Epithelial-mesenchymal transition in chemoradiation-induced lung damage: Mechanisms and potential treatment approaches.

Pulmonary injury is one of the key restricting factors for the therapy of malignancies with chemotherapy or following radiotherapy for chest cancers. The lung is a sensitive organ to some severely toxic antitumor drugs, consisting of bleomycin and alkylating agents. Furthermore, treatment with radiotherapy may drive acute and late adverse impacts on the lung. The major consequences of radiotherapy and chemotherapy in the lung are pneumonitis and fibrosis. Pneumonitis may arise some months to a few years behind cancer therapy. However, fibrosis is a long-term effect that appears years after chemo/or radiotherapy. Several mechanisms such as oxidative stress and severe immune reactions are implicated in the progression of pulmonary fibrosis. Epithelial-mesenchymal transition (EMT) is offered as a pivotal mechanism for lung fibrosis behind chemotherapy and radiotherapy. It seems that pulmonary fibrosis is the main consequence of EMT after chemo/radiotherapy. Several biological processes, consisting of the liberation of pro-inflammatory and pro-fibrosis molecules, oxidative stress, upregulation of nuclear factor of κB and Akt, epigenetic changes, and some others, may participate in EMT and pulmonary fibrosis behind cancer therapy. In this review, we aim to discuss how chemotherapy or radiotherapy may promote EMT and lung fibrosis. Furthermore, we review potential targets and effective agents to suppress EMT and lung fibrosis after cancer therapy.

Microwave-assisted synthesis, characterization, and in vitro biological evaluation of a novel nanocomposite using molybdenum and [2,2'-bipyridine]-4,4'-dicarboxylic acid.

Currently, nanocomposites are synthesized and used in various fields. One of the applications of these nanostructures is in the medical field. Therefore, the synthesis of new composites with biological properties is important. In this study, under microwave conditions, a new nanocomposite containing molybdenum and [2,2'-bipyridine]-4,4'-dicarboxylic acid (Mo/BPDA) was synthesized. The synthesized Mo/BPDA composite was subjected to biological evaluations such as antibacterial and antifungal properties by clinical and laboratory standards institute guidelines, and anticancer properties by MTT method. Characterization and structure characteristics of the Mo/BPDA nanocomposite were evaluated using XRD (X-ray diffraction pattern), FT-IR (Fourier-transform infrared), EDAX (energy-dispersive X-ray), EA (elemental analysis), TGA/DTG (thermogravimetric analysis/differential thermogravimetry), SEM (scanning electron microscopy) and BET (Brunauer-Emmett-Teller) analysis. The results indicated relatively high thermal stability (300 °C), high specific surface area (35 cm3 g-1) and uniform morphology of the synthesized Mo/BPDA nanocomposite. In antibacterial and antifungal activity, minimum inhibitory concentration (between 2 and 256 µg mL-1), minimum bactericidal concentration (between 4 and 128 µg mL-1), and minimum fungicidal concentration (between 64 and 256 µg mL-1) were tested and reported. The results showed that the antibacterial and antifungal activity of Mo/BPDA nanocomposite is higher than that of antibiotic drugs such as ampicillin, cefazolin, ketoconazole, and nystatin. In the investigation of the anticancer activity that was tested against bone cancer cells and breast cancer cells for 24 and 48 hours, cell proliferation and viability (37.3648-82.0674 tan control) and IC50 (33-43 µg mL-1) were observed. As a final result, it can be stated that the synthesized Mo/BPDA nanocomposite after the additional biological evaluations, such as in vivo study, can be used as an efficient option in treating bone cancer cells and breast cancer cells and a strong antibiotic on a wide range of infectious diseases.

Exploring Uncommon Neurologic Complication in Young Diabetics with Osmotic Demyelination Syndrome: A Case Series and Literature Review.

ABSTRACT: Osmotic demyelination syndrome (ODS) is well known to be associated with the rapid correction of hyponatremia. However, there is limited literature on its link to persistent or corrected hyperglycemic states in diabetic patients. We report two young patients with ODS and hyperglycemia. Neuroimaging and blood tests indicated central pontine and extrapontine myelinolysis with a hyperglycemic hyperosmolar state (HHS). These unusual cases provide insight into the neurologic complications of hyperglycemia.

Monogenic lupus with neuroregression in an infant due to rare compound heterozygous variants in C1QA gene: Case based review.

BACKGROUND: Monogenic lupus is a rare variant of systemic lupus erythematosus (SLE) that develops in patients with a single gene disorder. Early complement component deficiencies were the first forms of monogenic lupus to be described and C1Q gene mutations are one of the most common forms. C1QA complement deficiency has been reported to occur usually due to biallelic variants in C1QA gene and compound heterozygous variants in C1QA gene have rarely been reported. Majority of the monogenic lupus patients with C1Q deficiency present with mucocutaneous, renal, and musculoskeletal manifestations. Our patient is an unusual case of monogenic lupus with severe neurological manifestations along with cutaneous, haematological, and hepatic manifestations secondary to rare compound heterozygous variants in C1QA gene and anti-ribosomal P autoantibody positivity. She was treated with glucocorticoids, rituximab and fresh frozen plasma with partial neurological recovery. Thus, we present a unique case of monogenic lupus due to a rare compound heterozygous variant in C1QA gene with a brief review of literature.

On-chip topological beamformer for multi-link terahertz 6G to XG wireless.

Terahertz (THz) wireless communication holds immense potential to revolutionize future 6G to XG networks with high capacity, low latency and extensive connectivity. Efficient THz beamformers are essential for energy-efficient connections, compensating path loss, optimizing resource usage and enhancing spectral efficiency. However, current beamformers face several challenges, including notable loss, limited bandwidth, constrained spatial coverage and poor integration with on-chip THz circuits. Here we present an on-chip broadband THz topological beamformer using valley vortices for waveguiding, splitting and perfect isolation in waveguide phased arrays, featuring 184 densely packed valley-locked waveguides, 54 power splitters and 136 sharp bends. Leveraging neural-network-assisted inverse design, the beamformer achieves complete 360° azimuthal beamforming with gains of up to 20 dBi, radiating THz signals into free space with customizable user-defined beams. Photoexciting the all-silicon beamformer enables reconfigurable control of THz beams. The low-loss and broadband beamformer enables a 72-Gbps chip-to-chip wireless link over 300 mm and eight simultaneous 40-Gbps wireless links. Using four of these links, we demonstrate point-to-4-point real-time HD video streaming. Our work provides a complementary metal-oxide-semiconductor-compatible THz topological photonic integrated circuit for efficient large-scale beamforming, enabling massive single-input multiple-output and multiple-input and multiple-output systems for terabit-per-second 6G to XG wireless communications.

Chandrayaan-3 APXS elemental abundance measurements at lunar high latitude.

The elemental composition of the lunar surface provides insights into mechanisms of the formation and evolution of the Moon1,2. The chemical composition of lunar regolith have so far been precisely measured using the samples collected by the Apollo, Luna and Chang'e 5 missions, which are from equatorial to mid-latitude regions3,4; lunar meteorites, whose location of origin on the Moon is unknown5,6; and the in situ measurement from the Chang'e 3 and Chang'e 4 missions7-9, which are from the mid-latitude regions of the Moon. Here we report the first in situ measurements of the elemental abundances in the lunar southern high-latitude regions by the Alpha Particle X-ray Spectrometer (APXS) experiment10 aboard the Pragyan rover of India's Chandrayaan-3 mission. The 23 measurements in the vicinity of the Chandrayaan-3 landing site show that the local lunar terrain in this region is fairly uniform and primarily composed of ferroan anorthosite (FAN), a product of the lunar magma ocean (LMO) crystallization. However, observation of relatively higher magnesium abundance with respect to calcium in APXS measurements suggests the mixing of further mafic material. The compositional uniformity over a few tens of metres around the Chandrayaan-3 landing site provides an excellent ground truth for remote-sensing observations.

Removal of mercury and lead ions from water using bioinspired N3Se3 type small sized moieties.

Mercury and lead toxicity in water has serious repercussions on human health. There is an urgent need to develop effective and efficient small moieties for their removal. The convenient one-pot synthesis of a few N3Se3 type small sized moieties is reported herein. The highest metal ion uptake capacity of Hg(II) and Pb(II) ions was found to be 314.3 mg g-1 and 93.5 mg g-1, respectively, by ICP-MS analysis. These ion uptake values are the highest for small sized moieties known in the literature to date.

Cellular stiffness sensing through talin 1 in tissue mechanical homeostasis.

Tissue mechanical properties are determined mainly by the extracellular matrix (ECM) and actively maintained by resident cells. Despite its broad importance to biology and medicine, tissue mechanical homeostasis remains poorly understood. To explore cell-mediated control of tissue stiffness, we developed mutations in the mechanosensitive protein talin 1 to alter cellular sensing of ECM. Mutation of a mechanosensitive site between talin 1 rod-domain helix bundles R1 and R2 increased cell spreading and tension exertion on compliant substrates. These mutations promote binding of the ARP2/3 complex subunit ARPC5L, which mediates the change in substrate stiffness sensing. Ascending aortas from mice bearing these mutations showed less fibrillar collagen, reduced axial stiffness, and lower rupture pressure. Together, these results demonstrate that cellular stiffness sensing contributes to ECM mechanics, directly supporting the mechanical homeostasis hypothesis and identifying a mechanosensitive interaction within talin that contributes to this mechanism.

Advances in Nickel-Containing High-Entropy Alloys: From Fundamentals to Additive Manufacturing.

High-entropy alloys (HEAs) are recognized as a class of advanced materials with outstanding mechanical properties and corrosion resistance. Among these, nickel-based HEAs stand out for their impressive strength, ductility, and oxidation resistance. This review delves into the latest advancements in nickel-containing HEAs, covering their fundamental principles, alloy design strategies, and additive manufacturing techniques. We start by introducing HEAs and their unique properties, emphasizing the crucial role of nickel. This review examines the complex relationships between alloy composition, valence electron concentration (VEC), and the resulting crystal structures. This provides insights into design principles for achieving desired microstructures and mechanical properties. Additive manufacturing (AM) techniques like selective laser melting (SLM), electron beam melting (EBM), and laser metal deposition (LMD) are highlighted as powerful methods for fabricating intricate HEA components. The review addresses the challenges of AM processes, such as porosity, fusion defects, and anisotropic mechanical properties, and discusses strategies to mitigate these issues through process optimization and improved powder quality. The mechanical behavior of AM-processed nickel-based HEAs is thoroughly analyzed, focusing on compressive strength, hardness, and ductility. This review underscores the importance of microstructural features, including grain size, phase composition, and deformation mechanisms, in determining the mechanical performance of these alloys. Additionally, the influence of post-processing techniques, such as heat treatment and hot isostatic pressing (HIP) on enhancing mechanical properties is explored. This review also examines the oxidation behavior of nickel-containing HEAs, particularly the formation of protective oxide scales and their dependence on aluminum content. The interplay between composition, VEC, and oxidation resistance is discussed, offering valuable insights for designing corrosion resistant HEAs. Finally, this review outlines the potential applications of nickel-based HEAs in industries such as aerospace, automotive, and energy, and identifies future research directions to address challenges and fully realize the potential of these advanced materials.

A novel green and efficient heterogeneous acid catalyst for the one-pot synthesis of benzopyrazine-aminoimidazole hybrids with antiproliferative potential.

A novel, green, efficient, and stable magnetically heterogeneous nanocatalyst was developed by immobilizing butanesulfonic acid (BuSO3H) onto the surface of MFe2O4 magnetic nanoparticles (MNPs). The resulting core-shell structure of the MFe2O4@PDA@BuSO3H nanocatalyst was thoroughly characterized using various analytical techniques, including Fourier-Transform Infrared Spectroscopy (FT-IR), X-ray Diffraction (XRD), Energy-Dispersive X-ray Spectroscopy (EDS), Field Emission Scanning Electron Microscopy (FESEM), Transmission Electron Microscopy (TEM), Vibrating Sample Magnetometry (VSM), and Brunauer-Emmett-Teller (BET) analysis. A nanocatalyst was used to synthesize 2-benzopyrazine-aminoimidazole hybrid derivatives through a domino multicomponent Knoevenagel-condensation-cyclization reaction (5a-p) in an environmentally friendly manner. The resulting compounds were then tested for their anticancer activity against three types of human cancer cells (MCF-7, A549, and U87) using the MTT assay. The experiment showed that the nanocatalyst had excellent catalytic activity, and the synthesized compounds exhibited promising antiproliferative activity. Notably, compounds 5g and 5h, containing a 2-naphthyl ring, showed the highest antiproliferative effects against MCF-7 cells, with IC50 values of 0.03 and 0.32 µM, respectively. Additionally, the activity of compounds 5g and 5h in tubulin polymerization, apoptosis induction, and cell cycle arrest in MCF-7 cells were investigated. The results demonstrated that these compounds effectively induced apoptosis and cell cycle arrest. The binding of representative compounds to the colchicine binding site of tubulin was confirmed through molecular modeling studies.

Unconventional localization of PAI-1 in PML bodies: A possible link with cellular growth of endothelial cells.

Plasminogen activator inhibitor-1 (PAI-1/Serpin E1) is classically known for its antifibrinolytic activity via inhibiting uPA and tPA of the fibrinolytic pathway. PAI-1 has a paradoxical role in tumor progression, and its molecular functions are poorly understood. PAI-1 is a widely accepted secretory protease inhibitor, however, a study suggested the localization of PAI-1 in the cytoplasm and the nucleus. Besides the plethora of its biological functions as a secretory protein, intracellular localization, and functions of PAI-1 remain unexplored at the molecular level. In this study, using various in silico approaches, we showed that PAI-1 possesses a nuclear export signal. Using the CRM1-specific inhibitor leptomycin B, we demonstrated that PAI-1 has a functional CRM1-dependent NES, indicating the possibility of its nuclear localization. Further, we confirm that PAI-1 is localized in the nucleus of endothelial cells using fluorescence microscopy and immunoprecipitation. Notably, we identified an unconventional distribution of PAI-1 in the PML bodies of the nucleus of normal endothelial cells, while the protein was restricted in the cytoplasm of slow-growing cells. The data showed that the localization of PAI-1 in PML bodies is highly correlated with the growth potential of endothelial cells. This conditional nucleocytoplasmic shuttling of PAI-1 during the aging of cells could impart a strong link to its age-related functions and tumor progression. Together, this study identifies the novel behavior of PAI-1 that might be linked with cell aging and may be able to unveil the elusive role of PAI-1 in tumor progression.

Disturbance and vegetational structure in an urban forest of Indian Siwaliks: an ecological assessment.

Urban forests face multiple human-mediated pressures leading to compromised ecosystem structure and functioning. Therefore, understanding ecosystem structure in response to ongoing pressures is crucial for sustaining ecological integrity and human well-being. We aim to assess the disturbance and its effects on the vegetation structure of urban forests in Chandigarh using a combination of remote sensing techniques and vegetation surveys. The disturbance was evaluated as a change in NDVI (Normalised Difference Vegetation Index) from 2001 to 2021 by applying the BFAST (Breaks For Additive Season and Trend) algorithm to the MODIS satellite imagery data. A vegetation survey was conducted to compare the species composition, taxonomic and phylogenetic diversity as measures of forest vegetational structure. While signals of disturbance were evident, the changes in vegetation structure were not well established from our study. Further, this analysis indicated no significant differences in vegetation composition due to disturbance (F1,12 = 0.91, p = 0.575). However, the phylogenetic diversity was substantially lower for disturbed plots than undisturbed plots, though the taxonomic diversity was similar among the disturbed and undisturbed plots. Our results confirmed that disturbance effects are more prominent on the phylogenetic than taxonomic diversity. These findings can be considered early signals of disturbance and its impact on the vegetation structure of urban forests and contribute to the knowledge base on urban ecosystems. Our study has implications for facilitating evidence-based decision-making and the development of sustainable management strategies for urban forest ecosystems.

Thermodynamic coupling of the tandem RRM domains of hnRNP A1 underlie its pleiotropic RNA binding functions.

The functional properties of RNA binding proteins (RBPs) require allosteric regulation through interdomain communication. Despite the importance of allostery to biological regulation, only a few studies have been conducted to describe the biophysical nature by which interdomain communication manifests in RBPs. Here, we show for hnRNP A1 that interdomain communication is vital for the unique stability of its amino-terminal domain, which consists of two RNA recognition motifs (RRMs). These RRMs exhibit drastically different stability under pressure. RRM2 unfolds as an individual domain but remains stable when appended to RRM1. Variants that disrupt interdomain communication between the tandem RRMs show a significant decrease in stability. Carrying these mutations over to the full-length protein for in vivo experiments revealed that the mutations affected the ability of the disordered carboxyl-terminal domain to engage in protein-protein interactions and influenced the protein's RNA binding capacity. Collectively, this work reveals that thermodynamic coupling between the tandem RRMs of hnRNP A1 accounts for its allosteric regulatory functions.

Sustainable soil management under drought stress through biochar application: Immobilizing arsenic, ameliorating soil quality, and augmenting plant growth.

Rise in climate change-induced drought occurrences have amplified pollution of metal(loid)s, deteriorated soil quality, and deterred growth of crops. Rice straw-derived biochars (RSB) and cow manure-enriched biochars (CEB) were used in the investigation (at doses of 0%, 2.5%, 5%, and 7.5%) to ameliorate the negative impacts of drought, improve soil fertility, minimize arsenic pollution, replace agro-chemical application, and maximize crop yields. Even in soils exposed to severe droughts, 3 months of RSB and CEB amendment (at 7.5% dose) revealed decreased bulk density (13.7% and 8.9%), and increased cation exchange capacity (6.0% and 6.3%), anion exchange capacity (56.3% and 28.0%), porosity (12.3% and 7.9%), water holding capacity (37.5% and 12.5%), soil respiration (17.8% and 21.8%), and nutrient contents (especially N and P). Additionally, RSB and CEB decreased mobile (30.3% and 35.7%), bio-available (54.7% and 45.3%), and leachable (55.0% and 56.5%) fractions of arsenic. Further, pot experiments with Bengal gram and coriander plants showed enhanced growth (62-188% biomass and 90-277% length) and reduced arsenic accumulation (49-54%) in above ground parts of the plants. Therefore, biochar application was found to improve physico-chemical properties of soil, minimize arsenic contamination, and augment crop growth even in drought-stressed soils. The investigation suggests utilisation of cow manure for eco-friendly fabrication of nutrient-rich CEB, which could eventually promote sustainable agriculture and circular economy. With the increasing need for sustainable agricultural practices, the use of biochar could provide a long-term solution to enhance soil quality, mitigate the effects of climate change, and ensure food security for future generations. Future research should focus on optimizing biochar application across various soil types and climatic conditions, as well as assessing its long-term effectiveness.

Environmental drivers behind the exceptional increase in cyanobacterial blooms in Okavango Delta, Botswana.

The Okavango Delta region in Botswana experienced exceptionally intense landscape-wide cyanobacterial harmful algal blooms (CyanoHABs) in 2020. In this study, the drivers behind CyanoHABs were determined from thirteen independent environmental variables, including vegetation indices, climate and meteorological parameters, and landscape variables. Annual Land Use Land Cover (LULC) maps were created from 2017 to 2020, with ∼89% accuracy to compute landscape variables such as LULC change. Generalized Additive Models (GAM) and Structural Equation Models (SEM) were used to determine the most important drivers behind the CyanoHABs. Normalized Difference Chlorophyll Index (NDCI) and Green Line Height (GLH) algorithms served as proxies for chlorophyll-a (green algae) and phycocyanin (cyanobacteria) concentrations. GAM models showed that seven out of the thirteen variables explained 89.9% of the variance for GLH. The models showcased that climate variables, including monthly precipitation (8.8%) and Palmer Severity Drought Index- PDSI (3.2%), along with landscape variables such as changes in Wetlands area (7.5%), and Normalized Difference Vegetation Index (NDVI) (5.4%) were the determining drivers behind the increased cyanobacterial activity within the Delta. Both PDSI and NDVI showed negative correlations with GLH, indicating that increased drought conditions could have led to large increases in toxic CyanoHAB activity within the region. This study provides new information about environmental drivers which can help monitor and predict regions at risk of future severe CyanoHABs outbreaks in the Okavango Delta, Botswana, and other similar data-scarce and ecologically sensitive areas in Africa. Plain Language Summary: The waters of the Okavango Delta in Northern Botswana experienced an exceptional increase in toxic cyanobacterial activity in recent years. Cyanobacterial blooms have been shown to affect local communities and wildlife in the past. To determine the drivers behind this increased bloom activity, we analyzed the effects of thirteen independent environmental variables using two different statistical models. Within this research, we focused on vegetation indices, meteorological, and landscape variables, as previous studies have shown their effect on cyanobacterial activity in other parts of the world. While driver determination for cyanobacteria has been done before, the environmental conditions most important for cyanobacterial growth can be specific to the geographic setting of a study site. The statistical analysis indicated that the increases in cyanobacterial bloom activity within the region were mainly driven by persistent drier conditions. To our knowledge, this is the first study to determine the driving factors behind cyanobacterial activity in this region of the world. Our findings will help to predict and monitor areas at risk of future severe cyanobacterial blooms in the Okavango Delta and other similar African ecosystems.

Design, Synthesis, and Biological Evaluation of 1,4-Dihydropyridine-Indole as a Potential Antidiabetic Agent via GLUT4 Translocation Stimulation.

In the quest for the discovery of antidiabetic compounds, a series of 27 1,4-dihydropyridine-indole derivatives were synthesized using a diversity approach. These compounds were systematically evaluated for their antidiabetic activity, starting with an in vitro assessment for GLUT4 translocation stimulation in L6-GLUT4myc myotubes, followed by in vivo antihyperglycemic activity evaluation in a streptozotocin (STZ)-induced diabetic rat model. Among the synthesized compounds, 12, 14, 15, 16, 19, 27, and 35 demonstrated significant potential to stimulate GLUT4 translocation in skeletal muscle cells. Compound 19 exhibited the highest potency and was selected for in vivo evaluation. A notable reduction of 21.6% (p < 0.01) in blood glucose levels was observed after 5 h of treatment with compound 19 in STZ-induced diabetic rats. Furthermore, pharmacokinetic studies affirmed that compound 19 was favorable to oral exposure with suitable pharmacological parameters. Overall, compound 19 emerged as a promising lead compound for further structural modification and optimization.

Paradoxical development of Kimura's disease in a patient treated with mepolizumab for bronchial asthma.

A male patient in his early 30s was diagnosed with bronchial asthma 3 years previously. He responded well to inhaled corticosteroids and long-acting beta-agonists. Approximately 18 months from the onset, the patient reported worsening symptoms. These symptoms included severe functional limitations, requiring frequent exposure to high-dose prednisolone. Mepolizumab was added to the treatment, leading to optimal control of bronchial asthma. Despite receiving seven doses of mepolizumab at monthly intervals, the patient developed cervical and postauricular lymphadenopathy and subcutaneous swelling of soft tissue. A cervical lymph node biopsy confirmed the diagnosis of Kimura disease. Following treatment with oral glucocorticoids and methotrexate, the patient experienced a complete resolution of symptoms. He has been in remission and off oral prednisolone for the last 13 months. In this case, we highlight the development of Kimura disease in a patient undergoing mepolizumab treatment.