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2.
J Egypt Natl Canc Inst ; 36(1): 22, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38910202

ABSTRACT

BACKGROUND: Innovations in cancer treatment have contributed to the improved survival rate of cancer patients. The cancer survival rates have been growing and nearly two third of those survivors have been exposed to clinical radiation during their treatment. The study of long-term radiation effects, especially secondary cancer induction, has become increasingly important. An accurate assessment of out-of-field/peripheral dose (PDs) is necessary to estimate the risk of second cancer after radiotherapy and the damage to the organs at risk surrounding the planning target volume. This study was designed to measure the PDs as a function of dose, distances, and depths from Telecobalt-60 (Co-60) beam in water phantom using thermoluminescent dosimeter-100 (TLD-100). METHODS: The PDs were measured for Co-60 beam at specified depths of 0 cm (surface), 5 cm, 10 cm, and 15 cm outside the radiation beam at distances of 5, 10, and 13 cm away from the radiation field edge using TLD-100 (G1 cards) as detectors. These calibrated cards were placed on the acrylic disc in circular tracks. The radiation dose of 2000 mGy of Co-60 beam was applied inside 10 × 10 cm2 field size at constant source to surface distance (SSD) of 80 cm. RESULTS: The results showed maximum and minimum PDs at surface and 5 cm depth respectively at all distances from the radiation field edge. Dose distributions out of the field edge with respect to distance were isotropic. The decrease in PDs at 5 cm depth was due to dominant forward scattering of Co-60 gamma rays. The increase in PDs beyond 5 cm depth was due to increase in the irradiated volume, increase in penumbra, increase in source to axis distance (SAD), and increase in field size due to inverse square factor. CONCLUSION: It is concluded that the PDs depends upon depth and distance from the radiation field edge. All the measurements show PDs in the homogenous medium (water); therefore, it estimates absorbed dose to the organ at risk (OAR) adjacent to cancer tissues/planning target volume (PTV). It is suggested that PDs can be minimized by using the SAD technique, as this technique controls sources of scattered radiation like inverse square factor and effect of penumbra up-to some extent.


Subject(s)
Cobalt Radioisotopes , Phantoms, Imaging , Radiotherapy Dosage , Thermoluminescent Dosimetry , Humans , Thermoluminescent Dosimetry/methods , Water , Radiotherapy Planning, Computer-Assisted/methods , Neoplasms/radiotherapy , Radiation Dosage , Organs at Risk/radiation effects
3.
Sci Rep ; 14(1): 13341, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38858506

ABSTRACT

Accurate channel state information (CSI) is crucial for optimizing wireless communication systems. In scenarios with varying user-to-base station angles, the angle-dependent coherence time impacts conventional pilot strategies. Due to small angles, the coherence time of the user decreases dramatically because of doppler shift, which causes an increase in the number of pilots. We introduces an innovative sub-block design approach for systems with different user angles. This method harmonizes coherence time of high and low-angle users, while maintaining a constant pilot count. This not only improves spectral efficiency but also ensures accurate channel estimation. Through simulations, we demonstrate the effectiveness of our approach in enhancing both spectral efficiency upt to 10 % and CSI precision. This breakthrough contributes to the advancement of channel estimation techniques in scenarios with angle-dependent coherence time, offering practical benefits to wireless communication systems.

4.
Chem Asian J ; 19(16): e202400308, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-38880773

ABSTRACT

Hydrogen-driven energy is fascinating among the everlasting energy sources, particularly for stationary and onboard transportation applications. Efficient hydrogen storage presents a key challenge to accomplishing the sustainability goals of hydrogen economy. In this regard, solid-state hydrogen storage in nanomaterials, either physically or chemically adsorbed, has been considered a safe path to establishing sustainability goals. Though metal hydrides have been extensively explored, they fail to comply with the set targets for practical utilization. Recently, MXenes, both in bare form and hybrid state with metal hydrides, have proven their flair in ascertaining the hydrides' theoretical and experimental hydrogen storage capabilities far beyond the fancy materials and current state-of-the-art technologies. This review encompasses the significant accomplishments achieved by MXenes (primarily in 2019-2024) for enhancing the hydrogen storage performance of various metal hydride materials such as MgH2, AlH3, Mg(BH4)2, LiBH4, alanates, and composite hydrides. It also discusses the bottlenecks of metal hydrides for hydrogen storage, the potential use of MXenes hybrids, and their challenges, such as reversibility, H2 losses, slow kinetics, and thermodynamic barriers. Finally, it concludes with a detailed roadmap and recommendations for mechanistic-driven future studies propelling toward a breakthrough in solid material-driven hydrogen storage using cost-effective, efficient, and long-lasting solutions.

5.
Chem Asian J ; 19(16): e202400320, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-38838273

ABSTRACT

Hydrogen (H2) is being acknowledged as the future energy carrier due to its high energy density and potential to mitigate the intermittency of other renewable energy sources. H2 also ensures a clean, carbon-neutral, and sustainable environment for current and forthcoming generations by contributing to the global missions of decarbonization in the transportation, industrial, and building sectors. Several H2 storage technologies are available and have been employed for its secure and economical transport. The existing H2 storage and transportation technologies like liquid-state, cryogenic, or compressed hydrogen are in use but still suffer from significant challenges regarding successful realization at the commercial level. These factors affect the overall operational cost of technology. Therefore, H2 storage demands novel technologies that are safe for mobility, transportation, long-term storage, and yet it is cost-effective. This review article presents potential opportunities for H2 storage technologies, such as physical and chemical storage. The prime characteristics and requirements of H2 storage are briefly explained. A detailed discussion of chemical-based hydrogen storage systems such as metal hydrides, chemical hydrides (CH3OH, NH3, and HCOOH), and liquid organic hydrogen carriers (LOHCs) is presented. Furthermore, the recent developments and challenges regarding hydrogen storage, their real-world applications, and prospects have also been debated.

6.
Commun Biol ; 7(1): 613, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773248

ABSTRACT

Understanding how to increase soybean yield is crucial for global food security. The genetic and epigenetic factors influencing seed size, a major crop yield determinant, are not fully understood. We explore the role of DNA demethylase GmDMEa in soybean seed size. Our research indicates that GmDMEa negatively correlates with soybean seed size. Using CRISPR-Cas9, we edited GmDMEa in the Dongnong soybean cultivar, known for small seeds. Modified plants had larger seeds and greater yields without altering plant architecture or seed nutrition. GmDMEa preferentially demethylates AT-rich transposable elements, thus activating genes and transcription factors associated with the abscisic acid pathway, which typically decreases seed size. Chromosomal substitution lines confirm that these modifications are inheritable, suggesting a stable epigenetic method to boost seed size in future breeding. Our findings provide insights into epigenetic seed size control and suggest a strategy for improving crop yields through the epigenetic regulation of crucial genes. This work implies that targeted epigenetic modification has practical agricultural applications, potentially enhancing food production without compromising crop quality.


Subject(s)
DNA Methylation , DNA Transposable Elements , Glycine max , Seeds , Glycine max/genetics , Seeds/genetics , Seeds/growth & development , DNA Transposable Elements/genetics , Epigenesis, Genetic , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolism , Plants, Genetically Modified/genetics
7.
Chem Asian J ; 19(16): e202400365, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-38705846

ABSTRACT

Hydrogen energy heralded for its environmentally friendly, renewable, efficient, and cost-effective attributes, stands poised as the primary alternative to fossil fuels in the future. Despite its great potential, the low volumetric density presents a formidable challenge in hydrogen storage. Addressing this challenge necessitates exploring effective storage techniques for a sustainable hydrogen economy. Solid-state hydrogen storage in nanomaterials (physically or chemically) holds promise for achieving large-scale hydrogen storage applications. Such approaches offer benefits, including safety, compactness, lightness, reversibility, and efficient generation of pure hydrogen fuel under mild conditions. This article presents solid-state nanomaterials, specifically nanoporous carbons (activated carbon, carbon fibers), metal-organic frameworks, covalently connected frameworks, nanoporous organic polymers, and nanoscale metal hydrides. Furthermore, new developments in hydrogen fuel cell technology for stationary and mobile applications have been demonstrated. The review outlines significant advancements thus far, identifies key barriers to practical implementation, and presents a perspective for future sustainable energy research. It concludes with recommendations to enhance hydrogen storage performance for cost-effective and long-lasting utilization.

8.
Mol Ecol ; : e17356, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38634782

ABSTRACT

DNA methylation has been proposed to be an important mechanism that allows plants to respond to their environments sometimes entirely uncoupled from genetic variation. To understand the genetic basis, biological functions and climatic relationships of DNA methylation at a population scale in Arabidopsis thaliana, we performed a genome-wide association analysis with high-quality single nucleotide polymorphisms (SNPs), and found that ~56% on average, especially in the CHH sequence context (71%), of the differentially methylated regions (DMRs) are not tagged by SNPs. Among them, a total of 3235 DMRs are significantly associated with gene expressions and potentially heritable. 655 of the 3235 DMRs are associated with climatic variables, and we experimentally verified one of them, HEI10 (HUMAN ENHANCER OF CELL INVASION NO.10). Such epigenetic loci could be subjected to natural selection thereby affecting plant adaptation, and would be expected to be an indicator of accessions at risk. We therefore incorporated these climate-related DMRs into a gradient forest model, and found that the natural A. thaliana accessions in Southern Europe that may be most at risk under future climate change. Our findings highlight the importance of integrating DNA methylation that is independent of genetic variations, and climatic data to predict plants' vulnerability to future climate change.

11.
Sci Rep ; 14(1): 4528, 2024 Feb 24.
Article in English | MEDLINE | ID: mdl-38402301

ABSTRACT

The orthogonal frequency division multiplexing (OFDM) system applies coherent demodulation to achieve high spectral efficiency at a bandwidth cost by the pilot tones. Considering the statistical property of the down-link channels to the users, it can be found that there is an opportunity to reduce the pilot number in the conventional designs while maintaining the same signal demodulation performances. The design philosophy involves utilizing the difference of the channel coherent bandwidths (CCBs) by allocating data to appropriate positions upon the fact that different CCBs can tolerate different minimized pilot spacing. The proposed design allows each user's equipment's data not to exceed its CCB with the sparser pilots. The theoretical analysis is carried out based on the concept of channel frequency response using linear interpolation with channel estimation employing the least squares (LS) method. The gain of the proposed method is demonstrated in terms of the ergodic capacities and confirmed by the simulations.

12.
J Exp Zool B Mol Dev Evol ; 342(2): 85-100, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38369890

ABSTRACT

TRPS1 serves as the causative gene for tricho-rhino phalangeal syndrome, known for its craniofacial and skeletal abnormalities. The Trps1 gene encodes a protein that represses Wnt signaling through strong interactions with Wnt signaling inhibitors. The identification of genomic cis-acting regulatory sequences governing Trps1 expression is crucial for understanding its role in embryogenesis. Nevertheless, to date, no investigations have been conducted concerning these aspects of Trps1. To identify deeply conserved noncoding elements (CNEs) within the Trps1 locus, we employed a comparative genomics approach, utilizing slowly evolving fish such as coelacanth and spotted gar. These analyses resulted in the identification of eight CNEs in the intronic region of the Trps1 gene. Functional characterization of these CNEs in zebrafish revealed their regulatory potential in various tissues, including pectoral fins, heart, and pharyngeal arches. RNA in-situ hybridization experiments revealed concordance between the reporter expression pattern induced by the identified set of CNEs and the spatial expression pattern of the trps1 gene in zebrafish. Comparative in vivo data from zebrafish and mice for CNE7/hs919 revealed conserved functions of these enhancers. Each of these eight CNEs was further investigated in cell line-based reporter assays, revealing their repressive potential. Taken together, in vivo and in vitro assays suggest a context-dependent dual functionality for the identified set of Trps1-associated CNE enhancers. This functionally characterized set of CNE-enhancers will contribute to a more comprehensive understanding of the developmental roles of Trps1 and can aid in the identification of noncoding DNA variants associated with human diseases.


Subject(s)
Fingers/abnormalities , Hair Diseases , Langer-Giedion Syndrome , Nose/abnormalities , Regulatory Sequences, Nucleic Acid , Zebrafish , Animals , Mice , Humans , Zebrafish/genetics , Zebrafish/metabolism , Genome , Base Sequence , Gene Expression , Mammals/genetics , Repressor Proteins/genetics , Repressor Proteins/metabolism
13.
PLoS One ; 19(2): e0291309, 2024.
Article in English | MEDLINE | ID: mdl-38324592

ABSTRACT

This study investigates the impact of board governance mechanism on investment efficiency (IE) in PSX-listed firms. The study also examines the role of institutional ownership (IO) in board-IE relationships. In addition, we extend our analysis to re-examine this relationship by splitting the sample into two groups, i.e., the introductory phase of corporate governance (CG) i.e., 2004 to 2013, and revised codes of CG (2014 to 2018) to examine the impact of these separately on IE. The sample data comprises 155 non-financial PSX-listed firms from 2004 to 2018. IE is measured using firms' growth opportunities. The random effect model is used to test the study's hypotheses. A robustness test is also performed to validate the study's findings. The paired-sample t-test results show a significant improvement in IE after revising the CG codes in 2012. According to the regression results, board size has a significant direct, whereas board diversity has a significant inverse effect on IE. Regarding moderating effect, IO was found to moderate the relationship between board independence and IE significantly. Furthermore, it was discovered that following the issuance of revised CG codes-2012, the level of board independence and diversity increased in PSX-listed firms; however, only diversity positively impacted IE, and board independence had no impact on IE from 2014 to 2018. Despite the issuance of revised CG codes-2012, the level of CG among PSX-listed firms is low, which is a source of concern for regulators such as the Securities and Exchange Commission of Pakistan.


Subject(s)
Health Facilities , Ownership , Investments , Pakistan
14.
Pak J Med Sci ; 40(3Part-II): 526-533, 2024.
Article in English | MEDLINE | ID: mdl-38356832

ABSTRACT

Objectives: To review published clinical trials which assessed the effects of deep transverse friction massage on pain and range of motion in patients with adhesive capsulitis. Methods: A systematic review was conducted according to PRISMA guidelines. Literature search was performed in MEDLINE, AMED, EMBASE, HMIC, CINAHL, PEDRO, and SPORTDiscus. Two independent reviewers performed screening of the articles retrieved from different databases. Clinical trials published in English language from the earliest record to March 2022 that reported effects of deep transverse friction massage/Cyriax's friction massage on pain and/or range of motion in patients with diagnosis of adhesive capsulitis were included. The Critical Appraisal Skills Programme was used for quality assessment of the included studies. Results: A total of six studies reporting on 226 adhesive capsulitis patients were included in the systematic review. All the six studies were randomized controlled clinical trials. On the Critical Appraisal Skills Programme tool, four of the six studies had a score of 8/11, while the other two studies received a score of 7/11 and 6/11. Out of these six trials, four reported that pain was significantly (P<0.05) improved in the deep transverse friction massage group as compared to the control group. Regarding range of motion outcome, five studies showed that range of motion was significantly (P<0.05) improved in the deep transverse friction massage group while only one study showed non-significant results. Conclusion: It can be concluded that deep transverse friction massage significantly relieves pain and improves the range of motion in individuals with adhesive capsulitis.

15.
Small ; 20(23): e2310946, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38229536

ABSTRACT

Owing to their extraordinary photophysical properties, organometal halide perovskites are emerging as a new material class for X-ray detection. However, the existence of toxic lead makes their commercialization questionable and should readily be replaced. Accordingly, several lead alternatives have been introduced into the framework of conventional perovskites, resulting in various new perovskite dimensionalities. Among these, Pb-free lower dimensional perovskites (LPVKs) not only show promising X-ray detecting properties due to their higher ionic migration energy, wider and tunable energy bandgap, smaller dark currents, and structural versatility but also exhibit extended environmental stability. Herein, first, the structural organization of the PVKs (including LPVKs) is summarized. In the context of X-ray detectors (XDs), the outstanding properties of the LPVKs and active layer synthesis routes are elaborated afterward. Subsequently, their applications in direct XDs are extensively discussed and the device performance, in terms of the synthesis method, device architecture, active layer size, figure of merits, and device stability are tabulated. Finally, the review is concluded with an in-depth outlook, thoroughly exploring the present challenges to LPVKs XDs, proposing innovative solutions, and future directions. This review provides valuable insights into optimizing non-toxic Pb-free perovskite XDs, paving the way for future advancements in the field.

16.
Phytomedicine ; 125: 155350, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38237512

ABSTRACT

BACKGROUND: Myostatin (MSTN) inhibition has demonstrated promise for the treatment of diseases associated with muscle loss. In a previous study, we discovered that Glycyrrhiza uralensis (G. uralensis) crude water extract (CWE) inhibits MSTN expression while promoting myogenesis. Furthermore, three specific compounds of G. uralensis, namely liquiritigenin, tetrahydroxymethoxychalcone, and Licochalcone B (Lic B), were found to promote myoblast proliferation and differentiation, as well as accelerate the regeneration of injured muscle tissue. PURPOSE: The purpose of this study was to build on our previous findings on G. uralensis and demonstrate the potential of its two components, Licochalcone A (Lic A) and Lic B, in muscle mass regulation (by inhibiting MSTN), aging and muscle formation. METHODS: G. uralensis, Lic A, and Lic B were evaluated thoroughly using in silico, in vitro and in vivo approaches. In silico analyses included molecular docking, and dynamics simulations of these compounds with MSTN. Protein-protein docking was carried out for MSTN, as well as for the docked complex of MSTN-Lic with its receptor, activin type IIB receptor (ACVRIIB). Subsequent in vitro studies used C2C12 cell lines and primary mouse muscle stem cells to acess the cell proliferation and differentiation of normal and aged cells, levels of MSTN, Atrogin 1, and MuRF1, and plasma MSTN concentrations, employing techniques such as western blotting, immunohistochemistry, immunocytochemistry, cell proliferation and differentiation assays, and real-time RT-PCR. Furthermore, in vivo experiments using mouse models focused on measuring muscle fiber diameters. RESULTS: CWE of G. uralensis and two of its components, namely Lic A and B, promote myoblast proliferation and differentiation by inhibiting MSTN and reducing Atrogin1 and MuRF1 expressions and MSTN protein concentration in serum. In silico interaction analysis revealed that Lic A (binding energy -6.9 Kcal/mol) and B (binding energy -5.9 Kcal/mol) bind to MSTN and reduce binding between it and ACVRIIB, thereby inhibiting downstream signaling. The experimental analysis, which involved both in vitro and in vivo studies, demonstrated that the levels of MSTN, Atrogin 1, and MuRF1 were decreased when G. uralensis CWE, Lic A, or Lic B were administered into mice or treated in the mouse primary muscle satellite cells (MSCs) and C2C12 myoblasts. The diameters of muscle fibers increased in orally treated mice, and the differentiation and proliferation of C2C12 cells were enhanced. G. uralensis CWE, Lic A, and Lic B also promoted cell proliferation in aged cells, suggesting that they may have anti-muslce aging properties. They also reduced the expression and phosphorylation of SMAD2 and SMAD3 (MSTN downstream effectors), adding to the evidence that MSTN is inhibited. CONCLUSION: These findings suggest that CWE and its active constituents Lic A and Lic B have anti-mauscle aging potential. They also have the potential to be used as natural inhibitors of MSTN and as therapeutic options for disorders associated with muscle atrophy.


Subject(s)
Chalcones , Muscle Fibers, Skeletal , Myostatin , Mice , Animals , Myostatin/metabolism , Molecular Docking Simulation , Cell Differentiation , Muscle Fibers, Skeletal/metabolism , Cell Proliferation , Muscle, Skeletal/metabolism
17.
Sci Rep ; 14(1): 449, 2024 01 03.
Article in English | MEDLINE | ID: mdl-38172191

ABSTRACT

The coronavirus (COVID-19) pandemic has not only had a severe impact on global health but also poses a threat to the environment. This research aims to explore an innovative approach to address the issue of increased waste generated by the pandemic. Specifically, the study investigates the utilization of discarded face masks in combination with recycled concrete aggregate (RCA) and Silica Fume (SFM) in civil construction projects. The disposable face masks were processed by removing the ear loops and nose strips, and then cutting them into small fibers measuring 20 mm in length, 5 mm in width, and 0.46 mm in thickness, resulting in an aspect ratio of 24. Various proportions of SFM and RCA were incorporated into the concrete mix, with a focus on evaluating the compressive strength, split tensile strength, and durability of the resulting material. The findings indicate that the addition of SFM led to improvements in both compressive and split tensile strength, while no significant impact on durability was observed.


Subject(s)
Waste Management , Waste Management/methods , Silicon Dioxide , Masks , Construction Materials , Industrial Waste/analysis
18.
Environ Sci Pollut Res Int ; 31(4): 6460-6480, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38148456

ABSTRACT

Management of organic waste addresses the issue of cleanliness and sanitation in developing nations such as Pakistan, where improper waste management usually leads to significant health problems and early mortality. The control of organic waste in rural regions of Pakistan and other developing nations needs to be undertaken using effective solutions. This study contributes to satisfying local needs such as cooking, lighting, and maintaining a comfortable temperature in anaerobic locations and works as a guideline for converting to biogas. This research aims to ascertain households' most substantial challenges concerning biogas production using domestic organic waste and locally sourced materials. The analysis is conducted on data from 81 respondents gathered using a comprehensive questionnaire assessment. Respondents were carefully chosen with the purposive sampling process. Primary data were collected from a structured questionnaire and partial least squares structural equation modeling (PLS-SEM) to evaluate the formulated assumptions. The results indicate that managing organic waste positively influences the sustainable improvement of biogas using human organic waste and locally resourced materials. The selected variables and their moderating effect significantly and favorably influence this conceptual model. Furthermore, all manipulating influences are constructively connected with implementing biogas technology using organic waste and locally resourced material, minimizing household energy expenses, and satisfying local needs. This study concludes that the government's green energy policy and economic incentives encourage households to use biogas energy produced from organic waste and locally resourced material. The government should use modern technology, resident training, and expert methodological assistance to induce households into biogas production using domestic organic waste and locally resourced material. Finally, the study's limitations and suggestions for further research are also addressed.


Subject(s)
Social Media , Waste Management , Humans , Biofuels , Waste Management/methods , Bioreactors , Technology , Anaerobiosis
19.
Plant Physiol Biochem ; 206: 108126, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38147709

ABSTRACT

Heavy metal cadmium (Cd) hinders plants' growth and productivity by causing different morphological and physiological changes. Nanoparticles (NPs) are promising for raising plant yield and reducing Cd toxicity. Nonetheless, the fundamental mechanism of nanoparticle-interfered Cd toxicity in Brassica parachineses L. remains unknown. A novel ZnO nanoparticle (ZnO-NPs) was synthesized using a microalgae strain (Chlorella pyrenoidosa) through a green process and characterized by different standard parameters through TEM, EDX, and XRD. This study examines the effect of different concentrations of ZnO-NPs (50 and 100 mgL-1) in B. parachineses L. under Cd stress through ultra-high-performance liquid chromatography/high-resolution mass spectrometry-based untargeted metabolomics profiling. In the presence of Cd toxicity, foliar spraying with ZnO-NPs raised Cu, Fe, Zn, and Mg levels in the roots and/or leaves, improved seedling development, as demonstrated by increased plant height, root length, and shoot and root fresh weight. Furthermore, the ZnO-NPs significantly enhanced the photosynthetic pigments and changed the antioxidant activities of the Cd-treated plants. Based on a metabolomics analysis, 481 untargeted metabolites were accumulated in leaves under normal and Cd-stressed conditions. These metabolites were highly enriched in producing organic acids, amino acids, glycosides, flavonoids, nucleic acids, and vitamin biosynthesis. Surprisingly, ZnO-NPs restored approximately 60% of Cd stress metabolites to normal leaf levels. Our findings suggest that green synthesized ZnO-NPs can balance ions' absorption, modulate the antioxidant activities, and restore more metabolites associated with plant growth to their normal levels under Cd stress. It can be applied as a plant growth regulator to alleviate heavy metal toxicity and improve crop yield in heavy metal-contaminated regions.


Subject(s)
Chlorella , Metals, Heavy , Nanoparticles , Soil Pollutants , Zinc Oxide , Zinc Oxide/pharmacology , Zinc Oxide/chemistry , Cadmium/analysis , Antioxidants , Chlorella/metabolism , Nanoparticles/chemistry , Metals, Heavy/toxicity , Soil Pollutants/metabolism
20.
J Biomol Struct Dyn ; : 1-10, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38100571

ABSTRACT

The enzyme dipeptidyl peptidase 4 (DPP4) is a potential therapeutic target for type 2 diabetes (T2DM). Many synthetic anti-DPP4 medications are available to treat T2DM. The need for secure and efficient medicines has been unmet due to the adverse side effects of existing DPP4 medications. The present study implemented a combined approach to machine learning and structure-based virtual screening to identify DPP4 inhibitors. Two ML models were trained based on DPP4 IC50 datasets. The ML models random forest (RF) and multilayer perceptron (MLP) neural network showed good accuracy, with the area under the curve being 0.93 and 0.91, respectively. The natural compound library was screened through ML models, and 1% (217) of compounds were selected for further screening. Structure-based virtual screening was performed along with positive control sitagliptin to obtain more specific and selective leads for DPP4. Based on binding affinity, drug-likeness properties, and interaction with DPP4, Z-614 and Z-997 compounds showed high binding affinity and specificity in the catalytic pocket of DPP4. Finally, the stability conformation of the DPP4 enzyme complex was checked by a molecular dynamics (MD) simulation. The MD simulation showed that both compounds bind better in the catalytic pocket, but the Z-614 compound altered the DPP4 native conformation. Therefore, Z-614 showed a high deviation in the backbone. This combined approach (ML and structure-based) study reported that Z-997 binds most stably to DPP4 in their catalytic pocket with a binding free energy of -70.3 kJ/mol, suggesting its therapeutic potential as a treatment option for T2DM disease.Communicated by Ramaswamy H. Sarma.

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