth of mixed crystal of transition metal dichalcogenides (TMDs) Mo1-xWxS2 (0 ≤ 𝑥 ≤ 1) thin films using simple and scalable solution-based method, i.e. spin coating for enhanced hydrogen evolution reaction (HER). For this purpose, a mixture of single source Mo/W precursors (with different Mo/W ratios) solution was spin coated onto a planer substrate, followed by moderate temperature sulfurization in a reducing environment. The composition of the mixed crystal was precisely tuned by varying Mo:W precursor ratio. The uniformity and surface coverage of the obtained thin films was confirmed by optical microscopy, AFM and SEM. High resolution AFM image revealed a nanoflower type nanostructure which has potentially higher active edge sites. Raman, XPS and UV-Vis spectroscopy verified successful formation of mixed crystal films and revealed systematic shift in the structural and electronic signature with changing composition. Electrochemical study revealed a strong influence of the composition of the mixed crystal on the catalytic performance. For instance, mixed crystal Mo0.5W0.5S2 showed superior HER activity compared to MoS2 and WS2 in its pure form, with overpotential of 229 mV at 10 mA/cm 2, Tafel slope 69 mV/dec and charge transfer resistance of 75 ohm. These enhancements in the catalytic activities are attributed to optimization of electronic band structure of the alloy and defect induced activation sites. Overall, this work shows the potential of solution-based growth of mixed crystal as an economical, scalable approach for enhance hydrogen evolution reaction.

Abstract Ethiopia possesses one of Africa's most diverse cattle gene pools and enjoys favorable agro-ecological conditions and strong cultural demand for dairy products; however, productivity remains constrained by persistent socioeconomic and technical bottlenecks. This study examined how farmer demographics, production goals, management strategies, and systemic constraints influenced the effectiveness of dairy cattle genetic improvement across two agro-ecological zones and major milk-shed areas in the Amhara region. A multistage sampling survey involving 355 smallholder dairy producers (253 mid and 102 highland areas) was conducted using semi-structured questionnaires. Respondents had, on average, 12.19 ± 6.50 years of dairy experience and were 48.19 years old. Breeding-related expenditures showed strong spatial variation: farmers in the midlands and Gondar milk-shed paid substantially higher costs for natural mating and informal AI services, whereas highland farmers benefitted from lower AI fees and shorter distances to service centers (1.40 ± 1.88 km). The Wilcoxon signed-rank test confirmed that milk production was the dominant objective for raising hybrid dairy cattle across both agro-ecologies (overall weighted index: 0.41), signaling a clear transition toward more specialized, market-oriented dairying. Major constraints limiting genetic improvement included security-related disruptions (top constraint, overall index = 0.30; p = 0.002), which restricted access to grazing and AI delivery. Additional challenges included shortages of AI technicians (p = 0.04), escalating feed costs and scarcity, and the inconsistent availability of quality semen. Collectively, these limitations contributed to poor conception outcomes and undermined the performance of AI-driven genetic improvement initiatives. The evaluation of breed and blood level effects demonstrated substantial genetic and economic differences. Holstein Friesian (HF) hybrids exhibited superior productivity, showing the highest average daily milk yields (13.52 ± 4.69 L/day) and significantly outperforming local dairy cows (1.99 ± 0.81 L/day). This translated directly to economic benefits, as HF hybrids generated the highest average Income Per Lactation (peaking at 275,693.93 ETB at &gt; 75% blood level), far exceeding the income from local breeds (35,500 ETB). Furthermore, HF hybrids showed significantly earlier maturity, with a shorter Age at First Service Mating (AAFSM) (1.66 ± 2.10 years) compared to local breeds (3.35 years). Conversely, Jersey hybrids demonstrated better reproductive efficiency with a lower Number of Service Per Conception (NSPC) (1.40 ± 0.58) and higher Conception Rate (CR) (81.29 ± 24.01%), compared to HF hybrids (NSPC: 1.49 ± 0.57; CR: 76.03 ± 24.39). Notably, NSPC declined as the HF exotic blood level increased up to 75%, indicating a sweet spot for optimal crossbred performance. This variable performance across traits highlights an unstable performance paradox. Strengthening reproductive service delivery, improving feed and market systems, investing in breeding infrastructure, and addressing security barriers are essential for advancing sustainable dairy genetic improvement in Northwest Ethiopia.

The molecular mechanisms guiding cochlear development remain incompletely understood. Here, we used conditional deletion mouse models (both sexes) to define the spatiotemporal roles of the transcription factors NEUROD1 and ISL1 during cochlear neurosensory development. Delayed deletion of Neurod1 using Atoh1Cre had no detectable effect on cochlear structure or hearing function. In contrast, Atoh1Cre-mediated Isl1 deletion disrupted sensory epithelium organization, producing ectopic inner hair cells and supernumerary outer hair cell rows, and altered spiral ganglion development. Although Atoh1Cre targeted only a subset of developing spiral ganglion neurons, Isl1 loss resulted in aberrant spiral ganglion morphology, reduced neuronal density, impaired innervation, and defective neuronal migration. These abnormalities arose through a combination of cell-autonomous effects in Isl1-deficient neurons and non-cell-autonomous effects on untargeted, neighboring neurons. The resulting neurosensory abnormalities compromised hearing function, evidenced by elevated auditory brainstem response thresholds, abnormal low-frequency acoustic stimulus processing, and reduced distortion product otoacoustic emissions. Together, these findings further substantiate the essential role of ISL1 in auditory neuron development and establish ISL1 as a key regulator of cochlear neurosensory development.

l-Glutamate (l-Glu) is one of the primary excitatory neurotransmitters in the nervous system, functioning through both ionotropic and metabotropic receptors. The release of l-Glu into the synaptic cleft, its interaction with receptors, and its reuptake are meticulously regulated by excitatory amino acid transporters. The structural similarity of various compounds to l-glutamate is crucial to their ability to interact with NMDA, AMPA, and kainate receptors. These interactions can significantly influence neural communication and function. Overstimulation of these receptors, which operate as ion channels, results in an increased level of calcium ion influx, a phenomenon known as excitotoxicity, which is often linked to neurodegeneration. Many neurodegenerative conditions are linked to both acute and chronic exposures to neurotoxins, whether they originate within the body (endogenous) or from external sources (exogenous). These neurotoxins often function as l-glutamate receptor agonists, potentially contributing to the progression of these diseases. This perspective focuses on key neurotoxins, including β-N-methylamino-l-alanine (l-BMAA), quinolinic acid (QUIN), domoic acid, β-N-oxalyl-l-α,β-diaminopropionic acid (β-ODAP), homocysteine (Hcy), and l-homocysteate, all of which exhibit complementary mechanisms of action. We will explore their structural characteristics and mechanisms through which they induce neurotoxicity. Understanding the neurotoxic mechanisms of these compounds is essential for elucidating the pathology of neurodegenerative diseases, such as amyotrophic lateral sclerosis, neurolathyrism, and amnesic shellfish poisoning. This review summarizes the findings of 64 studies to clarify these relationships involving classic events associated with neurodegeneration such as mitochondrial damage, oxidative stress, and activation of proapoptotic pathways. In summary, the distinctive properties of these neurotoxins provide valuable insights that could help in the development of future therapeutic drugs aimed at treating and alleviating the effects of neurodegenerative diseases. Understanding how these neurotoxins interact with neuronal pathways can guide researchers in designing more effective interventions.