Characterization of ES10 lytic bacteriophage isolated from hospital waste against multidrug-resistant uropathogenic E. coli.

Escherichia coli is the major causative agent of urinary tract infections worldwide and the emergence of multi-drug resistant determinants among clinical isolates necessitates the development of novel therapeutic agents. Lytic bacteriophages efficiently kill specific bacteria and seems promising approach in controlling infections caused by multi-drug resistant pathogens. This study aimed the isolation and detailed characterization of lytic bacteriophage designated as ES10 capable of lysing multidrug-resistant uropathogenic E. coli. ES10 had icosahedral head and non-contractile tail and genome size was 48,315 base pairs long encoding 74 proteins. Antibiotics resistance, virulence and lysogenic cycle associated genes were not found in ES10 phage genome. Morphological and whole genome analysis of ES10 phage showed that ES10 is the member of Drexlerviridae. Latent time of ES10 was 30 min, burst size was 90, and optimal multiplicity of infection was 1. ES10 was stable in human blood and subsequently caused 99.34% reduction of host bacteria. Calcium chloride shortened the adsorption time and latency period of ES10 and significantly inhibited biofilm formation of host bacteria. ES10 caused 99.84% reduction of host bacteria from contaminated fomites. ES10 phage possesses potential to be utilized in standard phage therapy.

Aspongopus chinensis Dallas induces pro-apoptotic and cell cycle arresting effects in hepatocellular carcinoma cells by modulating miRNA and mRNA expression.

Aspongopus chinensis Dallas is a traditional Chinese medicinal insect with several anticancer properties can inhibit cancer cell growth, by inhibiting cell division, autophagy and cell cycle. However, the precise therapeutics effects and mechanisms of this insect on liver cancer are still unknown. This study examined the inhibitory influence of A. chinensis on the proliferation of hepatocellular carcinoma (HCC) cells and explore the underlying mechanism using high-throughput sequencing. The results showed that A. chinensis substantially reduced the viability of Hep G2 cells. A total of 33 miRNAs were found to be upregulated, while 43 miRNAs were downregulated. Additionally, 754 mRNAs were upregulated and 863 mRNAs were downregulated. Significant enrichment of differentially expressed genes was observed in signaling pathways related to tumor cell growth, cell cycle regulation, and apoptosis. Differentially expressed miRNAs exhibited a targeting relationship with various target genes, including ARC, HSPA6, C11orf86, and others. Hence, cell cycle and apoptosis were identified by flow cytometry. These findings indicate that A. chinensis impeded cell cycle advancement, halted the cell cycle in the G0/G1 and S stages, and stimulated apoptosis. Finally, mouse experiments confirmed that A. chinensis significantly inhibits tumor growth in vivo. Therefore, our findings indicate that A. chinensis has a notable suppressive impact on the proliferation of HCC cells. The potential mechanism of action could involve the regulation of mRNA expression via miRNA, ultimately leading to cell cycle arrest and apoptosis. The results offer a scientific foundation for the advancement and application of A. chinensis in the management of HCC.

Multi-scale spatiotemporal attention network for neuron based motor imagery EEG classification.

BACKGROUND: In recent times, the expeditious expansion of Brain-Computer Interface (BCI) technology in neuroscience, which relies on electroencephalogram (EEG) signals associated with motor imagery, has yielded outcomes that rival conventional approaches, notably due to the triumph of deep learning. Nevertheless, the task of developing and training a comprehensive network to extract the underlying characteristics of motor imagining EEG data continues to pose challenges. NEW METHOD: This paper presents a multi-scale spatiotemporal self-attention (SA) network model that relies on an attention mechanism. This model aims to classify motor imagination EEG signals into four classes (left hand, right hand, foot, tongue/rest) by considering the temporal and spatial properties of EEG. It is employed to autonomously allocate greater weights to channels linked to motor activity and lesser weights to channels not related to movement, thus choosing the most suitable channels. Neuron utilises parallel multi-scale Temporal Convolutional Network (TCN) layers to extract feature information in the temporal domain at various scales, effectively eliminating temporal domain noise. RESULTS: The suggested model achieves accuracies of 79.26%, 85.90%, and 96.96% on the BCI competition datasets IV-2a, IV-2b, and HGD, respectively. COMPARISON WITH EXISTING METHODS: In terms of single-subject classification accuracy, this strategy demonstrates superior performance compared to existing methods. CONCLUSION: The results indicate that the proposed strategy exhibits favourable performance, resilience, and transfer learning capabilities.

Aspongopus chinensis ach-miR-276a-3p induces breast cancer cell cycle arrest by targeting APPL2 to regulate the CDK2-Rb-E2F1 signaling pathway.

Breast cancer, the most common cancer, presents a significant challenge to the health and longevity of women. Aspongopus chinensis Dallas is an insect with known anti-breast cancer properties. However, the anti-breast cancer effects and underlying mechanisms have not been elucidated. Exogenous microRNAs (miRNAs), which are derived from plants and animals, have been revealed to have notable capacities for controlling the proliferation of cancerous cells. To elucidate the inhibitory effects of miRNAs derived from A. chinensis and the regulatory mechanism involved in the growth of breast cancer cells, miRNA sequencing was initially employed to screen for miRNAs both in A. chinensis hemolymph and decoction and in mouse serum and tumor tissue after decoction gavage. Subsequently, the experiments were performed to assess the suppressive effect of ach-miR-276a-3p, the miRNA screened out from a previous study, on the proliferation of MDA-MB-231 and MDA-MB-468 breast cancer cell lines in vitro and in vivo. Finally, the regulatory mechanism of ach-miR-276a-3p in MDA-MB-231 and MDA-MB-468 breast cancer cells was elucidated. The results demonstrated that ach-miR-276a-3p notably inhibited breast cancer cell proliferation, migration, colony formation, and invasion and induced cell cycle arrest at the G0/G1 phase. Moreover, the ach-miR-276a-3p mimics significantly reduced the tumor volume and weight in xenograft tumor mice. Furthermore, ach-miR-276a-3p could induce cell cycle arrest by targeting APPL2 and regulating the CDK2-Rb-E2F1 signaling pathway. In summary, ach-miR-276a-3p, derived from A. chinensis, has anti-breast cancer activity by targeting APPL2 and regulating the CDK2-Rb-E2F1 signaling pathway and can serve as a promising candidate anticancer agent.

Human epidermal growth receptor polymorphisms (HER1-rs11543848 and HER2-rs1136201) exhibited significant association with breast cancer risk in Pashtun population of Khyber Pakhtunkhwa, Pakistan.

Background and Aims: Breast cancer is the most common type of cancer in women. The genetic polymorphism in HER (HER1-rs11543848 and HER2-rs1136201) were found to be associated with breast cancer risk in different ethnicities worldwide with inconsistent results. The aim of this research study was to evaluate the association of HER1-rs11543848 and HER2-rs1136201 polymorphisms as a risk of breast cancer in Pashtun population of Khyber Pakhtunkhwa, Pakistan. Methods: A total of 314 women including 164 breast cancer patients and 150 age and gender-matched healthy controls were enrolled from June 2021 to May 2022. All the samples were subjected to DNA extraction followed by Tetra-ARMS-PCR for genotyping and gel electrophoresis. Results: Our results indicated that HER1-rs11543848 risk allele A (p = 0.0001) and heterozygous genotype GA (p = 0.0001) displayed highly significant association with breast cancer, while the homozygous mutant genotype AA indicated association but nonsignificant results (odds ratio [OR] = 2.637, 95% confidence interval [CI] = 1.2258-5.6756, p = 0.0833). Similarly, the HER2-rs1136201 risk allele G (p = 0.0023), the heterozygous genotype AG (p = 0.0530) and homozygous mutant genotype GG showed significant association (OR = 2.5946, 95% CI = 0.9876-6.8165, p = 0.0530) with breast cancer risk. Both the SNPs presented a higher but nonsignificant risk of breast cancer in postmenopausal women (OR = 2.242, p = 0.08 and OR = 2.009, p = 0.06). However, both the SNPs showed significant association (p < 0.005) with family history, metastasis, stage, luminal B, and TNBC. Conclusion: In conclusion, HER1-rs11543848 and HER2-rs1136201 polymorphisms are significantly associated with the higher risk of breast cancer in Pashtun population of Khyber Pakhtunkhwa, Pakistan. These findings advocate for further exploration with larger datasets, offering promising avenues for personalized approaches in breast cancer research and potentially enhancing clinical practices for better risk assessment and targeted management strategies.

Cell-free DNA as a potential diagnostic biomarker in academic stress: A case-control study in young adults.

Background: Stress is a pervasive issue in modern life, affecting both physical and mental health. Identifying biomarkers like cell-free DNA (cfDNA) could provide insights into stress response and help detect individuals at risk for stress-related disorders. Objective: The aim of this study is to investigate the potential use of cfDNA as a diagnostic biomarker in individuals experiencing stress. Methodology: A case-control analysis was conducted using convenient sampling on university participants (N = 285 cases, N = 500 controls) aged 18-24. The study assessed haematological and lipid profile parameters using the Sysmex XP-300TM automated analyzer and an automated biochemistry analyzer, and cfDNA was extracted using a standardized in house developed Phenol-Chloroform protocol and estimated using Agarose Gel Electrophoresis and Nanodrop. Statistical analysis was performed using SPSS ver. 21.0. Results: The results indicated a significant difference between stressed individuals and healthy controls in demographic, haematological and biochemical parameters. Specifically, stressed cases had significantly higher levels of cholesterol, LDL cholesterol, triglycerides, glucose, VLDL cholesterol, and lower levels of HDL compared to healthy controls. Stressed cases also showed significantly elevated levels of circulating cfDNA relative to healthy controls. Conclusion: These findings suggest that cfDNA may have potential as a diagnostic biomarker for stress.

In silico analysis of the Val66Met mutation in BDNF protein: implications for psychological stress.

The brain-derived neurotrophic factor (BDNF) involves stress regulation and psychiatric disorders. The Val66Met polymorphism in the BDNF gene has been linked to altered protein function and susceptibility to stress-related conditions. This in silico analysis aimed to predict and analyze the consequences of the Val66Met mutation in the BDNF gene of stressed individuals. Computational techniques, including ab initio, comparative, and I-TASSER modeling, were used to evaluate the functional and stability effects of the Val66Met mutation in BDNF. The accuracy and reliability of the models were validated. Sequence alignment and secondary structure analysis compared amino acid residues and structural components. The phylogenetic analysis assessed the conservation of the mutation site. Functional and stability prediction analyses provided mixed results, suggesting potential effects on protein function and stability. Structural models revealed the importance of BDNF in key biological processes. Sequence alignment analysis showed the conservation of amino acid residues across species. Secondary structure analysis indicated minor differences between the wild-type and mutant forms. Phylogenetic analysis supported the evolutionary conservation of the mutation site. This computational study suggests that the Val66Met mutation in BDNF may have implications for protein stability, structural conformation, and function. Further experimental validation is needed to confirm these findings and elucidate the precise effects of this mutation on stress-related disorders.

Benzimidazole Derivative (N-{4-[2-(4-Methoxyphenyl)-1H-Benzimidazole-1-Sulfonyl] Phenyl} Acetamide) Ameliorates Methotrexate-Induced Intestinal Mucositis by Suppressing Oxidative Stress and Inflammatory Markers in Mice.

Methotrexate (MTX)-induced intestinal mucositis (IM) is a common side effect in cancer treatment that impairs the immune system and gut microbes, resulting in loss of mucosal integrity and gut barrier dysfunction. The quality of life and outcomes of treatment are compromised by IM. The present study was designed to investigate the mucoprotective potential of the benzimidazole derivative N-{4-[2-(4-methoxyphenyl)-1H-benzimidazole-1-sulfonyl] phenyl} acetamide (B8) on MTX-induced IM in mice. IM was induced by a single dose of MTX in mice and assessed by physical manifestations as well as biochemical, oxidative, histological, and inflammatory parameters. B8 (1, 3, 9 mg/kg) significantly reduced diarrhea score, mitigated weight loss, increased feed intake and, survival rate in a dose-dependent manner. Notably, B8 exhibited a mucoprotective effect evident through the mitigation of villus atrophy, crypt hypoplasia, diminished crypt mitotic figures, mucin depletion, and oxidative stress markers (GSH, SOD, MDA, and catalase concentration). Gene expression analysis revealed that B8 downregulated the mRNA expression of tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), IL-1ß, and nuclear factor-κB (NF-κB) and concurrently upregulated IL-10 expression in contrast to the MTX group. Further, B8 significantly improved the luminal microflora profile by augmenting the growth of Lactobacillus spp. and reducing the number of pathogenic bacteria (E. coli). Additionally, the enzyme-linked immunoassay showed that B8 decreased the levels of pro-inflammatory cytokines. Our findings suggest that B8 had mucoprotective effects against MTX-induced IM and could be used as an adjunct in chemotherapy to deter this side effect.

RETRACTED: Khan et al. Poly (N-vinylcaprolactam-grafted-sodium alginate) Based Injectable pH/Thermo Responsive In Situ Forming Depot Hydrogels for Prolonged Controlled Anticancer Drug Delivery; In Vitro, In Vivo Characterization and Toxicity Evaluation. Pharmaceutics 2022, 14, 1050.

The journal retracts the article, "Poly (N-vinylcaprolactam-grafted-sodium alginate) Based Injectable pH/Thermo Responsive In Situ Forming Depot Hy-drogels for Prolonged Controlled Anticancer Drug Delivery; In Vitro, In Vivo Characterization and Toxicity Evaluation" [...].

Assessment of HER1 (rs11543848) and HER2 (rs1136201) polymorphism and their association with colorectal cancer susceptibility in Khyber Pakhtunkhwa, Pakistan.

BACKGROUND: Colorectal cancer (CRC) is a widespread malignancy characterized by uncontrolled growth in the colon or rectum and remains a leading cause of cancer-related mortality globally. Various genes polymorphisms have been linked with the risk of CRC, but our study aimed to investigate the association between HER1 (rs11543848) and HER2 (rs1136201) polymorphisms with the risk of CRC in the Khyber Pakhtunkhwa (KPK) population of Pakistan. The association of the selected polymorphisms (rs11543848 and rs1136201) with CRC risk has been investigated in various ethnic groups, but their impact remains unexplored in Pakistan, particularly within the KPK population, highlighting the need of the study in this region. METHODS: In this study 120 CRC patients and 120 healthy controls were enrolled. The DNA was extracted from the blood by salting-out method and genotyping was done using ARMS-PCR. RESULTS: Our investigations provided convincing evidence of a strong association between HER1 (rs11543848) and the risk of CRC. Both the genotypes heterozygous GA (OR = 2.07, CI = 1.18 to 3.64, P = 0.01) and homozygous AA (OR = 6.22, CI = 2.56 to 15.08, P = 0.0001) showed higher risk and significant association with the CRC risk. Similarly, heterozygous genotype AG of HER2 (rs1136201) was significantly associated (OR = 3.16, 95% CI = 1.78 to 5.58, P = 0.0001) while mutant genotype GG showed higher risk but non-significant association (OR = 3.23, 95% CI = 0.84 to 12.43, P = 0.08) with CRC patients. HER1 (rs11543848) demonstrated a significant association (P = 0.003) with the age at diagnosis in CRC patients, while HER2 (rs1136201) showed a non-significant association (P = 0.434). Both the SNPs were non-significantly associated with gender (P = 0.793 and 0.117), metastasis (P = 0.582 and 0.129), location of the tumor (P = 0.555 and 0.993), tumor grade (P = 0.290 and 0.920), tumor size (P = 0.535 and 0.289) and stages of cancer (P = 0.892 and 0.352). CONCLUSION: In conclusion, both the polymorphisms rs11543848 and rs1136201 displayed susceptibility with CRC in the KPK population. However, further investigations are recommended while using whole exome sequencing on a larger sample size for more precise results.

Identification, Genome Sequencing, and Characterizations of Helicobacter pylori Sourced from Pakistan.

The stomach's colonization by Helicobacter pylori (H. pylori) results in gastritis, ulcers, and stomach cancer. Frequently, pain is treated with medication, but resistant H. pylori infections are not. Therefore, it is important to find pharmacological targets and improved treatments for resistant H. pylori strains. The aim of the current study was sampling, identification, drug susceptibility testing following genome sequencing and comparative genome-wide analysis of selected H. pylori strains from Pakistan with three representative strains for virulence and drug-resistant characteristics. Based on culture, biochemistry, and molecular biology, 84 strains of H. pylori were identified, which made up 47% of the enrolled cases. Among all H. pylori strains, the highest resistance was reported for metronidazole with 82 H. pylori strains (98%), followed by clarithromycin with 62 resistant strains (74%). Among metronidazole-resistant strains, 38 strains (46%) were also resistant to clarithromycin, contributing 61% of clarithromycin resistant cases. Two strains, HPA1 and HPA2, isolated from 'gastritis' and 'gastric ulcer' patients, respectively, were further processed for WGS. The draft genome sequences of H. pylori strains HPA1 and HPA2 encode 1.66 Mbp and 1.67 Mbp genome size, 24 and 4 contiguous DNA sequences, and 1650 and 1625 coding sequences, respectively. Both the genomes showed greater than 90% similarity with the reference strain H. pylori ATCC 43504/PMSS1. The antibiotic-resistant genes were identified among all the strains with overall similarity above 95%, with minor differences in the sequence similarity. Using the virulent gene data obtained from the Virulence Factor Database, 75 to 85 virulent genes were identified in the five genome assemblies with various key genes such as cytolethal distending toxin (cdt), type IV secretion system, cag PAI, plasticity region, cell-motility- and flagellar-associated genes, neutrophil-activating protein (HP-NAP), T4SS effector cytotoxin-associated gene A (cagA), and urease-associated genes ureA and ureB, etc. Sequence similarity between the virulence factors found in this study and reference genes was at least 90%. In summary, the results of our study showed the relationship between clinical results and specific H. pylori strains' (HPA1 and HPA2) genetics such as antibiotic resistance and specific virulence factors. These findings provide valued understanding of the epidemiology of H. pylori-associated diseases. Moreover, identification and genomics analysis have provided insights into the epidemiology, genetic diversity, pathogenicity, and potential drug resistance genes of H. pylori strains, offering a foundation for developing more targeted and effective medical interventions, including anti-virulent medications.

Natural compound targeting BDNF V66M variant: insights from in silico docking and molecular analysis.

Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin gene family gene that encodes proteins vital for the growth, maintenance, and survival of neurons in the nervous system. The study aimed to screen natural compounds against BDNF variant (V66M), which affects memory, cognition, and mood regulation. BDNF variant (V66M) as a target structure was selected, and Vitamin D, Curcumin, Vitamin C, and Quercetin as ligands structures were taken from PubChem database. Multiple tools like AUTODOCK VINA, BIOVIA discovery studio, PyMOL, CB-dock, IMOD server, Swiss ADEMT, and Swiss predict ligands target were used to analyze binding energy, interaction, stability, toxicity, and visualize BDNF-ligand complexes. Compounds Vitamin D3, Curcumin, Vitamin C, and Quercetin with binding energies values of - 5.5, - 6.1, - 4.5, and - 6.7 kj/mol, respectively, were selected. The ligands bind to the active sites of the BDNF variant (V66M) via hydrophobic bonds, hydrogen bonds, and electrostatic interactions. Furthermore, ADMET analysis of the ligands revealed they exhibited sound pharmacokinetic and toxicity profiles. In addition, an MD simulation study showed that the most active ligand bound favorably and dynamically to the target protein, and protein-ligand complex stability was determined. The finding of this research could provide an excellent platform for discovering and rationalizing novel drugs against stress related to BDNF (V66M). Docking, preclinical drug testing and MD simulation results suggest Quercetin as a more potent BDNF variant (V66M) inhibitor and forming a more structurally stable complex.

The WATCHMAN Device Review: A New Era for Stroke Prophylaxis.

Atrial fibrillation (AF) is a major risk factor for ischemic stroke, accounting for more than 37 million cases worldwide. In AF, the left atrial appendage (LAA) is the most common site of thrombus formation, and its ligation/closure with the WATCHMAN device is a good alternative to long-term oral anticoagulation, especially in patients with contraindications to warfarin. However, the implantation procedure is associated with various risks and complications. A short-term anticoagulant and antithrombotic administration are essential after implantation. However, no consensus has been reached on the optimal regimen. The WATCHMAN device is non-inferior to warfarin and is a safe alternative for the prevention of stroke and systemic embolization related to non-valvular atrial fibrillation (NVAF). Important procedure-related complications include pericardial effusion (PE), device embolization, procedure-related ischemic stroke, and device-related thrombosis (DRT) formation. It is essential to optimize post-implantation therapy according to individual patient bleeding risk, DRT formation, and contraindication to direct oral anticoagulants (DOACs). Recent studies have also shown that DOACs are a convenient and non-inferior substitute for warfarin. Furthermore, patients with absolute contraindications to OACs/DOACs can only be managed with dual antiplatelet therapy (DAPT). Transesophageal echocardiography (TEE) should be used to assess residual peridevice flow and possible DRT formation at days 45 and 12 months. Low molecular weight heparin (LMWH) and OAC are excellent choices for DRT treatment if detected. This review summarizes the most important complications of the WATCHMAN device in the existing literature and discusses various anticoagulation strategies and challenges post-implementation.

Utilizing Black Soldier Fly Larvae to Improve Bioconversion and Reduce Pollution: A Sustainable Method for Efficient Treatment of Mixed Wastes of Wet Distiller Grains and Livestock Manure.

Widespread environmental contamination caused by huge amounts of wastes generated by human activities has become a critical global concern that requires urgent action. The black soldier fly (BSFL) has gradually been used to treat different wastes due to high efficiency and low cost. However, little information is available regarding the treatment of mixed wastes by BSFLs. The impact of BSFLs on conversion of cow manure (COM) and pig manure (PM) via the incorporation of wet distiller grains (WDG) was assessed. Results demonstrate that the waste reduction rate was increased by 20% by incorporating 45% WDG to COM and PM. The bioconversion rate of BSFLs in COM and PM also increased from 1.20 ± 0.02% and 0.92 ± 0.02% to 10.54 ± 0.06% and 10.05 ± 0.11%, respectively. Total nitrogen content and δ15N/14N ratios of WDG + COM and WDG + PM were found to be significantly lower than those of COM and PM alone (p < 0.01). The organic matter changes during manure degradation were further analyzed by combing ultraviolet-visible spectrum (UV-vis) with excitation-emission matrix (EEM) spectroscopy techniques and fluorescence area integration (FRI) method. The UV-vis spectra results indicate that the addition of WDG to manures resulted in the decreased aromaticity and molecular weight of the waste. EEM spectra demonstrated that the accumulative Pi,n values of regions III and V in COM, COM + WDG, PM, and PM + WDG were 58%, 49%, 52% and 63%, respectively. These results not only provide new insights into the potential of mixed wastes for BSFL treatment but also contribute to the basis for the formulation of effective management measurements that reduce and/or reuse these wastes.

Lung Tumor Image Segmentation from Computer Tomography Images Using MobileNetV2 and Transfer Learning.

BACKGROUND: Lung cancer is one of the most fatal cancers worldwide, and malignant tumors are characterized by the growth of abnormal cells in the tissues of lungs. Usually, symptoms of lung cancer do not appear until it is already at an advanced stage. The proper segmentation of cancerous lesions in CT images is the primary method of detection towards achieving a completely automated diagnostic system. METHOD: In this work, we developed an improved hybrid neural network via the fusion of two architectures, MobileNetV2 and UNET, for the semantic segmentation of malignant lung tumors from CT images. The transfer learning technique was employed and the pre-trained MobileNetV2 was utilized as an encoder of a conventional UNET model for feature extraction. The proposed network is an efficient segmentation approach that performs lightweight filtering to reduce computation and pointwise convolution for building more features. Skip connections were established with the Relu activation function for improving model convergence to connect the encoder layers of MobileNetv2 to decoder layers in UNET that allow the concatenation of feature maps with different resolutions from the encoder to decoder. Furthermore, the model was trained and fine-tuned on the training dataset acquired from the Medical Segmentation Decathlon (MSD) 2018 Challenge. RESULTS: The proposed network was tested and evaluated on 25% of the dataset obtained from the MSD, and it achieved a dice score of 0.8793, recall of 0.8602 and precision of 0.93. It is pertinent to mention that our technique outperforms the current available networks, which have several phases of training and testing.

Unraveling the Radioprotective Mechanisms of UV-Resistant Bacillus subtilis ASM-1 Extracted Compounds through Molecular Docking.

Radioresistant microorganisms possess inimitable capabilities enabling them to thrive under extreme radiation. However, the existence of radiosensitive microorganisms inhabiting such an inhospitable environment is still a mystery. The current study examines the potential of radioresistant microorganisms to protect radiosensitive microorganisms in harsh environments. Bacillus subtilis strain ASM-1 was isolated from the Thal desert in Pakistan and evaluated for antioxidative and radioprotective potential after being exposed to UV radiation. The strain exhibited 54.91% survivability under UVB radiation (5.424 × 103 J/m2 for 8 min) and 50.94% to mitomycin-C (4 µg/mL). Extracellular fractions collected from ASM-1 extracts showed significant antioxidant potential, and chemical profiling revealed a pool of bioactive compounds, including pyrrolopyrazines, amides, alcoholics, and phenolics. The E-2 fraction showed the maximum antioxidant potential via DPPH assay (75%), and H2O2 scavenging assay (68%). A combination of ASM-1 supernatant with E-2 fraction (50 µL in a ratio of 2:1) provided substantial protection to radiosensitive cell types, Bacillus altitudinis ASM-9 (MT722073) and E. coli (ATCC 10536), under UVB radiation. Docking studies reveal that the compound supported by literature against the target proteins have strong binding affinities which further inferred its medical uses in health care treatment. This is followed by molecular dynamic simulations where it was observed among trajectories that there were no significant changes in major secondary structure elements, despite the presence of naturally flexible loops. This behavior can be interpreted as a strategy to enhance intermolecular conformational stability as the simulation progresses. Thus, our study concludes that Bacillus subtilis ASM-1 protects radiosensitive strains from radiation-induced injuries via biofilm formation and secretion of antioxidative and radioprotective compounds in the environment.

Micro array patch assisted transdermal delivery of high dose, ibuprofen sodium using thermoresponsive sodium alginate/poly (vinylcaprolactam) in situ gels depot.

Current study reports the combined technique of microneedle array patches and thermoresponsive gels. Microneedles array patch mediated insitu skin depots were evaluated for sustain drug delivery using sodium alginate/Poly (vinylcaprolactam) thermoresponsive gels. Their phase transition property from sol-gel state was monitored with AR2000 rheometer. Ibuprofen sodium was loaded in optimized formulations. The non-soluble cross-linked microneedle array patches (MAPs) were prepared from variable biocompatible polymers using silicone micromoulds. The fabricated MAPs were evaluated for mechanical stability, inskin dissolution, insertion forces and moisture contents. The penetration depth of MAPs in neonatal rabbit skin was tracked by optical coherence tomography. The optimized MAPs (GP10000) were used as microporation source in skin owing to their stable nature. Pores formation in skin samples after MAPs treatment was confirmed by optical coherence tomography, dye binding and skin integrity analysis. The invitro permeation of Ibuprofen sodium from formulations was studied using Franz cells across intact skin and MAPs applied skin. It was concluded from the results that Ibuprofen sodium permeation was observed for longer time through MAPs treated skin as compared to intact skin. Confocal study confirmed the diffusion of drug loaded formulations in deeper tissues with higher intensity.

Field assessment of yield and its contributing traits in cowpea treated with lower, intermediate, and higher doses of gamma rays and sodium azide.

Across the globe, plant breeders of different organizations are working in collaboration to bring preferred traits to crops of economic importance. Among the traits, "high yielding potential" is the most important as it is directly associated with food security and nutrition, one of the sustainable development goals. The Food and Agriculture Organization acknowledges plant breeders' role and efforts in achieving local and global food security and nutrition. Recognizing the importance of pulses and increasing pressure on food security, the United Nations General Assembly declared 2016 the "International year of Pulses" owing to their preferred traits such as climate change resilience, wide adaptability, low agriculture input, and protein- and nutrient-rich crops. Keeping all these developments in consideration, we initiated an induced mutagenesis program by treating cowpea (Vigna unguiculata L. Walp.) with different doses of gamma rays and sodium azide aiming to enhance the yielding potential of an otherwise outstanding variety viz., Gomati VU-89 and Pusa-578. We noticed a substantial increase in mean values of agronomic traits in putative mutants raised from seeds treated with lower and intermediate doses of mutagens. Statistical analysis such as correlation, path, hierarchical clustering analysis (HCA), and principal component analysis (PCA) were used to assess the difference between mutagenized and control populations. A significant and positive correlation of yield with yield-attributing traits was recorded. However, among all the yield attributing traits, seeds per pod (SPP) depicted the maximum direct impact upon yield, and therefore, working on this trait may yield better results. A widely used PCA revealed 40.46% and 33.47% of the total variation for var. Gomati VU-89 and var. Pusa-578, respectively. Cluster analysis clustered treated and control populations into separate clusters with variable cluster sizes. Cluster V in the variety Gomati VU-89 and cluster V and VI in the variety Pusa 578 comprised of putative mutants were higher yielding and hence could be recommended for selection in future breeding programs. We expect to release such mutant lines for farmer cultivation in Northern parts of India depending on the performance of such high-yielding mutant lines at multilocations.

Assessment of Bio-physiological damages and cytological aberrations in cowpea varieties treated with gamma rays and sodium azide.

The assessment of mutagen induced biological damage forms an important study in determining the mutagenic potency and genotypic sensitivity, a vital aspect in mutation breeding programs. A prior assessment of lethal dose (LD50), mutagen induced biological damage (alterations in bio-physiological traits and frequency of cytological aberrations) is a prerequisite for determining an optimum mutagen dose in a successful mutation breeding experiment. Therefore, in a multi-year project of mutation breeding, two widely cultivated varieties of cowpea viz., Gomati VU-89 and Pusa-578, were treated with gamma (γ) rays and sodium azide (SA) doses. The results reflected a proportionate increase in bio-physiological damages with the increase in mutagenic doses and caused a substantial reduction in mean seed germination and seedling height. Different cytological aberrations such as cytomixis, univalents, chromosome stickiness, precocious separation, unequal separation, bridges, laggards, disturbed polarity, dyads, triads, and polyads were observed in both varieties. All the mutagen doses induced a broader spectrum of cytological aberrations with varying frequencies.