Phytogenic-Mediated Zinc Oxide Nanoparticles Using the Seed Extract of Citrullus lanatus and Its Integrated Potency against Multidrug Resistant Bacteria.

In the current research study, zinc oxide nanoparticles (ZnO-NPs) were synthesized via a green synthesis technique using the seed extract of Citrullus lanatus. The study further intended to evaluate the potential synergistic effects of ZnO-NPs with antibiotics against multidrug resistant (MDR) bacteria. It was observed that C. lanatus seed extracts obtained by n-hexane and methanolic solvents revealed the presence of constituents, such as tannins, flavonoids, and terpenoids. Furthermore, the extract of n-hexane displayed the strongest antibacterial activity against Yersinia species (17 ± 1.2 mm) and Escherichia coli (17 ± 2.6 mm), while the methanolic extract showed the maximum antibacterial activity against E. coli (17 ± 0.8 mm). Additionally, the ZnO-NP synthesis was confirmed by ultraviolet-visible analysis with a characteristic absorption peak at 280 nm. The Fourier transform infrared spectroscopy analysis suggested the absorption peaks in the 500-3800 cm-1 range, which corresponds to various groups of tertiary alcohol, aldehyde, amine, ester, aromatic compounds, thiol, amine salt, and primary amine. The scanning electron microscopy spectra of ZnO-NPs demonstrated the presence of zero-dimensional spherical particles with well-dispersed character. Moreover, encapsulation with ZnO-NPs improved the antimicrobial activity of antibiotics against the panel of MDR bacteria, and the increases in the effectiveness of particular antibiotics against MDR bacteria were significant (P = 0.0005). In essence, the synthesized ZnO-NPs have the potential as drug carriers with powerful bactericidal properties that work against MDR bacterial strains. These outcomes are an indication of such significance in pharmaceutical science, giving possibilities for further research and development in this field.

Visible light-activated curcumin-doped zinc oxide nanoparticles integrated into orthodontic adhesive on Micro-tensile bond strength, degree of conversion, and antibacterial effectiveness against Staphylococcus Aureus. An investigation using scanning electron microscopy and energy-dispersive X-ray spectroscopy.

AIM: To acquire a thorough comprehension of the photoactivated Cur-doped ZnONPs at different concentrations 0%, 2.5%, and 5% on the physical qualities, antibacterial efficacy, degree of conversion, and µshear bond strength between orthodontic brackets and the enamel surface. MATERIAL AND METHODS: An extensive investigation was carried out utilizing a range of analytical methods, scanning electron microscopy (SEM) combined with energy-dispersive X-ray spectroscopy (EDX), Fourier-transform infrared (FTIR) spectroscopy, micro tensile bond strength (µTBS) testing, and evaluation of antibacterial effectiveness. Cur-doped ZnONPs at concentrations of 2.5% and 5% were blended with Transbond XT, a light-curable orthodontic adhesive. A control group without the addition of Cur-doped ZnONPs was also prepared. The tooth samples were categorized into three groups based on the weight percentage of NPs: Group 1 (control) with 0% Cur-doped ZnONPs, Group 2 with 2.5 wt% Cur-doped ZnONPs, and Group 3 with 5 wt% Cur-doped ZnONPs. The SEM technique was employed to analyze the morphological characteristics of Cur-doped ZnONPs and ZnONPs. The composition and elemental distribution of the modified Cur-doped ZnONPs were assessed using energy-dispersive X-ray spectroscopy. The effectiveness of NPs at various concentrations against S.Mutans was gauged through the pour plate method. DC of Cur-doped ZnONPs at a region of 1608 cm-1 to 1636 cm-1 for the cured area, whereas the uncured area spanned the same range of 1608 cm-1 to 1636 cm-1 was assessed. The Adhesive Remnant Index (ARI) approach was utilized to investigate the bond failure of orthodontic brackets, while a Universal Testing Machine (UTM) was utilized to test µTBS. The Kruskal-Wallis test was employed to investigate variations in S.mutans survival rates. To determine the µTBS values, analysis of variance (ANOVA) and the post hoc Tukey multiple comparisons test were used. RESULTS: The maximum µTBS was given and documented in group 3: 5 wt% Cur-doped ZnONPs (21.21 ± 1.53 MPa). The lowest µTBS was given in group 2: 2.5 wt% Cur-doped ZnONPs (19.58 ± 1.27 MPa). The highest efficacy against S.mutans was documented in group 3 in which 5 wt% Cur-doped ZnONPs (0.39 ± 0.15). The lowest efficacy was seen in group 1 in which no Cur-doped ZnONPs were used (6.47 ± 1.23). The ARI analysis indicated that the predominant failure was between scores 0 and 1 among all experimental groups. Control group 1 which was not modified showed the highest DC (73.11 ± 4.19). CONCLUSION: Orthodontic adhesive, containing 5% Cur-doped ZnONPs photoactivated with visible light exhibited a favorable impact on µTBS and indicated enhanced antibacterial efficacy against S.mutans. Nevertheless, it was observed that the addition of Cur-doped ZnONPs at different concentrations (2.5%,5%) resulted in a decrease in the monomer-to-polymer ratio compromising DC.

Therapeutic potential of popular fermented dairy products and its benefits on human health.

In the current arena of time, the transformation of society has improved the standard of living in terms of lifestyle and their nutritional demands and requirements. The microorganisms under controlled conditions and the enzymatic transformation of dietary components are the processes that resulted in fermented foods and beverages. Fermented dairy products with high nutritional value are "the pearls of the dairy industry." During fermentation, fermented dairy products produce bioactive compounds and metabolites derived from bacteria. Research indicates the beneficial effects of probiotics found in dairy products on human health is making lightning-fast headway these days. The utilization of lactic acid bacteria as probiotics for the prevention or treatment of disease has been a driving force behind the discovery of novel potential probiotics found in naturally fermented milk. Probiotics such as lactic acid bacteria and bifidobacteria found in fermented dairy products have a variety of health benefits, including innate immune enhancement, diarrhea treatment, inflammatory bowel disease, diabetes, Tuberculosis, and obesity, relieving irritable bowel disease symptoms, preventing cancer, improving lactose tolerance, lowering cholesterol, enhancing antioxidant activity, and antimicrobial activity against pathogens. This review aims to evaluate the therapeutic efficacy and nutritional and microbiological properties of popular fermented dairy products and their health benefits.

Pepper defense against Ralstonia solanacearum and High-temperature stress is positively regulated by CaMYB59.

We have functionally evaluated a transcription factor CaMYB59 for its role in pepper immune responses to Ralstonia solanacearum attack and high temperature-high humidity (HTHH). Exposure to R. solanacearum inoculation (RSI) and HTHH resulted in up-regulation of this nucleus-localized TF. Function of this TF was confirmed by performing loss of function assay of CaMYB59 by VIGS (virus-induced gene silencing). Plants with silenced CaMYB59 displayed not only compromised pepper immunity against RSI but also impaired tolerance to HTHH along with decreased hypersensitive response (HR). This impairment in defense function was fully linked with low induction of stress-linked genes like CaPO2, CaPR1, CaAcc and thermo-tolerance linked CaHSP24 as well as CaHsfB2a. Conversely, transient overexpression of CaMYB59 enhanced pepper immunity. This reveals that CaMYB59 positively regulated host defense against RSI and HTHH by means of HR like mimic cell death, H2O2 production and up-regulation of defense as well as thermo-tolerance associated genes. These changes in attributes collectively confirm the role of CaMYB59 as a positive regulator of pepper immunity against R. solanacearum. We recommend that such positive regulation of pepper defense is dynamically supported by phyto-hormone signaling and transcriptional web of defense genes. These integrated and interlinked events stabilize plant growth and survival under abiotic and biotic stresses.

Identification and expression analysis of SBP-Box-like (SPL) gene family disclose their contribution to abiotic stress and flower budding in pigeon pea (Cajanus cajan).

The SPL gene family (for Squamosa Promoter-binding like Proteins) represents specific transcription factors that have significant roles in abiotic stress tolerance, development and the growth processes of different plants, including initiation of the leaf, branching and development of shoot and fruits. The SPL gene family has been studied in different plant species; however, its role is not yet fully explored in pigeon pea (Cajanus cajan ). In the present study, 11 members of the CcSPL gene family were identified in C. cajan . The identified SPLs were classified into nine groups based on a phylogenetic analysis involving SPL protein sequences from C. cajan , Arabidopsis thaliana , Cicer arietinum , Glycine max , Phaseolus vulgaris , Vigna unguiculata and Arachis hypogaea . Further, the identification of gene structure, motif analysis, domain analysis and presence of cis -regulatory elements in the SPL family members were studied. Based on RNA-sequencing data, gene expression analysis was performed, revealing that CcSPL2.1, 3 and 13A were significantly upregulated for salt-tolerance and CcSPL14 and 15 were upregulated in a salt-susceptible cultivar. Real-time qPCR validation indicated that CcSPL3, 4, 6 and 13A were upregulated under salt stress conditions. Therefore, molecular docking was performed against the proteins of two highly expressed genes (CcSPL3 and CcSPL14 ) with three ligands: abscisic acid, gibberellic acid and indole-3-acetic acid. Afterward, their binding affinity was obtained and three-dimensional structures were predicted. In the future, our study may open avenues for harnessing CcSPL genes in pigeon pea for enhanced abiotic stress resistance and developmental traits.

3D-DXA Based Finite Element Modelling for Femur Strength Prediction: Evaluation Against QCT.

Osteoporosis is characterised by the loss of bone density resulting in an increased risk of fragility fractures. The clinical gold standard for diagnosing osteoporosis is based on the areal bone mineral density (aBMD) used as a surrogate for bone strength, in combination with clinical risk factors. Finite element (FE) analyses based on quantitative computed tomography (QCT) have been shown to estimate bone strength better than aBMD. However, their application in the osteoporosis clinics is limited due to exposure of patients to increased X-rays radiation dose. Statistical modelling methods (3D-DXA) enabling the estimation of 3D femur shape and volumetric bone density from dual energy X-ray absorptiometry (DXA) scan have been shown to improve osteoporosis management. The current study used 3D-DXA based FE analyses to estimate femur strength from the routine clinical DXA scans and compared its results against 151 QCT based FE analyses, in a clinical cohort of 157 subjects. The linear regression between the femur strength predicted by QCT-FE and 3D-DXA-FE models correlated highly (coefficient of determination R2 = 0.86) with a root mean square error (RMSE) of 397 N. In conclusion, the current study presented a 3D-DXA-FE modelling tool providing accurate femur strength estimates noninvasively, compared to QCT-FE models.

Integrated virtual screening and molecular dynamics simulation approaches revealed potential natural inhibitors for DNMT1 as therapeutic solution for triple negative breast cancer.

Triple negative breast cancers (TNBC) are clinically heterogeneous but mostly aggressive malignancies devoid of expression of the estrogen, progesterone, and HER2 (ERBB2 or NEU) receptors. It accounts for 15-20% of all cases. Altered epigenetic regulation including DNA hypermethylation by DNA methyltransferase 1 (DNMT1) has been implicated as one of the causes of TNBC tumorigenesis. The antitumor effect of DNMT1 has also been explored in TNBC that currently lacks targeted therapies. However, the actual treatment for TNBC is yet to be discovered. This study is attributed to the identification of novel drug targets against TNBC. A comprehensive docking and simulation analysis was performed to optimize promising new compounds by estimating their binding affinity to the target protein. Molecular dynamics simulation of 500 ns well complemented the binding affinity of the compound and revealed strong stability of predicted compounds at the docked site. Calculation of binding free energies using MMPBSA and MMGBSA validated the strong binding affinity between compound and binding pockets of DNMT1. In a nutshell, our study uncovered that Beta-Mangostin, Gancaonin Z, 5-hydroxysophoranone, Sophoraflavanone L, and Dorsmanin H showed maximum binding affinity with the active sites of DNMT1. Furthermore, all of these compounds depict maximum drug-like properties. Therefore, the proposed compounds can be a potential candidate for patients with TNBC, but, experimental validation is needed to ensure their safety.Communicated by Ramaswamy H. Sarma.

Transcriptional Factors Mediated Reprogramming to Pluripotency.

A unique kind of pluripotent cell, i.e., Induced pluripotent stem cells (iPSCs), now being targeted for iPSC synthesis, are produced by reprogramming animal and human differentiated cells (with no change in genetic makeup for the sake of high efficacy iPSCs formation). The conversion of specific cells to iPSCs has revolutionized stem cell research by making pluripotent cells more controllable for regenerative therapy. For the past 15 years, somatic cell reprogramming to pluripotency with force expression of specified factors has been a fascinating field of biomedical study. For that technological primary viewpoint reprogramming method, a cocktail of four transcription factors (TF) has required: Kruppel-like factor 4 (KLF4), four-octamer binding protein 34 (OCT3/4), MYC and SOX2 (together referred to as OSKM) and host cells. IPS cells have great potential for future tissue replacement treatments because of their ability to self-renew and specialize in all adult cell types, although factor-mediated reprogramming mechanisms are still poorly understood medically. This technique has dramatically improved performance and efficiency, making it more useful in drug discovery, disease remodeling, and regenerative medicine. Moreover, in these four TF cocktails, more than 30 reprogramming combinations were proposed, but for reprogramming effectiveness, only a few numbers have been demonstrated for the somatic cells of humans and mice. Stoichiometry, a combination of reprogramming agents and chromatin remodeling compounds, impacts kinetics, quality, and efficiency in stem cell research.

mecA and fdh: markers of pathogenicity and commensalism in Staphylococcus epidermidis of pediatric origin from Pakistan.

Staphylococcus epidermidis is an opportunistic bacterial pathogen. The study screened isolates of S. epidermidis of pediatric origin for genetic markers of discriminatory potential. 103 isolates (n = 75 clinical; n = 28 community) were screened for methicillin resistance (mecA), formate dehydrogenase (fdh) and an array of virulence factors through multiplex PCR and Congo red assay. The isolates were typed in four distinct categories, based on the presence of selected virulent factors. The type A clinical isolates carrying icaADBC operon (n = 22; 29.3%, P = 0.117) were not significantly differentiating the origin of isolates. The type B clinical isolates representing methicillin resistant S. epidermidis (MRSE) (n = 73; 97.3%, P < 0.00001) and the type C clinical isolates lacking formate dehydrogenase fdh (n = 62; 82.6%, P < 0.00001) were having significant discriminatory potential of clinical isolates, respectively. All type D community isolates were carrying fdh (n = 28; 100%, P < 0.00001). MecA and fdh are significant differential markers of pathogenicity and commensalism in S. epidermidis of pediatric origin.

Machine learning-based assessment and simulation of land use modification effects on seasonal and annual land surface temperature variations.

Rapid urban sprawl adversely impacts the local climate and the ecosystem components. Islamabad, one of South Asia's green and environment-friendly capitals, has experienced major Land Use Land Cover (LULC) changes over the past three decades consequently, elevating the seasonal and annual Land Surface Temperature (LST) in planned and unplanned urban areas. The focus of this study was to quantify the fluctuations in LULC and LST in planned and unplanned urban areas using Landsat data and Machine Learning algorithms involving the Support Vector Machine (SVM) over the 1990-2020 data period. Moreover, hybrid Cellular Automata-Markov (CA-Markov) and Artificial Neural Network (ANN) models were employed to project the future changes in LULC and annual LST, respectively, for the years 2035 and 2050. The findings of the study reveal a distinct difference in seasonal and annual LST in planned and unplanned areas. Results showed an increase of ∼22 % in the built-up area but vegetation and bare soil decreased by ∼10 % and ∼12 %, respectively. Built-up land showed a maximum annual mean LST followed by bare-soil and vegetative surfaces. Seasonal analysis showed that summer months experience the highest LST, followed by spring, autumn and winter. Future projections revealed that the built-up areas (∼27 % in 2020) are likely to increase to ∼37 % and ∼50 %, and the areas under the highest annual mean LST class i.e., ≥28 °C are likely to increase to ∼19 % and ∼21 % in planned, and ∼38 % and ∼42 % in unplanned urban areas for the years 2035 and 2050, respectively. Planned areas have better temperature control with urban green spaces, and controlled infrastructure. The Capital Development Authority of Islamabad may be advised to control the expansion of built-up areas, grow urban forests, and thus mitigate the possible Urban Heat Island (UHI) effect.

Evaluation of Knowledge and Attitudes of the Population of Tabuk City Regarding Parkinson's Disease: A Cross-Sectional Study.

BACKGROUND: The lack of awareness and information about PD may be a barrier to early diagnosis and the delivery of the best care to patients with the condition, given its rising prevalence. In order to determine the variables that are connected to these parameters, this study sought to ascertain the general public's knowledge and awareness of PD in Tabuk City. METHODS:  In Tabuk City, a cross-sectional demographic survey was carried out. A validated structured questionnaire was used to interview adult respondents by random sampling regarding specific knowledge, attitudes, and awareness related to Parkinson's disease. According to the density of the city, a total of 426 members of the general population were chosen at random and interviewed by skilled interviewers. RESULTS:  Age and educational attainment were independently linked to PD awareness. Bachelor's degree subjects and those between the ages of 18 and 45 displayed a greater awareness of PD. Those above 60 and those between the ages of 46 and 60 lacked sufficient knowledge. The majority of participants demonstrated adequate understanding and awareness of PD in their respective occupations. CONCLUSIONS:  Age, gender, occupation, and level of education were all adequately covered by knowledge and understanding of PD. To increase public knowledge, attitudes, and awareness of PD, however, suitable educational tactics and approaches targeting particular subgroups are required.

Evaluation of Organic and Inorganic Foulant Interaction Using Modified Fouling Models in Constant Flux Dead-End Operation with Microfiltration Membranes.

The goal of this study was to elucidate the interaction of complex feed solutions under modified membrane fouling models for constant flux operation. The polyvinylidene fluoride membrane (PVDF) was tested for three types of solutions containing inorganic foulants (Al, Mn, and Fe), organic foulants, and suspended solids at 0.5 mM Ca2+ ionic strength. The membrane's performance was evaluated by measuring the increase in transmembrane pressure (TMP) during two different filtration scenarios: continuous filtration lasting 1 h and cyclic filtration lasting 12 min, with 3 min backwashing cycles included. Statistical analysis (linear regression results (R2), p-value) was used to verify the fouling model propagation along with the determination of the contributing constant of each fouling model. An increasing TMP percentage of 164-302%, 155-300%, and 208-378% for S1 (HA + Ca2+), S2 (inorganics + kaolin + Ca2+), and S3 (HA + inorganics + kaolin + Ca2+) was recorded for 1 h filtration, respectively. Furthermore, a five percent increase in irreversible resistance was noted for the S3 solution due to the strong adsorption potential of foulants for the PVDF membrane caused by the electrostatic and hydration forces of foulants. In addition to that, the participation equation elucidated the contribution of the fouling model and confirmed that complete blocking and cake layer contribution were dominant for the S1 and S3 solutions, while standard blocking was dominant for the S2 solution with a high significance ratio. Moreover, R2 and cyclic filtration analysis also confirmed the propagation of these fouling models. The statistical confirmation and regression results analysis of the modified model gave comparative results and satisfied the filtration mechanism and can be used for the constant flux dead filtration analysis of water treatment.

Fine mapping and candidate gene analysis of a major QTL for oil content in the seed of Brassica napus.

KEY MESSAGE: By integrating QTL fine mapping and transcriptomics, a candidate gene responsible for oil content in rapeseed was identified. The gene is anticipated to primarily function in photosynthesis and photosystem metabolism pathways. Brassica napus is one of the most important oil crops in the world, and enhancing seed oil content is an important goal in its genetic improvement. However, the underlying genetic basis for the important trait remains poorly understood in this crop. We previously identified a major locus, OILA5 responsible for seed oil content on chromosome A5 through genome-wide association study. To better understand the genetics of the QTL, we performed fine mapping of OILA5 with a double haploid population and a BC3F2 segregation population consisting of 6227 individuals. We narrowed down the QTL to an approximate 43 kb region with twelve annotated genes, flanked by markers ZDM389 and ZDM337. To unveil the potential candidate gene responsible for OILA5, we integrated fine mapping data with transcriptome profiling using high and low oil content near-isogenic lines. Among the candidate genes, BnaA05G0439400ZS was identified with high expression levels in both seed and silique tissues. This gene exhibited homology with AT3G09840 in Arabidopsis that was annotated as cell division cycle 48. We designed a site-specific marker based on resequencing data and confirmed its effectiveness in both natural and segregating populations. Our comprehensive results provide valuable genetic information not only enhancing our understanding of the genetic control of seed oil content but also novel germplasm for advancing high seed oil content breeding in B. napus and other oil crops.

Disparities in Outcomes of Hospitalizations Due to Multiple Myeloma: A Nationwide Comparison.

Background With the advent of novel treatments, there is a declining trend in the multiple myeloma (MM) mortality rate with an increasing hospitalization rate. However, there is limited population-based data on trends and outcomes of hospitalizations due to MM in the United States (US). Methods We analyzed the publicly available Nationwide Inpatient Sample (NIS) from 2007 to 2017 to identify MM hospitalizations. Results Hospitalizations for MM increased from 17,100 (8.71%) in 2007 to 19,490 (9.92%) in 2017. The in-hospital mortality rate declined from 8.4% in 2007 to 4.9% in 2017 (P <0.001) and discharge to facilities decreased from 20.4% in 2007 to 17.4% in 2017 (P <0.001). The odds of in-hospital mortality were higher with increasing age (odds ratio (OR): 1.46; 95% confidence interval (CI): 1.38 -1.54; P <0.0001), pneumonia (OR: 4.18; 95% CI: 3.63 - 4.81, P <0.0001), septicemia (OR: 2.50; 95% CI: 2.22 - 2.82; P <0.0001), renal failure (OR: 1.48; 95% CI: 1.34 -1.64; P <0.0001), uninsured/self-pay insurance status (OR: 2.69; 95% CI: 2.18 - 3.3; P <0.0001), rural hospital (OR: 2.26; 95% CI: 1.88 -2.72; P<0.0001), and urban-non-teaching hospitals (OR: 1.38; 95% CI: 1.23 - 1.56; P <0.0001). Also, increasing age (OR: 1.14; 95% CI: 1.11-1.18, P <0.0001), Black race (OR: 1.12; 95% CI: 1.02-1.23, P <0.0001), and multiple comorbidities were associated with higher disability. Conclusion Hospitalizations for MM continued to increase, whereas in-hospital mortality continued to decrease. Advanced age, sepsis, pneumonia, and renal failure were associated with higher odds of mortality in MM patients.

Assessment of molybdenum application on soybean physiological characteristics in maize-soybean intercropping.

Soybean is a leguminous crop known for its efficient nitrogen utilization and ease of cultivation. However, its intercropping with maize may lead to severe reduction in its growth and yield due to shading effect of maize. This issue can be resolved by the appropriate application of essential plant nutrient such as molybdenum (Mo). Aim of this study was to assess the effect of Mo application on the morphological and physiological characteristics of soybean intercropped with maize. A two-year field experiment was conducted for this purpose, and Mo was applied in the form of sodium molybdate (Na2MoO4), and four different levels were maintained i.e., 0, 60, 120 and 180 g ha-1. Soybean exhibited varying responses to different levels of molybdenum (Mo) application. Notably, in both sole and intercropped cropping systems, the application of Mo at a rate of 120 g ha-1 demonstrated the highest level of promise compared to other application levels. However, most significant outcomes were pragmatic in soybean-maize intercropping, as application of Mo @ 120 g ha-1 significantly improved soybean growth and yield attributes, including leaf area index (LAI; 434 and 441%), total plant biomass (430 and 461%), transpiration rate (15 and 18%), stomatal conductance (9 and 11%), and yield (15 and 20%) during year 2020 and 2021 respectively, as compared to control treatment. Similarly, Mo @ 120 g ha-1 application resulted in highest total grain yield (626.0 and 725.3 kg ha-1) during 2020 and 2021 respectively, which exceeded the grain yields of other Mo levels under intercropping. Moreover, under Mo application level (120 g ha-1), grain NPK and Mo contents during years 2020 and 2021 were found to be 1.15, 0.22, 0.83 and 68.94 mg kg-1, and 1.27, 0.25, 0.90 and 72.18 mg kg-1 under intercropping system increased the value as compared to control treatment. Findings of current study highlighted the significance of Mo in enhancing soybean growth, yield, and nutrient uptake efficiency in maize-soybean intercropping systems.

Field response and molecular screening of European wheat germplasm against powdery mildew at the Himalayan region of Pakistan.

Wheat powdery mildew possesses a significant threat to wheat crops not only on a global scale but also in the northern region of Pakistan. Recognizing the need for effective measures, the exploration and utilization of exotic germplasm take on critical importance. To address this, a series of trials were made to investigate the response of 30 European (EU) lines, in addition to the local checks (Siran, Atta-Habib (AH) and Ghanimat-e-IBGE) against wheat powdery mildew at the Himalayan region of Pakistan. The study involved field testing from 2018 to 2022 across multiple locations, resulting in 38 different environments (location × year). In addition to field evaluations, molecular genotyping was also performed. The disease was absent on the tested lines during 2018, 2019, and 2020 whereas it ranged from 0 to 100% at Chitral location during 2021, where 100% was observed only for one EU wheat line "Matrix." The disease prevailed only at Gilgit location (0-60% for EU wheat line "F236") and at Nagar location (0-10% for EU wheat lines Substance and Nelson) during the disease season of 2022. Most of the EU wheat lines showed very low ACI values, due to an overall low disease pressure. Matrix showed the maximum ACI (1.54) followed by Ritter (1.25) and Bli_autrichion (0.87), whereas the minimum (0.1) was for Substance, JB_Asano, and KWS_Loft followed by Canon (0.19), all exhibiting partial resistance. The molecular marker-based screening revealed that Pm38 was the most prevalent and detected in 100% of wheat lines followed by Pm39 (60%) and Pm8 (30%). Six wheat lines (20%) possessed all three Pm genes (Pm8, Pm38, and Pm39) concurrently. The variability observed in this study can be utilized in future breeding efforts aimed at developing resistant wheat varieties.

Systematic elucidation of the multi-target pharmacological mechanism of Terminalia arjuna against congestive cardiac failure via network pharmacology and molecular modelling approaches.

Congestive cardiac failure (CCF) is a pathophysiologic state when the heart is not able to maintain its cardiac output to meet the demand of metabolising tissues. CCF is responsible for approximately 2.9 million deaths worldwide. The heterogeneous nature of CCF draws the attention of researchers to find more enthralling and promising diagnostic and treatment options. Terminalia arjuna (Arjuna) is an evergreen, deciduous tree exhibited various astringent, anti-bacterial, and anti-microbial properties. T. arjuna is being used in various regions for anginal pain, hypertension, congestive heart failure, and dyslipidemia. Although previous in vitro studies have demonstrated the therapeutic potential of T. arjuna, the exact molecular mechanism underlying its protective effect on the heart remains unclear. In this study, a network pharmacology technique was used to explore the active ingredients, potential targets in T. arjuna for the treatment of CCF. In the framework of this study, we explored the active ingredient-target-pathway network and figured out that oleanolic acid, arjunolic acid, luteolin, kaempferol, cholesterol, ellagic acid 4-O-xylopyranoside 3,3'-dimethyl ether, and cyclohexyl (2,4-dimethyl phenyl) methanone contributed significantly to the development of CCF by affecting AKT1, MAPK14, TNF, IL6, ESR1, and HSP90AA1 genes. Molecular docking analysis further validated the activities of these compounds against potential targets. To sum up, integrated network pharmacology and docking analysis revealed that T. arjuna exerts its cardioprotective effect by acting on various signalling pathways, including the thyroid hormone, VEGF signalling pathway, AGE-RAGE signalling pathway in diabetic complications, HIF signalling pathway, sphingolipid signalling pathway, and oestrogen signalling pathways. Overall, this study provides valuable insights into the molecular mechanism of T. arjuna in CCF and highlights its potential as a promising preventive treatment for this condition.

Heavy metals in five commonly consumed fish species from River Swat, Pakistan, and their implications for human health using multiple risk assessment approaches.

This study analyzed the levels of heavy metals bioaccumulation in commonly consumed riverine fish species, including G. cavia, T. macrolepis, G. gotyla, S. plagiostomus, and M. armatus from River Swat in Pakistan, and quantify their potential risk to children and adults in general and fisherfolk communities using multiple pollution and risk assessment approaches. The highest metal detected by inductive coupled plasma mass spectrometry (ICP-MS) was Zn, which ranged from 49.61 to 116.83 mg/kg, followed by Fe (19.25-101.33 mg/kg) > Mn (5.25-40.35 mg/kg) > Cr (3.05-14.59 mg/kg) > Ni (4.26-11.80 mg/kg) > Al (1.59-12.25 mg/kg) > Cu (1.24-8.59 mg/kg) > Pb (0.29-1.95 mg/kg) > Co (0.08-0.46 mg/kg) > Cd (0.01-0.29 mg/kg), demonstrating consistent fluctuation with the safe recommendations of global regulatory bodies. The average bioaccumulation factor (BAF) values in the examined fish species were high (BAF > 5000) for Pb, Zn, Mn, Cu, Cr, Ni, and Cd, bioaccumulate (1000 > BAF < 5000) for Co, and probable accumulative (BAF <1000) for Fe, and Al, while the overall ∑heavy metals pollution index (MPI) values were greater than one (MPI > 1) indicating sever heavy metals toxicity in G. cavia, followed by S. plagiostomus, M. armatus, G. gotyla, and T. macrolepis. The multivariate Pearson's correlation analysis identified the correlation coefficients between heavy metal pairs (NiCr, CuCr, PbCr, AlCo, CuNi, and PbNi), the hierarchical cluster analysis (CA) determined the origin by categorizing heavy metal accumulation into Cluster-A, Cluster-B, and Cluster-C, and the principal component analysis (PCA) discerned nearby weathering, mining, industrial, municipal, and agricultural activities as the potential sources of heavy metals bioaccumulation in riverine fish. As per human risk perspective, S.plagiostomus contributed significantly to the estimated daily intake (EDI) of heavy metals, followed by G.cavia > M.armatus > G.gotyla > T.macrolepis in dependent children and adults of the fisherfolk followed by the general population. The non-carcinogenic target hazard quotient (THQ) and hazard index (HI) values for heavy metal intake through fish exposure were < 1, while the carcinogenic risk (CR) for individual metal intake and the total carcinogenic risk (TCR) for cumulative Cr, Cd, and Pb intake were within the risk threshold of 10-6-10-4, suggesting an acceptable to high non-carcinogenic and carcinogenic risk for both children and adults in the fisherfolk, followed by the general population.

Unveiling the multi-target compounds of Rhazya stricta: Discovery and inhibition of novel target genes for the treatment of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a prevalent kidney malignancy with a pressing need for innovative therapeutic strategies. In this context, emerging research has focused on exploring the medicinal potential of plants such as Rhazya stricta. Nevertheless, the complex molecular mechanisms underlying its potential therapeutic efficacy remain largely elusive. Our study employed an integrative approach comprising data mining,network pharmacology,tissue cell type analysis, and molecular modelling approaches to identify potent phytochemicals from R. stricta, with potential relevance for ccRCC treatments. Initially, we collected data on R. stricta's phytochemical from public databases. Subsequently, we integrated this information with differentially expressed genes (DEGs) in ccRCC, which were derived from microarray datasets(GSE16441,GSE66270, and GSE76351). We identified potential intersections between R. stricta and ccRCC targets, which enabled us to construct a compound-genes-pathway network using Cytoscape software. This helped illuminate R. stricta's multi-target pharmacological effects on ccRCC. Moreover, tissue cell type analysis added another layer of insight into the cellular specificity of potential therapeutic targets in the kidney. Through further Kaplan-Meier survival analysis, we pinpointed MMP9,ACE,ERBB2, and HSP90AA1 as prospective diagnostic and prognostic biomarkers for ccRCC. Notably, our study underscores the potential of R. stricta derived compounds-namely quebrachamine,corynan-17-ol, stemmadenine,strictanol,rhazinilam, and rhazimolare-to impede ccRCC progression by modulating the activity of MMP9,ACE,ERBB2, and HSP90AA1 genes. Further, molecular docking and dynamic simulations confirmed the plausible binding affinities of these compounds. Despite these promising findings, we recognize the need for comprehensive in vivo and in vitro studies to further investigate the pharmacokinetics and biosafety profiles of these compounds.