Dengue determinants: Necessities and challenges for universal dengue vaccine development.

Dengue illness can range from mild illness to life-threatening haemorrhage. It is an Aedes-borne infectious disease caused by the dengue virus, which has four serotypes. Each serotype acts as an independent infectious agent. The antibodies against one serotype confer homotypic immunity but temporary protection against heterotypic infection. Dengue has become a growing health concern for up to one third of the world's population. Currently, there is no potent anti-dengue medicine, and treatment for severe dengue relies on intravenous fluid management and pain medications. The burden of dengue dramatically increases despite advances in vector control measures. These factors underscore the need for a vaccine. Various dengue vaccine strategies have been demonstrated, that is, live attenuated vaccine, inactivated vaccine, DNA vaccine, subunit vaccine, and viral-vector vaccines, some of which are at the stage of clinical testing. Unfortunately, the forefront candidate vaccine is less than satisfactory, and its performance depends on serostatus and age factors. The lessons from clinical studies depicted ambiguity concerning the efficacy of dengue vaccine. Our study highlighted that viral structural heterogeneity, epitope accessibility, autoimmune complications, genetic variants, genetic diversities, antigen competition, virulence variation, host-pathogen specific interaction, antibody-dependent enhancement, cross-reactive immunity among Flaviviruses, and host-susceptibility determinants not only influence infection outcomes but also hampered successful vaccine development. This review integrates dengue determinants allocated necessities and challenges, which would provide insight for universal dengue vaccine development.

Spatial variation in iodine content with relation to soil physicochemical properties in lower Himalayan region.

Topography of a place has a significant impact on soil characteristics that ultimately influence soil iodine levels. Lower Himalayan region (LHR) in Pakistan has a wide range of climatic and geological variations. Hence, an investigation was conducted to analyze the iodine concentration and other physicochemical properties of soils in two LHR districts, Haripur and Mansehra. Spatial analysis indicated a decrease in iodine levels in the mountainous regions in comparison to the flat portions of LHR. Soil samples obtained from different locations across Haripur had a stronger affinity for iodine due to variations in solubility and adsorption of iodine to soil clay components, which can be attributed to lower pH, higher organic matter, and a higher cation exchange capacity (CEC). In contrast to the plains of Haripur, elevated locations in the Mansehra district had decreased levels of iodine, along with a higher soil pH and reduced soil organic matter. The soil erosion and depletion of soil micronutrients in the hilly region of Mansehra may be attributed to the unfavorable soil conditions and excessive precipitation. Presence of clay, iron (Fe), and aluminum (Al) in the soil led to a rise in iodine levels. Iodine concentrations exhibited an inverse relationship with soil acidity. Study revealed a direct correlation between soil iodine levels and their cation exchange capacity (CEC) and clay content. This study aims to gather fundamental data for the chosen regions of LHR to address illnesses caused by iodine deficiency.

Improving the substrate binding of acetyl-CoA carboxylase (AccB) from Streptomyces antibioticus through computational enzyme engineering.

Malonyl-CoA serves as the main building block for the biosynthesis of many important polyketides, as well as fatty acid-derived compounds, such as biofuel. Escherichia coli, Corynebacterium gultamicum, and Saccharomyces cerevisiae have recently been engineered for the biosynthesis of such compounds. However, the developed processes and strains often have insufficient productivity. In the current study, we used enzyme-engineering approach to improve the binding of acetyl-CoA with ACC. We generated different mutations, and the impact was calculated, which reported that three mutations, that is, S343A, T347W, and S350W, significantly improve the substrate binding. Molecular docking investigation revealed an altered binding network compared to the wild type. In mutants, additional interactions stabilize the binding of the inner tail of acetyl-CoA. Using molecular simulation, the stability, compactness, hydrogen bonding, and protein motions were estimated, revealing different dynamic properties owned by the mutants only but not by the wild type. The findings were further validated by using the binding-free energy (BFE) method, which revealed these mutations as favorable substitutions. The total BFE was reported to be -52.66 ± 0.11 kcal/mol for the wild type, -55.87 ± 0.16 kcal/mol for the S343A mutant, -60.52 ± 0.25 kcal/mol for T347W mutant, and -59.64 ± 0.25 kcal/mol for the S350W mutant. This shows that the binding of the substrate is increased due to the induced mutations and strongly corroborates with the docking results. In sum, this study provides information regarding the essential hotspot residues for the substrate binding and can be used for application in industrial processes.

Investigations of Limeum Indicum Plant for Diabetes Mellitus and Alzheimer's Disease Dual Therapy: Phytochemical, GC-MS Chemical Profiling, Enzyme Inhibition, Molecular Docking and In-Vivo Studies.

Limeum indicum has been widely utilized in traditional medicine but no experimental work has been done on this herb. The primary objective of this study was to conduct a phytochemical analysis and assess the multifunctional capabilities of aforementioned plant in dual therapy for Alzheimer's disease (AD) and Type 2 diabetes (T2D). The phytochemical screening of ethanol, methanol extract, and their derived fractions of Limeum indicum was conducted using GC-MS, HPLC, UV-analysis and FTIR. The antioxidant capacity was evaluated by DPPH method. The inhibitory potential of the extracts/fractions against α-, ß-glucosidase acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and monoaminine oxidases (MAO-A & B) was evaluated. Results revealed that acetonitrile fraction has highest inhibitory potential against α-glucosidase (IC50=68.47±0.05 µg/mL), methanol extract against ß-glucosidase (IC50=91.12±0.07 µg/mL), ethyl acetate fraction against AChE (IC50=59.0±0.02 µg/mL), ethanol extract against BChE (28.41±0.01 µg/mL), n-hexane fraction against MAO-A (IC50=150.5±0.31 µg/mL) and methanol extract for MAO-B (IC50=75.95±0.13 µg/mL). The docking analysis of extracts\fractions suggested the best binding scores within the active pocket of the respective enzymes. During the in-vivo investigation, ethanol extract produced hypoglycemic effect (134.52±2.79 and 119.38±1.40 mg/dl) after 21 days treatment at dose level of 250 and 500 mg/Kg. Histopathological findings further supported the in-vivo studies.

Human plasma derived exosomes: Impact of active and passive drug loading approaches on drug delivery.

The aim of the current study was to explore the potential of human plasma-derived exosomes as versatile carriers for drug delivery by employing various active and passive loading methods. Exosomes were isolated from human plasma using differential centrifugation and ultrafiltration method. Drug loading was achieved by employing sonication and freeze thaw methods, facilitating effective drug encapsulation within exosomes for delivery. Each approach was examined for its effectiveness, loading efficiency and ability to preserve membrane stability. Methotrexate (MTX), a weak acid model drug was loaded at a concentration of 2.2 µM to exosomes underwent characterization using various techniques such as particle size analysis, transmission electron microscopy and drug loading capacity. Human plasma derived exosomes showed a mean size of 162.15 ± 28.21 nm and zeta potential of -30.6 ± 0.71 mV. These exosomes were successfully loaded with MTX demonstrated a better drug encapsulation of 64.538 ± 1.54 % by freeze thaw method in comparison 55.515 ± 1.907 % by sonication. In-vitro drug release displayed 60 % loaded drug released within 72 h by freeze thaw method that was significantly different from that by sonication method i.e., 99 % within 72 h (p value 0.0045). Moreover, cell viability of exosomes loaded by freeze thaw method was significantly higher than that by sonication method (p value 0.0091) suggested that there was membrane disruption by sonication method. In conclusion, this study offers valuable insights into the potential of human plasma-derived exosomes loaded by freeze thaw method suggest as a promising carrier for improved drug loading and maintenance of exosomal membrane integrity.

Diazene Chemistry: Metal-Free Models of N2 Reduction Intermediates.

Interest in main group chemistry related to the Haber-Bosch process has drawn less attention than that of transition metal species. Herein, we show that the steric demands in (tBuO2CN)2 block initial interaction of B(C6F5)3 with nitrogen and prompt loss of methylpropene and CO2 to diazene (N2H2) borane adduct 1 and the analogous hydrazine (N2H4) adduct 2. These species react with basic phosphines to give anions of 3 and 5 containing N2H and N2H3 fragments, respectively. While these species are not derived directly from N2, they represent metal-free species containing N2Hn (n = 1-4) fragments, which model plausible intermediates in the reduction of N2.

Repetitive transcranial magnetic stimulation (rTMS) is associated with increased abstinence in substance use disorders and comorbid depression.

BACKGROUND: Substance use disorders (SUDs) are associated with high rates of comorbid depression. Finding effective treatments for many of the substances of abuse is still an area of developing research. Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for depression, but its effects in SUDs are less conclusive. Therefore, we aimed to investigate the effect of rTMS in patients with SUDs and comorbid major depressive disorder (MDD). METHODS: We conducted a retrospective observational study of 55 patients with SUDs and comorbid MDD who were eligible for rTMS. Craving was measured using the Brief Substance Craving Scale (BSCS). Severity of MDD was measured using the Clinical Global Impression-Severity (CGI-S) scale. RESULTS: We found a statistically significant difference between baseline and posttreatment scores in patients receiving rTMS on both CGI-S scores and BSCS scores. The number of rTMS sessions significantly predicted increased days of abstinence in the community, even after controlling for confounders. CONCLUSIONS: Patients with SUDs and MDD who received rTMS significantly improved in the areas of severity of depression and craving. The number of rTMS sessions significantly predicted increased abstinence.

Synthesis and biological evaluation of carboxamide and quinoline derivatives as P2X7R antagonists.

P2X7 receptor (P2X7R) has a key role in different pathological conditions, importantly overexpressed and activated in cancers. We explored the structure activity relationship (SAR) of three novel pyrazines, quinoline-carboxamide and oxadiazole series. Their selective inhibitory potency in Ca2+ mobilization assay using h-P2X7R-MCF-7 cells improved with phenyl ring substitutions (-OCF3, -CF3, and -CH3) in carboxamide and oxadiazole derivatives, respectively. However, highly electronegative fluoro, chloro, and iodo substitutions enhanced affinity. 1e, 2f, 2e, 1d, 2 g and 3e were most potent and selective toward h-P2X7R (IC50 values 0.457, 0.566, 0.624, 0.682, 0.813 and 0.890 µM, respectively) and were inactive at h-P2X4R, h-P2X2R, r-P2Y6R, h-P2Y2R, t-P2Y1R expressed in MCF-7 and 1321N1 astrocytoma cells. Cell viability (MTT assay at 100 µM, cell line) for 3e was 62% (HEK-293T), 70% (1321N1 astrocytoma) and 85% (MCF-7). >75% cell viability was noted for 2 g and >80% for 2e and 1d in all non-transfected cell lines. Anti-proliferative effects, compared to control (Bz-ATP), of selective antagonists (10 µM) were 3e (11%) 1d, (19%) 1e, (70%, P = 0.005) and 2f, (24%), indicating involvement of P2X7R. Apoptotic cell death by flow cytometry showed 1e to be most promising, with 35% cell death (PI positive cells), followed by 2e (25%), 2f (20%), and 1d (19%), compared to control. Fluorescence microscopic analysis of apoptotic changes in P2X7R-transfected cell lines was established. 1e and 2f at 1X and 2X IC50 increased cellular shrinkage, nuclear condensation and PI/DAPI fluorescence. In-silico antagonist modeling predicted ligand receptor interactions, and all compounds obeyed Lipinski rules. These results suggest that pyrazine, quinoline-carboxamide and oxadiazole derivatives could be moderately potent P2X7R antagonists for in vivo studies and anti-cancer drug development.

Functionalization of curcumin nanomedicines: a recent promising adaptation to maximize pharmacokinetic profile, specific cell internalization and anticancer efficacy against breast cancer.

Owing to its diverse heterogeneity, aggressive nature, enormous metastatic potential, and high remission rate, the breast cancer (BC) is among the most prevalent types of cancer associated with high mortality. Curcumin (Cur) is a potent phytoconstituent that has gained remarkable recognition due to exceptional biomedical viability against a wide range of ailments including the BC. Despite exhibiting a strong anticancer potential, the clinical translation of Cur is restricted due to intrinsic physicochemical properties such as low aqueous solubility, chemical instability, low bioavailability, and short plasma half-life. To overcome these shortcomings, nanotechnology-aided developments have been extensively deployed. The implication of nanotechnology has pointedly improved the physicochemical properties, pharmacokinetic profile, cell internalization, and anticancer efficacy of Cur; however, majority of Cur-nanomedicines are still facing grandeur challenges. The advent of various functionalization strategies such as PEGylation, surface decoration with different moieties, stimuli-responsiveness (i.e., pH, light, temperature, heat, etc.), tethering of specific targeting ligand(s) based on the biochemical targets (e.g., folic acid receptors, transferrin receptors, CD44, etc.), and multifunctionalization (multiple functionalities) has revolutionized the fate of Cur-nanomedicines. This study ponders the biomedical significance of various Cur-nanomedicines and adaptable functionalizations for amplifying the physicochemical properties, cytotoxicity via induction of apoptosis, cell internalization, bioavailability, passive and active targeting to the tumor microenvironment (TME), and anticancer efficacy of the Cur while reversing the multidrug resistance (MDR) and reoccurrence in BC. Nevertheless, the therapeutic outcomes of Cur-nanomedicines against the BC have been remarkably improved after adaptation of various functionalizations; however, this evolving strategy still demands extensive research for scalable clinical translation.

Workplace violence against pharmacists: A systematic review and meta-analysis.

BACKGROUND: The rate of violence against health care workers is increasing worldwide. Pharmacists are the most accessible and frequently visited health care team members and are potentially more susceptible to violence than other health care workers. OBJECTIVE(S): This systematic review and meta-analysis aimed to estimate the magnitude of workplace violence toward pharmacists. METHODS: We comprehensively searched PubMed, Scopus, and Embase from their inception till December 2021 for pertinent studies that reported workplace violence incidents against pharmacists. Rates of workplace violence against pharmacists were calculated in a meta-analysis using a random-effects model. RESULTS: Overall, 624 articles were found, and 6 studies comprising 1896 pharmacists met the criteria for meta-analysis. The pooled estimate of workplace violence was 45% (95% confidence interval [CI]: 30-60%), and 39% (95% CI: 24-55%) experienced violent events over preceding 12 months. Considerable proportion of pharmacists experienced some form of violence (65%, 95% CI: 41-88%), verbal abuse (50%, 95% CI: 36-65%), threats (42%, 95% CI: 26-59%) or assaults (27%, 95% CI: 9-46%). Moreover, 56% (95% CI: 23-89%) of pharmacists reported experiencing physical and/or verbal violence over the previous 12 months. CONCLUSION: The analysis reveals the high rate of workplace violence in the pharmacy environment, with nearly half of pharmacists affected. While more studies are required, the limited evidence suggests the need to ensure safe workspaces in pharmacy environments through implementation of appropriate policies and legislation.

Microfluidics in drug delivery: review of methods and applications.

Microfluidics technology has emerged as a promising methodology for the fabrication of a wide variety of advanced drug delivery systems. Owing to its ability for accurate handling and processing of small quantities of fluidics as well as immense control over physicochemical properties of fabricated micro and nanoparticles (NPs), microfluidic technology has significantly improved the pharmacokinetics and pharmacodynamics of drugs. This emerging technology has offered numerous advantages over the conventional drug delivery methods for fabricating of a variety of micro and nanocarriers for poorly soluble drugs. In addition, a microfluidic system can be designed for targeted drug delivery aiming to increase the local bioavailability of drugs. This review spots the light on the recent advances made in the area of microfluidics including various methods of fabrication of drug carriers, their characterization, and unique features. Furthermore, applications of microfluidic technology for the robust fabrication and development of drug delivery systems, the existing challenges associated with conventional fabrication methodologies as well as the proposed solutions offered by microfluidic technology have been discussed in details.HighlightsMicrofluidic technology has revolutionized fabrication of tunable micro and nanocarriers.Microfluidic platforms offer several advantages over the conventional fabrication methods.Microfluidic devices hold great promise in controlling the physicochemical features of fabricated drug carriers.Micro and nanocarriers with controllable release kinetics and site-targeting efficiency can be fabricated.Drug carriers fabricated by microfluidic technology exhibited improved pharmacokinetic and pharmacodynamic profiles.

Effects of transport-carbon intensity, transportation, and economic complexity on environmental and health expenditures.

Health and the environment are complex components of the countries, influenced by several factors, especially transport, and economics. Thus, this paper assesses the role of transportation and economic complexity in the environment and public health for the Organization for Economic Co-operation Development (OECD) countries from 2001 to 2020. This study also focuses on the relationship between transport and economic complexity with environmental and healthcare expenditures. Precisely, transport and economic activities stimulate healthcare expenditures through multiple channels. The current study employs the STIRPAT model to investigate the association with transportation, economic complexity, transport-carbon intensity, and healthcare expenditure. Besides, the current research confirms the plausible cross-sectional dependency across countries, and it adopts a second-generation technique. Analytical findings suggest that transportation-carbon intensity is positively and significantly associated with healthcare expenditures. Healthcare and transport-household expenditures increase transport-carbon intensity (TCI) by 75% and 45%, respectively, in the long run. In the contrast, TCI and transport-household expenditures have also a remarkable impact on healthcare expenditures and are estimated approximately 95% in the long run. Moreover, economic growth also upsurges TCI and healthcare expenditures through multiple economic activities. Besides, transport-household expenditures (THE) drastically impact transport-carbon intensity and healthcare expenditures (HEX) through passenger traffic (PTF). Diagnostic upshots unveil that the joint effect of THE and PTF increases TCI and HEX by 4 and 3%, respectively. Finally, findings recommend some policy implications and future research directions for the countries based on empirical outcomes. Countries should regulate economic activities to reduce transport carbon emissions.

Ambiphilic Behavior of Ge(II)-Pseudohalides in Inter- and Intramolecular Frustrated Lewis Pair Alkyne Addition Reactions.

The reaction of the germylene chloride (NacNac)GeCl (1, NacNac = CH{(CMe)(2,6-iPr2C6H3N)}2), phenylacetylene, and B(C6F5)3 gives the intermolecular frustrated Lewis pair (FLP) addition product 2. In this case, the Ge(II) center acts as a base. In contrast, the analogous reaction of germylene thiocyanate 3 reacts independently with B(C6F5)3 to give the germylene cation salt [(NacNac)Ge][SCNB(C6F5)3] 4. Subsequent in the presence of alkynes, the Ge(II) cation and γ-C of 4 act as a Lewis acidic and basic center, respectively, to affect the addition of alkynes, affording products [(NacNac)Ge(RCCR')][SCNB(C6F5)3] 5 and 6. Compound 4 also reacts with Me3SiCN to give the cyanide-bridged Ge/B species 7, which also reacts with phenylacetylene to give CN abstraction and intramolecular addition yielding the salt [(NacNac)Ge(PhCCH)][NCB(C6F5)3] 8. Despite the similarity of 1 and 3, DFT calculations show that the highest occupied molecular orbital (HOMO) of 1 is mainly located at the more sterically hindered germylene center, while the HOMO of 3 is located on the less sterically hindered NCS group, prompting markedly different FLP addition products.

Recent progress on adsorption of cadmium ions from water systems using metal-organic frameworks (MOFs) as an efficient class of porous materials.

Various articles have been written about MOFs, which are organic-inorganic polymer structures that are unique in three-dimensional porosity, crystalline structure, and their ability to adsorb cadmium ion pollutants from aqueous solutions. These materials possess active metal sites, highly porous structures, high specific surfaces, high chemical functionality, and porous topologies. It is necessary to study adsorption kinetics, isotherms, and mechanisms in order to better understand the adsorption process. Adsorption kinetics can provide information about the adsorption rate and reaction pathway of adsorbents. Adsorption isotherms analyze the possibility of absorbances based on the Gibbs equation and thermodynamic theories. Moreover, in practical applications, knowledge of the adsorption mechanism is essential for predicting adsorption reactions and designing MOFs structures. In this review, the latest suggested adsorption mechanisms, kinetics, and isotherms of MOFs-based materials for removing cadmium ions are presented. A comparison is then conducted between different MOFs and the mechanisms of cadmium ion removal. We also discuss the future role of MOFs in removing environmental contaminants. Lastly, we discuss the gap in research and limitations of MOFs as adsorbents in actual applications, and probable technology development for the development of cost-efficient and sustainable MOFs for metal ion removal.

Promising Application of D-Amino Acids toward Clinical Therapy.

The versatile roles of D-amino acids (D-AAs) in foods, diseases, and organisms, etc., have been widely reported. They have been regarded, not only as biomarkers of diseases but also as regulators of the physiological function of organisms. Over the past few decades, increasing data has revealed that D-AAs have great potential in treating disease. D-AAs also showed overwhelming success in disengaging biofilm, which might provide promise to inhibit microbial infection. Moreover, it can effectively restrain the growth of cancer cells. Herein, we reviewed recent reports on the potential of D-AAs as therapeutic agents for treating neurological disease or tissue/organ injury, ameliorating reproduction function, preventing biofilm infection, and inhibiting cancer cell growth. Additionally, we also reviewed the potential application of D-AAs in drug modification, such as improving biostability and efficiency, which has a better effect on therapy or diagnosis.

Nanomedicine Strategies for Management of Drug Resistance in Lung Cancer.

Lung cancer (LC) is one of the leading causes of cancer occurrence and mortality worldwide. Treatment of patients with advanced and metastatic LC presents a significant challenge, as malignant cells use different mechanisms to resist chemotherapy. Drug resistance (DR) is a complex process that occurs due to a variety of genetic and acquired factors. Identifying the mechanisms underlying DR in LC patients and possible therapeutic alternatives for more efficient therapy is a central goal of LC research. Advances in nanotechnology resulted in the development of targeted and multifunctional nanoscale drug constructs. The possible modulation of the components of nanomedicine, their surface functionalization, and the encapsulation of various active therapeutics provide promising tools to bypass crucial biological barriers. These attributes enhance the delivery of multiple therapeutic agents directly to the tumor microenvironment (TME), resulting in reversal of LC resistance to anticancer treatment. This review provides a broad framework for understanding the different molecular mechanisms of DR in lung cancer, presents novel nanomedicine therapeutics aimed at improving the efficacy of treatment of various forms of resistant LC; outlines current challenges in using nanotechnology for reversing DR; and discusses the future directions for the clinical application of nanomedicine in the management of LC resistance.

Fine root densities of grasses and perennial sugarcane significantly reduce stream channel erosion in southern China.

Stream Channel (SC) erosion results in immense soil and nutrient losses and eutrophication of downstream lakes and rivers. Among other factors, the lack of vegetation cover within SCs and on adjacent soils can accelerate soil and nutrient losses. The combined impact of perennial sugarcane plantation and grass cover on increasing SC erosion losses have not been previously studied. Current study determined SC erosion and associated nutrient losses and clarified the effect of grass roots within SCs and the ratooned sugarcane grown on adjacent lands in Nala watershed in southern subtropics of China. Six SCs in two sub-watersheds (SW1 and SW2) surveyed after revegetation during 2019 were compared with initial survey conducted in 2017 and 2018. The SC erosion was significantly (P < 0.05) reduced by 84.2% (5.19 ± 2.16 Mg ha-1) in entire watershed in 2019 compared to 2018 (43.9 ± 15.2 Mg ha-1). It notably decreased by 99.23% and 96.50% in SC-1-3 at SW1 and SC2-3 at SW2, respectively. Total N and P losses decreased by 84.9% and 82.5%, respectively, in entire watershed. The decreases in SC erosion and nutrient losses are attributed to increasing vegetative cover (R2 = 0.7543, P < 0.001), and grass root densities of <1 mm (R2 = 0.7543, P < 0.001), 1-2 mm (R2 = 0.7051, P < 0.001) and >2 mm (R2 = 0.5746, P < 0.001). Principal component regression analysis confirmed that root densities of SC grasses, perennial sugarcane, and organic matter had positive impacts on controlling SC erosion and consequent nutrient losses.

HantavirusesDB: Vaccinomics and RNA-based therapeutics database for the potentially emerging human respiratory pandemic agents.

Hantaviruses are etiological agents of several severe respiratory illnesses in humans and their human-to-human transmission has been reported. To cope with any potential pandemic, this group of viruses needs further research and a data platform. Therefore, herein we developed a database "HantavirusesDB (HVdb)", where genomics, proteomics, immune resource, RNAi based therapeutics and information on the 3D structures of druggable targets of the Orthohantaviruses are provided on a single platform. The database allows the researchers to effectively map the therapeutic strategies by designing multi-epitopes subunit vaccine and RNA based therapeutics. Moreover, the ease of the web interface allow the users to retrieve specific information from the database. Because of the high quality and excellent functionality of the HVdb, therapeutic research of Hantaviruses can be accelerated, and data analysis might be a foundation to design better treatment strategies targeting the hantaviruses. The database is accessible at http://hvdb.dqweilab-sjtu.com/index.php.

Proteome wide vaccine targets prioritization and designing of antigenic vaccine candidate to trigger the host immune response against the Mycoplasma genitalium infection.

Mycoplasma genitalium is a small size, sexually transmitted bacterial pathogen that causes urethritis in males and cervicitis in females. Being resistant to antibiotics, difficulty in diagnosis, treatment, and control of this cosmopolitan infection, vaccination is the alternating method for its effective management. Herein, this study was conducted to computationally design a multi-epitope vaccine to boost host immune responses against M. genitalium. To achieve the study aim, immunoinformatics approaches were applied to the said pathogen's proteomics sequence data. B and T cell epitopes were projected from the three shortlisted vaccine proteins; MG014, MG015, Hmw3MG317. The final vaccine ensemble comprises cytotoxic and helper T cell epitopes fused through appropriate linkers. The epitopes peptide is then liked to an adjuvant for efficient recognition and processing by the host immune system. The various physicochemical parameters such as allergenicity, antigenicity, theoretical pI, GRAVY, and molecular weight of the vaccine were checked and found safe and effective to be used in post-experimental studies. The stability and binding affinity of the vaccine with the TLR1/2 heterodimer were ensured by performing molecular docking. The best-docked complex was considered, ranked top having the lowest binding energy and strong intermolecular binding and stability. Finally, the vaccine constructs better expression was obtained by in silico cloning into the pET28a (+) vector in Escherichia coli K-12 strain, and immune simulation validated the immune response. In a nutshell, all these approaches lead to developing a multi-epitope vaccine that possessed the ability to induce cellular and antibody-mediated immune responses against the pathogen used.

Expression profile analysis to identify circular RNA expression signatures in hair follicle of Hu sheep lambskin.

CircRNAs are involved in the regulation of various cellular and biological processes, but none of the studies have focused on hair follicle in sheep. In this study, the expression profile of circRNAs between small waves (SM) and straight wool (ST) groups was investigated using RNA-Seq. The results showed that a total of 5,527 circRNAs were identified and 114 of them were differentially expressed between two groups. Enrichment analysis revealed that the host genes with DE circRNAs were mainly enriched in TGF-beta pathway, Notch pathway. Miranda software was used to found that 129 miRNAs might be binding to 114 DE circRNAs, including miR-10a, miR-143, miR-let-7a, miR-199a-3p, miR-200a, which also had important influence on hair follicle morphogenesis. Furthermore, the coding potential of circRNAs was predicted, and 11 circRNAs were simultaneously identified with coding potential. In summary, circRNAs have important effects on hair follicle growth and development, and these results will provide a basis for molecular mechanism of pattern formation.