Nanomaterials as drug delivery agents for overcoming the blood-brain barrier: A comprehensive review.

Background and Purpose: The blood-brain barrier (BBB), a critical interface of specialized endothelial cells, plays a pivotal role in regulating molecular and ion transport between the central nervous system (CNS) and systemic circulation. Experimental Approach: This review aims to delve into the intricate architecture and functions of the BBB while addressing challenges associated with delivering therapeutics to the brain. Historical milestones and contemporary insights underscore the BBB's significance in protecting the CNS. Key Results: Innovative approaches for enhanced drug transport include intranasal delivery exploiting olfactory and trigeminal pathways, as well as techniques like temporary BBB opening through chemicals, receptors, or focused ultrasound. These avenues hold the potential to reshape conventional drug delivery paradigms and address the limitations posed by the BBB's selectivity. Conclusion: This review underscores the vital role of the BBB in maintaining CNS health and emphasizes the importance of effective drug delivery through this barrier. Nanoparticles emerge as promising candidates to overcome BBB limitations and potentially revolutionize the treatment of CNS disorders. As research progresses, the application of nanomaterials shows immense potential for advancing neurological therapeutics, albeit with careful consideration of safety aspects.

Computational Exploration of Naturally Occurring Flavonoids as TGF-ß Inhibitors in Breast Cancer: Insights from Docking and Molecular Dynamics Simulations and In-vitro Cytotoxicity Study.

Breast cancer is a global health concern, demanding innovative treatments. Targeting the Transforming Growth Factor-beta (TGF-ß) signaling pathway, pivotal in breast cancer, is a promising approach. TGF-ß inhibits proliferation via G1 phase cell cycle arrest, acting as a suppressor initially, but in later stages, it promotes progression by enhancing motility, invasiveness, and metastasis formation. This study explores naturally occurring flavonoids' interactions with TGF-ß. Using molecular docking against the protein's crystal structure (PDB Id: 1PY5), Gossypin showed the highest docking score and underwent molecular dynamics simulation, revealing complex flexibility and explaining how flavonoids impede TGF-ß signaling in breast cancer. ADMET predictions adhered to Lipinski's rule of Five. Insights into flavonoid-TGF-ß binding offer a novel angle for breast cancer treatment. Flavonoids having a good docking score like gossypin, morin, luteolin and taxifolin shown potent cytotoxic effect on breast cancer cell line, MCF-7. Understanding these interactions could inspire flavonoid-based therapies targeting TGF-ß to halt breast cancer growth. These findings pave the way for personalized, targeted breast cancer therapies, offering hope against this formidable disease.

Differences in outcomes by race/ethnicity after thoracic surgery in a large integrated health system.

Background: Disparities exist throughout surgery. We aimed to assess for racial/ethnic disparities among outcomes in a large thoracic surgery patient population. Methods: We reviewed all thoracic surgery patients treated at our integrated health system from January 1, 2016-December 31, 2020. Post-operative outcomes including length of stay (LOS), 30-day return to the emergency department (30d-ED), 30-day readmission, 30- and 90-day outpatient appointments, and 30- and 90-day mortality were compared by race/ethnicity. Bivariate analyses and multivariable logistic regression were performed. Our multivariable models adjusted for age, sex, body mass index, Charlson Comorbidity Index, surgery type, neighborhood deprivation index, insurance, and home region. Results: Of 2730 included patients, 59.4 % were non-Hispanic White, 15.0 % were Asian, 11.9 % were Hispanic, 9.6 % were Black, and 4.1 % were Other. Median (Q1-Q3) LOS (in hours) was shortest among non-Hispanic White (37.3 (29.2-76.1)) and Other (36.5 (29.3-75.4)) patients followed by Hispanic (46.8 (29.9-78.1)) patients with Asian (51.3 (30.7-81.9)) and Black (53.7 (30.6-101.6)) patients experiencing the longest LOS (p < 0.01). 30d-ED rates were highest among Hispanic patients (21.3 %), followed by Black (19.2 %), non-Hispanic White (18.1 %), Asian (13.4 %), and Other (8.0 %) patients (p < 0.01). On multivariable analysis, Hispanic ethnicity (Odds Ratio (OR) 1.43 (95 % CI 1.03-1.97)) and Medicaid insurance (OR 2.37 (95 % CI 1.48-3.81)) were associated with higher 30d-ED rates. No racial/ethnic disparities were found among other outcomes. Conclusions: Despite parity across multiple surgical outcomes, disparities remain related to patient encounters within our system. Health systems must track such disparities in addition to standard clinical outcomes. Key message: While our large integrated health system has been able to demonstrate parity across many major surgical outcomes among our thoracic surgery patients, race/ethnicity disparities persist including in the number of post-operative return trips to the emergency department. Tracking outcome disparities to a granular level such as return visits to the emergency department and number of follow up appointments is critical as health systems strive to achieve equitable care.

Bacteriophages as a potential substitute for antibiotics: A comprehensive review.

Over the years, the administration of antibiotics for the purpose of addressing bacterial infections has become increasingly challenging due to the increased prevalence of antimicrobial resistance exhibited by various strains of bacteria. Multidrug-resistant (MDR) bacterial species are rising due to the unavailability of novel antibiotics, leading to higher mortality rates. With these conditions, there is a need for alternatives in which phage therapy has made promising results. Phage-derived endolysins, phage cocktails, and bioengineered phages are effective and have antimicrobial properties against MDR and extensively drug-resistant strains. Despite these, it has been observed that phages can give antimicrobial activity to more than one bacterial species. Thus, phage cocktail against resistant strains provides broad spectrum treatment and magnitude of effectivity, which is many folds higher than antibiotics. Many commercially available endolysins such as Staphefekt SA.100, Exebacase (CF-301), and N-Rephasin®SAL200 are used in biofilm penetration and treating plant diseases. The role of CMP1 phage endolysin in transgenic tomato plants in preventing Clavibacter michiganensis infection and the effectiveness of phage in protecting Atlantic salmon from vibriosis have been reported. Furthermore, phage-derived endolysin therapy, such as TSPphg phage exogenous treatment, can aid in disrupting cell walls, leading to bacterial cell lysis. As animals in aquaculture and slaughterhouses are highly susceptible to bacterial infections, effective phage therapy instead of antibiotics can help treat poultry animals, preserve them, and facilitate disease-free trade. Using bioengineered phages and phage cocktails enhances the effectiveness by providing a broad spectrum of phages and target specificity. Research is currently being conducted on clinical trials to confirm the efficacy of engineered phages and phage cocktails in humans. Although obtaining commercial approval may be time-consuming, it will be beneficial in the postantibiotic era. This review provides an overview of the significance of phage therapy as a potential alternative to antibiotics in combating resistant bacterial strains and its application to various fields and emphasizes the importance of safeguarding and ensuring treatment efficacy.

On population structure and breeding biology of burrowing crab Dotilla blanfordi Alcock, 1900.

Background: The present study investigated the population structure and breeding biology of the burrowing brachyuran crab species Dotilla blanfordi Alcock, 1900, which is commonly found on the sandy beach of Bhavnagar, located on the Gulf of Kachchh, Gujarat coast, India. Methods: Monthly sampling was conducted from February 2021 to January 2022 at the time of low tide using three line transects perpendicular to the water line, intercepted by a quadrate (0.25 m2) each at three different levels of the middle intertidal region: 20 m, 70 m, and 120 m. The quadrate area was excavated up to 30 cm and sieved for specimen collection. The collected specimens were categorised into different sexes viz., male, non-ovigerous female, or ovigerous female. For the fecundity study of D. blanfordi, the carapace width (mm) as a measure of size as well as their wet weight (g), size, number, and mass of their eggs were also recorded. Results: The study revealed sexual dimorphism among the population, with females having significantly smaller sizes as compared to males. The overall population was skewed towards females, with a bimodal distribution of males and females. The occurrence of ovigerous females throughout the year suggests that the population breeds incessantly throughout the year, with the highest occurrence in August and September. A positive correlation was observed between the morphology of crabs (carapace width and wet body weight) and the size, number, and mass of eggs.

Zero budget natural farming components Jeevamrit and Beejamrit augment Spinacia oleracea L. (spinach) growth by ameliorating the negative impacts of the salt and drought stress.

The growth of crop plants, particularly spinach (Spinacia oleracea L.), can be significantly impeded by salinity and drought. However, pre-treating spinach plants with traditional biofertilizers like Jeevamrit and Beejamrit (JB) substantially reverses the salinity and drought-induced inhibitory effects. Hence, this study aims to elucidate the underlying mechanisms that govern the efficacy of traditional fertilizers. The present work employed comprehensive biochemical, physiological, and molecular approaches to investigate the processes by which JB alleviates abiotic stress. The JB treatment effectively boosts spinach growth by increasing nutrient uptake and antioxidant enzyme activity, which mitigates the detrimental effects of drought and salinity-induced stress. Under salt and drought stress conditions, the application of JB resulted in an impressive rise in germination percentages of 80 and 60%, respectively. In addition, the application of JB treatment resulted in a 50% decrease in electrolyte leakage and a 75% rise in the relative water content of the spinach plants. Furthermore, the significant reduction in proline and glycine betaine levels in plants treated with JB provides additional evidence of the treatment's ability to prevent cell death caused by environmental stressors. Following JB treatment, the spinach plants exhibited substantially higher total chlorophyll content was also observed. Additionally, using 16S rRNA sequencing, we discovered and characterized five plant-beneficial bacteria from the JB bio-inoculants. These bacterial isolates comprise a number of traits that contribute to growth augmentation in plants. These evidences suggest that the presence of the aforesaid microorganisms (along with additional ones) is accountable for the JB-mediated stimulation of plant growth and development.

Exploring the role of antioxidants in sepsis-associated oxidative stress: a comprehensive review.

Sepsis is a potentially fatal condition characterized by organ dysfunction caused by an imbalanced immune response to infection. Although an increased inflammatory response significantly contributes to the pathogenesis of sepsis, several molecular mechanisms underlying the progression of sepsis are associated with increased cellular reactive oxygen species (ROS) generation and exhausted antioxidant pathways. This review article provides a comprehensive overview of the involvement of ROS in the pathophysiology of sepsis and the potential application of antioxidants with antimicrobial properties as an adjunct to primary therapies (fluid and antibiotic therapies) against sepsis. This article delves into the advantages and disadvantages associated with the utilization of antioxidants in the therapeutic approach to sepsis, which has been explored in a variety of animal models and clinical trials. While the application of antioxidants has been suggested as a potential therapy to suppress the immune response in cases where an intensified inflammatory reaction occurs, the use of multiple antioxidant agents can be beneficial as they can act additively or synergistically on different pathways, thereby enhancing the antioxidant defense. Furthermore, the utilization of immunoadjuvant therapy, specifically in septic patients displaying immunosuppressive tendencies, represents a promising advancement in sepsis therapy.

Secretory molecules from secretion systems fine-tune the host-beneficial bacteria (PGPRs) interaction.

Numerous bacterial species associate with plants through commensal, mutualistic, or parasitic association, affecting host physiology and health. The mechanism for such association is intricate and involves the secretion of multiple biochemical substances through dedicated protein systems called secretion systems SS. Eleven SS pathways deliver protein factors and enzymes in their immediate environment or host cells, as well as in competing microbial cells in a contact-dependent or independent fashion. These SS are instrumental in competition, initiation of infection, colonization, and establishment of association (positive or negative) with host organisms. The role of SS in infection and pathogenesis has been demonstrated for several phytopathogens, including Agrobacterium, Xanthomonas, Ralstonia, and Pseudomonas. Since there is overlap in mechanisms of establishing association with host plants, several studies have investigated the role of SSs in the interaction of plant and beneficial bacteria, including symbiotic rhizobia and plant growth bacteria (PGPB). Therefore, the present review updates the role of different SSs required for the colonization of beneficial bacteria such as rhizobia, Burkholderia, Pseudomonas, Herbaspirillum, etc., on or inside plants, which can lead to a long-term association. Most SS like T3SS, T4SS, T5SS, and T6SS are required for the antagonistic activity needed to prevent competing microbes, including phytopathogens, ameliorate biotic stress in plants, and produce substances for successful colonization. Others are required for chemotaxis, adherence, niche formation, and suppression of immune response to establish mutualistic association with host plants.

A Systematic Review on Microplastic Contamination in Fishes of Asia: Polymeric Risk Assessment and Future Prospectives.

Microplastics (MPs) have attracted global concern because of their harmful effects on marine biota; their toxic properties can negatively impact aquatic ecosystems. Fish is an essential source of protein for humans, playing a crucial role in daily food intake. Until recently, MPs were addressed primarily as environmental pollutants, but they are now increasingly recognized as contaminants in the food supply. The present review has comprehended the current knowledge of MP contamination in freshwater and marine fishes of Asia, including 112 peer-reviewed sources from 2016 to 2023. The review recorded 422 Asian fishes (345 marine and 77 freshwater) to be contaminated with MPs. Clarias gariepinus and Selaroides leptolepi have shown maximum MP contamination in the freshwater and marine environments of Asia, respectively. Omnivorous and carnivorous fishes exhibited higher susceptibility to ingesting MPs. Benthopelagic, demersal, and reef-associated habitats were identified as more prone to MP accumulation. In both freshwater and marine environments, China has the highest number of contaminated species among all the countries. Pollution indices indicated high MP contamination in both freshwater and marine environments. A prevalence of fibers was recorded in all fishes. Black- and blue-colored MPs of <500 µm-1 mm size were found dominantly. Polyethylene terephthalate and polyethylene were recorded as the prevalent plastic polymers in freshwater and marine fish, respectively. Overall, the review served as a comprehensive understanding of MP concentrations and variations between species, between feeding habits, and between geographic locations, which can be pivotal for addressing pressing environmental challenges, protecting human health, and fostering global sustainability efforts in the face of escalating plastic pollution. Environ Toxicol Chem 2024;43:671-685. © 2024 SETAC.

Discovery of novel anticancer flavonoids as potential HDAC2 inhibitors: virtual screening approach based on molecular docking, DFT and molecular dynamics simulations studies.

Virtual screening of a library of 329 flavonoids obtained from the NPACT database was performed to find out potential novel HDAC2 inhibitors. Eleven out of 329 selected flavonoids were screened based on molecular docking studies, as they have higher binding affinities than the standard drugs vorinostat and panobinostat. All screened compounds occupying the catalytic site of HDAC2 showed important molecular interaction with Zn2+ and other important amino acids in the binding pocket. The screened compounds were validated using ADMET filtration and bioactivity prediction from which we obtained six compounds, NPACT00270, NPACT00676, NPACT00700, NPACT001008, NPACT001054, and NPACT001407, which were analyzed using DFT studies. DFT studies were performed for all six screened flavonoids. In DFT studies, three flavonoids, NPACT00700, NPACT001008, and NPACT001407, were found to be better based on HOMO-LUMO and molecular electrostatic potential (MEP) analyses. Furthermore, MD simulations were performed for 100 ns for the three compounds. In the MD analysis, NPACT001407 was found to be more stable in the active site of HDAC2 as zinc formed a coordination bond with ASP181, HIS183, ASP269, and GLY305, along with two hydroxyl groups of the ligand. Our findings reveal that these flavonoids can interact as ligands with the active site of HDAC2. Because of the absence of a hydroxamate group in flavonoids, there are no possibilities for the formation of isocyanate. This suggests that the major drawback of current HDACs inhibitors may be solved. Further experimental validation is needed to understand the selectivity of flavonoids as HDAC2 inhibitors. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03912-5.

MRI-based prostate cancer classification using 3D efficient capsule network.

BACKGROUND: Prostate cancer (PCa) is the most common cancer in men and the second leading cause of male cancer-related death. Gleason score (GS) is the primary driver of PCa risk-stratification and medical decision-making, but can only be assessed at present via biopsy under anesthesia. Magnetic resonance imaging (MRI) is a promising non-invasive method to further characterize PCa, providing additional anatomical and functional information. Meanwhile, the diagnostic power of MRI is limited by qualitative or, at best, semi-quantitative interpretation criteria, leading to inter-reader variability. PURPOSES: Computer-aided diagnosis employing quantitative MRI analysis has yielded promising results in non-invasive prediction of GS. However, convolutional neural networks (CNNs) do not implicitly impose a frame of reference to the objects. Thus, CNNs do not encode the positional information properly, limiting method robustness against simple image variations such as flipping, scaling, or rotation. Capsule network (CapsNet) has been proposed to address this limitation and achieves promising results in this domain. In this study, we develop a 3D Efficient CapsNet to stratify GS-derived PCa risk using T2-weighted (T2W) MRI images. METHODS: In our method, we used 3D CNN modules to extract spatial features and primary capsule layers to encode vector features. We then propose to integrate fully-connected capsule layers (FC Caps) to create a deeper hierarchy for PCa grading prediction. FC Caps comprises a secondary capsule layer which routes active primary capsules and a final capsule layer which outputs PCa risk. To account for data imbalance, we propose a novel dynamic weighted margin loss. We evaluate our method on a public PCa T2W MRI dataset from the Cancer Imaging Archive containing data from 976 patients. RESULTS: Two groups of experiments were performed: (1) we first identified high-risk disease by classifying low + medium risk versus high risk; (2) we then stratified disease in one-versus-one fashion: low versus high risk, medium versus high risk, and low versus medium risk. Five-fold cross validation was performed. Our model achieved an area under receiver operating characteristic curve (AUC) of 0.83 and 0.64 F1-score for low versus high grade, 0.79 AUC and 0.75 F1-score for low + medium versus high grade, 0.75 AUC and 0.69 F1-score for medium versus high grade and 0.59 AUC and 0.57 F1-score for low versus medium grade. Our method outperformed state-of-the-art radiomics-based classification and deep learning methods with the highest metrics for each experiment. Our divide-and-conquer strategy achieved weighted Cohen's Kappa score of 0.41, suggesting moderate agreement with ground truth PCa risks. CONCLUSIONS: In this study, we proposed a novel 3D Efficient CapsNet for PCa risk stratification and demonstrated its feasibility. This developed tool provided a non-invasive approach to assess PCa risk from T2W MR images, which might have potential to personalize the treatment of PCa and reduce the number of unnecessary biopsies.

Single-Position Prone Lateral Lumbar Interbody Fusion Technique Guide: Surgical Tips and Tricks.

Lateral lumbar interbody fusion (LLIF) is a popular technique as it allows for the placement of a large interbody implant through a retroperitoneal, transpsoas working corridor. Historically, the interbody is placed with the patient in lateral decubitus and then repositioned to prone for the posterior instrumentation. While this has been an effective and successful technique, removing the interoperative flip would improve the efficiency of these cases. This has led to modified LLIF approaches including single-position prone LLIF (pLLIF). This modification has shown to be an efficient and powerful technique; however, learning to navigate the LLIF approach in the prone position has its own challenges. The purpose of this article is to provide a detailed description of our pLLIF technique while simultaneously introducing surgical tips to overcome the challenges of the approach and optimize the implantation of the interbody device.

Robust use of phenotypic heterogeneity at drug target genes for mechanistic insights: Application of cis-multivariable Mendelian randomization to GLP1R gene region.

Phenotypic heterogeneity at genomic loci encoding drug targets can be exploited by multivariable Mendelian randomization to provide insight into the pathways by which pharmacological interventions may affect disease risk. However, statistical inference in such investigations may be poor if overdispersion heterogeneity in measured genetic associations is unaccounted for. In this work, we first develop conditional F statistics for dimension-reduced genetic associations that enable more accurate measurement of phenotypic heterogeneity. We then develop a novel extension for two-sample multivariable Mendelian randomization that accounts for overdispersion heterogeneity in dimension-reduced genetic associations. Our empirical focus is to use genetic variants in the GLP1R gene region to understand the mechanism by which GLP1R agonism affects coronary artery disease (CAD) risk. Colocalization analyses indicate that distinct variants in the GLP1R gene region are associated with body mass index and type 2 diabetes (T2D). Multivariable Mendelian randomization analyses that were corrected for overdispersion heterogeneity suggest that bodyweight lowering rather than T2D liability lowering effects of GLP1R agonism are more likely contributing to reduced CAD risk. Tissue-specific analyses prioritized brain tissue as the most likely to be relevant for CAD risk, of the tissues considered. We hope the multivariable Mendelian randomization approach illustrated here is widely applicable to better understand mechanisms linking drug targets to diseases outcomes, and hence to guide drug development efforts.

Untargeted metabolomics-based identification of bioactive compounds from Mangifera indica L. seed extracts in drug discovery through molecular docking and assessment of their anticancer potential.

BACKGROUND: Mangifera indica L. (mango), a medicinal plant rich in biologically active compounds, has potential to be used in disease-preventing and health-promoting products. The present investigation reveals and uncovers bioactive metabolites with remarkable therapeutic efficiency from mango (family: Anacardiaceae) seeds. RESULTS: Biological activity was determined by antimicrobial, antioxidant and anticancer assays, and metabolite profiling was performed on gas chromatography coupled to quadrupole time-of-flight mass spectrometry (GC-QTOF-MS) and liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) platforms. Validation of active metabolites was carried out by in silico molecular docking (Molinspiration Cheminformatics Server and PASS). Extracted and identified metabolites were screened; 54 compounds associated with various groups were selected for the in silico interaction study. CONCLUSIONS: Molecular docking revealed lead molecules with a potential binding energy score, efficacy and stable modulation with a selected protein domain. Investigation, directed by in vitro and in silico analysis, confirms mango seeds as an excellent source of potential metabolites as a therapeutic agent. © 2024 Society of Chemical Industry.

Implementation of a Novel Chart Rounds Application to Facilitate Peer Review in a Virtual Academic Environment.

Purpose: Peer review in the form of chart rounds is a critical component of quality assurance and safety in radiation therapy treatments. Radiation therapy departments have undergone significant changes that impose challenges to meaningful review, including institutional growth and increasing use of virtual environment. We discuss the implementation of a novel chart rounds (NCR) format and application adapted to modern peer review needs at a single high-volume multisite National Cancer Institute designated cancer center. Methods and Materials: A working group was created to improve upon the prior institutional chart rounds format (standard chart rounds or SCR). Using a novel in-house application and format redesign, an NCR was created and implemented to accomplish stated goals. Data regarding the SCR and NCR system were then extracted for review. Results: SCR consisted of 2- 90-minute weekly sessions held to review plans across all disease sites, review of 49 plans per hour on average. NCR uses 1-hour long sessions divided by disease site, enabling additional time to be spent per patient (11 plans per hour on average) and more robust discussion. The NCR application is able to automate a list of plans requiring peer review from the institutional treatment planning system. The novel application incorporates features that enable efficient and accurate review of plans in the virtual setting across multiple sites. A systematic scoring system is integrated into the application to record feedback. Over 5 months of use of the NCR, 1160 plans have been reviewed with 143 scored as requiring minor changes, 32 requiring major changes and 307 with comments. Major changes triggered treatment replan. Feedback from scoring is incorporated into physician workflow to ensure changes are addressed. Conclusion: The presented NCR format and application enables standardized and highly reliable peer review of radiation therapy plans that is robust across a variety of complex planning scenarios and could be implemented globally.

A Review on the Development of Novel Heterocycles as α-Glucosidase Inhibitors for the Treatment of Type-2 Diabetes Mellitus.

One of the most effective therapeutic decencies in the treatment of Type 2 Diabetes Mellitus is the inhibition of α-glucosidase enzyme, which is present at the brush border of the intestine and plays an important role in carbohydrate digestion to form mono-, di-, and polysaccharides. Acarbose, Voglibose, Miglitol, and Erniglitate have been well-known α-glucosidase inhibitors in science since 1990. However, the long synthetic route and side effects of these inhibitors forced the researchers to move their focus to innovate simple and small heterocyclic scaffolds that work as excellent α-glucosidase inhibitors. Moreover, they are also effective against the postprandial hyperglycemic condition in Type 2 Diabetes Mellitus. In this aspect, this review summarizes recent progress in the discovery and development of heterocyclic molecules that have been appraised to show outstanding inhibition of α-glucosidase to yield positive effects against diabetes.

Recent advances in Bacillus-mediated plant growth enhancement: a paradigm shift in redefining crop resilience.

The Bacillus genus has emerged as an important player in modern agriculture, revolutionizing plant growth promotion through recent advances. This review provides a comprehensive overview of the critical role Bacillus species play in boosting plant growth and agricultural sustainability. Bacillus genus bacteria benefit plants in a variety of ways, according to new research. Nitrogen fixation, phosphate solubilization, siderophore production, and the production of growth hormones are examples of these. Bacillus species are also well-known for their ability to act as biocontrol agents, reducing phytopathogens and protecting plants from disease. Molecular biology advances have increased our understanding of the complex interplay between Bacillus species and plants, shedding light on the genetic and metabolic underpinnings of these interactions. Furthermore, novel biotechnology techniques have enabled the development of Bacillus-based biofertilizers and biopesticides, providing sustainable alternatives to conventional chemical inputs. Apart from this, the combination of biochar and Bacillus species in current biotechnology is critical for improving soil fertility and encouraging sustainable agriculture through enhanced nutrient retention and plant growth. This review also emphasizes the Bacillus genus bacteria's ability to alleviate environmental abiotic stresses such as drought and salinity, hence contributing to climate-resilient agriculture. Moreover, the authors discuss the challenges and prospects associated with the practical application of Bacillus-based solutions in the field. Finally, recent advances in Bacillus-mediated plant growth promotion highlight their critical significance in sustainable agriculture. Understanding these improvements is critical for realizing the full potential of Bacillus genus microorganisms to address current global food production concerns.

Emerging green synthetic routes for thiazole and its derivatives: Current perspectives.

This review article provides an overview of the green synthesis of thiazole derivatives, emphasizing sustainable and environmentally friendly methodologies. Thiazole derivatives possess significant value and find diverse applications across various fields. However, conventional synthesis methods often involve hazardous reagents and generate substantial waste, posing environmental concerns. The green synthesis of thiazole derivatives employs renewable starting materials, nontoxic catalysts, and mild reaction conditions to minimize environmental impact. Innovative techniques such as microwave irradiation, ultrasound synthesis, green solvents, a green catalyst-based approach, and mechanochemistry-mediated synthesis are employed, offering advantages in terms of scalability, cost-effectiveness, and purification simplicity. The resulting thiazole derivatives exhibit comparable or enhanced biological activities, showcasing the feasibility and practicality of green synthesis in drug discovery. This review paper underscores the importance of sustainable approaches in functional molecular synthesis and encourages further research in this domain.

Intra-arterial Fractional Flow Reserve Measurements Provide an Objective Assessment of the Functional Significance of Peripheral Arterial Stenoses.

OBJECTIVE: Peripheral arterial stenoses (PAS) are commonly investigated with duplex ultrasound (DUS) and angiography, but these are not functional tests. Fractional flow reserve (FFR), a pressure based index, functionally assesses the ischaemic potential of coronary stenoses, but its utility in PAS is unknown. FFR in the peripheral vasculature in patients with limb ischaemia was investigated. METHODS: Patients scheduled for angioplasty and or stenting of isolated iliac and superficial femoral artery stenoses were recruited. Resting trans-lesional pressure gradient (Pd/Pa) and FFR were measured after adenosine provoked hyperaemia using an intra-arterial 0.014 inch flow and pressure sensing wire (ComboWire XT, Philips). Prior to revascularisation, exercise ABPI (eABPI) and DUS derived peak systolic velocity ratio (PSVR) of the index lesion were determined. Calf muscle oxygenation was measured using blood oxygenation level dependent cardiovascular magnetic resonance prior to and after revascularisation. RESULTS: Forty-one patients (32, 78%, male, mean age 65 ± 11 years) with 61 stenoses (iliac 32; femoral 29) were studied. For lesions < 80% stenosis, resting Pd/Pa was not influenced by the degree of stenosis (p = .074); however, FFR was discriminatory, decreasing as the severity of stenosis increased (p = .019). An FFR of < 0.60 was associated with critical limb threatening ischaemia (area under the curve [AUC] 0.87; 95% CI 0.75 - 0.95), in this study performing better than angiographic % stenosis (0.79; 0.63 - 0.89), eABPI (0.72; 0.57 - 0.83), and PSVR (0.65; 0.51 - 0.78). FFR correlated strongly with calf oxygenation (rho, 0.76; p < .001). A greater increase in FFR signalled resolution of symptoms and signs (ΔFFR 0.25 ± 0.15 vs. 0.13 ± 0.09; p = .009) and a post-angioplasty and stenting FFR of > 0.74 predicted successful revascularisation (combined sensitivity and specificity of 95%; AUC 0.98; 0.91 - 1.00). CONCLUSION: This pilot study demonstrates that FFR can objectively measure the functional significance of PAS that compares favourably with visual and DUS based assessments. Its role as a quality control adjunct that confirms optimal vessel patency after angioplasty and or stenting also merits further investigation.