Recent studies have demonstrated a close interaction between neuroinflammatory responses, increased production of inflammatory mediators, and neurodegeneration. Pathological findings in neurological ...diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease have shown common signs of neuroinflammation and neurodegeneration. Lupeol, a natural pentacyclic triterpene, has revealed a number of pharmacological properties including an anti-inflammatory activity. This study aimed to evaluate the effect of lupeol against lipopolysaccharide (LPS)-induced neuroinflammation in the cortex and hippocampus of adult mice. Our results showed that systemic administration of LPS induced glial cell production of proinflammatory cytokines, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), and interleukin (IL)-1β, while co-treatment with lupeol significantly inhibited the LPS-induced activation of microglia and astrocytes, and decreased the LPS-induced generation of TNF-α, iNOS, and IL-1β. The intracellular mechanism involved in the LPS-induced activation of inflammatory responses includes phosphorylation of P38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK), which was significantly inhibited by lupeol. We further elucidated that lupeol inhibited the LPS-induced activation of the mitochondrial apoptotic pathway and reversed the LPS-induced expression of apoptotic markers such as Bax, cytochrome C, caspase-9, and caspase-3. Taken together; our results suggest that lupeol inhibits LPS-induced microglial neuroinflammation via the P38-MAPK and JNK pathways and has therapeutic potential to treat various neuroinflammatory disorders.
Osteoarthritis (OA) is a prevalent musculoskeletal disorder, predominantly affecting the knee joint and resulting in significant pain and functional limitations. The Kellgren-Lawrence (KL) grading ...system, traditionally utilized by radiologists, assesses OA severity through radiographic evaluation of knee bones on both sides. Recent advancements in computer-aided methods have focused on enhancing diagnostic precision and efficiency, leveraging automated classification models with Knee X-rays which represent a cornerstone imaging modality for OA severity assessment. In this study, a novel hybrid model combining Convolutional Neural Networks (CNN) and VGG16 architectures is proposed to achieve accurate OA detection. Various neural networks, including CNN, VGG16, VGG19, ResNet50, and CNN-ResNet, are implemented and compared alongside the proposed method. Additionally, data augmentation techniques are employed to address class imbalance, leading to enhanced accuracies across all models. Analysis demonstrates robust performance of all models on the training set. The proposed hybrid method (CNN-ResNet50) outperforms other state-of-the-art approaches, providing precise results across all five stages of OA according to the KL grading system by achieving an accuracy exceeding 93% on training, validation, and testing datasets.
Photocatalytic water splitting is a promising route to alleviate energy crises and provide clean renewable energy. However, finding the right materials for photocatalytic water splitting is ...challenging owing to its multilevel complexity. Herein, transition metal sulfide and selenide (TMSS) monolayers were screened to find the best possible monolayers for overall water splitting. Properties such as suitable band edges, oxidation and reduction potential, catalytic activities and solar to hydrogen (STH) efficiency were considered. Among various TMSS monolayers, MoS
2
, WS
2
, PtSe
2
, PdSe
2
, and NiSe
2
have suitable conduction and valence band edges to trigger the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) simultaneously in acidic media. Moreover, the MoS
2
, PtSe
2
, PdSe
2
and NiSe
2
monolayers can effectively resist oxidative and reductive photo-corrosion in acidic and WS
2
monolayers in neutral environments during water splitting. All monolayers have robust catalytic activities in the predicted electrolytes with HER overpotential near zero, and OERs are 0.53, 1.01 and 0.99 V for PtSe
2
, PdSe
2
and NiSe
2
monolayers, respectively. The STH efficiencies were also found to be high for MoS
2
(10.4%), PtSe
2
(22.2%), PdSe
2
(19.6%), NiSe
2
(20.1%) in acidic medium and WS
2
(11.1%) in neutral medium. The predicted monolayers show promise for practical application as bifunctional photocatalysts in acidic and neutral environments.
A systematic study was carried out to identify transition metal sulfide and selenide (TMSS) monolayers, which resist both photo-degradation and photo-corrosion in a single electrolyte towards overall water splitting (OWS).
Oxidative stress and energy imbalance strongly correlate in neurodegenerative diseases. Repeated concussion is becoming a serious public health issue with uncontrollable adverse effects in the human ...population, which involve cognitive dysfunction and even permanent disability. Here, we demonstrate that traumatic brain injury (TBI) evokes oxidative stress, disrupts brain energy homeostasis, and boosts neuroinflammation, which further contributes to neuronal degeneration and cognitive dysfunction in the mouse brain. We also demonstrate that melatonin (an anti-oxidant agent) treatment exerts neuroprotective effects, while overcoming oxidative stress and energy depletion and reducing neuroinflammation and neurodegeneration. Male C57BL/6N mice were used as a model for repetitive mild traumatic brain injury (rmTBI) and were treated with melatonin. Protein expressions were examined via Western blot analysis, immunofluorescence, and ELISA; meanwhile, behavior analysis was performed through a Morris water maze test, and Y-maze and beam-walking tests. We found elevated oxidative stress, depressed phospho-5'AMP-activated protein kinase (p-AMPK) and phospho- CAMP-response element-binding (p-CREB) levels, and elevated p-NF-κB in rmTBI mouse brains, while melatonin treatment significantly regulated p-AMPK, p-CREB, and p-NF-κB in the rmTBI mouse brain. Furthermore, rmTBI mouse brains showed a deregulated mitochondrial system, abnormal amyloidogenic pathway activation, and cognitive functions which were significantly regulated by melatonin treatment in the mice. These findings provide evidence, for the first time, that rmTBI induces brain energy imbalance and reduces neuronal cell survival, and that melatonin treatment overcomes energy depletion and protects against brain damage via the regulation of p-AMPK/p-CREB signaling pathways in the mouse brain.
Methicillin-resistant Staphylococcus aureus (MRSA) is a prevailing nosocomial pathogen that is increasingly isolated in community settings. It shows resistance against all beta-lactam drugs and has ...acquired mechanisms to resist other groups of antibiotics. To tackle this emerging issue of MRSA, there is an urgent need for antibiotic alternatives, and utilizing lytic bacteriophages is one of the most promising therapeutic approaches. In the present study, a lytic bacteriophage TSP was isolated from hospital wastewater against MRSA. The phage efficiently inhibited bacterial growth for up to 12 h at MOI of 1 and 10. TSP phage showed activity against various isolates of MRSA and MSSA, isolated from different clinical samples, with variable antibiotic susceptibility patterns. The bacteriophage TSP showed stability at varying temperatures (25 °C, 37 °C) and pH values (5-9), while its maximum storage stability was observed at 4 °C. It had a short latent period (20 min) and burst size of 103 ± 5pfu/infected cells. TSP genome sequence and restriction analysis revealed that its genome has a linear confirmation and length of 17,987 bp with an average GC content of 29.7%. According to comparative genomic analysis and phylogenetic tree,TSP phage can be considered a member of genus "P68viruses". The strong lytic activity and short latent period in addition to its lytic nature makes it a good candidate for phage therapy against MRSA infections, if it proves to be effective in in-vivo studies.
Women library professionals are greatly underrepresented in key leadership positions, especially in the developing countries. This study explored the women academic library leadership in Pakistan and ...investigated the major challenges faced by women leaders during their ascending to the top, the key indicator of their success, as well as the community services and professional contributions made by them during the course of their careers. Qualitative research design was used and data were collected by conducting in-depth interviews of 16 senior woman library leaders in Pakistan. The findings indicated that organizational challenges, family responsibilities, and gender discrimination were the major barriers that hindered the women leaders during their career progression. The key indicators of their success were effective use of technology, professional commitment, academic contributions, community services, family support, international exposure, and continuous learning. The implications of the study highlight the various areas of improvement for women library leadership.
The physical and chemical properties of monolayers can be tuned by selective combinations so as to be useful for device applications. Here we present a density functional theory study on the ...structural, electronic and optical properties of three transition metal dichalcogenide (TMD) heterobilayers, ZrS2/HfS2, ZrSe2/HfSe2 and SnS2/SnSe2. These heterobilayers are predicted to be energetically and dynamically stable structures. The band structure calculation result shows that ZrS2/HfS2, ZrSe2/HfSe2 and SnS2/SnSe2 heterobilayers are semiconductors with indirect band gaps. The efficient charge carrier separation in ZrS2/HfS2 and ZrSe2/HfSe2 heterobilayers indicates that they can be employed in energy harvesting devices. Contrary to the previous report on the ZrS2/HfS2 heterobilayer, we found it to have an intrinsic type-II band alignment which is required in p-n junction diodes and tunnel field effect transistors, and the same behavior was observed in ZrSe2/HfSe2 and SnS2/SnSe2 for the first time. The ZrS2/HfS2 and ZrSe2/HfSe2 heterobilayers reveal enhanced optical absorption both in the ultraviolet and visible regions as compared to their respective monolayers, whereas the parallel and perpendicular part of the optical absorption of the SnS2/SnSe2 heterobilayer revealed an anisotropic behavior; the perpendicular part is largely improved in the higher energy region, and the parallel part of the optical absorption is improved in the ultraviolet region.
Health assumptions to the population due to the utilization of contaminated vegetables have been a great concern all over the world. In this study, an investigation has been conducted to ascertain ...metal concentrations in the wastewater, soil and commonly consumed vegetables from the vicinity of Gadoon Industrial Estate Swabi, Khyber Pakhtunkhwa Pakistan. Physicochemical parameters such as pH, electrical conductivity (EC), total dissolved solids (TDS), total suspended solids (TSS) and total solids (TS) and heavy metals such as Pb, Cr, Cd, Ni, Zn, Cu, Fe, Mn were determined using Atomic Absorption Spectrophotometer (AAS). Moreover, possible health risks due to the consumption of vegetables have also been estimated. pH and TSS in wastewater were found to be higher than the permissible limit set by WHO (1996). These results revealed that Cr concentration in the wastewater was above the permissible limits of United States Environmental Protection Agency (USEPA) which may lead to a detrimental effect on soil quality deterioration, ultimately leading to food contamination. ANOVA analysis demonstrated a significant difference in soil samples for Pb, Cr, Cd, Ni, Zn and Cu at p ≤ 0.001, for Mn at p ≤ 0.05 while no significant difference was observed for Fe respectively. ANOVA analysis also exhibited the highest mean value for Pb, Cr, Cd and Zn in vegetables. A substantial positive correlation was found among the soil and vegetable contamination. The transfer factor for Cr, Pb, Zn, Mn, Ni, Cd and Cu was greater than 0.5 due to contamination caused by domestic discharges and industrial effluents. Health assessment via consumption of dietary vegetables revealed a higher level than the permissible limit (HRI > 1) for Pb and Cd in children and adults. Enrichment factor (EF) due to consumption of vegetables was found higher for Pb and Cr respectively. Based on the findings of this study, there would be a significant risk to the consumers associated with consumptions of vegetables being cultivated in Gadoon Industrial Estate area of district Swabi. Therefore, strict regulatory control measures are highly recommended for the safety of vegetables originated from the study area.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The study deals with the LM and SEM (light microscopy and scanning electron microscopy) of Datura stramonium L. extract and to evaluate its phytochemical, antimicrobial, and antioxidant activities. ...The plant sample collected from different Lahore region was dried under shade. The plant extract was prepared using different solvents (n‐hexane, chloroform, ethyl acetate, and methanol). Phytochemical screening performed qualitatively for alkaloids, carbohydrates, flavonoids, saponins, and tannins. Radical scavenging potential of plant extracts was estimated and ethyl acetate extract exhibited maximum percentage scavenging ability of 92.2 ± 0.09. Total antioxidant capacity of different extracts was measured by phosphomolybdate method. The ethyl acetate and methanolic extracts showed maximum values of 72.3 ± 0.08% and 79 ± 0.15% with respect to gallic acid. Total phenolic contents were determined through Folin‐Ciocalteau method and highest value of 495.2 ± 3.4 was obtained by methanolic extract. DPPH‐TLC autography was used for the visual detection of antioxidant compounds in different plant extracts. Antibacterial activity of plant extract was measured by disc diffusion method against microorganisms named Bacillus licheniformis, Bacillus subtilis (Gram positive), and Salmonella typhimurium, and Proteus mirabilis (Gram negative). Because of the vast medicinal importance of D. stramonium L. it would be beneficial to study LM and SEM for correct identification of plant and to determine phytochemicals.
Research Highlights
LM and SEM (light microscopy and scanning electron microscopy) of Datura stramonium L. was studied for the exact identification of plant.
To evaluate the biological activities of pharmaceutically important plant.
Antioxidant and antimicrobial activity were determined.
D. stramonium L. proved to be medicinally important plant.
scheme of experimental work.
Multidrug-resistant Klebsiella pneumoniae is a nosocomial pathogen, produces septicemia, pneumonia and UTI. Excessive use of antibiotics contributes towards emergence of multidrug-resistance. ...Bacteriophage-therapy is a potential substitute of antibiotics with many advantages. In this investigation, microbiological and genome characterization of TSK1 bacteriophage and its biofilm elimination capability are presented. TSK1 showed narrow host range and highest stability at pH 7 and 37 °C. TSK1 reduced the growth of K. pneumoniae during the initial 14 hours of infection. Post-treatment with TSK1 against different age K. pneumoniae biofilms reduced 85-100% biomass. Pre-treatment of TSK1 bacteriophage against the biofilm of Klebsiella pneumoniae reduced > 99% biomass in initial 24 hr of incubation. The genome of TSK1 phage comprised 49,836 base pairs with GC composition of 50.44%. Total seventy-five open reading frames (ORFs) were predicted, 25 showed homology with known functional proteins, while 50 were called hypothetical, as no homologs with proved function exists in the genome databases. Blast and phylogenetic analysis put it in the Kp36 virus genus of family Siphoviridae. Proposed packaging strategy of TSK1 bacteriophage genome is headful packaging using the pac sites. The potential of TSK1 bacteriophage could be used to reduce the bacterial load and biofilm in clinical and non-clinical settings.
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