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Abstract Primary human hepatocyte (PHH) transplantation is a promising alternative to liver transplantation, whereby liver function could be restored by partial repopulation of the diseased organ with healthy cells. However, currently PHH engraftment efficiency is low and benefits are not maintained long-term. Here we refine two male mouse models of human chronic and acute liver diseases to recapitulate compromised hepatocyte proliferation observed in nearly all human liver diseases by overexpression of p21 in hepatocytes. In these clinically relevant contexts, we demonstrate that transient, yet robust expression of human hepatocyte growth factor and epidermal growth factor in the liver via nucleoside-modified mRNA in lipid nanoparticles, whose safety was validated with mRNA-based COVID-19 vaccines, drastically improves PHH engraftment, reduces disease burden, and improves overall liver function. This strategy may overcome the critical barriers to clinical translation of cell therapies with primary or stem cell-derived hepatocytes for the treatment of liver diseases.

Background: Cognitive behavior therapy is an important treatment for various psychiatric and psychological problems. Different psychotherapeutic treatments are used for improvement in patients. The study aimed to compare Clozapine and Fluoxetine with Choline on the progress of cognition and cognitive behavior in rats. Methods: This experimental study was conducted in the pharmacology department of Karachi University on locally bred male albino rats (n=24). These were divided into four treatment groups (Saline, Fluoxetine, Clozapine, and Choline) and measured the output at the 1st, 3rd, 5th, and 7th weeks. Familiar and Novel object recognition test and Passive avoidance test was used to observe learning and memory as well as the mechanism of cognition. One way-ANOVA and post-hoc analysis was done between groups. The p-value 0.05) in the Novel and Familiar Object Recognition test. However, at week three it was highest for Fluoxetine (58.15±3.35) compared to Choline, Clozapine and Saline for the novel object. However, in Familiar objects, it was found highest for Clozapine (58.88±3.05) (p

الملخص: أهداف البحث: يهدف هذا البحث إلى تقييم الآثار قبل السريرية المضادة للسرطان للميتفورمين في نموذج طُعم أجنبي لسرطان الثدي. طرق البحث: أجريت هذه التجربة التداخلية خلال فترة محددة مدتها خمسة أشهر (أغسطس ٢٠١٦ - يناير ٢٠١٧). حيث استخدمنا نموذج طُعم أجنبي من الفئران بلب/ج عارية. وكان حجم العينة ٥٠ فأرا، وُزعت لمجموعتين المجموعة أ والمجموعة ب لمجموعتي الميتفورمين والتحكم السلبية، على التوالي. وتم تقييم النشاط السرطاني للميتفورمين من خلال مقارنة حجم الورم، ووزن الورم، ونسبة تراجع الورم، ونسبة التراجع المئوية ومعدل البقاء على قيد الحياة. النتائج: بالمقارنة مع مجموعة التحكم، خفض الميتفورمين بشكل كبير تطور الورم في نموذج الطُعم الأجنبي لسرطان الثدي الناجم حسب مؤسسة ميتشغان للسرطان-٧. وقد انعكس ذلك من خلال اختلافات كبيرة في حجم الورم في المتابعة النهائية. وقد تم دعم النتائج التي توصلنا إليها من خلال انخفاض كبير في معدل نمو الورم ووزن الورم في مجموعة الميتفورمين مقارنة بمجموعة التحكم. وبالمثل، كان معدل البقاء الكلي وتراجع الورم مرتبطين بشكل أكبر في مجموعة الميتفورمين. الاستنتاجات: أثبتت هذه الدراسة أن الميتفورمين يمكن أن يقلل بشكل كبير من نمو الورم ويمكن أن يزيد من معدل البقاء على قيد الحياة في نموذج الطُعم الأجنبي لسرطان الثدي. Abstract: Objective: This research aims to evaluate the preclinical meritorious and anticancer effects of Metformin in a Xenograft model of breast cancer. Methods: This interventional trial was conducted during a defined period of 5 months (August 2016 January 2017). We used a Xenograft model of nude BALB/c mice. A sample size of 50 mice, allocated into two groups and designated as Group A and Group B for Metformin and negative control groups, respectively. The anticancer activity of Metformin has been evaluated by comparing the tumour volume, tumour weight, tumour regression ratio, percentage regression, and survival rate. Results: Compared with the control group, Metformin can significantly reduce the progression of tumour in the Xenograft model of breast cancer induced by MCF-7. This is reflected by significant differences in tumour volume at the final follow-up (p =

When severely or chronically injured, the liver loses ability to regenerate. Here, the authors utilize transient lipid nanoparticle-enclosed HGF and EGF-encoding mRNA delivery to induce hepatocyte proliferation and harness recovery of liver function in murine acute and chronic liver injury models.

With the recent availability of the SARS-CoV-2 mRNA-based vaccines, public attention has been drawn to this new technology and how it may be applied to other indications. Temporal activation of key hepatic regenerative pathways can induce liver regeneration, overcoming the lack of donor organs for liver transplantation and ineffectiveness of alternative treatments. Recombinant protein therapies and genetic therapies that target these pathways require frequent and repeated injections or, when integrated into the genome, may lead to deleterious effects. In contrast, nucleoside-modified mRNA encapsulated in lipid nanoparticles (mRNA-LNP) are non-integrative and induce transient yet robust expression of proteins that could serve as an ideal therapeutic tool to treat specific liver diseases. For instance, our recent publication in Nature Communications used mRNA-LNP to express hepatic mitogens, hepatocyte growth factor, and epidermal growth factor to induce liver regeneration following both acute and chronic liver injuries. Initial testing with firefly luciferase mRNA-LNP transfection and in vivo imaging confirmed specific hepatotropic delivery. In this protocol, we describe in detail the necessary steps to deliver mRNA-LNP to the murine liver and, following intravenous injection of eGFP mRNA-LNP, verify transfection efficiency using flow cytometry and liver cell specificity using immunofluorescence analyses. This procedure presents an unprecedented tool that can be customized with mRNA-LNP encoding any protein of interest to be expressed by virtually all hepatocytes, ~70% endothelial cells, and ~40% Kupffer cells for promoting liver function and/or regeneration.Graphic abstract:Experimental Design of mRNA-LNP IV Injection and Analysis of Liver Cell Specificity and Efficiency of Transfection (Created with BioRender.com)

Cilia both receive and send information, the latter in the form of extracellular vesicles (EVs). EVs are nano-communication devices that influence cell, tissue, and organism behavior. Mechanisms driving ciliary EV biogenesis are almost entirely unknown. Here, we show that the ciliary G-protein Rab28, associated with human autosomal recessive cone-rod dystrophy, negatively regulates EV levels in the sensory organs of Caenorhabditis elegans in a cilia specific manner. Sequential targeting of lipidated Rab28 to periciliary and ciliary membranes is highly dependent on the BBSome and the prenyl-binding protein phosphodiesterase 6 subunit delta (PDE6D), respectively, and BBSome loss causes excessive and ectopic EV production. We also find that EV defective mutants display abnormalities in sensory compartment morphogenesis. Together, these findings reveal that Rab28 and the BBSome are key in vivo regulators of EV production at the periciliary membrane and suggest that EVs may mediate signaling between cilia and glia to shape sensory organ compartments. Our data also suggest that defects in the biogenesis of cilia-related EVs may contribute to human ciliopathies.

Abstract In this study, sufaid chonsa mango pulp aqueous extracts from different ripening stages (RS I-V) was utilized to synthesize silver nanoparticles (Ag NPs). The Ag NPs were characterized using UV-vis spectrometry, X-ray diffraction analysis (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and Energy dispersice X-ray analysis (EDX). Additionally, antioxidative potential and phenolic and flavonoid-like properties of synthesized Ag NPs were also accessed. UV-vis spectrophotometer analysis showed peaks in around 400 nm. XRD analysis confirmed the crystalline structure of the green-synthesized Ag NPs, with sizes ranging from 2.11 to 11.72 nm. FTIR verified the attachment of functional groups from the mango pulp extract to the Ag NPs. SEM analyses revealed that the morphology of the Ag NPs was primarily spherical that were agglomerated. The total antioxidant capacity, measured by the DPPH assay, showed 51% radical scavenging activity for RSIII extract synthesized NPs. The highest total antioxidant capacity was observed to be 80.22 and 79.14 µg AAE/mg NPs by RSI and RSIV synthesized NPs, respectively, while the maximum total reduction potential was 28.67 µg AAE/mg for Ag NPs synthesized by RSII extract. Ag NPs derived from RSIV exhibited phenolic-like property of 70.84 µg GAE/mg, while those derived from RSII had a maximum flavonoid-like property of 35.37 µg QE/mg. This study demonstrates that mango pulp at different ripening stages produces Ag NPs with distinct characteristics, making them suitable for various environmental and biomedical applications.

Transfusion transmitted infections are major problem associated with blood transfusion. Accurate estimates of risk of TTIs are essential for monitoring the safety of blood supply and evaluating the efficacy of currently employed screening procedures. The present study was carried out to assess the percentage of voluntary donors and replacement donors and to find out prevalence and changing trends of various TTIs blood donors in recent years. A study was carried out on blood units of voluntary and replacement donors which were collected from January 2008 to December 2012. On screening of 180,371 replacement units, seropositivity of transfusion transmitted disease in replacement donors was 0.15% in HIV, 1.67% in hepatitis B surface antigen, 0.49% in hepatitis C virus, 0.01% in VDRL, and 0.009% in malaria. Of 11,977 voluntary units, seropositivity of transfusion transmitted disease in voluntary donors was 0.08% in HIV, 0.24% in hepatitis B surface antigen, 0.001% in hepatitis C virus, 0.008% in VDRL (sexually transmitted disease), and 0.01% in malaria. From results it has been concluded that prevalence of transfusion transmitted infection (HIV, HBV, HCV, VDRL, and malaria) was more in replacement donors in comparison to voluntary donors. Extensive donor selection and screening procedures will help in improving the blood safety.

Abstract Early blight (EB), caused by Alternaria solani, is a serious problem in tomato production. Plant growth-promoting rhizobacteria promote plant growth and inhibit plant disease. The present study explored the bio-efficacy of synergistic effect of rhizobacterial isolates and ginger powder extract (GPE) against tomato EB disease, singly and in combination. Six fungal isolates from symptomatic tomato plants were identified as A. solani on the basis of morphological features i.e., horizontal septation (6.96 to 7.93 µm), vertical septation (1.50 to 2.22 µm), conidia length (174.2 to 187.6 µm), conidial width (14.09 to 16.52 µm), beak length (93.06 to 102.26 µm), and sporulation. Five of the twenty-three bacterial isolates recovered from tomato rhizosphere soil were nonpathogenic to tomato seedlings and were compatible with each other and with GPE. Out of five isolates tested individually, three isolates (St-149D, Hyd-13Z, and Gb-T23) showed maximum inhibition (56.3%, 48.3%, and 42.0% respectively) against mycelial growth of A. solani. Among combinations, St-149D + GPE had the highest mycelial growth inhibition (76.9%) over the untreated control. Bacterial strains molecularly characterized as Pseudomonas putida, Bacillus subtilis, and Bacillus cereus and were further tested in pot trials through seed bacterization for disease control. Seeds treated with bacterial consortia + GPE had the highest disease suppression percentage (78.1%), followed by St-149D + GPE (72.2%) and Hyd-13Z + GPE (67.5%). Maximum seed germination was obtained in the bacterial consortia + GPE (95.0 ± 2.04) followed by St-149D + GPE (92.5 ± 1.44) and Hyd-13Z + GPE (90.0 ± 2.04) over control (73.8 ± 2.39) and chemical control as standard treatment (90.0 ± 2). Ginger powder extracts also induce the activation of defence-related enzymes (TPC, PO, PPO, PAL, and CAT) activity in tomato plants. These were highly significant in the testing bacterial inoculants against A. solani infection in tomato crops.

Abstract Maize (Zea mays) is an influential crop in its production across the world. However, the invasion of many phytopathogens greatly affects the maize crop yield at various hotspot areas. Of many diseases, bacterial stalk rot of maize caused by Dickeya zeae results in severe yield reduction, thus the need for efficient management is important. Further, to produce epidemiological information for control of disease outbreaks in the hot spot regions of Sialkot District, Punjab Pakistan, extensive field surveys during 2021 showed that out of 266 visited areas, the highest disease incidence ranging from 66.5 to 78.5% while the lowest incidence was ranging from 9 to 20%. The Maxent modeling revealed that among 19 environmental variables, four variables including temperature seasonality (bio-4), mean temperature of the wettest quarter (bio-8), annual precipitation (bio-12), and precipitation of driest month (bio-14) were significantly contributing to disease distribution in current and coming years. The study outcomes revealed that disease spread will likely increase across four tehsils of Sialkot over the years 2050 and 2070. Our findings will be helpful to policymakers and researchers in devising effective disease management strategies against bacterial stalk rot of maize outbreaks in Sialkot, Pakistan.

Business dynamics have undergone a remarkable transformation in recent years, primarily driven by the digital revolution. Micro, Small, and Medium Enterprises (MSMEs) are recognized as the cornerstone of economic growth and development, and their adaptability to this digital era is paramount. This empirical investigation explores the complex relationship between entrepreneurs' awareness, perceptions, and intentions and their influence on the adoption of digitalization, with a focus on the digital initiatives of the Small Industries Development Bank of India (SIDBI), which aims to transform MSMEs digitally. Various constructs, such as entrepreneurs' awareness, perceptions, and intentions, are used to evaluate digital adoption in small businesses. By examining entrepreneurs' levels of awareness, perceptions, and intentions, we aim to uncover the fundamental factors that shape their strategic choices regarding digital adoption. This study employs structural equation Modeling (SEM) through AMOS and adopts an explanatory survey method. It involved engaging Indian MSMEs with a total of 300 participants. Of these, 220 successfully submitted fully filled-out questionnaires through Google Forms. It is noteworthy that the examination of the research model revealed promising results by meeting the thresholds of CFI, RMSEA, and other similar measures. Findings reveal that entrepreneurs' awareness and intention positively influence digital adoption in MSMEs, whereas entrepreneurs' perception has no significant influence on digital adoption in MSMEs. This study has significant practical implications for policy formulation, entrepreneurial decision-making, collaborative efforts, risk mitigation, and future research directions in the context of digitalization within the MSME sector.

Background: Cross-infection control is extremely pivotal to halt the propagation of contiguous diseases amongst people as they pose a tremendously increasing disease burden on our health care system. Therefore, this study aimed to assess the knowledge and adherence to cross-infection control measures among dental students in public and private institutions in Karachi. Methods: This descriptive study was performed among dental students of public and private sector dental colleges in Karachi from January 2020 – February 2020. The questionnaire assessed the knowledge and adherence of dental students toward cross-infection control protocols during their clinical rotations. The chi-square test was used to analyze the relationship between students’ knowledge and practice of cross-infection control measures. Results: A total of 202 students participated in this study. The students demonstrated adequate knowledge of cross-infection control measures. However, the practice of wearing gloves was positive (98%) in contrast to the use of masks (79%), gowns (46%), and eyewear (13%). A statistically significant relation was seen in their knowledge and attitude toward hand hygiene. The immunization status of students from both government (72%) and private (88%) sectors raised concerns. Although students demonstrated good practice of measures to avoid transmission of contagious diseases (p=

Background: Children with Cerebral Palsy (CP) face malfunctioning in the motor system and go through difficulties in hearing, eating, sight, and musculoskeletal systems and are also mentally impaired. This may render them unable to maintain proper oral hygiene. The objective of this study was to evaluate oral hygiene in children with cerebral palsy in Karachi’s special schools. Methods: A cross-sectional study with a total of 80 CP children was conducted in special schools in Karachi using a purposive sampling technique. CP children aged 12-15, who consented via guardians/school and were able to comply with the procedure were included. CP children on medications or systemic diseases were excluded. Proforma containing demographic details, and dental history questions were asked. Oral examination was done using the Plaque index, Gingival index, and Oral hygiene index simplified was observed. Results: In this study, there were 48 (60%) males and 32 (40%) females. The mean ± SD of age was 14.4 ±1.4. Independent t-test showed that there was a significant association of gingival index means with the institutes selected (p=0.004). The other parameters PI and OHIS did not show any association. Mean PI (mean 1.99, SD 0.62) and GI (mean 1.9, SD 0.60) showed moderate plaque and gingival inflammation and poor oral hygiene index (mean 3.31, SD 1.3). ANOVA showed associations of PI, GI & and OHIS with dental habits. Conclusion: CP children have poor oral hygiene status and therefore need early diagnosis and prompt treatment to prevent complications.

Anthropogenic activities have significantly polluted the natural environments all over the world. Leather processing industries release toxic heavy metals through their effluents posing a great threat to the environment. Chromium (Cr) is the major component of tannery effluents. We designed this experiment with the aim to remediate Cr from effluents of tanneries through phytoremediation. We selected three native macrophytes i.e. Pistia stratiotes, Eichhornia crassipes, and Typha latifolia to grow in a set of Constructed Wetland systems (CWs) with a continuous supply of tannery wastewater. T. latifolia was the most efficient phytoremediator of these macrophytes as it reduced the Cr content by 96.7%. The effluent after passing through the CWs containing T. latifolia showed only 0.426 mg/L Cr content. All macrophytes showed an enhanced phytochemical activity such as total antioxidant activity (TAA), total reduction potential (TRP), total phenolic content (TPC), total flavonoid content (TFC), and DPPH radical scavenging activity (DPPH) substantially. The activation of antioxidant mechanism may have contributed towards robust defense system of these plants for survival in excessive Cr contaminated media. Also, these macrophytes showed a positive relationship in reducing Cr content from tannery wastewater. Results of this study could help in effective sustainable management of aquatic environments contaminated with metal pollutants from human activities.

Aim . This study aimed to assess the effectiveness of 3 interventions—skit video, pictorial, and sign language—in improving the oral hygiene of children with hearing impairment. Materials and Methods . Sixty children randomly divided into 3 groups: Skit video, Pictorial, and Sign language. The mean gingival and Oral Hygiene Index scores were recorded before and after interventions. A 1-way ANOVA was used for statistically significant difference between pre and post intervention scores. Results . A significant difference in mean oral hygiene and gingival index scores before and after interventions was found in Group A ( P

BackgroundDespite strong and growing interest in ending the ongoing opioid health crisis, there has been limited success in reducing the prevalence of opioid addiction and the number of deaths associated with opioid overdoses. Further, 1 explanation for this is that existing interventions target those who are opiate-dependent but do not prevent opioid-naïve patients from becoming addicted. ObjectiveLeveraging behavioral economics at the patient level could help patients successfully use, discontinue, and dispose of their opioid medications in an acute pain setting. The primary goal of this project is to evaluate the effect of the 3 versions of the Opioid Management for You (OPY) tool on measures of opioid use relative to the standard of care by leveraging a pragmatic randomized controlled trial (RCT). MethodsA team of researchers from the Center for Learning Health System Sciences (CLHSS) at the University of Minnesota partnered with M Health Fairview to design, build, and test the 3 versions of the OPY tool: social influence, precommitment, and testimonial version. The tool is being built using the Epic Care Companion (Epic Inc) platform and interacts with the patient through their existing MyChart (Epic Systems Corporation) personal health record account, and Epic patient portal, accessed through a phone app or the MyChart website. We have demonstrated feasibility with pilot data of the social influence version of the OPY app by targeting our pilot to a specific cohort of patients undergoing upper-extremity procedures. This study will use a group sequential RCT design to test the impact of this important health system initiative. Patients who meet OPY inclusion criteria will be stratified into low, intermediate, and high risk of opiate use based on their type of surgery. ResultsThis study is being funded and supported by the CLHSS Rapid Prospective Evaluation and Digital Technology Innovation Programs, and M Health Fairview. Support and coordination provided by CLHSS include the structure of engagement, survey development, data collection, statistical analysis, and dissemination. The project was initially started in August 2022. The pilot was launched in February 2023 and is still running, with the data last counted in August 2023. The actual RCT is planned to start by early 2024. ConclusionsThrough this RCT, we will test our hypothesis that patient opioid use and diverted prescription opioid availability can both be improved by information delivery applied through a behavioral economics lens via sending nudges directly to the opioid users through their personal health record. Trial RegistrationClinicalTrials.gov NCT06124079; https://clinicaltrials.gov/study/NCT06124079 International Registered Report Identifier (IRRID)PRR1-10.2196/52882

Microplastics are often found in the greatest quantities in terrestrial environments, in addition to those found along coasts and in oceans. They may get into water bodies from a variety of different sources such as deposition from the atmosphere, runoff from polluted land, and effluent from municipal treatment plants. The objective of this study is to conduct a comprehensive evaluation of the existing scientific literature related to microplastics in wastewater. Specifically, the focus is on investigating the possible impacts of wastewater containing microplastics on both aquatic and terrestrial biota. Additionally, this study attempts to identify any gaps in the current research, with the intention of informing future research priorities in this field. A comprehensive selection of over 200 scientific papers on the subject of microplastic pollution, covering the years 2000–2023, has been selected from a prominent scientific database. These papers encompass a wide range of topics, including recent advancements in the study of microplastics in wastewater, their origins, behaviour in aquatic and terrestrial environments, and their potential adverse impacts on various organisms such as aquatic and terrestrial animals, soil microbial communities, plants, and finally humans. The results showed that using wastewater for irrigation can lead to the presence of microplastics in terrestrial ecosystems and can facilitate the transmission of contaminants in both terrestrial and aquatic ecosystems by interacting with a wide range of pollutants. The findings also indicate that although there has been significant scientific investigation into marine microplastics, research on the prevalence of microplastic contamination in freshwater and terrestrial environments is comparatively limited and requires greater attention for a better understanding of the fate, transport, and consequences of microplastics in relation to water, soil qualities, polymer composition, forms, and various types of land use.

Chili (Capsicum annuum L.) is the utmost significant cash crop of Pakistan. Annually, about 50% chili yield is reduced by chili anthracnose disease caused by Colletotrichum capsici. The current study was conducted to explore the antifungal potential of plant extracts in comparison with commercial fungicides against C. capsici. Morphologically recognized strains of C. capsici were subjected to pathogenicity assay where strain CC-2 showed a highly virulent response. Results from in-vitro studies showed that Ginger (15 % concentration) inhibited fungal mycelial growth and spore germination and results were comparable to Nativo and Antracol at 1000 ppm. From the protective and curative trials, among plant extracts, Ginger at 15% showed maximum crop protective activity (84%) and maximum curative activity (70%). Consequently, among fungicides, Antracol at 1000 ppm showed highest crop protective activity (92%) and maximum curative efficacy (96%). The results of pot experiments showed that among the plant extracts, Ginger significantly inhibited C. capsici and increased plant growth while among fungicides, Antracol was found to be more effective than Nativo. PCA explored the correlation between growth parameters of chili plants treated with plant extracts and fungicides. Biochemical profiling and phytochemical characterization indicated the presence of tannins, phenols, terpenoids, flavonoids, alkaloids, reducing sugars and anthraquinones in ginger and chicory extracts. Ginger showed the highest DPPH scavenging activity (64.9 ± 1.85) as compared to chicory (54.6 ± 2.8). GC–MS analysis of plant extracts revealed the presence of various bioactive compounds including Ethanol, Acetone, 2-Butanone, Trichloromethane, 2-Butanone, 4-(4‑hydroxy-3-methoxyphenyl)-, Gingerol, 1, 2-Benzenedicarboxylic acid, diisooctyl ester, Hexane, Glycerin, Sucrose, Hexadecanoic acid, methyl ester, 9-Octadecenoic acid (Z)-, methyl ester, 1,2-Benzenedicarboxylic acid, mono (2-ethylhexyl) ester, n-Hexadecanoic acid, cis-Vaccenic acid, 1-Monolinoleoylglycerol trimethylsilyl ether, and 9,12,15-Octadecatrienoic acid, 2-[(trimethylsilyl)oxy]-1-[[(trimethylsilyl)oxy] methyl]ethyl ester, (Z,Z,Z). FTIR analysis showed 12, 8 and 13 peak values respectively indicating the presence of important functional groups. NMR analysis showed 4 and 7 peak values of ginger and chicory extracts indicating the structures of functional groups. There is a need to test the disease suppressive potential of plant extracts under field conditions to manage other fatal plant pathogens.

Heavy metal concentrations exceeding permissible limits threaten human life, plant life, and all other life forms. Different natural and anthropogenic activities emit toxic heavy metals in the soil, air, and water. Plants consume toxic heavy metals from their roots and foliar part inside the plant. Heavy metals may interfere with various aspects of the plants, such as biochemistry, bio-molecules, and physiological processes, which usually translate into morphological and anatomical changes. They use various strategies to deal with the toxic effects of heavy metal contamination. Some of these strategies include restricting heavy metals to the cell wall, vascular sequestration, and synthesis of various biochemical compounds, such as phyto-chelators and organic acids, to bind the free moving heavy metal ions so that the toxic effects are minimized. This review focuses on several aspects of genetics, molecular, and cell signaling levels, which integrate to produce a coordinated response to heavy metal toxicity and interpret the exact strategies behind the tolerance of heavy metals stress. It is suggested that various aspects of some model plant species must be thoroughly studied to comprehend the approaches of heavy metal tolerance to put that knowledge into practical use.

Objective: To determine the effectiveness of Tocilizumab in covid-19 related severe pneumonia. Introduction: COVID-19 is a global health problem causing respiratory infection. This is triggered by IL-6 characterized by raised inflammatory markers that is called cytokine release storm. Severe disease leads to hospitalization, oxygen requirement and poor outcome. Methods: This interventional study (descriptive analytic) was conducted from July-December 2021 at Intensive Care Unit, after ethical approval. Seventy cases of COVID-19 pneumonia with cytokine storm were included. Twenty cases were dropped either refusal to tocilizumab, pregnancy or having contraindication to tocilizumab, leaving 50 study participants. The patient’s demography, clinical, laboratory and radiological findings, timing and response variables of tocilizumab were recorded. The temporal readings of inflammatory markers, oxygen requirement and clinical status were compared at admission and after tocilizumab. SPSS version 25 was used for data analysis. Chi-square test was applied with significant p-value < 0.05. Results: There was male predominance of 66% with mean age of 58.6±14.8 years. Mean day of illness and hospital stay was 8th day and 17.56 days respectively. C-reactive protein levels improved in all cases 50(100%) (p

Nanofluids have already proven great potential in the thermal amplification of several manufacturing industries and have been widely employed in energy technologies in recent times. Therefore, the current framework investigates the characteristics of the Jeffrey nanofluid flow with the influence of activation energy and motile microorganisms over a sheet is considered. The influence of the magnetic field is another important physical parameter in the flow analysis and has been regarded in this review. The remarkable properties of nanofluid are demonstrated by thermophoresis and Brownian motion characteristics. Thermophoresis has relevance in mass transport processes in many higher temperature gradient operating systems. An appropriate similarities transformation is utilized make convenient to partial differential equation into ordinary differential equations. The well-known shooting tactic is utilized to estimate numerical outcomes of obtained ordinary system of flow. The governing dimensionless equations are integrated subject to the aid of the bvp4c scheme in the built-in software of MATLAB to find out the solution. The procedure assumed employing MATLAB. The characteristics of physical parameters against the velocity of fluid, temperature, concentration, and motile microorganisms are elaborated through graphs and tables. The dynamic physical declaration of attained results reveals that buoyancy ratio parameter and bioconvection Rayleigh number plays a vibrant role in the declining flow of Jeffery nanofluid while contrasting nature is analyzed for mixed convection parameter. The increasing behavior of temperature is observed for larger variations of heat sink/source parameters and thermophoresis parameter while it shows conflicting nature for increasing values of Prandtl number. The concentration of nanoparticle is reduced with the advanced values of Prandtl number, Lewis number and Brownian motion, perceived from the results. The mounting valuation of the Peclet number and Bioconvection Lewis number caused a reduction in motile microorganism concentration. The envisaged hypotheses could be beneficial for modifications to extrusion systems, bio-mimetic systems, efficient energy generation, bio-molecules and improved production systems.

Cancer formation is a highly regulated and complex process, largely dependent on its microenvironment. This complexity highlights the need for developing novel target-based therapies depending on cancer phenotype and genotype. Autophagy, a catabolic process, removes damaged and defective cellular materials through lysosomes. It is activated in response to stress conditions such as nutrient deprivation, hypoxia, and oxidative stress. Oxidative stress is induced by excess reactive oxygen species (ROS) that are multifaceted molecules that drive several pathophysiological conditions, including cancer. Moreover, autophagy also plays a dual role, initially inhibiting tumor formation but promoting tumor progression during advanced stages. Mounting evidence has suggested an intricate crosstalk between autophagy and ROS where they can either suppress cancer formation or promote disease etiology. This review highlights the regulatory roles of autophagy and ROS from tumor induction to metastasis. We also discuss the therapeutic strategies that have been devised so far to combat cancer. Based on the review, we finally present some gap areas that could be targeted and may provide a basis for cancer suppression.

Weeds are important components of the agroecosystems due to their role as primary producers within the farming systems, yet they are considered as major constraints to crop production. A phytosociological study was conducted to assess the composition and spatial distribution of existing weed species under the influence of various edaphic factors in the 15 wheat fields. Quadrat method was applied and different phytosociological attributes including abundance, density, and frequency were estimated by randomly laying down 10 square-shaped quadrats of size 1m2 in each wheat field. A total of 34 weed species belonging to 17 families and 30 genera were explored from 150 quadrats. Fabaceae and Asteraceae were ubiquitous plant families. Various edaphic factors such as; soil texture, electrical conductivity, soil pH, total dissolved solids, nitrogen, calcium carbonate, organic matter, NaCl, calcium, phosphorous, potassium, sodium, and zinc were determined. Pearson's correlation was employed to correlate weeds and the potential edaphic variables. The results depicted that most of these weed pairs' associations correlated positively. Simultaneously, the abundant weed species including Trifolium repens, Coronopus didymus, and Urtica dioica showed a positive correlation with most of the investigated ecological variables.

A study was undertaken in order to investigate the effects of SO2 (25, 50, and 75 ppb) exposure for five hours on alternate days for three months on the susceptibility of five cucurbits to the infection of Meloidogyne incognita, causing root-knot disease. Four-week-old cucurbit plants were inoculated with 2000 J2 of M. incognita. SO2 levels of 50 and 75 ppb caused noticeable injury to foliage and reduced the plant growth parameters and biomass production of cucurbits (p ≤ 0.05). Nematode-inoculated plants caused characteristic oval, fleshy and large galls. The galls were formed closely, and as a result they coalesced, giving bead-like impressions especially in pumpkin and sponge gourds. Disease severity became aggravated on plants exposed to SO2 at 50 or 75 ppb concentrations. The nematode and SO2 interaction varied with the levels of SO2 and the response of the plant to M. incognita. SO2 at 50 or 75 ppb concentrations stimulated the pathogenesis of M. incognita on cucurbit species. The combined effect of 75 ppb SO2 and M. incognita suppressed plant length by 34% against the sum of decreases observed by M. incognita and SO2 individually (14–18%). At 50 ppb SO2, the fecundity of M. incognita was decreased and combined effect of SO2 and M. incognita was more than the sum of their singular effects. The study has proven that root-knot disease might become aggravated in the regions contaminated with elevated levels of SO2.

Food security will be a substantial issue in the near future due to the expeditiously growing global population. The current trend in the agriculture industry entails the extravagant use of synthesized pesticides and fertilizers, making sustainability a difficult challenge. Land degradation, lower production, and vulnerability to both abiotic and biotic stresses are problems caused by the usage of these pesticides and fertilizers. The major goal of sustainable agriculture is to ameliorate productivity and reduce pests and disease prevalence to such a degree that prevents large-scale damage to crops. Agriculture is a composite interrelation among plants, microbes, and soil. Plant microbes play a major role in growth promotion and improve soil fertility as well. Bacillus spp. produces an extensive range of bio-chemicals that assist in plant disease control, promote plant development, and make them suitable for agricultural uses. Bacillus spp. support plant growth by N fixation, P and K solubilization, and phytohormone synthesis, in addition to being the most propitious biocontrol agent. Moreover, Bacilli excrete extracellular metabolites, including antibiotics, lytic enzymes, and siderophores, and demonstrate antagonistic activity against phytopathogens. Bacillus spp. boosts plant resistance toward pathogens by inducing systemic resistance (ISR). The most effective microbial insecticide against insects and pests in agriculture is Bacillus thuringiensis (Bt). Additionally, the incorporation of toxin genes in genetically modified crops increases resistance to insects and pests. There is a constant increase in the identified Bacillus species as potential biocontrol agents. Moreover, they have been involved in the biosynthesis of metallic nanoparticles. The main objective of this review article is to display the uses and application of Bacillus specie as a promising biopesticide in sustainable agriculture. Bacillus spp. strains that are antagonistic and promote plant yield attributes could be valuable in developing novel formulations to lead the way toward sustainable agriculture.

Objectives: In preterm infants, hyperbilirubinemia is common and can impair the central nervous system. The tests available for measuring bilirubin is to collect blood from heel pricking and occasionally taking blood samples from inserted cannulas, which is painful. Therefore, there is a need to develop a non-invasive device to detect bilirubin levels in newborns and interpret the severity of jaundice. Methods: We conducted a cross-sectional study of 100 neonates. Patient data was collected between June 2015 and December 2016 from King Khalid Hospital at Al-Majma’ah, Saudi Arabia, and Alpine Hospital, Gurgaon, India. The mean gestational age of neonates was 39.0 weeks. Total bilirubin was measured using a transcutaneous bilirubinometer on the forehead and obtaining optical imaging through scanning of conjunctiva of eyes, also referred to as BiliChek and BiliCapture, respectively. Later the blood samples were obtained from these patients and tested in the laboratory to determine total serum bilirubin (TSB) levels. Results: The concentration of bilirubin as measured from serum, BiliChek, and BiliCapture were 10.7±2.0, 11.6±2.7, and 13.1±2.3 mg/dL, respectively. Correlation was high between TSB and BiliChek (r2 = 0.88) and between TSB and BiliCapture (r2 = 0.73). The Bland-Altman plots showed good agreement when comparing bilirubin values for both BiliChek and BiliCapture devices. Bilirubin measurement was further checked for the sensitivity and specificity and was 88.0% and 76.0% using BiliChek and 92.0% and 75.6% using BiliCapture, respectively. Conclusions: The optical imaging of conjunctiva for bilirubin assay is a safe alternative to a laboratory bilirubin assay and transcutaneous bilirubinometer BiliChek.

Pythium myriotylum is a notorious soil-borne oomycete that causes post-emergence damping-off in chili pepper. Of various disease management strategies, utilization of plant growth promoting rhizobacteria (PGPR) in disease suppression and plant growth promotion is an interesting strategy. The present study was performed to isolate and characterize PGPR indigenous to the chili rhizosphere in Pakistan, and to test the potential to suppress the damping-off and plant growth promotion in chili. Out of a total of 28 antagonists, eight bacterial isolates (4a2, JHL-8, JHL-12, 1C2, RH-24, 1D, 5C, and RH-87) significantly suppressed the colony growth of P. myriotylum in a dual culture experiment. All the tested bacterial isolates were characterized for biochemical attributes, and 16S rRNA sequence based phylogenetic analysis identified these isolates as Flavobacterium spp., Bacillus megaterium, Pseudomonas putida, Bacillus cereus, and Pseudomonas libanensis. All the tested bacterial isolates showed positive test results for ammonia production, starch hydrolase (except 4a2), and hydrogen cyanide production (except 4a2 and 1D). All the tested antagonists produced indole-3-acetic acid (13.4–39.0 μg mL–1), solubilized inorganic phosphate (75–103 μg mL–1), and produced siderophores (17.1–23.7%) in vitro. All the tested bacterial isolates showed varying levels of susceptibility and resistance response against different antibiotics and all these bacterial isolates were found to be non-pathogenic to chili seeds and notably enhanced percentage seed germination, plumule, redical length, and vigor index over un-inoculated control. Additionally, under pathogen pressure, bacterization increased the defense related enzymes such as Peroxidase (PO), polyphenol oxidase (PPO), and phenylalanine ammonia-lyase (PAL) activates. Moreover, the treatment of chili seeds with these bacterial isolates significantly suppressed the damping-off caused by P. myriotylum and improved PGP traits compared to the control. In addition, a positive correlation was noticed between shoot, root length, and dry shoot and root weight, and there was a negative correlation between dry shoot, root weight, and seedling percentage mortality. These results showed that native PGPR possesses multiple traits beneficial to the chili plants and can be used to develop eco-friendly and effective seed treatment formulation as an alternative to synthetic chemical fungicides.