Iron Deficiency and Incident Heart Failure in Older Community-Dwelling Individuals.

AIMS: Among persons with prevalent heart failure (HF), iron deficiency has been linked to HF admissions, and intravenous iron replacement improves HF outcomes. Recent studies in persons with chronic kidney disease (CKD) demonstrate that iron deficiency is associated with incident HF. This study aimed to determine the relationship of iron status with incident HF in community-dwelling older adults irrespective of their kidney function. METHODS: In this case-cohort study, 1,006 Cardiovascular Health Study participants (785 from the random sub-cohort [including 193 HF cases] and 221 additional HF cases [N = 414 total HF cases]) aged ≥ 65 years without HF (41% with CKD), we used weighted Cox models to evaluate associations of iron status with incident HF. Participants were categorized based on quartiles of transferrin saturation and ferritin as "iron replete" (27.3%), "functional iron deficiency" (7.7%), "iron deficiency" (11.8%), "mixed iron deficiency" (5.6%), "high iron" (9.3%) and "non-classified" (38.1%), consistent with prior studies. RESULTS: Compared to older persons who were iron replete, those with iron deficiency were at higher risk of incident HF (HR 1.47; 1.02-2.11) in models adjusting for demographics, HF risk factors, and estimated glomerular filtration rate. Other iron categories did not associate with incident HF. The relationship of iron deficiency with incident HF did not differ by CKD status (interaction P value 0.2). CONCLUSIONS: Among community-dwelling elders, iron deficiency is independently associated with incident HF, an association that was similar irrespective of CKD status. Our findings support conduct of clinical trials of iron replacement for prevention of HF in older adults with iron deficiency.

Controlled formation of multi-scale porosity in ionosilica templated by ionic liquid.

Mesoporous systems are ubiquitous in membrane science and applications due to their high internal surface area and tunable pore size. A new synthesis pathway of hydrolytic ionosilica films with mesopores formed by ionic liquid (IL) templating is proposed and compared with the traditional non-hydrolytic strategy. For both pathways, the multi-scale formation of pores has been studied as a function of IL content, combining the results of thermogravimetric analysis (TGA), nitrogen sorption, and small-angle X-ray scattering (SAXS). The combination of TGA and nitrogen sorption provides access to ionosilica and pore volume fractions, with contributions of meso- and macropores. We then elaborate an original and quantitative geometrical model to analyze the SAXS data based on small spheres (Rs = 1-2 nm) and cylinders (Lcyl = 10-20 nm) with radial polydispersity provided by the nitrogen sorption isotherms. As a result, we found that for a given incorporation of a templating IL, both synthesis pathways produce very similar pore geometries, but the better incorporation efficacy of the new hydrolytic films provides higher mesoporosity. Our combined study provides a coherent view of mesopore geometry, and thereby an optimization pathway of porous ionic membranes in terms of accessible mesoporosity contributing to the specific surface. Possible applications include electrolyte membranes with improved ionic properties, e.g., in fuel cells and batteries, as well as molecular storage.

Plasma proenkephalin A and incident chronic kidney disease and albuminuria in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort.

BACKGROUND: Plasma proenkephalin A (PENK-A) is a precursor of active enkephalins. Higher blood concentrations have been associated with estimated glomerular filtration rate (eGFR) decline in European populations. Due to the significant disparity in incident chronic kidney disease (CKD) between White and Black people, we evaluated the association of PENK-A with incident CKD and other kidney outcomes among a biracial cohort in the U.S. METHODS: In a nested cohort of 4,400 participants among the REasons for Geographic And Racial Differences in Stroke, we determined the association between baseline PENK-A concentration and incident CKD using the creatinine-cystatin C CKD-EPI 2021 equation without race coefficient, significant eGFR decline, and incident albuminuria between baseline and a follow-up visit 9.4 years later. We tested for race and sex interactions. We used inverse probability sampling weights to account for the sampling design. RESULTS: At baseline, mean (SD) age was 64 (8) years, 49% were women, and 52% were Black participants. 8.5% developed CKD, 21% experienced ≥ 30% decline in eGFR and 18% developed albuminuria. There was no association between PENK-A and incident CKD and no difference by race or sex. However, higher PENK-A was associated with increased odds of progressive eGFR decline (OR: 1.12; 95% CI 1.00, 1.25). Higher PENK-A concentration was strongly associated with incident albuminuria among patients without diabetes mellitus (OR: 1.29; 95% CI 1.09, 1.53). CONCLUSION: While PENK-A was not associated with incident CKD, its associations with progression of CKD and incident albuminuria, among patients without diabetes, suggest that it might be a useful tool in the evaluation of kidney disease among White and Black patients.

Cloning, expression, and characterization of a novel thermo-acidophilic l-asparaginase of Pseudomonas aeruginosa CSPS4.

In the present investigation, a soil isolate Pseudomonas aeruginosa CSPS4 was used for retrieving the l-asparaginase encoding gene (Asn_PA) of size 1089 bp. The gene was successfully cloned into the pET28a (+) vector and expressed into E. coli BL21(DE3) for characterization of the protein. The recombinant rAsn_PA enzyme was purified by affinity chromatography using Ni-NTA2+ resins. Molecular weight analysis using SDS-PAGE unveiled rAsn_PA as a monomeric protein of molecular weight ~ 35 kDa. On characterization, the recombinant rAsn_PA showed optimum pH and temperature of 6.0 and 60 °C, respectively, along with significant stability at 50-70 °C, along with 50% residual activity at 80 °C after 3 h of incubation. Similarly, the rAsn_PA exhibited asparaginase activity over a broad pH range between 4 and 8. The enzyme was not significantly inhibited in the presence of detergents. The rAsn_PA was grouped into the asparaginase-glutaminase family II due to the glutaminase activity. The purified rAsn_PA showed antitumor activity by exhibiting a cytotoxic effect on three different cell lines, where IC50 of purified rAsn_PA was 2.3 IU, 3.7 IU, and 20.5 IU for HL-60, MOLM-13, and K-562 cell lines, respectively. Thus, recombinant rAsn_PA of P. aeruginosa CSPS4 may also be explored as an antitumor agent after reducing or minimizing the glutaminase activity. Thermo-acidophilic properties of rAsn_PA make it a novel enzyme that needs to be further investigated.

Plasma GDNF levels in spinal dysraphism and its relation with neurological impairment in children: A point of care study.

AIMS: GDNF plays a crucial role in the stimulation of recovery, neuroplasticity and synaptic reorganization after spinal cord injury providing neuroprotection and neuroregeneration. Plasma GDNF levels are upregulated in cases of spina bifida owing to the intrauterine damage of the exposed spinal cord. Our aim was to compare the plasma GDNF levels in patients of spina bifida with non-spina bifida cases and assess the correlation with neurological impairment at one year of follow up. METHODS: Single centre prospective analysis of cases of spina bifida from 2020 to 2022 at presentation and after one year of follow up post-surgery. Cases with hernia and hydrocele without any other disorders were recruited into the control group. Plasma GDNF levels were assessed with immunoassay kits and compared with neurological involvement. RESULTS: 85 cases were included in the study. GDNF levels were elevated in cases compared to controls (mean 6.62 vs 1.76) with significant p value (<0.01). Same was observed for open and closed defects (mean 7.63 vs 4.86: p < 0.01). At follow up of 52 cases post-surgery cases with neurogenic bladder with abnormal urodynamic studies, sphincter involvement and motor impairment had significantly elevated baseline levels of GDNF compared with those who did not have this neurological impairment (p < 0.01). DISCUSSION: The neurotrophic factor up-regulation can reflect an endogenous attempt at neuroprotection against the biochemical and molecular cascades triggered by the spinal cord damage. This upregulation can be represented as important biochemical markers of severe spinal cord damage and can be associated with severity of spine injury in MMC patients. Our results are in keeping with these findings, that, there were increased levels of plasma GDNF levels in cases of spinal dysraphism compared to control population. Also, the type of lesion reflecting the severity whether a closed or an open dysraphism, showed significant difference in levels between them suggesting, yet again, more damage in open defect as expected. The levels were higher with involvement of bladder, sphincter and lower limb power. CONCLUSION: There is significant elevation of plasma GDNF levels in cases of spina bifida and this elevation is proportional to the degree of spinal damage and hence the neurological impairment. GDNF levels are a good predictor for assessing the severity of the lesion and thus the outcome in these cases. Additional prospective and long-term studies with a larger cohort are needed for a better understanding of neurotrophin pattern modulation in MMC.

Chitosan nanocomposite for tissue engineering and regenerative medicine: A review.

Regenerative medicine and tissue engineering have emerged as a multidisciplinary promising field in the quest to address the limitations of traditional medical approaches. One of the key aspects of these fields is the development of such types of biomaterials that can mimic the extracellular matrix and provide a conducive environment for tissue regeneration. In this regard, chitosan has played a vital role which is a naturally derived linear bi-poly-aminosaccharide, and has gained significant attention due to its biocompatibility and unique properties. Chitosan possesses many unique physicochemical properties, making it a significant polysaccharide for different applications such as agriculture, nutraceutical, biomedical, food, nutraceutical, packaging, etc. as well as significant material for developing next-generation hydrogel and bio-scaffolds for regenerative medicinal applications. Moreover, chitosan can be easily modified to incorporate desirable properties, such as improved mechanical strength, enhanced biodegradability, and controlled release of bioactive molecules. Blending chitosan with other polymers or incorporating nanoparticles into its matrix further expands its potential in tissue engineering applications. This review summarizes the most recent studies of the last 10 years based on chitosan, blends, and nanocomposites and their application in bone tissue engineering, hard tissue engineering, dental implants, dental tissue engineering, dental fillers, and cartilage tissue engineering.

Percutaneous treatment of mechanical mitral valve thrombosis.

A 75-year-old female was found to have mechanical mitral valve thrombosis complicated by severe mitral stenosis, pulmonary edema, and right heart failure. She was at prohibitive risk for surgical intervention. She did not tolerate thrombolysis due to bleeding. We performed percutaneous intervention with cerebral protection with subsequent restoration of mechanical mitral valve function, resolution of the mitral valve stenosis, and no neurologic complications.

Trauma and sexual abuse in children-Epidemiology, challenges, management strategies and prevention in lower- and middle-income countries.

Trauma is rising as a cause of morbidity and mortality in lower- and middle-income countries (LMIC). This article describes the Epidemiology, Challenges, Management strategies and prevention of pediatric trauma in lower- and middle-income countries. The top five etiologies for non-intentional injuries leading to death are falls, road traffic injuries, burns, drowning and poisoning. The mortality rate in LMICs is twice that of High-Income Countries (HICs) irrespective of injury severity adjustment. The reasons for inadequate care include lack of facilities, transportation problems, lack of prehospital care, lack of resources and trained manpower to handle pediatric trauma. To overcome these challenges, attention to protocolized care and treatment adaptation based on resource availability is critical. Training in management of trauma helps to reduce the mortality and morbidity in pediatric polytrauma cases. There is also a need for more collaborative research to develop preventative measures to childhood trauma.

Crystallographic mining driven computer-guided approach to identify the ASK1 inhibitor likely to perturb the catalytic region.

The pathological levels of reactive oxygen species (ROS) and oxidative stress has been recognized as a critical driver for inflammatory disorders. Apoptosis signal-regulating kinase 1 (ASK1) has been reported to be activated by intracellular ROS and its inhibition leads to a down regulation of p38-and JNK-dependent signaling. ASK1 inhibitors are reported to have the potential to treat clinically important inflammatory pathologies including liver, pulmonary and renal disorders. In view of its biological and pathological significance, inhibition of ASK1 with small molecules has been pursued as an attractive strategy to combat human diseases such as non-alcoholic steatohepatitis (NASH). Despite several ASK1 inhibitors being developed, the failure in Phase 3 clinical trials of most advanced candidate selonsertib's, underscores to discover therapeutic agents with diverse chemical moiety. Here, by using structural pharmacophore and enumeration strategy on mining co-crystals of ASK1, different scaffolds were generated to enhance the chemical diversity keeping the critical molecular interaction in the catalytic site intact. A total of 15,772 compounds were generated from diverse chemical scaffolds and were evaluated using a virtual screening pipeline. Based on docking and MM-GBSA scores, a lead candidate, S3C-1-D424 was identified from top hits. A comparative molecular dynamics simulations (MD) of APO, Selonsertib and shortlisted potential candidates combined with pharmacokinetics profiling and thermodynamic analysis, demonstrating their suitability as potential ASK1 inhibitors to explore further for establishment towards hit-to-lead campaign.Communicated by Ramaswamy H. Sarma.

Anorectal malformations in low and middle-income countries- spectrum, burden and management.

The clinical presentation, diagnosis and management of anorectal malformation has been well described in the literature, however the experience with these conditions in low-and middle-income countries is often shaped in unique ways due to the social, cultural and economic factors at work in these regions. This leads to adaptation of modifications in management options for these babies that usually present as delayed cases with added poor prognostic factors like sepsis leading to need for emergency resuscitation and overall increased morbidity and mortality. This article explores the anomaly from a global surgery lens and outlines the spectrum of the anomaly, burden faced in the resource constrained environment and the management options adopted for successful management under the available circumstances.

Exploring the potential of Halalkalibacterium halodurans laccase for endosulfan and chlorophacinone degradation: insights from molecular docking and molecular dynamics simulations.

Pesticides are widely used in agriculture but at the same time, a majority of them are known to cause serious harm to health and the environment. In the recent past, laccases have been reported as key enzymes having the ability to degrade pollutants by converting them into less toxic forms. In this investigation, laccase from polyextremophilic bacterium Halalkalibacterium halodurans C-125 was analyzed for its structural, physicochemical, and functional characterization using in silico approaches. The 3D model of the said enzyme is unknown; therefore, the model was generated by template-independent modeling using ROBETTA, I-TASSER, and Alphafold server. The best-generated model from Alphafold with a confidence of 0.95 was validated from ERRAT and Verify 3D scores of 89.95 and 91.80%, respectively. The Ramachandran plot generated using the PROCHECK server further predicted the accuracy of the model with 93.7% and 5.9% of residues present in most favored and additional allowed regions of the plot respectively. The active sites, ion binding sites, and subcellular localization of laccase were also predicted. The generated model was docked with 121 pollutants (pesticides, insecticides, herbicides, fungicides, and rodenticides) for its degradation potential towards these pollutants. Two ligands chlorophacinone (based on the highest binding energy) and endosulfan (based on agricultural uses) were selected for molecular dynamic simulation studies. Endosulfan as a pesticide is banned but in some countries governments allow its use for special purposes which need serious consideration on developing bioremediation approaches for endosulfan degradation. MD simulation studies revealed that both chlorophacinone and endosulfan form hydrogen bonds and hydrophobic bonds with the active site of laccase and chlorophacinone-laccase complex were more stable in comparison to endosulfan. The present investigation provides insight into the structural features of laccase and its potential for the degradation of pesticides which can be further validated by experimental data.Communicated by Ramaswamy H. Sarma.

Screening of Multitarget-Directed Natural Compounds as Drug Candidates for Alzheimer's Disease Using In Silico Techniques: Their Extraction and In Vitro Validation.

Alzheimer's disease (AD) is a neurodegenerative disorder that impairs neurocognitive function. Acetylcholinesterase (AChE) and ß-site APP cleaving enzyme 1 (BACE1) are the two main proteins implicated in AD. Indeed, the major available commercial drugs (donepezil, rivastigmine, and galantamine) against Alzheimer's are AChE inhibitors. However, none of these drugs are known to reverse or reduce the pathophysiological condition of the disease since there are multiple contributing factors to AD. Therefore, there is a need to develop a multitarget-directed ligand approach for its treatment. In the present study, plant bioactive compounds were screened for their AChE and BACE1 inhibition potential by conducting molecular docking studies. Considering their docking score and pharmacokinetic properties, limonin, peimisine, serratanine B, and withanolide A were selected as the lead compounds. Molecular dynamics simulations of these protein-ligand complexes confirmed the conformational and energetically stabilized enzyme-inhibitor complexes. The inhibition potential of the lead compounds was validated by in vitro enzyme assay. Withanolide A inhibited AChE (IC50 value of 107 µM) and showed mixed-type inhibition. At this concentration, it inhibited BACE1 activity by 57.10% and was stated as most effective. Both the compounds, as well as their crude extracts, were found to have no cytotoxic effect on the SH-SY5Y cell line.

Erudition from primary posterior sagittal anorectoplasty for anorectal malformations over two decades.

PURPOSE: Perioperative and early post-operative outcomes of Primary Posterior sagittal anorectoplasty (P-PSARP) were evaluated. METHOD: Retrospective analysis of cases who underwent P-PSARP from 2004 to 2019 was done. Perioperative care, management, complications, voluntary bowel movement, soiling and constipation, graded by Krickenbeck criteria were studied. RESULTS: One hundred fifty six patients (134 girls) underwent P-PSARP at median age of 5 months (3 months to 14 years) in girls and 5(1-10) days in 21 boys. One male cloaca was operated at 5 months age. Of 20 boys, 5, 8, 4, 3 had rectobulbar urethral fistula, rectoprostatic urethral fistula, bladder neck fistula and male cloaca. Girls had vestibular fistula, rectovaginal fistula, vulval anus, anterior ectopic anus, pouch perineal fistulae and posterior anus with H type fistula in 114, 7, 6, 5, 1 and 1. Complications included wound infection, excoriation, oedema, mucosal prolapse, anal stricture, anal retraction and mortality in 6, 4, 5, 4, 4, 1 and 1, respectively. 35/155(12 neonates) required postoperative dilatations for 5(1-12) months. At follow-up, 96/114(84.2%) had voluntary bowel movements. 46/155 (29.7%) and 9/155 had constipation and soiling. 32:14:0 had grade 1:2:3 constipation, treated with diet (grade 1) and laxatives (grade 2) respectively. 4:3:2 had grade 1:2:3 soiling for initial 3 months, treated with bowel management programme. CONCLUSION: P-PSARP is feasible, subject to proper case selection and good perioperative care, once learning curve is achieved.

ChatGPT in action: Harnessing artificial intelligence potential and addressing ethical challenges in medicine, education, and scientific research.

Artificial intelligence (AI) tools, like OpenAI's Chat Generative Pre-trained Transformer (ChatGPT), hold considerable potential in healthcare, academia, and diverse industries. Evidence demonstrates its capability at a medical student level in standardized tests, suggesting utility in medical education, radiology reporting, genetics research, data optimization, and drafting repetitive texts such as discharge summaries. Nevertheless, these tools should augment, not supplant, human expertise. Despite promising applications, ChatGPT confronts limitations, including critical thinking tasks and generating false references, necessitating stringent cross-verification. Ensuing concerns, such as potential misuse, bias, blind trust, and privacy, underscore the need for transparency, accountability, and clear policies. Evaluations of AI-generated content and preservation of academic integrity are critical. With responsible use, AI can significantly improve healthcare, academia, and industry without compromising integrity and research quality. For effective and ethical AI deployment, collaboration amongst AI developers, researchers, educators, and policymakers is vital. The development of domain-specific tools, guidelines, regulations, and the facilitation of public dialogue must underpin these endeavors to responsibly harness AI's potential.

Mechanism of the interaction of toxic SOD1 fibrils with two potent polyphenols: curcumin and quercetin.

Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disease commonly caused due to the aggregation of superoxide dismutase 1 (SOD1) protein. Finding inhibitors of SOD1 aggregation is of prime concern, but understanding the mechanistic action of inhibitors is equally important. Recent experiments found that two polyphenols, curcumin, and quercetin, have the ability to inhibit SOD1 aggregation. Quercetin was experimentally proven to break pre-formed fibrils into shorter segments, while curcumin did not significantly affect the pre-formed species. Here, we delve deeper into understanding the mechanism of action of quercetin and curcumin on pre-formed octameric fibrils of SOD1 (28PVKVWGSIKGL38: chains A-H) with the help of molecular dynamics (MD) simulations of a fibril docked polyphenol complex. Our results suggest that quercetin shows π-π stacking interaction with one of the key residues for toxic amyloid formation, Trp 32 of chains D, E, and F, and breaks the peptide chains G, and H from the rest of the fibril. On the other hand, curcumin binds to the hydrophobic amino acids of almost all the chains B-H and stabilizes the fibril rather than destabilizing it. Binding free energy calculations using MM/PBSA showed that curcumin binds more strongly to the SOD1 fibril due to greater van der Waals interactions compared to quercetin. These findings provide insights for the development of potential ALS treatments.

Prevalence of antibiotic-resistant Gram-negative bacteria having extended-spectrum ß-lactamase phenotypes in polluted irrigation-purpose wastewaters from Indian agro-ecosystems.

Antibiotic resistance in bacteria has emerged as a serious public health threat worldwide. Aquatic environments including irrigation-purpose wastewaters facilitate the emergence and transmission of antibiotic-resistant bacteria and antibiotic resistance genes leading to detrimental effects on human health and environment sustainability. Considering the paramount threat of ever-increasing antibiotic resistance to human health, there is an urgent need for continuous environmental monitoring of antibiotic-resistant bacteria and antibiotic resistance genes in wastewater being used for irrigation in Indian agro-ecosystems. In this study, the prevalence of antibiotic resistance in Gram-negative bacteria isolated from irrigation-purpose wastewater samples from Sirmaur and Solan districts of Himachal Pradesh was determined. Bacterial isolates of genera Escherichia, Enterobacter, Hafnia, Shigella, Citrobacter, and Klebsiella obtained from 11 different geographical locations were found to exhibit resistance against ampicillin, amoxyclav, cefotaxime, co-trimoxazole, tobramycin, cefpodoxime and ceftazidime. However, all the isolates were sensitive to aminoglycoside antibiotic gentamicin. Enterobacter spp. and Escherichia coli showed predominance among all the isolates. Multidrug-resistance phenotype was observed with isolate AUK-06 (Enterobacter sp.) which exhibited resistant to five antibiotics. Isolate AUK-02 and AUK-09, both E. coli strains showed resistant phenotypes to four antibiotics each. Phenotypic detection revealed that six isolates were positive for extended-spectrum ß-lactamases which includes two isolates from Enterobacter spp. and E. coli each and one each from Shigella sp. and Citrobacter sp. Overall, the findings revealed the occurrence of antibiotic resistant and ESBL-positive bacterial isolates in wastewaters utilized for irrigation purpose in the study area and necessitate continuous monitoring and precautionary interventions. The outcomes of the study would be of significant clinical, epidemiological, and agro-environmental importance in designing effective wastewater management and environmental pollution control strategies.

Development of a template for operative reporting of pediatric cancer surgery in limited-resource settings by using a modified Delphi method.

PURPOSE: A comprehensive operative report for cancer surgery is crucial for accurate disease staging, risk stratification, and therapy escalation/de-escalation, which affects the outcome. Narrative operative reports may fail to include some critical findings. Furthermore, standardized operative reports can form the basis of a local registry, which is often lacking in limited-resource settings (LRSs). In adult literature, synoptic operative reports (SOR) contain more key findings than narrative operative reports. In the LRSs, where the capacity of diagnostic pathology services is typically suboptimal, the value of a thorough operative report is even greater. The aim of this study was to develop a SOR template to help standardize childhood cancer surgery reporting in LRSs. METHODS: Twenty-three experts in pediatric cancer with extensive experience practicing in LRSs were invited to participate in a modified Delphi procedure. SOR domains for pediatric oncology surgery were drafted based on a literature search and then modified based on experts' opinions. The experts anonymously answered multiple rounds of online questionnaires until all domains and subdomains reached a consensus, which was predefined as 70% agreement. RESULTS: Sixteen experts participated in the study, and two rounds of the survey were completed. Twenty-one domains were considered relevant, including demographics, diagnosis, primary site, preoperative disease stage, previous tumor biopsy or surgery, preoperative tumor rupture, neoadjuvant therapy, surgical access, type of resection, completeness of resection, tumor margin assessment, locoregional tumor extension, organ resection, intraoperative tumor spillage, vascular involvement, lymph node sampling, estimated blood loss, intraoperative complications and interventions to address them, specimen names, and specimen orientation. CONCLUSION: We developed a SOR template for pediatric oncology surgery in LRSs. Consensus for all 21 domains and associated subdomains was achieved using a modified Delphi procedure.

Linker-assisted engineering of chimeric xylanase-phytase for improved thermal tolerance of feed enzymes.

Biological enzymes are multifunctional macromolecules that can perform hundreds of reactions simultaneously. An enzyme must possess specific characteristics to meet industrial needs, such as stability over a wide pH and temperature range and high specific activity. A phytase and xylanase mixture is generally added to poultry feed to improve the bird's health and productivity. Despite this, animal farmers have noticed no difference in productivity, and a leading cause is the high temperature at which feed is pulverized, which inactivates enzymes. A thermo-stable enzyme system can overcome these hitches. Commonly, coatings and immobilization reduce losses caused by physical-chemical factors in feed processing and digestion. To this end, we engineered the multifunctional xylanase-phytase domains on a single polypeptide fused by a helical linker. First, the ideal linker sequence was chosen by computing each selected linker's root mean square deviation (RMSD). The selected helical linker provides sufficient structural flexibility for substrate binding and product release evaluated by molecular docking and molecular dynamic simulation studies. Furthermore, a domain-domain interaction has stabilized the bridging partners, attaining the thermal optima for xylanase and phytase at 90 °C. Even at the above-optimal temperature (100 °C), the recombinant PLX was relatively stable and retained 64.2% and 59.2% activity for xylanase and phytase, respectively, when surveyed for ten hours. So far, to this date, this is the highest degree of thermostability achieved by any recombinant phytase or xylanase.Communicated by Ramaswamy H. Sarma.

An update on stem cell and stem cell-derived extracellular vesicle-based therapy in the management of Alzheimer's disease.

Globally, neurological diseases pose a major burden to healthcare professionals in terms of the management and prevention of the disorder. Among neurological diseases, Alzheimer's disease (AD) accounts for 50%-70% of dementia and is the fifth leading cause of mortality worldwide. AD is a progressive, degenerative neurological disease, with the loss of neurons and synapses in the cerebral cortex and subcortical regions. The management of AD remains a debate among physicians as no standard and specific "disease-modifying" modality is available. The concept of 'Regenerative Medicine' is aimed at regenerating the degenerated neural tissues to reverse the pathology in AD. Genetically modified engineered stem cells modify the course of AD after transplantation into the brain. Extracellular vesicles (EVs) are an emerging new approach in cell communication that involves the transfer of cellular materials from parental cells to recipient cells, resulting in changes at the molecular and signaling levels in the recipient cells. EVs are a type of vesicle that can be transported between cells. Many have proposed that EVs produced from mesenchymal stem cells (MSCs) may have therapeutic promise in the treatment of AD. The biology of AD, as well as the potential applications of stem cells and their derived EVs-based therapy, were explored in this paper.