Post-Translational Modifications and Diabetes.

Diabetes and its associated complications have increasingly become major challenges for global healthcare. The current therapeutic strategies involve insulin replacement therapy for type 1 diabetes (T1D) and small-molecule drugs for type 2 diabetes (T2D). Despite these advances, the complex nature of diabetes necessitates innovative clinical interventions for effective treatment and complication prevention. Accumulative evidence suggests that protein post-translational modifications (PTMs), including glycosylation, phosphorylation, acetylation, and SUMOylation, play important roles in diabetes and its pathological consequences. Therefore, the investigation of these PTMs not only sheds important light on the mechanistic regulation of diabetes but also opens new avenues for targeted therapies. Here, we offer a comprehensive overview of the role of several PTMs in diabetes, focusing on the most recent advances in understanding their functions and regulatory mechanisms. Additionally, we summarize the pharmacological interventions targeting PTMs that have advanced into clinical trials for the treatment of diabetes. Current challenges and future perspectives are also provided.

Fabricating orientated nanofibrous meshes with a bespoke ultra-cost-effective electrospinning machine.

Electrospinning's production method has been streamlined and perfected because to advancements in technology and increased demand. While working with electrospun fibers, it is crucial to ensure that they are collected in the correct orientation. Electrospun fibers can be either aligned or random. In contrast to randomly oriented fibers, all aligned ones will point in the same direction. Our results show that a low-cost, tailored electrospinning device can achieve equivalent performance to that of a commercially available system. High voltage (up to 36 kV) and nanofiber orientation adjustments are now being made to the proposed device. A high-voltage direct-current electrical power supply that is custom-built per order and wired by hand. Two specialized collectors, one portable and manufactured from conductive material for random nanofibers, and the other an inexpensive rotational drum collector for aligned nanofibers, have been developed to allow for precise orientation control. By applying Image J software to scanning electron micrographs, we were able to determine the average diameter and orientation of the fibers produced by the electrospinning apparatus, demonstrating its potential to produce nanoscale directed fibers. Because of this research, it's possible that schools will be able to afford an electrospinning system at a price far lower than the current market price.

Activation of SIRT6 Deacetylation by DNA Strand Breaks.

SIRT6 is an emerging regulator of longevity. Overexpression of SIRT6 extends the lifespan of mice. Conversely, SIRT6 knockout mice demonstrate severe metabolic defects and a shortened lifespan. The discrepancy between SIRT6's weak in vitro activity and robust in vivo activity has led to the hypothesis that this enzyme can be activated in response to DNA damage in cells. Here, we demonstrate that the deacetylase activity of SIRT6 can be stimulated by DNA strand breaks for synthetic peptide and histone substrates. The mechanism of activation is further explored by using an integrative chemical biology approach. SIRT6 can be preferentially activated by DNA lesions harboring a 5'-phosphate. The N- and C-termini of SIRT6 are strictly required for DNA break-induced activation. Additionally, the defatty-acylase activity of SIRT6 is also sensitive to DNA breaks, although the physiological significance needs further investigation. Collectively, our study sheds important light on the cellular regulation of diverse SIRT6 activities and suggests possible strategies for effective SIRT6 activation.

IoT Solutions and AI-Based Frameworks for Masked-Face and Face Recognition to Fight the COVID-19 Pandemic.

A global health emergency resulted from the COVID-19 epidemic. Image recognition techniques are a useful tool for limiting the spread of the pandemic; indeed, the World Health Organization (WHO) recommends the use of face masks in public places as a form of protection against contagion. Hence, innovative systems and algorithms were deployed to rapidly screen a large number of people with faces covered by masks. In this article, we analyze the current state of research and future directions in algorithms and systems for masked-face recognition. First, the paper discusses the importance and applications of facial and face mask recognition, introducing the main approaches. Afterward, we review the recent facial recognition frameworks and systems based on Convolution Neural Networks, deep learning, machine learning, and MobilNet techniques. In detail, we analyze and critically discuss recent scientific works and systems which employ machine learning (ML) and deep learning tools for promptly recognizing masked faces. Also, Internet of Things (IoT)-based sensors, implementing ML and DL algorithms, were described to keep track of the number of persons donning face masks and notify the proper authorities. Afterward, the main challenges and open issues that should be solved in future studies and systems are discussed. Finally, comparative analysis and discussion are reported, providing useful insights for outlining the next generation of face recognition systems.

Social Media Devices' Influence on User Neck Pain during the COVID-19 Pandemic: Collaborating Vertebral-GLCM Extracted Features with a Decision Tree.

The prevalence of neck pain, a chronic musculoskeletal disease, has significantly increased due to the uncontrollable use of social media (SM) devices. The use of SM devices by younger generations increased enormously during the COVID-19 pandemic, being-in some cases-the only possibility for maintaining interpersonal, social, and friendship relationships. This study aimed to predict the occurrence of neck pain and its correlation with the intensive use of SM devices. It is based on nine quantitative parameters extracted from the retrospective X-ray images. The three parameters related to angle_1 (i.e., the angle between the global horizontal and the vector pointing from C7 vertebra to the occipito-cervical joint), angle_2 (i.e., the angle between the global horizontal and the vector pointing from C1 vertebra to the occipito-cervical joint), and the area between them were measured from the shape of the neck vertebrae, while the rest of the parameters were extracted from the images using the gray-level co-occurrence matrix (GLCM). In addition, the users' ages and the duration of the SM usage (H.mean) were also considered. The decision tree (DT) machine-learning algorithm was employed to predict the abnormal cases (painful subjects) against the normal ones (no pain). The results showed that angle_1, area, and the image contrast significantly increased statistically with the time of SM-device usage, precisely in the range of 2 to 9 h. The DT showed a promising result demonstrated by classification accuracy and F1-scores of 94% and 0.95, respectively. Our findings confirmed that the objectively detected parameters, which elucidate the negative impacts of SM-device usage on neck pain, can be predicted by DT machine learning.

Developments and Clinical Applications of Noninvasive Optical Technologies for Skin Cancer Diagnosis.

Skin cancer has shown a sharp increase in prevalence over the past few decades and currently accounts for one-third of all cancers diagnosed. The most lethal form of skin cancer is melanoma, which develops in 4% of individuals. The rising prevalence and increased number of fatalities of skin cancer put a significant burden on healthcare resources and the economy. However, early detection and treatment greatly improve survival rates for patients with skin cancer. Since the rising rates of both the incidence and mortality have been particularly noticeable with melanoma, significant resources have been allocated to research aimed at earlier diagnosis and a deeper knowledge of the disease. Dermoscopy, reflectance confocal microscopy, optical coherence tomography, multiphoton-excited fluorescence imaging, and dermatofluorescence are only a few of the optical modalities reviewed here that have been employed to enhance noninvasive diagnosis of skin cancer in recent years. This review article discusses the methodology behind newly emerging noninvasive optical diagnostic technologies, their clinical applications, and advantages and disadvantages of these techniques, as well as the potential for their further advancement in the future.

Biomechanical Sensing Systems for Cardiac Activity Monitoring.

Cardiovascular disease is consistently ranked high among the causes of death on a global scale. Monitoring of cardiovascular signs throughout the course of a long period of time and in real time is necessary in order to discover anomalies and begin early intervention at the appropriate time. To this purpose, a significant amount of interest among researchers has been directed toward the creation of flexible sensors that may be worn or implanted and are capable of constant, immediate observation of a variety of main physiological indicators. The real-time readings of the heart and arteries' pressure fluctuations can be reflected directly by mechanical sensors, which are one of the many types of sensors. Potential benefits of mechanical sensors include excellent accuracy and considerable versatility. Capacitive, piezoresistive, piezoelectric, and triboelectric principles are the foundations of the four types of mechanical sensors that are discussed in this article as recent developments for the purpose of monitoring the cardiovascular system. The biomechanical systems that are present in the cardiovascular system are then detailed, along with their monitoring, and this includes blood and endocardial pressure, pulse wave, and heart rhythm. In conclusion, we examine the usefulness of the use of continuous health monitoring for the treatment of vascular disease and highlight the difficulties associated with its translation into clinical practice.

Emerging Development of Auto-Charging Sensors for Respiration Monitoring.

In recent years, the development of biomedical monitoring systems, including respiration monitoring systems, has been accelerated. Wearable and implantable medical devices are becoming increasingly important in the diagnosis and management of disease and illness. Respiration can be monitored using a variety of biosensors and systems. Auto-charged sensors have a number of advantages, including low cost, ease of preparation, design flexibility, and a wide range of applications. It is possible to use the auto-charged sensors to directly convert mechanical energy from the airflow into electricity. The ability to monitor and diagnose one's own health is a major goal of auto-charged sensors and systems. Respiratory disease model output signals have not been thoroughly investigated and clearly understood. As a result, figuring out their exact interrelationship is a difficult and important research question. This review summarized recent developments in auto-charged respiratory sensors and systems in terms of their device principle, output property, detecting index, and so on. Researchers with an interest in auto-charged sensors can use the information presented here to better understand the difficulties and opportunities that lie ahead.

Validation of earlobe site as an alternative blood glucose testing approach.

BACKGROUND: Drawing blood from the fingertips for glucose testing is painful and likely to cause tissue damage over time. Earlobes are an alternative site for glucose measurement. OBJECTIVE: This work aims to validate the earlobe as an alternate test site for blood glucose testing by demonstrating valid and reliable statistically significant differences between the earlobes and standard reference sites. METHODS: Blood glucose concentrations from 50 volunteers were measured and statistically analysed from the reference sites (forearm and fingertip) and earlobe. The analysis included: 1) one-way analysis of variance (ANOVA), 2) regression analysis, 3) Bland Altman analysis, and 4) Clarke Error Grid analysis. RESULTS: The results indicated that there is no statistically significant difference between the three blood glucose-testing methods. For the forearm-earlobe and fingertip-earlobe, all measurements were grouped around the mean of 3.7 ± 1.96 SD and 2.96± 1.96 SD, respectively. Error grid analysis showed > 97% of all earlobe and references measurements fell in Zones A and B and were in the clinically acceptable level. CONCLUSIONS: The results have shown that the earlobe is a valid substitute for blood glucose measurements.

Recent Applications of Electrospun Nanofibrous Scaffold in Tissue Engineering.

Tissue engineering is a relatively new area of research that combines medical, biological, and engineering fundamentals to create tissue-engineered constructs that regenerate, preserve, or slightly increase the functions of tissues. To create mature tissue, the extracellular matrix should be imitated by engineered structures, allow for oxygen and nutrient transmission, and release toxins during tissue repair. Numerous recent studies have been devoted to developing three-dimensional nanostructures for tissue engineering. One of the most effective of these methods is electrospinning. Numerous nanofibrous scaffolds have been constructed over the last few decades for tissue repair and restoration. The current review gives an overview of attempts to construct nanofibrous meshes as tissue-engineered scaffolds for various tissues such as bone, cartilage, cardiovascular, and skin tissues. Also, the current article addresses the recent improvements and difficulties in tissue regeneration using electrospinning.

Mutation in the CX3C Motif of G Protein Disrupts Its Interaction with Heparan Sulfate: A Calorimetric, Spectroscopic, and Molecular Docking Study.

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in children and infants. To date, there is no effective vaccine available against RSV. Heparan sulfate is a type of glycosaminoglycan that aids in the attachment of the RSV to the host cell membrane via the G protein. In the present study, the effect of amino acid substitution on the structure and stability of the ectodomain G protein was studied. Further, it was investigated whether mutation (K117A) in the CX3C motif of G protein alters the binding with heparan sulfate. The point mutation significantly affects the conformational stability of the G protein. The mutant protein showed a low binding affinity with heparan sulfate as compared to the wild-type G protein, as determined by fluorescence quenching, isothermal titration calorimetry (ITC), and molecular docking studies. The low binding affinity and decreased stability suggested that this mutation may play an important role in prevention of attachment of virion to the host cell receptors. Collectively, this investigation suggests that mutation in the CX3C motif of G protein may likely improve the efficacy and safety of the RSV vaccine.

Structural Characterization of Ectodomain G Protein of Respiratory Syncytial Virus and Its Interaction with Heparan Sulfate: Multi-Spectroscopic and In Silico Studies Elucidating Host-Pathogen Interactions.

The global burden of disease caused by a respiratory syncytial virus (RSV) is becoming more widely recognized in young children and adults. Heparan sulfate helps in attaching the virion through G protein with the host cell membrane. In this study, we examined the structural changes of ectodomain G protein (edG) in a wide pH range. The absorbance results revealed that protein maintains its tertiary structure at physiological and highly acidic and alkaline pH. However, visible aggregation of protein was observed in mild acidic pH. The intrinsic fluorescence study shows no significant change in the λmax except at pH 12.0. The ANS fluorescence of edG at pH 2.0 and 3.0 forms an acid-induced molten globule-like state. The denaturation transition curve monitored by fluorescence spectroscopy revealed that urea and GdmCl induced denaturation native (N) ↔ denatured (D) state follows a two-state process. The fluorescence quenching, molecular docking, and 50 ns simulation measurements suggested that heparan sulfate showed excellent binding affinity to edG. Our binding study provides a preliminary insight into the interaction of edG to the host cell membrane via heparan sulfate. This binding can be inhibited using experimental approaches at the molecular level leading to the prevention of effective host-pathogen interaction.

Autocharging Techniques for Implantable Medical Applications.

Implantable devices have successfully proven their reliability and efficiency in the medical field due to their immense support in a variety of aspects concerning the monitoring of patients and treatment in many ways. Moreover, they assist the medical field in disease diagnosis and prevention. However, the devices' power sources rely on batteries, and with this reliance, comes certain complications. For example, their depletion may lead to surgical interference or leakage into the human body. Implicit studies have found ways to reduce the battery size or in some cases to eliminate its use entirely; these studies suggest the use of biocompatible harvesters that can support the device consumption by generating power. Harvesting mechanisms can be executed using a variety of biocompatible materials, namely, piezoelectric and triboelectric nanogenerators, biofuel cells, and environmental sources. As with all methods for implementing biocompatible harvesters, some of them are low in terms of power consumption and some are dependent on the device and the place of implantation. In this review, we discuss the application of harvesters into implantable devices and evaluate the different materials and methods and examine how new and improved circuits will help in assisting the generators to sustain the function of medical devices.

Structural exploration of Y-domain reveals its essentiality in HEV pathogenesis.

Hepatitis E virus (HEV) is a major causative agent of hepatitis E infections across the globe. Although the essentiality of HEV nonstructural polyprotein (pORF1) putative Y-domain (Yd) has been established in viral pathogenesis, its structural-functional role remains elusive. The current research discusses the novel exploration on Yd protein expression, purification, biophysical characterization and structure-based docking analysis. The codon optimized synthetic gene and optimized expression parameters i.e., 5 h induction with 0.25 mM IPTG at 37 °C, resulted in efficient production of Yd protein (~40 kDa) in E. coli BL21(DE3) cells. Majority of the recombinant Yd (rYd) protein expressed as inclusion bodies was solubilized in 0.5% N-lauroylsarcosine and purified using Ni-NTA chromatography. Circular dichroism (CD) and UV visible absorption spectroscopic studies on Yd revealed both secondary and tertiary structure stability in alkaline range (pH 8.0-10.0), suggesting correlation with its physiological activity. Thus, loss in structure at low pH perhaps play crucial role in cytoplasmic-membrane interaction. The biophysical data were in good agreement with insilico structural analyses, which suggested mixed α/ß fold, non-random and basic nature of Yd protein. Furthermore, due to Yd protein essentiality in HEV replication and pathogenesis, it was considered as a template for docking and drug-likeness analyses. The 3D modeling of Yd protein and structure-based screening and drug-likeness of inhibitory compounds, including established antiviral drugs led to the identification of top nine promising candidates. Nonetheless, in vitro studies on the predicted interaction of Yd with intracellular-membrane towards establishing replication-complexes as well as validations of the proposed therapeutic agents are warranted.

Structural Characterization and Binding Studies of the Ectodomain G Protein of Respiratory Syncytial Virus Reveal the Crucial Role of pH with Possible Implications in Host-Pathogen Interactions.

Respiratory syncytial virus (RSV) is a leading viral pathogen causing acute lower respiratory tract infection in children. The G protein of RSV is involved in attachment with the host cell. It is a neutralizing antigen and thus a vaccine candidate. Heparan sulfate is a type of glycosaminoglycan (GAG) present on the host cell membrane that is involved in attachment with the G protein of RSV. We describe a novel approach for efficient expression and purification of the ectodomain G protein in the prokaryotic system and its biophysical characterization. The native ectodomain G protein was purified using a two-step process by Ni-NTA and DEAE weak anion-exchange chromatography through the supernatant obtained after cell lysis. In addition, the denatured form of the protein was also purified from the solubilized inclusion bodies (IBs) by Ni-NTA affinity chromatography with a higher yield. Dynamic light scattering (DLS) was performed to confirm the homogeneity of the purified protein. The effect of pH on the stability and structure of the purified protein was studied by circular dichroism (CD), fluorescence, and absorbance spectroscopy techniques. Isothermal titration calorimetry (ITC) and microscale thermophoresis (MST) were exploited to demonstrate the interaction of heparan sulfate with the ectodomain G protein. The dynamic light scattering results showed that the purified protein was homogenic and had a well-folded native conformation. Biophysical characterization of the protein revealed that it was stable and had intact secondary and tertiary structures at pH 7.5. CD analysis revealed that the protein showed a loss in the secondary structure at pH values 5.5 and 3.5, while absorbance spectroscopy suggested a stable tertiary structure at pH values 7.5 and 5.5 with a probable aggregation pattern at pH 3.5. This loss in the structure of the ectodomain G protein at low pH can be correlated with its physiological activity. A slight change in pH might play a crucial role in host-pathogen interactions. The fluorescence intensity of the protein decreased on moving toward a lower pH with no spectral shift in emission maxima. In addition, isothermal titration calorimetry and microscale thermophoresis results showed strong binding affinity of the ectodomain G protein with heparan sulfate. The binding of heparan sulfate with protein was probably due to the electrostatic interaction of positively charged amino acid residues of the heparin-binding domain of the protein and the negatively charged group of GAGs. Future studies may involve the development of possible therapeutic agents interacting with the G protein and affecting the overall charge and pH that might hinder the host-pathogen interaction.