Extracellular Vesicular miRNA in Pancreatic Cancer: From Lab to Therapy.

Pancreatic cancer is a prevalent lethal gastrointestinal cancer that generally does not show any symptoms until it reaches advanced stages, resulting in a high mortality rate. People at high risk, such as those with a family history or chronic pancreatitis, do not have a universally accepted screening protocol. Chemotherapy and radiotherapy demonstrate limited effectiveness in the management of pancreatic cancer, emphasizing the urgent need for innovative therapeutic strategies. Recent studies indicated that the complex interaction among pancreatic cancer cells within the dynamic microenvironment, comprising the extracellular matrix, cancer-associated cells, and diverse immune cells, intricately regulates the biological characteristics of the disease. Additionally, mounting evidence suggests that EVs play a crucial role as mediators in intercellular communication by the transportation of different biomolecules, such as miRNA, proteins, DNA, mRNA, and lipids, between heterogeneous cell subpopulations. This communication mediated by EVs significantly impacts multiple aspects of pancreatic cancer pathogenesis, including proliferation, angiogenesis, metastasis, and resistance to therapy. In this review, we delve into the pivotal role of EV-associated miRNAs in the progression, metastasis, and development of drug resistance in pancreatic cancer as well as their therapeutic potential as biomarkers and drug-delivery mechanisms for the management of pancreatic cancer.

Flagellin conjugated Per a 10 and its T cell peptides attenuate airway inflammation and restore cellular function.

Adjuvants were used to modulate response towards relevant immune cells. The present study aims to investigate FlaA-conjugated Per a 10 and T cell peptides in amelioration of allergic airway disease in mice. Mice given Per a 10 showed allergic features with higher cellular infiltration, IgE, Th-2 cytokines and alarmins. Fusion protein treatment reduced lung inflammation (p < 0.0001) and cellular infiltrates (p < 0.001) with higher IgG2a/IgE indicating resolution of disease. Immunotherapy with FPT1 and FPT3 reduces IL-4, IL-5 and IL-13 levels (p < 0.0001) with a fourfold increase in IFN-γ secretion in BALF. FPT1- and FPT3-treated mice have increased IL-10 and TGF-ß levels (p < 0.001) with CD4+Foxp3+ T cells (p < 0.01) indicating Treg response. There was enhanced expression of claudin-1 (1.7-fold) and occludin (fourfold) in lungs of FPT1- and FPT3-treated mice with reduced TSLP (p < 0.01) and IL-33 (p < 0.0001) secretion in BALF indicating recovery of epithelial function. Peptide-conjugated FlaA proteins showed protective immunity in mice and have potential for immunotherapy with restoration of cellular function.

Molecular insights to in vitro biocompatibility of endodontic Pulpotec with macrophages determined by oxidative stress and apoptosis.

Pulp therapy has been emerged as a one of the efficient therapies in the field of endodontics. Among different types of new endodontic materials, pulpotec has been materialized as a recognized material for vital pulp therapy. However, its efficacy has been challenged due to lack of information about its cellular biocompatibility. This study evaluates the mechanistic biocompatibility of pulpotec cement with macrophage cells (RAW 264.7) at cellular and molecular level. The biocompatibility was evaluated using experimental and computational techniques like MTT assay, oxidative stress analysis and apoptosis analysis through flow cytometry and fluorescent microscopy. The results showed concentration-dependent cytotoxicity of pulpotec cement extract to RAW 264.7 cells with an LC 50 of X/10-X/20. The computational analysis depicted the molecular interaction of pulpotec cement extract components with metabolic proteins like Sod1 and p53. The study revealed the effects of Pulpotec cement's extract, showing a concentration-dependent induction of oxidative stress and apoptosis. These effects were due to influential structural and functional abnormalities in the Sod1 and p53 proteins, caused by their molecular interaction with internalized components of Pulpotec cement. The study provided a detailed view on the utility of Pulpotec in endodontic applications, highlighting its biomedical aspects.

Structure-based virtual screening methods for the identification of novel phytochemical inhibitors targeting furin protease for the management of COVID-19.

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, is a highly contagious respiratory disease with widespread societal impact. The symptoms range from cough, fever, and pneumonia to complications affecting various organs, including the heart, kidneys, and nervous system. Despite various ongoing efforts, no effective drug has been developed to stop the spread of the virus. Although various types of medications used to treat bacterial and viral diseases have previously been employed to treat COVID-19 patients, their side effects have also been observed. The way SARS-CoV-2 infects the human body is very specific, as its spike protein plays an important role. The S subunit of virus spike protein cleaved by human proteases, such as furin protein, is an initial and important step for its internalization into a human host. Keeping this context, we attempted to inhibit the furin using phytochemicals that could produce minimal side effects. For this, we screened 408 natural phytochemicals from various plants having antiviral properties, against furin protein, and molecular docking and dynamics simulations were performed. Based on the binding score, the top three compounds (robustaflavone, withanolide, and amentoflavone) were selected for further validation. MM/GBSA energy calculations revealed that withanolide has the lowest binding energy of -57.2 kcal/mol followed by robustaflavone and amentoflavone with a binding energy of -45.2 kcal/mol and -39.68 kcal/mol, respectively. Additionally, ADME analysis showed drug-like properties for these three lead compounds. Hence, these natural compounds robustaflavone, withanolide, and amentoflavone, may have therapeutic potential for the management of SARS-CoV-2 by targeting furin.

Investigating the Potential Therapeutic Mechanisms of Puerarin in Neurological Diseases.

Plants and their derived phytochemicals have a long history of treating a wide range of illnesses for several decades. They are believed to be the origin of a diverse array of medicinal compounds. One of the compounds found in kudzu root is puerarin, a isoflavone glycoside commonly used as an alternative medicine to treat various diseases. From a biological perspective, puerarin can be described as a white needle crystal with the chemical name of 7-hydroxy-3-(4-hydroxyphenyl)-1-benzopyran-4-one-8-D-glucopyranoside. Besides, puerarin is sparingly soluble in water and produces no color or light yellow solution. Multiple experimental and clinical studies have confirmed the significant therapeutic effects of puerarin. These effects span a wide range of pharmacological effects, including neuroprotection, hepatoprotection, cardioprotection, immunomodulation, anticancer properties, anti-diabetic properties, anti-osteoporosis properties, and more. Puerarin achieves these effects by interacting with various cellular and molecular pathways, such as MAPK, AMPK, NF-κB, mTOR, ß-catenin, and PKB/Akt, as well as different receptors, enzymes, and growth factors. The current review highlights the molecular mechanism of puerarin as a neuroprotective agent in the treatment of various neurodegenerative and neurological diseases. Extensive cellular, animal, and clinical research has provided valuable insights into its effectiveness in conditions such as Alzheimer's disease, Parkinson's disease, epilepsy, cerebral stroke, depression, and more.

A rare case of isoniazid mono-resistant tuberculosis presenting as cardiac tamponade along with an anterior mediastinal mass in a 15-year-old immunocompetent patient.

ABSTRACT: A 15-year-old boy presented with a sudden onset of breathlessness for 7 days, gradual loss of weight of 17.6 lbs over the last month and progressive hoarseness of voice for 7 months. The contrast-enhanced computed tomography (CECT) scan revealed a heterogeneously enhancing lesion in the anterior mediastinum with multiple discrete lymph nodes in the cervical and mediastinal locations. The GeneXpert MTB/RIF assay performed on the CT-guided biopsy of the mass was negative, but the culture for Mycobacterium tuberculosis was positive at 7 weeks of incubation. There was a suboptimal radiological response after 6 months of treatment. First-line drug susceptibility testing (DST) performed by line probe assay (LPA) on the positive culture detected high-level resistance to isoniazid. The treatment was modified as per DST results to which the patient responded well.

Perilous paradigm of graphene oxide and its derivatives in biomedical applications: Insight to immunocompatibility.

With advancements in nanotechnology and innovative materials, Graphene Oxide nanoparticles (GONP) have attracted lots of attention among the diverse types of nanomaterials owing to their distinctive physicochemical characteristics. However, the usage at scientific and industrial level has also raised concern to their toxicological interaction with biological system. Understanding these interactions is crucial for developing guidelines and recommendations for applications of GONP in various sectors, like biomedicine and environmental technologies. This review offers crucial insights and an in-depth analysis to the biological processes associated with GONP immunotoxicity with multiple cell lines including human whole blood cultures, dendritic cells, macrophages, and multiple cancer cell lines. The complicated interactions between graphene oxide nanoparticles and the immune system, are highlighted in this work, which reveals a range of immunotoxic consequences like inflammation, immunosuppression, immunostimulation, hypersensitivity, autoimmunity, and cellular malfunction. Moreover, the immunotoxic effects are also highlighted with respect to in vivo models like mice and zebrafish, insighting GO Nanoparticles' cytotoxicity. The study provides invaluable review for researchers, policymakers, and industrialist to understand and exploit the beneficial applications of GONP with a controlled measure to human health and the environment.

Design, Synthesis, DFT, docking Studies, and antimicrobial evaluation of novel benzimidazole containing sulphonamide derivatives.

In silico approaches have been employed to design a new series of benzimidazole-containing sulphonamide derivatives and qualified compounds have been synthesized to analyze their potential as antimicrobial agents. Antibacterial screening of all synthesized compounds was done using the broth microdilution method against several human pathogenic bacteria, viz. Gram-positive bacteria [B. cerus (NCIN-2156), B. subtilis (ATCC-6051), S. aureus (NCIM-2079)] and Gram-negative bacteria [P. aeruginosa (NCIM-2036), E. coli (NCIM-2065), and a drug-resistant strain of E. coli (U-621)], and the compounds presented admirable MIC values, ranging between 100-1.56 µg/mL. The combinatorial analysis showed the magnificent inhibitory efficiency of the tested compounds, acquired equipotent to ten-fold more potency compared to original MIC values. An immense synergistic effect was exhibited by the compounds during combination studies with reference drugs chloramphenicol and sulfamethoxazole was presented as fractional inhibitory concentration (∑FIC). Enzyme inhibition studies of all synthesized compounds were done by using peptidyl transferase and dihydropteroate synthase enzymes isolated from E. coli and S. aureus and each of the compound presented the admirable IC50 values, where the lead compound 3 bound to peptidyl transferase (of S. aureus with IC50 363.51 ± 2.54 µM and E. coli IC50 1.04 ± 0.08 µM) & dihydropteroate synthase (of S. aureus IC50 3.51 ± 0.82 µM and E. coli IC50 2.77 ± 0.65 µM), might account for the antimicrobial effect, exhibited excellent inhibition potential. Antifungal screening was also performed employing food poisoning methods against several pathogenic fungal species, viz A. flavus, F. oxysporum, A. niger, and A. brassicae. The obtained result indicated that few compounds can prove to be a potent drug regimen against dreaded MDR strains of microbes. Structural activity relationship (SAR) analysis and docking studies reveal that the presence of electron-withdrawing, polar, and more lipophilic substituents positively favor the antibacterial activity, whereas, electron-withdrawing, more polar, and hydrophilic substituents favor the antifungal activities. A robust coherence has been found in in-silico and in-vitro biological screening results of the compounds.

Dietary anti-inflammatory and anti-bacterial medicinal plants and its compounds in bovine mastitis associated impact on human life.

Bovine mastitis (BM) is the most common bacterial mediated inflammatory disease in the dairy cattle that causes huge economic loss to the dairy industry due to decreased milk quality and quantity. Milk is the essential food in the human diet, and rich in crucial nutrients that helps in lowering the risk of diseases like hypertension, cardiovascular diseases and type 2 diabetes. The main causative agents of the disease include various gram negative, and positive bacteria, along with other risk factors such as udder shape, age, genetic, and environmental factors also contributes much for the disease. Currently, antibiotics, immunotherapy, probiotics, dry cow, and lactation therapy are commonly recommended for BM. However, these treatments can only decrease the rise of new cases but can't eliminate the causative agents, and they also exhibit several limitations. Hence, there is an urgent need of a potential source that can generate a typical and ideal treatment to overcome the limitations and eliminate the pathogens. Among the various sources, medicinal plants and its derived products always play a significant role in drug discovery against several diseases. In addition, they are also known for its low toxicity and minimum resistance features. Therefore, plants and its compounds that possess anti-inflammatory and anti-bacterial properties can serve better in bovine mastitis. In addition, the plants that are serving as a food source and possessing pharmacological properties can act even better in bovine mastitis. Hence, in this evidence-based study, we particularly review the dietary medicinal plants and derived products that are proven for anti-inflammatory and anti-bacterial effects. Moreover, the role of each dietary plant and its compounds along with possible role in the management of bovine mastitis are delineated. In this way, this article serves as a standalone source for the researchers working in this area to help in the management of BM.

Repurposing of SARS-CoV-2 compounds against Marburg Virus using MD simulation, mm/GBSA, PCA analysis, and free energy landscape.

The significant mortality rate associated with Marburg virus infection made it the greatest hazard among infectious diseases. Drug repurposing using in silico methods has been crucial in identifying potential compounds that could prevent viral replication by targeting the virus's primary proteins. This study aimed at repurposing the drugs of SARS-CoV-2 for identifying potential candidates against the matrix protein VP40 of the Marburg virus. Virtual screening was performed where the control compound, Nilotinib, showed a binding score of -9.99 kcal/mol. Based on binding scores, hit compounds 9549298, 11960895, 44545852, 51039094, and 89670174 were selected that had a lower binding score than the control. Subsequent molecular dynamics (MD) simulation revealed that compound 9549298 consistently formed a hydrogen bond with the residue Gln290. This was observed both in molecular docking and MD simulation poses, indicating a strong and significant interaction with the protein. 11960895 had the most stable and consistent RMSD pattern exhibited in 100 ns simulation, while 9549298 had the most identical RMSD plot compared to the control molecule. MM/PBSA analysis showed that the binding free energy (ΔG) of 9549298 and 11960895 was lower than the control, with -30.84 and -38.86 kcal/mol, respectively. It was observed by the PCA (principal component analysis) and FEL (free energy landscape) analysis that compounds 9549298 and 11960895 had lesser conformational variation. Overall, this study proposed 9549298 and 11960895 as potential binders of VP40 MARV that can cause its inhibition, however it inherently lacks experimental validation. Furthermore, the study proposes in-vitro experiments as the next step to validate these computational findings, offering a practical approach to further explore these compounds' potential as antiviral agents.Communicated by Ramaswamy H. Sarma.

Human alveolar lining fluid from the elderly promotes Mycobacterium tuberculosis intracellular growth and translocation into the cytosol of alveolar epithelial cells.

The elderly population is highly susceptible to developing respiratory diseases, including tuberculosis, a devastating disease caused by the airborne pathogen Mycobacterium tuberculosis (M.tb) that kills one person every 18 seconds. Once M.tb reaches the alveolar space, it contacts alveolar lining fluid (ALF), which dictates host-cell interactions. We previously determined that age-associated dysfunction of soluble innate components in human ALF leads to accelerated M.tb growth within human alveolar macrophages. Here we determined the impact of human ALF on M.tb infection of alveolar epithelial type cells (ATs), another critical lung cellular determinant of infection. We observed that elderly ALF (E-ALF)-exposed M.tb had significantly increased intracellular growth with rapid replication in ATs compared to adult ALF (A-ALF)-exposed bacteria, as well as a dampened inflammatory response. A potential mechanism underlying this accelerated growth in ATs was our observation of increased bacterial translocation into the cytosol, a compartment that favors bacterial replication. These findings in the context of our previous studies highlight how the oxidative and dysfunctional status of the elderly lung mucosa determines susceptibility to M.tb infection, including dampening immune responses and favoring bacterial replication within alveolar resident cell populations, including ATs, the most abundant resident cell type within the alveoli.

Anticancer Drug Discovery Based on Natural Products: From Computational Approaches to Clinical Studies.

Globally, malignancies cause one out of six mortalities, which is a serious health problem. Cancer therapy has always been challenging, apart from major advances in immunotherapies, stem cell transplantation, targeted therapies, hormonal therapies, precision medicine, and palliative care, and traditional therapies such as surgery, radiation therapy, and chemotherapy. Natural products are integral to the development of innovative anticancer drugs in cancer research, offering the scientific community the possibility of exploring novel natural compounds against cancers. The role of natural products like Vincristine and Vinblastine has been thoroughly implicated in the management of leukemia and Hodgkin's disease. The computational method is the initial key approach in drug discovery, among various approaches. This review investigates the synergy between natural products and computational techniques, and highlights their significance in the drug discovery process. The transition from computational to experimental validation has been highlighted through in vitro and in vivo studies, with examples such as betulinic acid and withaferin A. The path toward therapeutic applications have been demonstrated through clinical studies of compounds such as silvestrol and artemisinin, from preclinical investigations to clinical trials. This article also addresses the challenges and limitations in the development of natural products as potential anti-cancer drugs. Moreover, the integration of deep learning and artificial intelligence with traditional computational drug discovery methods may be useful for enhancing the anticancer potential of natural products.

Role of percutaneous CT-guided biopsy in the characterisation of pleural diseases.

Background: Computed tomography (CT)-guided biopsy is emerging as a preferred and safe method for obtaining tissue samples in pleural diseases. Objective: This study aimed to evaluate the diagnostic yield and safety of percutaneous CT-guided biopsy in pleural diseases and to find CT findings predictive of malignant neoplastic pleural disease. Material and Methods: This retrospective study included 77 patients with pleural disease who underwent CT-guided pleural biopsies from July 2013 to May 2020. All procedures were performed with a coaxial semi-automatic biopsy device. Histopathology was performed in all cases, and additional tests such as immunohistochemistry (IHC) or microbiological analysis were carried out depending on clinical suspicion. The correlation of CT findings with final diagnosis was performed by Chi-square, Fisher's exact test and logistic regression analysis. Results: The overall technical success rate of CT-guided pleural biopsy was 100% with a diagnostic yield of 96.1%. No major complication was encountered, with minor complications encountered in the form of minimal pneumothorax and chest pain. Malignant pleural conditions constituted the largest group including metastatic adenocarcinoma as the most common (31.2%), followed by metastatic squamous cell carcinoma and mesothelioma. Tubercular pleural involvement was the second most common category (16.9%). The cartridge-based nucleic acid amplification test (CB-NAAT) assay had 90% sensitivity on pleural tissue in tubercular cases. CT features predictive of malignancy were irregular and nodular pleural thickening, mediastinal and diaphragmatic pleural involvement and mediastinal/chest wall invasion. There was a good correlation between higher pleural thicknesses with malignant outcome. Conclusion: Percutaneous CT-guided biopsy is a safe method for obtaining pleural tissue samples with high diagnostic yield. CT findings provide clues, which favour malignant pleural involvement.

Mechanopathology of biofilm-like Mycobacterium tuberculosis cords.

Mycobacterium tuberculosis (Mtb) cultured axenically without detergent forms biofilm-like cords, a clinical identifier of virulence. In lung-on-chip (LoC) and mouse models, cords in alveolar cells contribute to suppression of innate immune signaling via nuclear compression. Thereafter, extracellular cords cause contact-dependent phagocyte death but grow intercellularly between epithelial cells. The absence of these mechanopathological mechanisms explains the greater proportion of alveolar lesions with increased immune infiltration and dissemination defects in cording-deficient Mtb infections. Compression of Mtb lipid monolayers induces a phase transition that enables mechanical energy storage. Agent-based simulations demonstrate that the increased energy storage capacity is sufficient for the formation of cords that maintain structural integrity despite mechanical perturbation. Bacteria in cords remain translationally active despite antibiotic exposure and regrow rapidly upon cessation of treatment. This study provides a conceptual framework for the biophysics and function in tuberculosis infection and therapy of cord architectures independent of mechanisms ascribed to single bacteria.

A Study on the Attitude and Perception of Bachelor of Medicine and Bachelor of Surgery (MBBS) Students Regarding Post-MBBS Compulsory Service Bond in Uttar Pradesh, India.

Background To increase the availability of doctors in the public healthcare delivery system, the state government of Uttar Pradesh, India, has implemented a two-year compulsory service bond since 2018. Students of the 2018 batch are going to complete their Bachelor of Medicine, Bachelor of Surgery (MBBS) in 2023 and are supposed to serve through this bond. There are many dilemmas in the minds of medical students regarding their compulsory service bond. Hence, there is a need to know their attitude and perceptions regarding the compulsory service bond. This study was conducted to assess the attitude and perception of undergraduate medical students toward compulsory service bonds. Methods This was a mixed-method study conducted in July-September 2022 among undergraduate medical students at Baba Raghav Das Medical College, Gorakhpur, Uttar Pradesh, India. For quantitative data, a structured questionnaire was developed using Google Forms (Google LLC, Mountain View, California, United States) and circulated via WhatsApp (Meta Platforms, Inc., Menlo Park, California, United States) through the random sampling method. Focused group discussions were carried out to collect the qualitative data. Result Regarding the compulsory service bond after MBBS, 100 (31.8%) medical students were found to be interested and 56 (17.8%) were disinterested. The majority (n=158; 50.4%) of participants were neutral, while 278 (88.6%) medical students perceived it as an opportunity to help poor people. Higher possibilities of social recognition and respect were some noticeable perceptions of 243 (77.4%) MBBS students. Lack of confidence to tackle serious cases without a senior doctor's supervision was perceived as an important hurdle by 286 (91%) participants. Non-availability of advanced medical facilities, issues like the safety of doctors, and the lack of availability of electricity, roads, and infrastructure were also perceived as hurdles. Conclusions and recommendations Students perceived the compulsory service bond as an opportunity if met with certain conditions like a transparent method of posting and basic facilities or an incentive for accommodation and transportation. The compulsory service bond for addressing the shortfall of doctors in the public healthcare delivery system may be more effective if these hurdles are corrected and certain opportunities are met, as mentioned in the present study. This will help the government move smoothly towards achieving Universal Health Coverage (UHC).

Design, synthesis and antimicrobial activity of novel quinoline derivatives: an in silico and in vitro study.

A series of new quinoline derivatives has been designed, synthesized and evaluated as antibacterial and antifungal agents functioning as peptide deformylase enzyme (PDF) inhibitors and fungal cell wall disruptors on the basis of computational and experimental methods. The molecular docking and ADMET assessment aided in the synthesis of quinoline derivatives starting from 6-amino-4-methyl-1H-quinoline-2-one substituted with different types of sulfonyl/benzoyl/propargyl moieties. These newly synthesized compounds were evaluated for their in vitro antibacterial and antifungal activity. Antibacterial screening of all compounds showed excellent MIC value (MIC, 50 - 3.12 µg/mL) against bacterial strains, viz. Bacillus cerus, Staphylococcus, Pseudomonas and Escherichia coli. Compounds 2 and 6 showed better activity. Fractional inhibitory concentration (FIC) values of compounds were lowered by 1/2 to 1/128 of the original MIC values when a combinatorial screening with reference drugs was performed. Further, antifungal screening against fungal strains, viz. A. flavus, A. niger, F. oxysporum and C. albicans also showed that all compounds were potentially active and compound 6 being the most potent. Further, the cytotoxicity experiments revealed that compound 6 was the least toxic molecule. The molecular dynamics (MD) simulation investigations elucidated the conformational stability of compound 6-PDF complex with flexible binding pocket residues. The highest number of stable hydrogen bonds with the PDF residues during the entire simulation time illustrated strong binding affinity of compound 6 with PDF.Communicated by Ramaswamy H. Sarma.

The impact of RNA stability and degradation in different tissues to the determination of post-mortem interval: A systematic review.

Postmortem interval (PMI) in legal medicine is extremely important for both criminal and civil cases, and several sorts of techniques have been recommended. This systematic review solely focuses on approaches linked to RNA analysis, instead of including all proposed methods for determining the PMI. The term PMI will be used in this review to indicate the time between a person's death and the postmortem examination of the body. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines when conducting this systematic review. The majority of studies on various tissues at various time intervals at various temperatures are non-human, and just a small number are on humans. The results are then provided using various statistical approaches. To calculate the PMI, post-mortem RNA degradation was examined using several tissues. The result so obtained had an opposite polarity. While some studies show that RNA stability in various tissues remained constant for several days after death, the other group of studies showed evident RNA degradation over time post-mortem, which was significantly influenced by temperature and other agonal factors. These factors have an impact on the multi-parametric mathematical model of ante and post-mortem factors on RNA degradation, as well as its applicability and feasibility. The estimation of PMI using RNA degradation can prove to be highly objective and efficient after controlling for the various factors and challenges that pose the estimation of RNA in forensic samples difficult.

A survey and perspective on neuromorphic continual learning systems.

With the advent of low-power neuromorphic computing systems, new possibilities have emerged for deployment in various sectors, like healthcare and transport, that require intelligent autonomous applications. These applications require reliable low-power solutions for sequentially adapting to new relevant data without loss of learning. Neuromorphic systems are inherently inspired by biological neural networks that have the potential to offer an efficient solution toward the feat of continual learning. With increasing attention in this area, we present a first comprehensive review of state-of-the-art neuromorphic continual learning (NCL) paradigms. The significance of our study is multi-fold. We summarize the recent progress and propose a plausible roadmap for developing end-to-end NCL systems. We also attempt to identify the gap between research and the real-world deployment of NCL systems in multiple applications. We do so by assessing the recent contributions in neuromorphic continual learning at multiple levels-applications, algorithms, architectures, and hardware. We discuss the relevance of NCL systems and draw out application-specific requisites. We analyze the biological underpinnings that are used for acquiring high-level performance. At the hardware level, we assess the ability of the current neuromorphic platforms and emerging nano-device-based architectures to support these algorithms in the presence of several constraints. Further, we propose refinements to continual learning metrics for applying them to NCL systems. Finally, the review identifies gaps and possible solutions that are not yet focused upon for deploying application-specific NCL systems in real-life scenarios.

Comparison of SGLT1, SGLT2, and Dual Inhibitor biological activity in treating Type 2 Diabetes Mellitus.

Diabetes Mellitus Type 2 (T2D) is an emerging health burden in the USand worldwide, impacting approximately 15% of Americans. Current front-line therapeutics for T2D patients include sulfonylureas that act to reduce A1C and/or fasting blood glucose levels, or Metformin that antagonizes the action of glucagon to reduce hepatic glucose production. Next generation glucomodulatory therapeutics target members of the high-affinity glucose transporter Sodium-Glucose-Linked-Transporter (SGLT) family. SGLT1 is primarily expressed in intestinal epithelium, whose inhibition reduces dietary glucose uptake, whilst SGLT2 is highly expressed in kidney - regulating glucose reabsorption. A number of SGLT2 inhibitors are FDA approved whilst SGLT1 and dual SGLT1 & 2 inhibitor are currently in clinical trials. Here, we discuss and compare SGLT2, SGLT1, and dual inhibitors' biochemical mechanism and physiological effects.

Expression of human cardiac-specific genes: a novel method for post-mortem interval estimation.

In legal medicine, the determination of post-mortem interval (PMI) is not only an important but also one of the most difficult aspects. Several methods are used to estimate PMI such as physicochemical, entomological, biochemical, metabolic, autolytic, and physical methods. These methods provide a wide range of PMI as they are affected by different factors. The approach behind the present study is to calculate an accurate PMI by using mRNA degradation and fold change expression (FCE) of cardiac-specific genes viz. N-terminal pro-B-type natriuretic peptide (NPPB) and cardiac troponin I (TNNI3). Seventeen cadaver heart tissues were analysed within a time frame of up to 12 hours from the time since death, at different time intervals at room temperature. Gene expression was determined and the data were analysed using the value of average delta Ct (ΔCt) value of the assessed gene and housekeeping gene. Delta delta Ct (ΔΔCt) method was used to calculate the FCE at the different 7-time groups. The FCE of TNNI3 was almost stable till 15 hours of PMI and then after 15 hours, expression shows a decrease up to 24 hours after death; whereas, NPPB shows that FCE was stable till 12 hours of PMI and then after 12 hours, expression shows a decrease up to 24 hours after death. The FCE of NPPB and TNNI3 was almost stable till 12 hours. Thus, the estimation of PMI by analysis of the FCE of cardiac-specific genes can be a new promising method in forensic medicine.