Comparative study of functional outcomes of arthroscopic anterior cruciate ligament reconstruction using anteromedial portal and translateral all-inside technique.

Background: Anterior Cruciate Ligament (ACL) injuries are common in the active population of the Armed Forces. Symptomatic instability prompts individuals to seek a cure or a sheltered appointment. Despite the increasing numbers of ACL reconstructions performed, the outcomes have not been so spectacular with only a meager percentage of our patients returning to preinjury levels of activity. With the premise that an all-inside ACL reconstruction is likely to result in better functional outcomes, the aim of this study was to compare the short-term functional outcomes of a large consecutive series of patients undergoing ACL reconstruction using the translateral all-inside ACL reconstruction technique (AI) and standard anteromedial portal technique (AM) with a minimum follow-up of one year. Methods: A total of 240 patients with isolated ACL tear underwent ACL reconstruction via the AI or AM technique. Their preoperative and postoperative scores were compared to look for any significant differences in functional outcomes. Results: The two groups were matched for age, BMI, mechanism of injury, and interval from injury to surgery. There was no difference in their preoperative scores. Postoperatively, although there were significant improvements across both groups, there was no significant difference between the groups at any point of time. Conclusion: The AI technique has garnered interest in recent literature in addressing ACL injuries. This study found no discernible benefit of the AI technique when compared to the AM technique in terms of functionality following an ACL reconstruction at any point of time up to 1 year following surgery.

Bacterial biopesticides: Biodiversity, role in pest management and beneficial impact on agricultural and environmental sustainability.

Agro-environmental sustainability is based upon the adoption of efficient resources in agro-practices that have a nominal impact on the ecosystem. Insect pests are responsible for causing severe impacts on crop productivity. Wide ranges of agro-chemicals have been employed over the last 50 years to overcome crop yield losses due to insect pests. But better knowledge about the hazards due to chemical pesticides and other pest resistance and resurgence issues necessitates an alternative for pest control. The applications of biological pesticides offer a best alternate that is safe, cost-effective, easy to adoption and successful against various insect pests and pathogens. Like other organisms, insects can get a wide range of diseases from various microbes, such as bacteria, fungi, viruses, protozoa, and nematodes. In order to create agricultural pest management practices that are environmentally beneficial, bacterial entomopathogens are being thoroughly studied. Utilization of bacterial biopesticides has been adopted for the protection of agricultural products. The different types of toxin complexes released by various microorganisms and their mechanisms of action are recapitulated. The present review described the diversity and biocontrol prospective of certain bacteria and summarised the potential of bacterial biopesticides for the management of agricultural pests, insects, and other phytopathogenic microorganisms in agricultural practices.

A meta-analysis of differentially expressed and regulatory genes with their functional enrichment analysis for brain transcriptome data in autism spectrum disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by persistent challenges in social interactions and repetitive behavioral patterns. It is a significant problem emerging worldwide, as one in 100 children is affected by this disorder globally. In this study, a meta-analysis was performed for the identification of differentially expressed genes (DEGs) along with the expression analysis of regulatory genes. Functional enrichment analysis was an integral part of current findings to notify the significant pathways of this complex disorder. The study was conducted with two RNA-Seq datasets, viz., GSE64018 and GSE62098, for ASD patients and control samples from the GEO database. The identification of up-regulatory and down-regulatory genes was performed by the interaction analysis of transcription factors (TF) and DEGs. As an outcome of the meta-analysis, 2543 DEGs were identified as common across both of the datasets in which 1402 DEGs exhibited upregulation and 1130 genes have shown downregulation. In network analysis, upregulatory genes have shown strong interaction while downregulatory genes exhibit weak or null interaction. Further, in the enrichment analysis of screened upregulatory DEGs, three major significant pathways were identified namely the ATP synthesis pathway, FAS signaling pathway, and the Huntington's disease pathway. The common expression of CYC 1 gene in all the identified pathways has indicated that it is an important key regulator gene for the majorly associated pathways. The study concludes that all the potential DEGs were found to show their related high expression in neurobiological regulations specifically with ASD.Communicated by Ramaswamy S. Sarma.

Emphasis on Nanostructured Lipid Carriers in the Ocular Delivery of Antibiotics.

BACKGROUND: Drug distribution to the eye is still tricky because of the eye's intricate structure. Systemic delivery, as opposed to more traditional methods like eye drops and ointments, is more effective but higher doses can be harmful. Objective- The use of solid lipid nanoparticles (SLNPs) as a method of drug delivery has been the subject of research since the 1990s. Since SLNPs are derived from naturally occurring lipids, they pose no health risks to the user. To raise the eye's absorption of hydrophilic and lipophilic drugs, SLNs can promote corneal absorption and improve the ocular bioavailability of SLNPs. Methods- To address problems related to ocular drug delivery, many forms of Nano formulation were developed. Some of the methods developed are, emulsification and ultra-sonication, High-speed stirring and ultra-sonication, Thin layer hydration, Adapted melt-emulsification, and ultrasonication techniques, hot o/w micro-emulsion techniques, etc. Results- Nanostructured lipid carriers are described in this review in terms of their ocular penetration mechanism, structural characteristic, manufacturing process, characterization, and advantages over other nanocarriers. Conclusion - Recent developments in ocular formulations with nanostructured bases, such as surface-modified attempts have been made to increase ocular bioavailability in both the anterior and posterior chambers by incorporating cationic chemicals into a wide variety of polymeric systems.

In vitro and in silico evaluations of actinomycin X2and actinomycin D as potent anti-tuberculosis agents.

Background: Multidrug-resistant tuberculosis (MDR-TB) is one of the world's most devastating contagious diseases and is caused by the MDR-Mycobacterium tuberculosis (MDR-Mtb) bacteria. It is therefore essential to identify novel anti-TB drug candidates and target proteins to treat MDR-TB. Here, in vitro and in silico studies were used to investigate the anti-TB potential of two newly sourced actinomycins, actinomycin-X2 (act-X2) and actinomycin-D (act-D), from the Streptomyces smyrnaeus strain UKAQ_23 (isolated from the Jubail industrial city of Saudi Arabia). Methods: The anti-TB activity of the isolated actinomycins was assessed in vitro using the Mtb H37Ra, Mycobacterium bovis (BCG), and Mtb H37Rv bacterial strains, using the Microplate Alamar Blue Assay (MABA) method. In silico molecular docking studies were conducted using sixteen anti-TB drug target proteins using the AutoDock Vina 1.1.2 tool. The molecular dynamics (MD) simulations for both actinomycins were then performed with the most suitable target proteins, using the GROningen MAchine For Chemical Simulations (GROMACS) simulation software (GROMACS 2020.4), with the Chemistry at HARvard Macromolecular Mechanics 36m (CHARMM36m) forcefield for proteins and the CHARMM General Force Field (CGenFF) for ligands. Results: In vitro results for the Mtb H37Ra, BCG, and Mtb H37Rv strains showed that act-X2 had minimum inhibitory concentration (MIC) values of 1.56 ± 0.0, 1.56 ± 0.0, and 2.64 ± 0.07 µg/mL and act-D had MIC values of 1.56 ± 0.0, 1.56 ± 0.0, and 1.80 ± 0.24 µg/mL respectively. The in silico molecular docking results showed that protein kinase PknB was the preferred target for both actinomycins, while KasA and pantothenate synthetase were the least preferred targets for act-X2and act-D respectively. The molecular dynamics (MD) results demonstrated that act-X2 and act-D remained stable inside the binding region of PknB throughout the simulation period. The MM/GBSA (Molecular Mechanics/Generalized Born Surface Area) binding energy calculations showed that act-X2 was more potent than act-D. Conclusion: In conclusion, our results suggest that both actinomycins X2 and D are highly potent anti-TB drug candidates. We show that act-X2is better able to antagonistically interact with the protein kinase PknB target than act-D, and thus has more potential as a new anti-TB drug candidate.

Understanding Mutations in Human SARS-CoV-2 Spike Glycoprotein: A Systematic Review & Meta-Analysis.

Genetic variant(s) of concern (VoC) of SARS-CoV-2 have been emerging worldwide due to mutations in the gene encoding spike glycoprotein. We performed comprehensive analyses of spike protein mutations in the significant variant clade of SARS-CoV-2, using the data available on the Nextstrain server. We selected various mutations, namely, A222V, N439K, N501Y, L452R, Y453F, E484K, K417N, T478K, L981F, L212I, N856K, T547K, G496S, and Y369C for this study. These mutations were chosen based on their global entropic score, emergence, spread, transmission, and their location in the spike receptor binding domain (RBD). The relative abundance of these mutations was mapped with global mutation D614G as a reference. Our analyses suggest the rapid emergence of newer global mutations alongside D614G, as reported during the recent waves of COVID-19 in various parts of the world. These mutations could be instrumentally imperative for the transmission, infectivity, virulence, and host immune system's evasion of SARS-CoV-2. The probable impact of these mutations on vaccine effectiveness, antigenic diversity, antibody interactions, protein stability, RBD flexibility, and accessibility to human cell receptor ACE2 was studied in silico. Overall, the present study can help researchers to design the next generation of vaccines and biotherapeutics to combat COVID-19 infection.

In Vitro and In Silico Approaches for the Evaluation of Antimicrobial Activity, Time-Kill Kinetics, and Anti-Biofilm Potential of Thymoquinone (2-Methyl-5-propan-2-ylcyclohexa-2,5-diene-1,4-dione) against Selected Human Pathogens.

Thymoquinone (2-methyl-5-propan-2-ylcyclohexa-2,5-diene-1,4-dione; TQ), a principal bioactive phytoconstituent of Nigella sativa essential oil, has been reported to have high antimicrobial potential. Thus, the current study evaluated TQ's antimicrobial potential against a range of selected human pathogens using in vitro assays, including time-kill kinetics and anti-biofilm activity. In silico molecular docking of TQ against several antimicrobial target proteins and a detailed intermolecular interaction analysis was performed, including binding energies and docking feasibility. Of the tested bacteria and fungi, S. epidermidis ATCC 12228 and Candida albicans ATCC 10231 were the most susceptible to TQ, with 50.3 ± 0.3 mm and 21.1 ± 0.1 mm zones of inhibition, respectively. Minimum inhibitory concentration (MIC) values of TQ are in the range of 12.5-50 µg/mL, while minimum biocidal concentration (MBC) values are in the range of 25-100 µg/mL against the tested organisms. Time-kill kinetics of TQ revealed that the killing time for the tested bacteria is in the range of 1-6 h with the MBC of TQ. Anti-biofilm activity results demonstrate that the minimum biofilm inhibitory concentration (MBIC) values of TQ are in the range of 25-50 µg/mL, while the minimum biofilm eradication concentration (MBEC) values are in the range of 25-100 µg/mL, for the tested bacteria. In silico molecular docking studies revealed four preferred antibacterial and antifungal target proteins for TQ: D-alanyl-D-alanine synthetase (Ddl) from Thermus thermophilus, transcriptional regulator qacR from Staphylococcus aureus, N-myristoyltransferase from Candida albicans, and NADPH-dependent D-xylose reductase from Candida tenuis. In contrast, the nitroreductase family protein from Bacillus cereus and spore coat polysaccharide biosynthesis protein from Bacillus subtilis and UDP-N-acetylglucosamine pyrophosphorylase from Aspergillus fumigatus are the least preferred antibacterial and antifungal target proteins for TQ, respectively. Molecular dynamics (MD) simulations revealed that TQ could bind to all four target proteins, with Ddl and NADPH-dependent D-xylose reductase being the most efficient. Our findings corroborate TQ's high antimicrobial potential, suggesting it may be a promising drug candidate for multi-drug resistant (MDR) pathogens, notably Gram-positive bacteria and Candida albicans.

Current Overviews on COVID-19 Management Strategies.

The coronavirus pandemic hit the world lately and caused acute respiratory syndrome in humans. The causative agent of the disease was soon identified by scientists as SARS-CoV-2 and later called a novel coronavirus by the general public. Due to the severity and rapid spread of the disease, WHO classifies the COVID-19 pandemic as the 6th public health emergency even after taking efforts like worldwide quarantine and restrictions. Since only symptomatic treatment is available, the best way to control the spread of the virus is by taking preventive measures. Various types of antigen/antibody detection kits and diagnostic methods are available for the diagnosis of COVID-19 patients. In recent years, various phytochemicals and repurposing drugs showing a broad range of anti-viral activities with different modes of actions have been identified. Repurposing drugs such as arbidol, hydroxychloroquine, chloroquine, lopinavir, favipiravir, remdesivir, hexamethylene amiloride, dexamethasone, tocilizumab, interferon-ß, and neutralizing antibodies exhibit in vitro anti-coronaviral properties by inhibiting multiple processes in the virus life cycle. Various research groups are involved in drug trials and vaccine development. Plant-based antiviral compounds such as baicalin, calanolides, curcumin, oxymatrine, matrine, and resveratrol exhibit different modes of action against a wide range of positive/negative sense-RNA/DNA virus, and future researches need to be conducted to ascertain their role and use in managing SARS-CoV-2. Thus this article is an attempt to review the current understanding of COVID- 19 acute respiratory disease and summarize its clinical features with their prospective control and various aspects of the therapeutic approach.

Decoding the Inter-Relationship between Sleep Disorders and Alzheimer's Disease Pathogenesis.

Alzheimer's Disease (AD), characterized by abnormally phosphorylated tau, Paired Helical Filaments (PHFs), Neurofibrillary Tangles (NFTs), deregulated mammalian Target Of Rapamycin (mTOR), and Aß deposits, is a multifactorial disease with sleep disorders being one of the causative agents. Therefore, we have reviewed the literature and have tried to decode the existence of positive feedback, reciprocal and a bidirectional relationship allying between sleep disturbances and AD. Much light has been thrown on the role of tau pathology and amyloid pathology in sleep pathology and its association with AD pathology. We have also discussed the role of melatonin in regulating sleep disorders and AD. The neuroprotective effect of melatonin via inhibiting tau hyperphosphorylation and Aß deposition has also been discussed. Moreover, astrocytes involvement in aggravating AD has also been highlighted in this review. Several therapeutic approaches aimed at improving both sleep disorders and AD have been duly discussed such as administration of antidepressants and antihistamines, immunotherapy, metal chelators, melatonin supplementation, light therapy and physical activity. Despite consistent efforts, the complete etiology concerning sleep disorder and AD is still unclear. Therefore, further research is needed to unravel the mechanism involved and also to develop strategies that may help in obstructing AD in its preclinical stage.

Isolation, characterization, anti-MRSA evaluation, and in-silico multi-target anti-microbial validations of actinomycin X2 and actinomycin D produced by novel Streptomyces smyrnaeus UKAQ_23.

Streptomyces smyrnaeus UKAQ_23, isolated from the mangrove-sediment, collected from Jubail,Saudi Arabia, exhibited substantial antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA), including non-MRSA Gram-positive test bacteria. The novel isolate, under laboratory-scale conditions, produced the highest yield (561.3 ± 0.3 mg/kg fermented agar) of antimicrobial compounds in modified ISP-4 agar at pH 6.5, temperature 35 °C, inoculum 5% v/w, agar 1.5% w/v, and an incubation period of 7 days. The two major compounds, K1 and K2, were isolated from fermented medium and identified as Actinomycin X2 and Actinomycin D, respectively, based on their structural analysis. The antimicrobial screening showed that Actinomycin X2 had the highest antimicrobial activity compared to Actinomycin D, and the actinomycins-mixture (X2:D, 1:1, w/w) against MRSA and non-MRSA Gram-positive test bacteria, at 5 µg/disc concentrations. The MIC of Actinomycin X2 ranged from 1.56-12.5 µg/ml for non-MRSA and 3.125-12.5 µg/ml for MRSA test bacteria. An in-silico molecular docking demonstrated isoleucyl tRNA synthetase as the most-favored antimicrobial protein target for both actinomycins, X2 and D, while the penicillin-binding protein-1a, was the least-favorable target-protein. In conclusion, Streptomyces smyrnaeus UKAQ_23 emerged as a promising source of Actinomycin X2 with the potential to be scaled up for industrial production, which could benefit the pharmaceutical industry.

Cross-Interplay between Osmolytes and mTOR in Alzheimer's Disease Pathogenesis.

Alzheimer's disease, categorized by the piling of amyloid-ß (Aß), hyperphosphorylated tau, PHFs, NFTs and mTOR hyperactivity, is a neurodegenerative disorder, affecting people across the globe. Osmolytes are known for osmoprotectants and play a pivotal role in protein folding, function and protein stability, thus, preventing proteins aggregation, and counteracting effects of denaturing solutes on proteins. Osmolytes (viz., sorbitol, inositol, and betaine) perform a pivotal function of maintaining homeostasis during hyperosmotic stress. The selective advantage of utilising osmolytes over inorganic ions by cells is in maintaining cell volume without compromising cell function, which is important for organs such as the brain. Osmolytes have been documented not only as neuroprotectors but they also seem to act as neurodegenerators. Betaine, sucrose and trehalose supplementation has been seen to induce autophagy thereby inhibiting the accumulation of Aß. In contrast, sucrose has also been associated with mTOR hyperactivity, a hallmark of AD pathology. The neuroprotective action of taurine is revealed when taurine supplementation is seen to inhibit neural damage, apoptosis and oxidative damage. Inositol stereoisomers (viz., scyllo-inositol and myo-inositol) have also been seen to inhibit Aß production and plaque formation in the brain, inhibiting AD pathogenesis. However, TMAO affects the aging process adversely by deregulating the mTOR signalling pathway and then kindling cognitive dysfunction via degradation of chemical synapses and synaptic plasticity. Thus, it can be concluded that osmolytes may act as a probable therapeutic approach for neurodevelopmental disorders. Here, we have reviewed and focussed upon the impact of osmolytes on mTOR signalling pathway and thereby its role in AD pathogenesis.

Temporal variations in microcystin-producing cells and microcystin concentrations in two fresh water ponds.

The relationship between microcystin production, microcystin-producing cyanobacteria, including Microcystis spp., and various biological and physicochemical parameters in Sankuldhara and Lakshmikund, situated in the same geographical area was studied over a period of 1.5 years. Seasonal variation in cyanobacterial 16S rRNA, Microcystis spp. 16S rRNA, mcyA and mcyB genes were quantitatively determined by real-time PCR. Microcystis was the dominant microcystin producer in both study sites constituting 67% and 97% of the total microcystin-producing cyanobacteria at Sankuldhara and Lakshmikund, respectively. Microcystin concentrations were 2.19-39.60 µg/L and 15.22-128.14 µg/L at Sankuldhara and Lakshmikund, respectively, as determined by LC-MS. Principal component analysis revealed a strong positive correlation between microcystin concentration and the copy number of mcyA and mcyB, chlorophyll a and cyanobacterial biomass at both sites. The higher microcystin concentrations in Lakshmikund pond were attributed to the high copy number of mcy genes present coupled with the pond's eutrophication status, as indicated by high total algal biomass, high chlorophyll a content, high nutrient load and low DO. Therefore, a significant difference in microcystin concentrations, correlating with these various biological and physicochemical parameters, confirms the importance of local environmental variables in the overall regulation of microcystins production.

Biohydrogen production from sugarcane bagasse by integrating dark- and photo-fermentation.

Hydrogen production from sugarcane bagasse (SCB) by integrating dark-fermentation by Enterobacter aerogenes MTCC 2822 and photo-fermentation by Rhodopseudomonas BHU 01 was investigated. The SCB was hydrolysed by sulphuric acid and the hydrolysate detoxified by passing through adsorbent resin column (Amberlite XAD-4) to remove the inhibitory furfural, and subjected to dark-fermentation. The cellulosic residue from acid hydrolysis was hydrolysed by the new isolate Cellulomonas fimi to release sugars for H2 production by E. aerogenes, through simultaneous saccharification, filtration and fermentation (SSFF). Cumulative H2 production during dark-fermentation and SSFF was 1000 and 613 ml/L, respectively. The spent media of dark-fermentation and SSFF were utilized for photo-fermentation by Rhodopseudomonas BHU 01. The cumulative H2 production was 755 ml/L for dark-fermentation and 351 ml/L for SSFF spent medium.

Biohydrogen production from cheese whey wastewater in a two-step anaerobic process.

Cheese whey-based biohydrogen production was seen in batch experiments via dark fermentation by free and immobilized Enterobacter aerogenes MTCC 2822 followed by photofermentation of VFAs (mainly acetic and butyric acid) in the spent medium by Rhodopseudomonas BHU 01 strain. E. aerogenes free cells grown on cheese whey diluted to 10 g lactose/L, had maximum lactose consumption (∼79%), high production of acetic acid (1,900 mg/L), butyric acid (537.2 mg/L) and H(2) yield (2.04 mol/mol lactose; rate,1.09 mmol/L/h). The immobilized cells improved lactose consumption (84%), production of acetic acid (2,100 mg/L), butyric acid (718 mg/L) and also H(2) yield (3.50 mol/mol lactose; rate, 1.91 mmol/L/h). E. aerogenes spent medium (10 g lactose/L) when subjected to photofermentation by free Rhodopseudomonas BHU 01 cells, the H(2) yield reached 1.63 mol/mol acetic acid (rate, 0.49 mmol/L/h). By contrast, immobilized Rhodopseudomonas cells improved H(2) yield to 2.69 mol/mol acetic acid (rate, 1.87 mmol/L/h). The cumulative H(2) yield for free and immobilized bacterial cells was 3.40 and 5.88 mol/mol lactose, respectively. Bacterial cells entrapped in alginate, had a sluggish start of H(2) production but outperformed the free cells subsequently. Also, the concomitant COD reduction for free cells (29.5%) could be raised to 36.08% by immobilized cells. The data suggest that two-step fermentative H(2) production from cheese whey involving immobilized bacterial cells, offers greater substrate to- hydrogen conversion efficiency, and the effective removal of organic load from the wastewater in the long-term.