Genomic inbreeding analysis reveals resilience and genetic diversity in Indian yak populations.

The yak (Bos grunniens), renowned for its adaptability to extreme cold and hypoxic conditions, stands as a remarkable domestic animal crucial for sustaining livelihoods in harsh climates. We conducted a comprehensive analysis of the whole genome sequence data from three distinct Indian yak populations: Arunachali yak (n = 10), Himachali yak (n = 10), and Ladakhi yak (n = 10). The genomic data for Indian yaks were meticulously generated by our laboratory and compared with their Chinese counterpart, the Jinchuan yak (n = 8), for a more nuanced understanding. Our investigation revealed a total of 37,437 runs of homozygosity (ROH) segments in 34 animals representing four distinct yak populations. The Jinchuan yak population exhibited the highest proportion, constituting 80.8 % of total ROHs, predominantly as small segments (<0.1 Mb), accounting for 63 % of the overall ROHs. Further analysis uncovered a significantly higher degree of inbreeding in Chinese yaks compared to their Indian counterparts. The Indian yak populations, in contrast, demonstrated relatively lower and consistent levels of inbreeding. Moreover, we identified ROH hotspots that covered at least 60 % of individuals in our study, indicating their pivotal role in environmental adaptation. A total of five hotspot regions were detected, housing genes such as ENSBGRG00000015023 (WNT2), YIPF4, SPAST, TLN2, and DSG4. These genes are associated with traits including hair follicle initiation, nutrient stress response, microtubule assembly, development of cardiac muscle, hair follicle, and coat color. This observation strongly suggests that there is substantial selection acting on these genes, emphasizing their important role in environmental adaptation among yak populations.

Enhancement of Curcumin's Anti-Psoriatic Efficacy via Formulation into Tea Tree Oil-Based Emulgel.

Psoriasis is a chronic inflammatory skin disease characterized by the hyperproliferation and aberrant differentiation of epidermal keratinocytes. It is a debilitating condition that can cause significant physical and emotional distress. Natural anti-psoriatic agents have been investigated as alternatives to conventional allopathic medications, as they have notable limitations and drawbacks. Curcumin and tea tree oil are cost-efficient and effective anti-inflammatory medicines with less adverse effects compared to synthetic psoriasis medications. Our research endeavors to harness the therapeutic potential of these natural compounds by developing an herbal anti-psoriatic topical drug delivery system. This novel method uses curcumin and tea tree oil to create a bi-phasic emulgel drug delivery system. Formulations F1 (gel) and F2 (emulgel) have high drug content percentages of 84.2% and 96.7%, respectively. The emulgel showed better spreadability for cutaneous applications, with a viscosity of 92,200 ± 943 cp compared to the gel's 56,200 ± 1725 cp. The emulgel released 94.48% of the drugs, compared to 87.58% for the gel. These formulations conform to the zero-order and Higuchi models, and their stability over a three-month period is crucial. In vivo, the emulgel healed psoriasis symptoms faster than the usual gel. The gathered results confirmed the emulgel's potential as a drug delivery method, emphasizing the complementary benefits of tea tree oil and curcumin as an effective new therapy for psoriasis.

Study of Biochemical Parameters as Predictors for Need of Invasive Ventilation in Severely Ill COVID-19 Patients.

Background: Though laboratory tests have been shown to predict mortality in COVID-19, there is still a dearth of information regarding the role of biochemical parameters in predicting the type of ventilatory support that these patients may require. Methods: The purpose of our retrospective observational study was to investigate the relationship between biochemical parameters and the type of ventilatory support needed for the intensive care of severely ill COVID-19 patients. We comprehensively recorded history, physical examination, vital signs from point-of-care testing (POCT) devices, clinical diagnosis, details of the ventilatory support required in intensive care and the results of the biochemical analysis at the time of admission. Appropriate statistical methods were used and P-values < 0.05 were considered significant. Receiver operating characteristics (ROC) analysis was performed and Area Under the Curve (AUC) of 0.6 to 0.7, 0.7 to 0.8, 0.8 to 0.9, and >0.9, respectively, were regarded as acceptable, fair, good, and exceptional for discrimination. Results: Statistically significant differences (p<0.05) in Urea (p = 0.0351), Sodium (p = 0.0142), Indirect Bilirubin (p = 0.0251), Albumin (p = 0.0272), Aspartate Transaminase (AST) (p = 0.0060) and Procalcitonin (PCT) (p = 0.0420) were observed between the patients who were maintained on non-invasive ventilations as compared to those who required invasive ventilation. In patients who required invasive ventilation, the levels of Urea, Sodium, Indirect bilirubin, AST and PCT were higher while Albumin was lower. On ROC analysis, higher levels of Albumin was found to be acceptable indicator of maintenance on non-invasive ventilation while higher levels of Sodium and PCT were found to be fair predictor of requirement of invasive ventilation. Conclusion: Our study emphasizes the role of biochemical parameters in predicting the type of ventilatory support that is needed in order to properly manage severely ill COVID-19 patients.

Histological and in vivo Study on Novel Polyelectrolyte Complex Vildagliptin Loaded Microbeads in Streptozotocin-induced Rat Model.

BACKGROUND: This study aimed to investigate the effect of vildagliptin-containing polyelectrolyte complex microbeads formulation in a streptozotocin-induced diabetic rat model. OBJECTIVE: Vildagliptin-containing polyelectrolyte complex microbeads were given to diabetic rats at a dose of 2.5 mg/kg body weight in order to study their antidiabetic, hypolipidemic histopathological conditions. METHODS: A portable glucometer was used to measure the blood glucose level using a reagent strip. After vildagliptin formulation was administered orally to healthy streptozotocin-induced rats, other parameters, such as liver profile and total lipid levels, were assessed. RESULT: Vildagliptin-containing polyelectrolyte complex microbeads were found to significantly decrease high glucose levels and improve kidney, liver, and hyperlipidaemia caused due to diabetes. Vildagliptin-containing polyelectrolyte complex microbeads also had a favourable impact on alterations in the liver and pancreatic histopathology in diabetes caused by streptozotocin. CONCLUSION: Vildagliptin-containing polyelectrolyte complex microbeads have the ability to enhance a variety of lipid profiles, including those related to body weight, liver, kidney, and total lipid profiles. Vildagliptin-containing polyelectrolyte complex microbeads have also been found to be effective in preventing the histological alterations in the liver and pancreas occurred in streptozotocin-induced diabetes.

Design and Statistical Optimization of Novel Polyelectrolyte Complex Microbeads to Improve Entrapment Efficiency and Release Study of Vildagliptin.

BACKGROUND: The current research focused on the improvement of drug entrapment efficiency and release study of hydrophilic drug through polymer complextation. OBJECTIVE: Ionotropic gelation technique was utilised for the preparation of Polyelectrolyte complex microbeads of Vildagliptin using Sodium alginate and Eudragit RL100 and their performance was optimized by Central composite design. METHODS: Fourier Transform Infrared Spectroscopy, Scanning Electron Microscope, Differential Scanning Calorimetry, particle size, Drug Entrapment Efficiency, X-ray diffraction and in vitro drug release at 10hr were chosen for evaluating formulated microbeads. The impact of independent variables like concentration of sodium alginate and eudragit RL100 was examined over dependent responses. RESULTS: The interpretation of XRD, SEM, DSC, and FTIR affirmed no drug excipients interference and confirmed formation of polyelectrolyte complex microbeads. For complex microbeads, the maximum and minimum drug release after 10 hours was obtained as 96.23.5% and 89.45%, respectively. The 32 central composite design was further used to obtain response surface graph and the values for the particle size, DEE and Drug release were retained as 0.197, 76.30 % and 92.15%, respectively for the optimize batch. CONCLUSION: The result suggested the combination of two polymers (Sodium alginate and Eudragit RL100) were suitable for improving the entrapment efficiency of hydrophilic drug (Vildagliptin). The central composite design (CCD) technique is an effective tool for obtaining optimal drug delivery systems of Vildagliptin polyelectrolyte complex microbeads.

Machine learning in fermentative biohydrogen production: Advantages, challenges, and applications.

Hydrogen can be produced in an environmentally friendly manner through biological processes using a variety of organic waste and biomass as feedstock. However, the complexity of biological processes limits their predictability and reliability, which hinders the scale-up and dissemination. This article reviews contemporary research and perspectives on the application of machine learning in biohydrogen production technology. Several machine learning algorithems have recently been implemented for modeling the nonlinear and complex relationships among operational and performance parameters in biohydrogen production as well as predicting the process performance and microbial population dynamics. Reinforced machine learning methods exhibited precise state prediction and retrieved the underlying kinetics effectively. Machine-learning based prediction was also improved by using microbial sequencing data as input parameters. Further research on machine learning could be instrumental in designing a process control tool to maintain reliable hydrogen production performance and identify connection between the process performance and the microbial population.

Indian Guidelines on Nebulization Therapy.

Inhalational therapy, today, happens to be the mainstay of treatment in obstructive airway diseases (OADs), such as asthma, chronic obstructive pulmonary disease (COPD), and is also in the present, used in a variety of other pulmonary and even non-pulmonary disorders. Hand-held inhalation devices may often be difficult to use, particularly for children, elderly, debilitated or distressed patients. Nebulization therapy emerges as a good option in these cases besides being useful in the home care, emergency room and critical care settings. With so many advancements taking place in nebulizer technology; availability of a plethora of drug formulations for its use, and the widening scope of this therapy; medical practitioners, respiratory therapists, and other health care personnel face the challenge of choosing appropriate inhalation devices and drug formulations, besides their rational application and use in different clinical situations. Adequate maintenance of nebulizer equipment including their disinfection and storage are the other relevant issues requiring guidance. Injudicious and improper use of nebulizers and their poor maintenance can sometimes lead to serious health hazards, nosocomial infections, transmission of infection, and other adverse outcomes. Thus, it is imperative to have a proper national guideline on nebulization practices to bridge the knowledge gaps amongst various health care personnel involved in this practice. It will also serve as an educational and scientific resource for healthcare professionals, as well as promote future research by identifying neglected and ignored areas in this field. Such comprehensive guidelines on this subject have not been available in the country and the only available proper international guidelines were released in 1997 which have not been updated for a noticeably long period of over two decades, though many changes and advancements have taken place in this technology in the recent past. Much of nebulization practices in the present may not be evidence-based and even some of these, the way they are currently used, may be ineffective or even harmful. Recognizing the knowledge deficit and paucity of guidelines on the usage of nebulizers in various settings such as inpatient, out-patient, emergency room, critical care, and domiciliary use in India in a wide variety of indications to standardize nebulization practices and to address many other related issues; National College of Chest Physicians (India), commissioned a National task force consisting of eminent experts in the field of Pulmonary Medicine from different backgrounds and different parts of the country to review the available evidence from the medical literature on the scientific principles and clinical practices of nebulization therapy and to formulate evidence-based guidelines on it. The guideline is based on all possible literature that could be explored with the best available evidence and incorporating expert opinions. To support the guideline with high-quality evidence, a systematic search of the electronic databases was performed to identify the relevant studies, position papers, consensus reports, and recommendations published. Rating of the level of the quality of evidence and the strength of recommendation was done using the GRADE system. Six topics were identified, each given to one group of experts comprising of advisors, chairpersons, convenor and members, and such six groups (A-F) were formed and the consensus recommendations of each group was included as a section in the guidelines (Sections I to VI). The topics included were: A. Introduction, basic principles and technical aspects of nebulization, types of equipment, their choice, use, and maintenance B. Nebulization therapy in obstructive airway diseases C. Nebulization therapy in the intensive care unit D. Use of various drugs (other than bronchodilators and inhaled corticosteroids) by nebulized route and miscellaneous uses of nebulization therapy E. Domiciliary/Home/Maintenance nebulization therapy; public & health care workers education, and F. Nebulization therapy in COVID-19 pandemic and in patients of other contagious viral respiratory infections (included later considering the crisis created due to COVID-19 pandemic). Various issues in different sections have been discussed in the form of questions, followed by point-wise evidence statements based on the existing knowledge, and recommendations have been formulated.

Biochemical Parameters as Prognostic Markers in Severely Ill COVID-19 Patients.

Background Prognostication plays a pivotal role in critical care medicine. Its importance is indisputable in the management of coronavirus disease 2019 (COVID-19), as the presentation of this disease may vary from docile, self-limiting symptoms to lethal conditions. Amid the COVID-19 pandemic, much emphasis was initially placed on molecular and serological testing. However, it was realized later that routine laboratory tests also provide key information in terms of the severity of the disease and thus could be used to predict the outcome of these patients. Methodology The aim of our study was to evaluate the biochemical parameters as prognostic markers in severely ill COVID-19 patients. We carried out a retrospective, case-control study. The study population was comprised of all severely ill COVID-19 patients admitted between October 2020 and January 2021 at our level 3 COVID hospital. Cases were defined as the patients who expired despite treatment and all resuscitative measures as per the standard operating procedures (SOPs) of our COVID intensive care unit (ICU) while controls were defined as the patients that were transferred out of the COVID ICU for further recovery. The detailed history, findings of physical examination, vitals recorded by point of care testing (POCT) devices at our ICU, clinical diagnosis, and the results of the biochemical analysis were recorded in a specially designed pro forma. The biochemical parameters recorded at the time of admission were compared between the groups of controls and cases in order to evaluate their role as predictors of mortality using appropriate statistical methods. P-values less than 0.05 were considered statistically significant. For all the parameters that showed a statistically significant difference, receiver operating characteristics (ROC) analysis was done to assess the utility of biochemical parameters as predictors of mortality or survival. Areas under the curve (AUCs) of 0.6 to 0.7, 0.7 to 0.8, 0.8 to 0.9, and >0.9 were considered acceptable, fair, good, and excellent for discrimination, respectively. Results Of the 178 severely ill COVID-19 patients enrolled in the study, 86 were controls and 92 were cases (52% mortality). Serum urea (p<0.0001), creatinine (p=0.0019), aspartate transaminase (AST) (p=0.0104), lactate dehydrogenase (LDH) (p=0.0001), procalcitonin (PCT) (p=0.0344), and interleukin 6 (IL-6) (p=0.0311) levels were significantly higher (p<0.05), while total protein (p=0.0086), albumin (p<0.0001), and indirect bilirubin (p=0.0147) levels were significantly lower (p<0.05) in cases as compared to controls. The difference was statistically insignificant (p>0.05) for serum sodium, potassium, total and direct bilirubin, globulin, alanine transaminase (ALT), alkaline phosphatase (ALP), D-dimer, and ferritin. On ROC analysis, urea was fair (AUC=0.721), creatinine (AUC=0.698) and IL-6 (AUC=0.698) were acceptable predictors of mortality, while albumin (AUC=0.698) was an acceptable predictor of survival in severely ill COVID-19 patients during their intensive care stay. Conclusion Understanding the pathophysiological changes associated with the severity of COVID-19 in terms of an alteration of biochemical parameters is a pressing priority. Our study highlights the importance of routine laboratory tests in predicting outcomes in severely ill COVID-19 patients.

Comparison of Maxillary Molar Roots with Maxillary Sinus in High-resolution CBCT: A Retrospective Study.

Background: The maxillary sinus is a pyramidal-shaped osseous cavity, and maxillary molars are found to be in close proximity to the sinus floor or even protruding into it. The present study was conducted to measure the relation between the roots and sinus floor and also the thickness of the bone using CBCT to determine age and gender differences. Materials and Methods: The individuals were separated into two groups based on age: Those under 40 and those over 40 years. There were 25 men and 25 females in the study. Axial, coronal, and sagittal slices of the CBCT images were obtained. Results: The first molar root distance and cortical bone thickness varied significantly between men and women, as well as across different ages. Mesiobuccal root with sinus floor was shown to have a substantial mean value for both sexes (P = 0.049 and P = 0.003). In females, the thickness of the buccal plate was 1.291 mm, whereas, in men, it was 2.447 mm (P = 0.000). There was a substantial difference in the thickness of the buccal plate between men and women who were at least 40 years old (P = 0.000). Conclusion: This study suggests how important it is to look at anatomical features and bone thickness when determining a person's age and gender.

Role of serine/threonine protein phosphatase PrpN in the life cycle of Bacillus anthracis.

Reversible protein phosphorylation at serine/threonine residues is one of the most common protein modifications, widely observed in all kingdoms of life. The catalysts controlling this modification are specific serine/threonine kinases and phosphatases that modulate various cellular pathways ranging from growth to cellular death. Genome sequencing and various omics studies have led to the identification of numerous serine/threonine kinases and cognate phosphatases, yet the physiological relevance of many of these proteins remain enigmatic. In Bacillus anthracis, only one ser/thr phosphatase, PrpC, has been functionally characterized; it was reported to be non-essential for bacterial growth and survival. In the present study, we characterized another ser/thr phosphatase (PrpN) of B. anthracis by various structural and functional approaches. To examine its physiological relevance in B. anthracis, a null mutant strain of prpN was generated and shown to have defects in sporulation and reduced synthesis of toxins (PA and LF) and the toxin activator protein AtxA. We also identified CodY, a global transcriptional regulator, as a target of PrpN and ser/thr kinase PrkC. CodY phosphorylation strongly controlled its binding to the promoter region of atxA, as shown using phosphomimetic and phosphoablative mutants. In nutshell, the present study reports phosphorylation-mediated regulation of CodY activity in the context of anthrax toxin synthesis in B. anthracis by a previously uncharacterized ser/thr protein phosphatase-PrpN.

Study of Utility of Basic Arterial Blood Gas Parameters and Lactate as Prognostic Markers in Patients With Severe Dengue.

Background The importance of prognostication in critical care cannot be over-emphasized, especially in the context of diseases like dengue, as their presentation may vary from mild fever to critical life-threatening illness. With the help of prognostic markers, it is possible to identify patients at higher risk and thus improve their outcome with timely intervention. Basic arterial blood gas (ABG) parameters, i.e., potential of hydrogen (pH), partial pressure of oxygen (PO2), partial pressure of carbon dioxide (PCO2) and bicarbonate are useful parameters, especially in critical care medicine as they are known to vary with the severity of illness. Hyperlactatemia is often referred to as a "powerful predictor of mortality". Basic ABG parameters and lactate have been used as an essential prognostic modality in critically ill patients for decades; however, the evidence remains limited for their role as prognostic markers in patients with severe dengue. Method We carried out an observational retrospective cohort study comprising 163 patients with severe dengue, admitted between July 2021 and November 2021 at Medical Intensive Care Unit (MICU) of Shri Ram Murti Smarak Institute of Medical Sciences (SRMS IMS), Bareilly, Uttar Pradesh, India. Basic ABG parameters and lactate levels at the time of admission to MICU were compared between survivor and non-survivor groups of patients with severe dengue in order to evaluate their prognostic utility as predictors of mortality. Results pH (p<0.0001), PO2 (p=0.01) and bicarbonate (<0.0001) levels were significantly lower, while PCO2 (p=0.002) and lactate (p<0.0001) levels were significantly higher in non-survivor group as compared to survivor group. Lactate was found to be the best prognostic marker with Area Under the Curve (AUC) of 88.7% on Receiver Operating Characteristics (ROC) analysis. Conclusion Basic arterial blood gas parameters and lactate can be used as feasible prognostic markers in patients with severe dengue.

Differential Effects of Cytopathic Hypoxia on Human Retinal Endothelial Cellular Behavior: Implication for Ischemic Retinopathies.

Loss of barrier integrity of retinal endothelial cells (RECs) is an early feature of ischemic retinopathies (IRs), but the triggering mechanisms remain incompletely understood. Previous studies have reported mitochondrial dysfunction in several forms of IRs, which creates a cytopathic hypoxic environment where cells cannot use oxygen for energy production. Nonetheless, the contribution of cytopathic hypoxia to the REC barrier failure has not been fully explored. In this study, we dissect in-depth the role of cytopathic hypoxia in impairing the barrier function of REC. We employed the electric cell-substrate impedance sensing (ECIS) technology to monitor in real-time the impedance (Z) and hence the barrier functionality of human RECs (HRECs) under cytopathic hypoxia-inducing agent, Cobalt(II) chloride (CoCl2). Furthermore, data were deconvoluted to test the effect of cytopathic hypoxia on the three key components of barrier integrity; Rb (paracellular resistance between HRECs), α (basolateral adhesion between HRECs and the extracellular matrix), and Cm (HREC membrane capacitance). Our results showed that CoCl2 decreased the Z of HRECs dose-dependently. Specifically, the Rb parameter of the HREC barrier was the parameter that declined first and most significantly by the cytopathic hypoxia-inducing agent and in a dose-dependent manner. When Rb began to fall to its minimum, other parameters of the HREC barrier, including α and Cm, were unaffected. Interestingly, the compromised effect of cytopathic hypoxia on Rb was associated with mitochondrial dysfunction but not with cytotoxicity. In conclusion, our results demonstrate distinguishable dielectric properties of HRECs under cytopathic hypoxia in which the paracellular junction between adjacent HRECs is the most vulnerable target. Such selective behavior could be utilized to screen agents or genes that maintain and strengthen the assembly of HRECs tight junction complex.

An integrated approach of designing functionality with security for distributed cyber-physical systems.

In this work, we propose a multi-tier architectural model to separate functionality and security concerns for distributed cyber-physical systems. On the line of distributed computing, such systems require the identification of leaders for distribution of work, aggregation of results, etc. Further, we propose a fault-tolerant leader election algorithm that can independently elect the functionality and security leaders. The proposed election algorithm identifies a list of potential leader capable nodes to reduce the leader election overhead. It keeps identifying the highest potential node as the leader, whenever needed, including the situation when one has failed. We also explain the proposed architecture and its management method through a case study. Further, we perform several experiments to evaluate the system performance. The experimental results show that the proposed architectural model improves the system performance in terms of latency, average response time, and the number of real-time tasks completed within the deadline.

QbD enabled Process Variable Study to Develop Sustained Release Chitosan-Alginate Embedded Delivery System for Improved Patient Compliance

Abstract The current investigation entail systematic Quality by Design (QbD)-enabled approach for the development of Sustained released embedded drug delivery systems of L-Arginine employing ionic gelation technique to attain improved patient compliance. Hence, in this QbD enabled systematic approach; quality target product profile (QTTP) was defined and critical quality attributes (CQAs) were identified. Further the risk assessment studies were undertaken through Ishikawa fish bone diagram to locate the critical material attributes (CMAs) and/or critical process parameters (CPPs) for the formulation of beads that may affect CQAs of drug product. A face centered central composite design (CCD) for two factors at three levels each with α =1 was employed for the optimization process to checkout the impact of concentration of sodium alginate and concentration of chitosan as CMAs which wereprior identified from risk assessment study and further evaluated for CQAs viz. bead size, swelling index and percent drug entrapment. The optimum formulation was embarked upon by using mathematical model being developed yielding desired CQAs. Thereby chitosan coated calcium-alginate delivery system was successfully developed by strategically employing QbD approach.In a nutshell, the presentinvestigation reports the successful development of optimized chitosan coated alginate beads employing QbD approach which can serve as a platform for other drugs too.

Potential Combination Drug Therapy to Prevent Redox Stress and Mitophagy Dysregulation in Retinal Müller Cells under High Glucose Conditions: Implications for Diabetic Retinopathy.

Chronic hyperglycemia-induced thioredoxin-interacting protein (TXNIP) expression, associated oxidative/nitrosative stress (ROS/RNS), and mitochondrial dysfunction play critical roles in the etiology of diabetic retinopathy (DR). However, there is no effective drug treatment to prevent or slow down the progression of DR. The purpose of this study is to examine if a combination drug treatment targeting TXNIP and the mitochondria-lysosome pathway prevents high glucose-induced mitochondrial stress and mitophagic flux in retinal Müller glial cells in culture, relevant to DR. We show that diabetes induces TXNIP expression, redox stress, and Müller glia activation (gliosis) in rat retinas when compared to non-diabetic rat retinas. Furthermore, high glucose (HG, 25 mM versus low glucose, LG 5.5 mM) also induces TXNIP expression and mitochondrial stress in a rat retinal Müller cell line, rMC1, in in vitro cultures. Additionally, we develop a mitochondria-targeted mCherry and EGFP probe tagged with two tandem COX8a mitochondrial target sequences (adenovirus-CMV-2×mt8a-CG) to examine mitophagic flux in rMC1. A triple drug combination treatment was applied using TXNIP-IN1 (which inhibits TXNIP interaction with thioredoxin), Mito-Tempo (mitochondrial anti-oxidant), and ML-SA1 (lysosome targeted activator of transient calcium channel MCOLN1/TRPML1 and of transcription factor TFEB) to study the mitochondrial-lysosomal axis dysregulation. We found that HG induces TXNIP expression, redox stress, and mitophagic flux in rMC1 versus LG. Treatment with the triple drug combination prevents mitophagic flux and restores transcription factor TFEB and PGC1α nuclear localization under HG, which is critical for lysosome biosynthesis and mitogenesis, respectively. Our results demonstrate that 2×mt8a-CG is a suitable probe for monitoring mitophagic flux, both in live and fixed cells in in vitro experiments, which may also be applicable to in vivo animal studies, and that the triple drug combination treatment has the potential for preventing retinal injury and disease progression in diabetes.

Relative Contribution of Different Mitochondrial Oxidative Phosphorylation Components to the Retinal Pigment Epithelium Barrier Function: Implications for RPE-Related Retinal Diseases.

Disruption of retinal pigment epithelial (RPE) barrier integrity is involved in the pathology of several blinding retinal diseases including age-related macular degeneration (AMD) and diabetic retinopathy (DR), but the underlying causes and pathophysiology are not completely well-defined. Mitochondria dysfunction has often been considered as a potential candidate implicated in such a process. In this study, we aimed to dissect the role of different mitochondrial components; specifically, those of oxidative phosphorylation (OxPhos), in maintaining the barrier functionality of RPE. Electric cell-substrate impedance sensing (ECIS) technology was used to collect multi-frequency electrical impedance data to assess in real-time the barrier formation of the RPE cells. For this purpose, the human retinal pigment epithelial cell line-ARPE-19-was used and treated with varying concentrations of specific mitochondrial inhibitors that target different steps in OxPhos: Rotenone for complex I (the largest protein complex in the electron transport chain (ETC)); oligomycin for ATP synthase; and carbonyl cyanide-p-trifluoromethoxyphenyl hydrazone (FCCP) for uncoupling ATP synthesis from the accompanying ETC. Furthermore, data were modeled using the ECIS-Zθ software to investigate in depth the effects of these inhibitors on three separate barrier parameters: cell-cell interactions (Rb), cell-matrix interactions (α), and the cell membrane capacitance (Cm). The viability of ARPE-19 cells was determined by lactate dehydrogenase (LDH) Cytotoxicity Assay. The ECIS program's modeling demonstrated that FCCP and thus OxPhos uncoupling disrupt the barrier function in the ARPE-19 cells across all three components of the total resistance (Rb, α, and Cm) in a dose-dependent manner. On the other hand, oligomycin and thus ATP synthase inhibition mostly affects the ARPE-19 cells' attachment to their substrate evident by a significant decrease in α resistance in a dose-dependent manner, both at the end and throughout the duration of the experiment. On the contrary, rotenone and complex I inhibition mostly affect the ARPE-19 paracellular resistance Rb in a dose-dependent manner compared to basolateral resistance α or Cm. Our results clearly demonstrate differential roles for different mitochondrial components in maintaining RPE cell functionality in which uncoupling of OxPhos is a major contributing factor to the disruption barrier function. Such differences can be used in investigating gene expression as well as for screening of selective agents that improve the OxPhos coupling efficiency to be used in the therapeutic approach for treating RPE-related retinal diseases.

Optical modulator based on a silicon-ITO grating embedded rib structure with a tunable group delay.

An optical modulator based on an engineered silicon-indium tin oxide (Si-ITO) structure is proposed with a tunable group delay. A large group delay is reported by slowing down the light in a Si-ITO grating embedded rib structure. Optical modulation and a tunable group delay are realized by utilizing the electrically tunable permittivity of ITO in the engineered waveguide. The extinction ratio over 8 dB for a 10 µm long device and the modulation efficiency around 12 V-µm are reported for a wide wavelength from 1530 to 1570 nm. The resulting modulation efficiency and the extinction ratio show a significant improvement as compared to conventional modulators based on rib waveguides. We also report around 82 psec electrical tuning in the group delay for a wide wavelength range. This concept is promising in view of realizing tunable delay lines, along with slow light modulators with a reduced device footprint and low energy dissipation.

Engineered nanophotonic waveguide with ultra-low dispersion.

A silicon-based engineered hybrid plasmonic waveguide with ultra-low dispersion is proposed. The ridge-shaped structure of the nanophotonic waveguide enables nano-scale confinement with electrically tunable characteristics using the plasma dispersion effect in silicon. The waveguide exhibits ultra-low dispersion of $1.28\;{{\rm ps}^2}/{\rm m}$ at telecommunication wavelength (1550 nm) in C band together with dual flatband dispersion over a wavelength range of 370 nm. The hybrid plasmonic mode is made to be confined in 15 nm thick ${{\rm SiO}_2}$ with a propagation loss of 15.3 dB/mm utilizing the engineered ridge structure comprising Si, ${{\rm SiO}_2}$, and gold. In addition, the proposed waveguide shows six zero-dispersion wavelengths. The imaginary and real parts of the effective refractive index of the guided hybrid plasmonic mode are reported to be tunable with the applied voltage. The reported numerical results can pave the way for achieving intensity modulators and other electrically tunable devices at telecommunication wavelengths. The ultra-low dispersion and electrical tuning make this nanophotonic waveguide an absolute contender for applications including efficient nonlinear signal processing such as wide wavelength conversion based on four-wave mixing, supercontinuum generation, and other nanoscale integrated photonic devices.

Optical switch with ultra high extinction ratio using electrically controlled metal diffusion.

An optical switch with ultra high extinction ratio is proposed. Optical switching is realized using the resistive switching effect through the lateral coupling between the input nanophotonic waveguide and output waveguide at a wavelength of 1550 nm. The coupled waveguide system is engineered to increase the number of mode beats in a unit length of the device. An increase in the number of mode beats and controlled diffusion of metal ions through a thin dielectric layer with an applied electric field is responsible for a high optical extinction ratio of 27 dB for a 20 µm long device. Compared to electrical control by plasma dispersion in silicon, the resistive switching effect enables a reduction in the coupling length and an increase in the waveguide absorption, leading to an almost 100 times higher extinction ratio. The proposed compact on-chip silicon-based nanophotonic resistive device is a potential candidate for a large-scale integrated photonic circuit for applications in optical switching, modulation, memory, and computation.