Enhancing agricultural output: Investigating the impact of advanced organic formulations on crop productivity, nutrient use efficiency, and profitability in a multi-crop system.

The significance of integrating agricultural by-products such as paddy husk ash (PHA) and potato peels with organic fertilizers lies in enhancing soil fertility, increasing crop yields, and reducing reliance on traditional organic fertilizers like farmyard manure (FYM) or compost alone. Grounded in sustainable agriculture and nutrient management frameworks, this study examines the impact of diverse formulations derived from agricultural waste on productivity, nutrient efficiency, and profitability in a pigeon pea-vegetable mustard-okra cropping system. A two-year field experiment (2020-2022) at ICAR-IARI, New Delhi tested seven nutrient sources viz., (T1) control, (T2) 100% RDN through FYM, (T3) 100% RDN through improved RRC, (T4) 100% RDN through PHA based formulation, (T5) 75% RDN through PHA based formulation, (T6) 100% RDN through PPC based formulation and (T7) 75% RDN through PPC based formulation that were tested in RBD and replicated thrice. Treatment T4 had significant effect on seed yield of pigeon pea (1.89 ± 0.09 and 1.97 ± 0.12 t ha-1), leaf yield of vegetable mustard (81.57 ± 4.59 and 82.97 ± 4.17 t ha-1), and fruit yield of okra (13.54 ± 0.82 and 13.78 ± 0.81 t ha-1) grown in rotation, followed by treatment T6 and T2 during both the years respectively over control. Enhanced system uptake of N, P and K along with system gross and net returns in T4, showed increases of 78.9%, 83.8%, 72.4%, 54.4% and 56.8% in the first year and 77.5%, 80.8%, 77.7%, 54.8% and 57.4% in the second year, respectively, over control. Treatment T4 significantly improved apparent recovery by 66.3% and 69.2% in pigeon pea, 64.7% and 47.9% in vegetable mustard, and 72.7% and 79.4% in okra over T3, averaged across two years. Based on the above findings, (T4) 100% RDN through PHA-based formulation, and (T6) 100% RDN through PPC-based formulation can be recommended for areas with a shortage of FYM but availability of rice husk ash/potato peels for sustainable agricultural wastes and improved sustainability.

Biological Cargo: Exosomes and their Role in Cancer Progression and Metastasis.

Cancer cells are among the many types of cells that release exosomes, which are nanovesicles. Because of their many potential applications, exosomes have recently garnered much attention from cancer researchers. The bioactive substances that exosomes release as cargo have been the subject of several investigations. The substances in question may operate as biomarkers for diagnosis or affect apoptosis, the immune system, the development and spread of cancer, and other processes. Others have begun to look at exosomes in experimental therapeutic trials because they believe they may be useful in the treatment of cancer. This review started with a short description of exosome biogenesis and key features. Next, the potential of tumor-derived exosomes and oncosomes to influence the immune system throughout the development of cancer, as well as alter tumor microenvironments (TMEs) and pre-metastatic niche creation, was investigated. Finally, there was talk of exosomes' possible use in cancer treatment. Furthermore, there is emerging consensus about the potential application of exosomes to be biological reprogrammers of cancer cells, either as carriers of naturally occurring chemicals, including anticancer medications, or as carriers of anticancer vaccines for immunotherapy as well as boron neutron capture therapy (BNCT). We briefly review the key ideas and logic behind this intriguing therapy recommendation.

Myeloid­derived suppressor cells as targets of emerging therapies and nanotherapies (Review).

Breast cancer (BC) is the leading cause of cancer-related mortality among women worldwide. Immunotherapies are a promising approach in cancer treatment, particularly for aggressive forms of BC with high mortality rates. However, the current eligibility for immunotherapy remains limited to a limited fraction of patients with BC. Myeloid-derived suppressor cells (MDSCs), originating from myeloid cells, are known for their dual role in immunosuppression and tumor promotion, significantly affecting patient outcomes by fostering the formation of premetastatic niches. Consequently, targeting MDSCs has emerged as a promising avenue for further exploration in therapeutic interventions. Leveraging nanotechnology-based drug delivery systems, which excel in accumulating drugs within tumors via passive or active targeting mechanisms, are a promising strategy for the use of MDSCs in the treatment of BC. The present review discusses the immunosuppressive functions of MDSCs, their role in BC, and the diverse strategies for targeting them in cancer therapy. Additionally, the present review discusses future advancements in BC treatments focusing on MDSCs. Furthermore, it elucidates the mechanisms underlying MDSC activation, recruitment and differentiation in BC progression, highlighting the clinical characteristics that render MDSCs suitable candidates for the therapy and targeted nanotherapy of BC.

Optimizing agricultural sustainability: enriched organic formulations for growth, yield, and soil quality in a multi-crop system.

Utilizing agricultural and industrial wastes, potent reservoirs of nutrients, for nourishing the soil and crops through composting embodies a sustainable approach to waste management and organic agriculture. To investigate this, a 2-year field experiment was conducted at ICAR-IARI, New Delhi, focusing on a pigeon pea-vegetable mustard-okra cropping system. Seven nutrient sources were tested, including a control (T1), 100% recommended dose of nitrogen (RDN) through farmyard manure (T2), 100% RDN through improved rice residue compost (T3), 100% RDN through a paddy husk ash (PHA)-based formulation (T4), 75% RDN through PHA-based formulation (T5), 100% RDN through a potato peel compost (PPC)-based formulation (T6), and 75% RDN through PPC-based formulation (T7). Employing a randomized block design with three replications, the results revealed that treatment T4 exhibited the significantly highest seed (1.89 ± 0.09 and 1.97 ± 0.12 t ha-1) and stover (7.83 ± 0.41 and 8.03 ± 0.58 t ha-1) yield of pigeon pea, leaf yield (81.57 ± 4.69 and 82.97 ± 4.17 t ha-1) of vegetable mustard, and fruit (13.54 ± 0.82 and 13.78 ± 0.81 t ha-1) and stover (21.64 ± 1.31 and 22.03 ± 1.30 t ha-1) yield of okra during both study years compared to the control (T1). Treatment T4 was on par with T2 and T6 for seed and stover yield in pigeon pea, as well as okra, and leaf yield in vegetable mustard over both years. Moreover, T4 demonstrated notable increase of 124.1% and 158.2% in NH4-N and NO3-N levels in the soil, respectively, over the control. The enhanced status of available nitrogen (N) and phosphorus (P) in the soil, coupled with increased soil organic carbon (0.41%), total bacteria population (21.1%), fungi (37.2%), actinomycetes (44.6%), and microbial biomass carbon (28.5%), further emphasized the positive impact of T4 compared to the control. Treatments T2 and T6 exhibited comparable outcomes to T4 concerning changes in available N, P, soil organic carbon, total bacteria population, fungi, actinomycetes, and microbial biomass carbon. In conclusion, treatments T4 and T6 emerge as viable sources of organic fertilizer, particularly in regions confronting farmyard manure shortages. These formulations offer substantial advantages, including enhanced yield, soil quality improvement, and efficient fertilizer utilization, thus contributing significantly to sustainable agricultural practices.

Effectiveness of Botulinum Toxin Injection With Casting in Children With Spastic Cerebral Palsy: A Randomized Controlled Trial.

BACKGROUND: The most common form of movement disorder presented in children with cerebral palsy is spasticity, and dynamic equinus is the most common spastic ankle deformity. Botulinum toxin (BT) injection is now an established first-line treatment for focal spasticity. AIM: To assess the effects of BT injection with casting in the treatment of dynamic equinus in children diagnosed with cerebral palsy with spastic diplegia. SETTING AND DESIGN: A prospective randomized controlled trial was conducted among patients aged 2-12 years with cerebral palsy and spastic diplegia, attending the general outpatient department and admitted to the indoor facility of the Department of Physical Medicine and Rehabilitation and the Department of Pediatric Orthopedics at King George's Medical University, Lucknow. MATERIAL AND METHODS: Two groups of 19 patients each were formed. Group A received BT injection with casting, whereas in group B, only a cast was applied. Outcome measures including spasticity by Modified Ashworth Scale (MAS), Modified Tardieu Scale (MTS), range of motion (ROM), passive ankle dorsiflexion, and Gross Motor Function Measure (GMFM-66) (dimensions D and E) were assessed before and after the intervention. RESULTS: The participants in groups A and B were age-matched. A statistically significant difference was seen within group A and group B for MAS, passive ROM-dorsiflexion (PROM-DF), and passive ROM-plantarflexion (PROM-PF) at various follow-ups. In the 3rd week, MAS in each group was statistically insignificant (p-value> 0.05). CONCLUSION: There was a significant improvement in tone and a significant increase in the passive range of motion in both groups.

A descriptive analysis of skin-only closure and Bogota bag techniques for achieving complete fascial closure in damage control abdominal surgery.

BACKGROUND: Temporary abdominal closure (TAC) techniques are essential in managing open abdomen cases, particularly in damage control surgery. Skin-only closure (SC) and Bogota bag closure (BBC) are commonly used methods for TAC, but their comparative effectiveness in achieving primary fascial closure (PFC) remains unclear. The objective of this study was to evaluate the rates of PFC between patients undergoing SC and BBC techniques for TAC in peritonitis or abdominal trauma cases at a tertiary care hospital. METHODS: A retrospective cross-sectional study was conducted at the Surgical A Unit of Hayatabad Medical Complex, Peshawar, from January 2022 to July 2023. Approval was obtained from the institutional review board, and patient consent was secured for data use. Patients undergoing temporary abdominal closure using either skin-only or Bogota bag techniques were included. Exclusions comprised patients younger than 15 or older than 75 years, those with multiple abdominal wall incisions, and those with prior abdominal surgeries. Data analysis utilized SPSS version 25. The study aimed to assess outcomes following damage control surgery, focusing on primary fascial closure rates and associated factors. Closure techniques (skin-only and Bogota bag) were chosen based on institutional protocols and clinical context. Indications for damage control surgery (DCS) included traumatic and non-traumatic emergencies. Intra-abdominal pressure (IAP) was measured using standardized methods. Patients were divided into SC and BBC groups for comparison. Criteria for reoperation and primary fascial closure were established, with timing and technique determined based on clinical assessment and multidisciplinary team collaboration. The decision to leave patients open during the index operation followed damage control surgery principles. RESULTS: A total of 193 patients were included in this study, with 59.0% undergoing skin-only closure (SC) and 41.0% receiving Bogota bag closure (BBC). Patients exhibited similar demographic characteristics across cohorts, with a majority being male (73.1%) and experiencing acute abdomen of non-traumatic origin (58.0%). Among the reasons for leaving the abdomen open, severe intra-abdominal sepsis affected 51.3% of patients, while 42.0% experienced hemodynamic instability. Patients who received SC had significantly higher rates of primary fascial closure (PFC) compared to BBC (85.1% vs. 65.8%, p = 0.04), with lower rates of fascial dehiscence (1.7% vs. 7.6%, p = 0.052) and wound infections (p = 0.010). Multivariate regression analysis showed SC was associated with a higher likelihood of achieving PFC compared to BBC (adjusted OR = 1.7, 95% CI: 1.3-3.8, p < 0.05). CONCLUSION: In patients with peritonitis or abdominal trauma, SC demonstrated higher rates of PFC compared to BBC for TAC in our study population. However, further studies are warranted to validate these results and explore the long-term outcomes associated with different TAC techniques.

Risk factors for mortality in post-myocardial infarction patients: insights from the improve SCA bridge study.

BACKGROUND: Underutilization of implantable cardioverter defibrillators (ICD) to prevent sudden cardiac death (SCD) in post-myocardial infarction (MI) patients remains an issue across several geographies. A better understanding of risk factors for SCD in post-MI patients from regions with low ICD adoption rates will help identify those who will benefit from an ICD. This analysis assessed risk factors for all-cause and cardiovascular-related mortality in post-MI patients from the Improve Sudden Cardiac Arrest (SCA) Bridge Trial. RESULTS: For the entire cohort, the overall 1-year mortality rate was 5.9% (88/1491) and 3.4% (51/1491) for all-cause and cardiovascular mortality, respectively, with 76.5% of all cardiac deaths being from SCD. A multivariate model determined increased age, reduced left ventricular ejection fraction (LVEF), increased time from myocardial infarction to hospital admission, being female, being from Southeast Asia (SEA), and having coronary artery disease to be significant risk factors for all-cause mortality. The risk factors for cardiovascular-related mortality revealed increased age, reduced LVEF, and being from SEA as significant risk factors. CONCLUSIONS: We show several characteristics as being predictors of cardiovascular-related mortality in post-MI patients from the Improve SCA Bridge study. Patients who experience an MI and present with these characteristics would benefit from a referral to an electrophysiologist for further SCD risk stratification and management and possible subsequent ICD implantation to reduce unnecessary death.

PIM kinase inhibitors: an updated patent review (2016-present).

INTRODUCTION: PIM Kinases (PIM-1, PIM-2, and PIM-3) have been reported to play crucial role in signaling cascades that govern cell survival, proliferation, and differentiation. Over-expression of these kinases leads to hematological malignancies such as diffuse large B cell lymphomas (DLBCL), multiple myeloma, leukemia, lymphoma and prostate cancer etc. PIM kinases as biomarkers and potential therapeutic targets have shown promise toward precision cancer therapy. The selective PIM-1, PIM-2, and/or PIM-3 isoform inhibitors have shown significant results in patients with advanced stages of cancer including relapsed/refractory cancer. AREAS COVERED: A comprehensive literature review of PIM Kinases (PIM-1, PIM-2, and PIM-3) in oncogenesis, the patented PIM kinase inhibitors (2016-Present), and their pharmacological and structural insights have been highlighted. EXPERT OPINION: Recently, PIM kinases viz. PIM-1, PIM-2, and PIM-3 (members of the serine/threonine protein kinase family) as therapeutic targets have attracted considerable interest in oncology especially in hematological malignancies. The patented PIM kinase inhibitors comprised of heterocyclic (fused)ring structure(s) like indole, pyridine, pyrazine, pyrazole, pyridazine, piperazine, thiazole, oxadiazole, quinoline, triazolo-pyridine, pyrazolo-pyridine, imidazo-pyridazine, oxadiazole-thione, pyrazolo-pyrimidine, triazolo-pyridazine, imidazo-pyridazine, pyrazolo-quinazoline and pyrazolo-pyridine etc. showed promising results in cancer chemotherapy.

Computational Investigation of Novel Compounds as Dual Inhibitors of AChE and GSK-3ß for the Treatment of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) stands out as one of the most devastating and prevalent neurodegenerative disorders known today. Researchers have identified several enzymatic targets associated with AD among which Glycogen synthase kinase-3ß (GSK-3ß) and Acetylcholinesterase (AChE) are prominent ones. Unfortunately, the market offers very few drugs for treating or managing AD, and none have shown significant efficacy against it. OBJECTIVES: To address this critical issue, the design and discovery of dual inhibitors will represent a potential breakthrough in the fight against AD. In the pursuit of designing novel dual inhibitors, we explored molecular docking and dynamics analyses of tacrine and amantadine uredio-linked amide analogs such as GSK-3ß and AChE dual inhibitors for curtailing AD. Tacrine and adamantine are the FDA-approved drugs that were structurally modified to design and develop novel drug candidates that may demonstrate concurrently dual selectivity towards GSK-3ß and AChE. METHODS: In the following study, molecular docking was executed by employing AutoDock Vina, and molecular dynamics and ADMET predictions were made using Desmond, Qikprop modules of Schrödinger. RESULTS: Our findings revealed that compounds DST2 and DST11 exhibited remarkable molecular interactions with active sites of GSK-3ß and AChE, respectively. These compounds effectively interacted with key amino acids, namely Lys85, Val135, Asp200, and Phe295, resulting in highly favourable docking energies of -9.7 and -12.7 kcal/mol. Furthermore, through molecular dynamics simulations spanning a trajectory of 100 ns, we confirmed the stability of ligands DST2 and DST11 within the active cavities of GSK-3ß and AChE. The compounds exhibiting the most promising docking results also demonstrated excellent ADMET profiles. Notably, DST21 displayed an outstanding human oral absorption rate of 76.358%, surpassing the absorption rates of other molecules. CONCLUSION: Overall, our in-silico studies revealed that the designed molecules showed potential as novel anti-Alzheimer agents capable of inhibiting both GSK-3ß and AChE simultaneously. So, in the future, the designing and development of dual inhibitors will harbinger a new era of drug design in AD treatment.

Giant Retinal Astrocytoma: A Case Report of an Uncommon Presentation of Tuberous Sclerosis in a Young Female.

Tuberous sclerosis (TS) is a rare multisystem autosomal dominant genetic disorder with characteristic pathognomonic genetic mutations involving the TSC (tuberous sclerosis complex) group of genes. Ocular signs are fairly common and include an achromic patch and retinal astrocytic hamartomas, which usually have a maximum size of between 0.5 and 5 mm. The incidence of tuberous sclerosis is estimated to be 1 in 5000-10,000 individuals, with both familial and sporadic cases reported. The diagnostic criteria for tuberous sclerosis include the presence of major and/or minor clinical features as well as genetic mutations. We present the case of a 15-year-old girl, presented with a history of seizures and blurred vision. Physical examination revealed angiofibroma on the face. Further evaluation, including contrast-enhanced MRI of the brain and ophthalmological consultation, led to the diagnosis of tuberous sclerosis. Additional imaging studies confirmed the presence of subependymal giant cell astrocytoma, retinal astrocytoma, lymphangioleiomyomatosis in the lungs, and renal angiomyolipoma. This case highlights the importance of considering tuberous sclerosis in patients presenting with seizures and ocular symptoms. This case sheds light on early diagnosis and appropriate management which are crucial in preventing complications and improving patient outcomes.

CRISPR/Cas9 Gene Editing: A Novel Approach Towards Alzheimer's Disease Treatment.

In defiance of the vast amount of information regarding Alzheimer's disease (AD) that has been learned over the past thirty years, progress toward developing an effective therapy has been difficult. A neurological ailment that progresses and cannot be reversed is Alzheimer's disease, which shows neurofibrillary tangles, beta-amyloid plaque, and a lack of cognitive processes that is created by tau protein clumps with hyperphosphorylation that finally advances to neuronal damage without a recognized treatment, which has stimulated research into new therapeutic strategies. The protein CAS9 is linked to CRISPR, which is a clustered Regularly Interspaced Short Palindromic Repeat that inactivates or corrects a gene by recognizing a gene sequence that produces a doublestranded break has enchanted a whole amount of interest towards its potency to cure gene sequences in AD. The novel CRISPR-Cas9 applications for developing in vitro and in vivo models to the benefit of AD investigation and therapies are thoroughly analyzed in this work. The discussion will also touch on the creation of delivery methods, which is a significant obstacle to the therapeutic use of CRISPR/Cas9 technology. By concentrating on specific genes, such as those that are significant early-onset AD risk factors and late-onset AD risk factors, like the apolipoprotein E4 (APOE4) gene, this study aims to evaluate the potential application of CRISPR/Cas9 as a possible treatment for AD.

GLP-1/GIP Agonist as an Intriguing and Ultimate Remedy for Combating Alzheimer's Disease through its Supporting DPP4 Inhibitors: A Review.

BACKGROUND: Alzheimer's disease (AD) is a widespread neurological illness in the elderly, which impacted about 50 million people globally in 2020. Type 2 diabetes has been identified as a risk factor. Insulin and incretins are substances that have various impacts on neurodegenerative processes. Preclinical research has shown that GLP-1 receptor agonists decrease neuroinflammation, tau phosphorylation, amyloid deposition, synaptic function, and memory formation. Phase 2 and 3 studies are now occurring in Alzheimer's disease populations. In this article, we present a detailed assessment of the therapeutic potential of GLP-1 analogues and DPP4 inhibitors in Alzheimer's disease. AIM: This study aimed to gain insight into how GLP-1 analogues and associated antagonists of DPP4 safeguard against AD. METHODS: This study uses terms from search engines, such as Scopus, PubMed, and Google Scholar, to explore the role, function, and treatment options of the GLP-1 analogue for AD. RESULTS: The review suggested that GLP-1 analogues may be useful for treating AD because they have been linked to anti-inflammatory, neurotrophic, and neuroprotective characteristics. Throughout this review, we discuss the underlying causes of AD and how GLP signaling functions. CONCLUSION: With a focus on AD, the molecular and pharmacological effects of a few GLP-1/GIP analogs, both synthetic and natural, as well as DPP4 inhibitors, have been mentioned, which are in the preclinical and clinical studies. This has been demonstrated to improve cognitive function in Alzheimer's patients.

Phase separation, aggregation, and complexation of triton-X100 and bovine serum albumin mixture: A combined cloud point and UV-visible spectroscopic approaches.

Phase separation and aggregation behaviour of triton X-100 (TX-100) and bovine serum albumin (BSA) mixture were investigated using cloud point and UV-visible spectroscopic techniques. The effects of various hydrotropes (HYTs) - namely, sodium salicylate (SS), sodium benzoate (SB), glycerol (Glyc), and 4-aminobenzoic acid (4-ABA) - on the cloud point (CP) of TX-100 + BSA were determined. The obtained CP values for the mixed system in the presence of HYTs followed the order: The measured critical micellization concentration (CMC) values of the TX-100 + BSA mixture were found to be significantly altered with varying amounts of BSA. The calculated free energy of clouding and micellization indicated the non-spontaneous nature of the phase transition and the spontaneous association of the TX-100 + BSA mixture. The non-spontaneity of phase separation decreased with increasing concentrations of HYTs. The enumerated values of ∆Hco and ∆Sco were consistently recorded as negative and positive magnitudes, respectively, in all aqueous HYTs media. The clouding process occurred due to a combination of hydrophobic and electrostatic interactions. The binding constant of the mixed system was determined employing the UV-vis spectroscopic method using the Benesi-Hildebrand equation.

Discovery of Novel Diesters Incorporating Kojic Acid With NSAIDs and Palmitic Acid as Dual Inhibitor of Melanogenesis and Inflammation.

Our study focuses on creating hybrid compounds and assessing their suitability for use in skincare products. The synergistic combination of Kojic acid, NSAIDs, and Palmitic acid proved to be an effective approach in inhibiting melanin production, making it a promising solution for individuals with hyperpigmentation concerns with Kojic acid (KA) Ibuprofen monoester (IBUM) and Ibuprofen-Kojic acid-Palmitic acid diester (IBUD) exhibiting a potential tyrosinase (38 % and 49 % inhibition at 200 µM) and anti-melanogenesis activity (77 % and 79 % inhibition at 100 µM). Furthermore, these compounds exhibited potent anti-inflammatory effects, Kojic acid-Diclofenac monoester (DICM) and Diclofenac-Kojic acid-Palmitic acid diester (DICD) offering potential benefits for inflammation by lowering the paw volume. A stability study under chemical conditions and enzymatic conditions was also performed, wherein DICM and DICD showed a better half-life of 515, 593 h under chemical stability and 6.3, 7.5 h under enzymatic stability studies respectively. The diester hybrids IBUD, DICD, Naproxen-Kojic acid-Palmitic acid diester (NAPD) showed a better permeation and penetration profiles compared to their parent drugs. In-vitro cell line studies were conducted to assess the safety and efficacy of these hybrid esters, with promising results. The dual inhibitor demonstrated minimal cytotoxicity and remarkable anti-melanogenic and anti-inflammatory activities, showing its potential as a versatile agent in addressing both melanogenesis and inflammation.

Navigating the Alzheimer's Treatment Landscape: Unraveling Amyloid-Beta Complexities and Pioneering Precision Medicine Approaches.

A variety of cutting-edge methods and good knowledge of the illness's complex causes are causing a sea change in the field of Alzheimer's Disease (A.D.) research and treatment. Precision medicine is at the vanguard of this change, where individualized treatment plans based on genetic and biomarker profiles give a ray of hope for customized therapeutics. Combination therapies are becoming increasingly popular as a way to address the multifaceted pathology of Alzheimer's by simultaneously attacking Aß plaques, tau tangles, neuroinflammation, and other factors. The article covers several therapeutic design efforts, including BACE inhibitors, gamma- secretase modulators, monoclonal antibodies (e.g., Aducanumab and Lecanemab), and anti- Aß vaccinations. While these techniques appear promising, clinical development faces safety concerns and uneven efficacy. To address the complicated Aß pathology in Alzheimer's disease, a multimodal approach is necessary. The statement emphasizes the continued importance of clinical trials in addressing safety and efficacy concerns. Looking ahead, it suggests that future treatments may take into account genetic and biomarker traits in order to provide more personalized care. Therapies targeting Aß, tau tangles, neuroinflammation, and novel drug delivery modalities are planned. Nanoparticles and gene therapies are only two examples of novel drug delivery methods that have the potential to deliver treatments more effectively, with fewer side effects, and with better therapeutic results. In addition, medicines that target tau proteins in addition to Aß are in the works. Early intervention, based on precise biomarkers, is a linchpin of Alzheimer's care, emphasizing the critical need for detecting the disease at its earliest stages. Lifestyle interventions, encompassing diet, exercise, cognitive training, and social engagement, are emerging as key components in the fight against cognitive decline. Data analytics and art are gaining prominence as strategies to mitigate the brain's inflammatory responses. To pool knowledge and resources in the fight against Alzheimer's, international cooperation between scientists, doctors, and pharmaceutical companies is still essential. In essence, a complex, individualized, and collaborative strategy will characterize Alzheimer's research and therapy in the future. Despite obstacles, these encouraging possibilities show the ongoing commitment of the scientific and medical communities to combat A.D. head-on, providing a glimmer of hope to the countless people and families touched by this savage sickness.

Noncoding RNAs in Alzheimer's Disease: Overview of Functional and Therapeutic Significance.

Alzheimer's disease (AD) is a multifactorial disorder resulting from the complex interaction between genetic, epigenetic, and environmental factors. It represents an impending epidemic and lacks effective pharmacological interventions. The emergence of high throughput sequencing techniques and comprehensive genome evaluation has uncovered a diverse spectrum of non-- coding RNA (ncRNA) families. ncRNAs are the critical modulators of an eclectic array of biological processes and are now transpiring as imperative players in diagnosing and treating various diseases, including neurodegenerative disorders. Several ncRNAs are explicitly augmented in the brain, wherein they potentially regulate cognitive abilities and other functions of the central nervous system. Growing evidence suggests the substantial role of ncRNAs as modulators of tau phosphorylation, Aß production, neuroinflammation, and neuronal survival. It indicates their therapeutic relevance as a biomarker and druggable targets against AD. The current review summarizes the existing literature on the functional significance of ncRNAs in AD pathogenesis and its imminent implications in clinics.

Machine learning-based virtual screening and molecular modelling studies for identification of butyrylcholinesterase inhibitors as anti-Alzheimer's agent.

Butyrylcholinesterase (BChE) is a hydrolase involved in the metabolism and detoxification of specific esters in the blood. It is also implicated in the progression of Alzheimer's disease, a type of dementia. As the disease progresses, the level of BChE tends to increase, opting for a major role as an acetylcholine-degrading enzyme and surpassing the role of acetylcholinesterase. Hence, the development of BChE inhibitors could be beneficial for the latter stages of the disease. In the present study, machine learning (ML) models were developed and employed to identify new BChE inhibitors. Further, the identified molecules were subjected to molecular property filters. The filtered ligands were studied through molecular modelling techniques, viz. molecular docking and molecular dynamics (MD). Support vector machine-based ML models resulted in the identification of 3291 compounds that would have predicted IC50 values less than 200 nM. The docking study showed that compounds ART13069594, ART17350769 and LEG19710163 have mean binding energies of -9.62, -9.26 and -8.93 kcal/mol, respectively. The MD study displayed that all the selected ligands showed stable complexes with BChE. The trajectories of all the ligands were stable similar to the standard BChE inhibitors.Communicated by Ramaswamy H. Sarma.

Charge Puddles Driven Complex Crossover of Magnetoresistance in Non-Topological Sulfur Doped Antimony Selenide Nanowires.

A race to achieve a crossover from positive to negative magnetoresistance is intense in the field of nanostructured materials to reduce the size of memory devices. Here, the unusual complex magnetoresistance in nonmagnetic sulfur-doped Sb2Se3 nanowires is demonstrated. Intentionally, sulfur is doped in such a way to nearly achieve the charge neutrality point that is evident from switching of carrier type from p-type to n-type at 13 K as inferred from the low-temperature thermoelectric power measurements. A change from 3D variable range hopping (VRH) to power law transport with α = 0.18  in resistivity measurement signifies a Luttinger liquid transport with weak links through the nanowires. Interestingly, high magnetic field induced negative magnetoresistance (NMR) occurring in hole dominated temperature regimes can only be explained by invoking the concept of charge puddles. Spot energy dispersive spectroscopy (EDS), magnetic force microscopy (MFM) measurements, Tmott and Regel plot indicate an enhanced disorder in these sulfurized nanowires that are found to be the precursor for the formation of these charge puddles. Tunability of conducting states in these nanowires is investigated in the light of interplay of carrier type, magnetic field, temperature, and intricate intra-inter wire transport that makes this nanowires potential for large scale spintronic devices.

Molecular Insight into the Apoptotic Mechanism of Cancer Cells: An Explicative Review.

Mitosis of somatic cells produces a daughter cell. Apoptosis, a naturally programmed cellular death mechanism, kills abnormal cells produced by mitosis. Cancer can develop when this equilibrium is disrupted, either by an upsurge in cell propagation or a reduction in tissue demise. Cancer therapy aims to cause cancer cells to die while inflicting little harm to healthy cells. This review of apoptotic mechanism processes improves our understanding of how certain malignancies begin and develop. The current cancer treatments can operate either by inducing apoptosis or causing direct cell damage. An insight into the resistance to apoptosis may explicate why malignancy treatments fail in some situations. New therapies grounded on our understanding of apoptotic processes are being developed to induce apoptosis of cancer cells while limiting the simultaneous death of normal cells. Various biological activities require redox equilibrium to function properly. Antineoplastic medications that cause oxidative stress by raising ROS and blocking antioxidant mechanisms have recently attracted much interest. The rapid accumulation of ROS impairs redox balance and damages cancer cells severely. Here, we discuss ROS-instigating malignancy therapy and the antineoplastic mechanism used by prooxidative drugs.

Study on the association and phase separation behavior of surfactants and promethazine hydrochloride: impact of ammonium electrolytes.

In the current study, the association and phase separation of cationic tetradecyltrimethylammonium bromide (TTAB) and nonionic Triton X-100 (TX-100) surfactants with promethazine hydrochloride (PMH) were investigated in aqueous ammonium-based solutions. The micellization nature of the TTAB and PMH drug mixture was examined by evaluating critical micelle concentration (CMC) and counterion binding extent (ß) at different salt contents and temperatures (298.15-323.15 K). Micelle formation in the TTAB + PMH mixture was enhanced in the presence of ammonium salts, whereas the process was delayed with an increase in temperature in the respective salt solution. With an increase in salt content, the cloud point (CP) of the TX-100 + PMH mixture decreased, which revealed that the respective progression occurred through the salting out phenomenon. In micellization and clouding processes, the changes in free energies ΔG0m and ΔG0c were found to be negative and positive, respectively, demonstrating that the corresponding processes are spontaneous and non-spontaneous. Standard enthalpies (ΔH0m/ΔH0c) and standard entropies (ΔS0m/ΔS0c) for the association and clouding processes, respectively, were also calculated and discussed. The core forces amid TTAB/TX-100 and PMH in the manifestation of electrolytes are dipole-dipole and hydrophobic forces among the employed components according to the values for ΔH0m/ΔH0c and ΔS0m/ΔS0c, respectively.