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For ensuring an ideal recycling rate, the extending producer responsibility (Extending Producer Responsibility) has been recognized by more and more governments. And an increasing number of original vehicle manufacturers (Original Vehicle Manufacturers) participated in their End-of-Life vehicles (End-of-Life Vehicles) reusing to fulfil their social responsibility. The Original Vehicle Manufacturers can do well in auto parts remanufacturing due to their knowledge and skills of vehicle manufacturing, and the third-party vehicle recyclers are more capable of recycling the End-of-Life Vehicles due to their skills and facilities of waste recycling. To better improve the End-of-Life Vehicle reusing businesses and improve the efficiency and quality of End-of-Life Vehicle recycling and remanufacturing, this research built a remanufacturing system with dual-cycle End-of-Life Vehicle recycling. Moreover, for the well operation of this system, the researchers established the game model between Original Vehicle Manufacturers and third-party recyclers with the government involved and analyzed this model with evolutionary game theory. This research found that there are two evolutionary stable strategies (ESS) for the two groups. For well operation of remanufacturing system with dual-cycle End-of-Life Vehicle recycling, the government need to use the Extending Producer Responsibility policy to impose strict restrictions on Original Vehicle Manufacturers doing End-of-Life Vehicle recycling through promoting Original Vehicle Manufacturers’ recycling quantity standard and the penalty for insufficient End-of-Life Vehicle recycling. Further, this research also found that the licensing fee that the third-party recycler needs to pay the Original Vehicle Manufacturer for getting the recycling business plays a vital role in the ESS.

The interaction of nanosized materials with living organisms is the central concern in the key applications of nanotechnology. In particular, the protein adsorption to nanomaterial surface has been a major focus of study in the past decade. Unfortunately, the underlying principles and molecular mechanisms are still not well understood, and there have been various approaches to address the issue. Bottom-up approaches like computational simulations at the atomistic level have already proved their potential. Several force fields and models have been developed to simulate realistic dynamics to mimic the interaction of solid surfaces and peptides, even in some cases, the whole protein. However, there are a few major limitations and bottlenecks of these studies, which remain mostly ignored and unexplored. Here, we review the studies that have been the major contributors to our present understanding of the nanoparticle (NP)-protein interaction. As the complexity of this phenomenon arises from different stages, the study of protein-NP interactions from multiple directions is necessary. In the perspective of bioapplications, we discuss the major challenges of this field and future scopes of research that can be designed rationally, sometimes coupled with numerous available experimental techniques to understand NP-protein docking in a more realistic manner.

Aim of Study: The goal of this paper is to find an association between the staining capacity of dental restorations used in pediatric patients and food items and to develop an optimum model to predict the most informative factor that causes the highest amount of color change through machine learning algorithms., Background: Color changes in restorative materials occur as a result of intrinsic and extrinsic factors, such as the type of restorative material, food items used, polished status of the material, and time interval., Materials and Methods: This was an " in vitro study" conducted at Aligarh Muslim University, Aligarh, Uttar Pradesh, India. The study included 200 specimens, that is, 40 in each group A (orange juice), group B (Amul Kool Café), group C (Pepsi), group D (Amul Kesar Milk), and group E (artificial saliva). The materials were glass ionomer cement (GIC), resin-modified glass ionomer cement (RMGIC), microhybrid composite resin, and nanohybrid composite resin. These were further divided into polished and unpolished groups. The optimum modeling of the prediction of color change in materials by different effective factors was done by machine learning decision tree. We applied two algorithms: Chi-square automatic interaction detector (CHAID) and classification and regression tree (CART). In prediction modeling in the decision tree by CHAID and CART, color change is taken as the dependent variable, and group (type of restorative material), food items, time interval, and polished status are taken as independent variables., Results: The various beverages caused significant color variation due to different pigmentation agents. The agent that caused the highest color change was Kool Café. The Kesar Milk had the lowest pigmentation capacity. The greatest color variation was found on Glasionomer FX-II submerged in Pepsi and the least on Ivoclar Te-Econom Plus in Kesar Milk. The mean absolute error for the training dataset in the CART model and CHAID model is 0.379 and 0.332, and for the testing data set, it is 0.398 and 0.333, respectively. Therefore, the prediction of color change by the CHAID model is optimum, and we found that the restorative materials have a maximum predictor importance of 0.86 (86%), time interval 0.07 (7%), food items 0.04 (4%), and polished status has the least importance, that is, 0.03 (3%)., Conclusion: The staining capacity of restorative material highly depends on the material itself, the initial time interval, and least on the food items used., Clinical Significance: The clinical performance of dental restorations could be affected by various beverages consumed by children. This study thus provides important clinical insights into esthetic dentistry by offering valuable information on long-term color stability and the effect of polishing on common esthetic restorative materials used in pediatric dentistry., How to Cite This Article: Varshney P, Khan SY, Jindal MK, et al. Quantification of Color Variation of Various Esthetic Restorative Materials in Pediatric Dentistry. Int J Clin Pediatr Dent 2024;17(7):754-765., Competing Interests: Source of support: Nil Conflict of interest: NoneConflict of interest: None, (Copyright © 2024; The Author(s).)

Background: For caries risk assessment (CRA) tools for young children to be evidence-based, it is important to systematically review the literature to identify factors associated with the onset of early childhood caries (ECC)., Aim: This updated systematic review aimed to identify current evidence on caries risk in young children., Design: A comprehensive and systematic literature search of relevant databases was conducted to update a previous systematic review and identify risk factors associated with ECC. Potential risk factors were identified based on strength of association using odds ratios, hazard ratios, relative risk, etc. GRADE was used for rating quality evidence through consensus., Results: Twenty-two studies met inclusion criteria for the search from mid-2017 to 2021. Twenty-five publications from the prior systematic review, from 1997 to mid-2017, were also included. Several socioeconomic, behavioral, and clinical variables were identified as ECC risk factors. Factors included the following: age, socioeconomic status, frequency of and supervised toothbrushing, fluoride exposure, breast- and bottle-feeding, feeding habits, absence of a dental home, past caries experience, active non-cavitated lesions, visible plaque, enamel defects, and microbiome., Conclusion: This study provides updated evidence of risk factors for ECC that could be included in CRA tools., (© 2023 The Authors. International Journal of Paediatric Dentistry published by BSPD, IAPD and John Wiley & Sons Ltd.)

Objective: The objective of this study was to determine the prevalence of early childhood caries in children with severe acute malnutrition (SAM) and also the hierarchy of association if any with malnutrition, anemia, and other risk factors with ECC using machine learning algorithms., Methods: A hospital-based preventive and interventional study was conducted on SAM children (age = 2 to <6 years) who were admitted to the malnutrition treatment unit (MTU). An oral examination for early childhood caries status was done using the deft index. The anthropometric measurements and blood examination reports were recorded. Oral health education and preventive dental treatments were given to the admitted children. Three machine learning algorithms (Random Tree, CART, and Neural Network) were applied to assess the relationship between early childhood caries, malnutrition, anemia, and the risk factors., Results: The Random Tree model showed that age was the most significant factor in predicting ECC with predictor importance of 98.75%, followed by maternal education (29.20%), hemoglobin level (16.67%), frequency of snack intake (9.17%), deft score (8.75%), consumption of snacks (7.1%), breastfeeding (6.25%), severe acute malnutrition (5.42%), frequency of sugar intake (3.75%), and religion at the minimum predictor importance of 2.08%., Conclusion: Anemia and malnutrition play a significant role in the prediction, hence in the causation of ECC. Pediatricians should also keep in mind that anemia and malnutrition have a negative impact on children's dental health. Hence, Pediatricians and Pediatric dentist should work together in treating this health problem., (Copyright © 2024 Copyright: © 2024 Journal of Indian Society of Pedodontics and Preventive Dentistry.)

Pre-clinical studies from the recent past have indicated that senescent cells can negatively affect health and contribute to premature aging. Targeted eradication of these cells has been shown to improve the health of aged experimental animals, leading to a clinical interest in finding compounds that selectively eliminate senescent cells while sparing non-senescent ones. In our study, we identified a senolytic capacity of statins, which are lipid-lowering drugs prescribed to patients at high risk of cardiovascular events. Using two different models of senescence in human vascular endothelial cells (HUVECs), we found that statins preferentially eliminated senescent cells, while leaving non-senescent cells unharmed. We observed that the senolytic effect of statins could be negated with the co-administration of mevalonic acid and that statins induced cell detachment leading to anoikis-like apoptosis, as evidenced by real-time visualization of caspase-3/7 activation. Our findings suggest that statins possess a senolytic property, possibly also contributing to their described beneficial cardiovascular effects. Further studies are needed to explore the potential of short-term, high-dose statin treatment as a candidate senolytic therapy.

Background: Widespread use of screening mammography has allowed breast cancer to be detected at earlier stages. This allows for increased customization of treatment and less aggressive management. De-escalation of therapy plays an important role in decreasing treatment burden and improving patient quality of life. This report examines cryoablation as the next step in the surgical de-escalation of breast cancer., Methods: Women with a diagnosis of clinically node-negative, estrogen receptor-positive (ER +), progesterone receptor-positive (PR +), human epidermal growth factor receptor 2-negative (HER2 -) infiltrating ductal carcinomas 1.5 cm or smaller underwent ultrasound-guided cryoablation. Either the Visica 2 treatment system (before 2020) or the ProSense treatment system (since 2020) was used to perform the cryoablation. Patients received mammograms and ultrasounds at a 6 months follow-up visit, and magnetic resonance images at baseline, then at 1 year follow-up intervals. Adjuvant therapy decisions and disease status were recorded., Results: This study enrolled 32 patients who underwent 33 cryoablation procedures (1 patient had bilateral cancer). One patient had a sentinel node biopsy in addition to clinical staging of the axilla. For all the patients, adjuvant endocrine therapy was recommended, and six patients (18.75%) received adjuvant radiation. Of the 32 patients, 20 (60.6%) have been followed up for 2 years or longer, with no residual or recurrent disease at the site of ablation., Conclusion: Cryoablation of the primary tumor foregoing sentinel node biopsy offers an oncologically safe and feasible minimally invasive office-based procedure option in lieu of surgery for patients with early-stage, low-risk breast cancer., (© 2023. The Author(s).)

Detection of tumor-infiltrating lymphocytes (TILs) in cancer images has gained significant importance as these lymphocytes can be used as a biomarker in cancer detection and treatment procedures. Our goal was to develop and apply a TILs detection tool that utilizes deep learning models, following two sequential steps. First, based on the guidelines from the International Immuno-Oncology Biomarker Working Group (IIOBWG) on Breast Cancer, we labeled 63 large pathology imaging slides and annotated the TILs in the stroma area to create the dataset required for model development. In the second step, various machine learning models were employed and trained to detect the stroma where U-Net deep learning structure was able to achieve 98% accuracy. After detecting the stroma area, a Mask R-CNN model was employed for the TILs detection task. The R-CNN model detected the TILs in various images and was used as the backbone analysis network for the GUI development of the TILs detection tool. This is the first study to combine two deep learning models for TILs detection at the cellular level in breast tumor histopathology slides. Our novel approach can be applied to scoring TILs in large cancer slides. Statistical analysis showed that the output of the implemented approach had 95% concordance with the scores assigned by the pathologists, with a p -value of 0.045 (n = 63). This demonstrated that the results from the developed software were statistically meaningful and highly accurate. The implemented approach in analyzing whole tumor histology slides and the newly developed TILs detection tool can be used for research purposes in biomedical and pathology applications and it can provide researchers and clinicians with the TIL score for various input images. Future research using additional breast cancer slides from various sources for further training and validation of the developed models is necessary for more inclusive, rigorous, and robust clinical applications.

Aim: To evaluate the effectiveness of the audiovisual distraction (AVD) technique and filmed modeling (FM) on anxiety and fear in pediatric dental patients., Materials and Methods: This experimental in vivo study was conducted on 80 subjects of age-groups 5-8 years coming to the Department of Pediatric and Preventive Dentistry for their first dental visit. Study subjects were subjected to noninvasive restorative treatment under AVD in group I, FM in group II, and a combination of AVD and FM in groups III and IV (control 0). To assess the level of pre and postoperative anxiety and fear, various biological parameters like pulse rate, oxygen saturation, body temperature, respiratory rate, and salivary cortisol estimation along with facial image scale (FIS), and fear assessment picture scale (FAPS) were used., Results: Group III (a combination of AVD and FM) came out to be better than other experimental groups and control groups in reducing dental anxiety and fear in pediatric dental patients., Conclusion: A combination of AVD and FM techniques can be recommended to be used as an effective behavior management technique., Clinical Significance: A child's disruptive behavior due to dental anxiety causes difficulty in delivering effective dental treatment. Thus, a child's behavior management is of paramount importance in the pediatric dental setup. Nonpharmacological behavior management techniques, that is, a combination of AVD and FM techniques can be recommended to be used as an effective behavior management technique to reduce dental anxiety and fear in pediatric dental patients., How to Cite This Article: Jamil F, Khan SY, Jindal MK. Effectiveness of Audiovisual Distraction Technique and Filmed Modeling on Anxiety and Fear in Pediatric Dental Patients. Int J Clin Pediatr Dent 2023;16(4):598-602., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2023; The Author(s).)

Background: Dishevelled paralogs (DVL1, 2, 3) are key mediators of Wnt pathway playing a role in constitutive oncogenic signaling influencing the tumor microenvironment. While previous studies showed correlation of β-catenin with T cell gene expression, little is known about the role of DVL2 in modulating tumor immunity. This study aimed to uncover the novel interaction between DVL2 and HER2-positive (HER2+) breast cancer (BC) in regulating tumor immunity and disease progression., Methods: DVL2 loss of function studies were performed with or without a clinically approved HER2 inhibitor, Neratinib in two different HER2+ BC cell lines. We analyzed RNA (RT-qPCR) and protein (western blot) expression of classic Wnt markers and performed cell proliferation and cell cycle analyses by live cell imaging and flow cytometry, respectively. A pilot study in 24 HER2+ BC patients was performed to dissect the role of DVL2 in tumor immunity. Retrospective chart review on patient records and banked tissue histology were performed. Data were analyzed in SPSS (version 25) and GraphPad Prism (version 7) at a significance p < 0.05., Results: DVL2 regulates the transcription of immune modulatory genes involved in antigen presentation and T cell maintenance. DVL2 loss of function down regulated mRNA expression of Wnt target genes involved in cell proliferation, migration, invasion in HER2+ BC cell lines (±Neratinib). Similarly, live cell proliferation and cell cycle analyses reveal that DVL2 knockdown (±Neratinib) resulted in reduced proliferation, higher growth arrest (G1), limited mitosis (G2/M) compared to non-targeted control in one of the two cell lines used. Analyses on patient tissues who received neoadjuvant chemotherapy (n = 14) further demonstrate that higher DVL2 expression at baseline biopsy pose a significant negative correlation with % CD8α levels (r = - 0.67, p < 0.05) while have a positive correlation with NLR (r = 0.58, p < 0.05), where high NLR denotes worse cancer prognosis. These results from our pilot study reveal interesting roles of DVL2 proteins in regulating tumor immune microenvironment and clinical predictors of survival in HER2+ BC., Conclusion: Our study demonstrates potential immune regulatory role of DVL2 proteins in HER2+ BC. More in-depth mechanistic studies of DVL paralogs and their influence on anti-tumor immunity may provide insight into DVLs as potential therapeutic targets benefiting BC patients., (© 2023. The Author(s).)

Background: Cryoablation has been established as a minimally invasive alternative to resection of early-stage breast cancer; however, there are no data on the cost and impact on patients' financial, psychosocial, sexual, physical, and cosmetic outcomes utilizing this approach. This study compares cost-effectiveness and patient-reported quality-of-life factors in cryoablation versus resection., Methods: Women with early-stage, low-risk infiltrating ductal carcinomas ≤ 1.5 cm underwent cryoablation or resection. Adjuvant therapy was provided according to tumor board recommendations. Direct and indirect costs were tracked for both groups. Financial toxicity and well-being outcome were measured by administering the Comprehensive Score of Financial Toxicity (COST) and BREAST-Q surveys, respectively, at 6-month follow-up., Results: Of the 34 eligible patients, 14 (41.1%) consented for cryoablation and 20 (58.8%) underwent resection. The median (centile) (range) follow-up was 35.0 (21.3) (15-50) months for cryoablation vs. 25 (20.8) (17-50) months for resection [p = 0.6479]. Mean (standard deviation) cost of care for cryoablation versus resection was $2221.70 (615.70) versus $16,896.50 (1332.40) [p < 0.0001], and median financial well-being scores for the cryoablation versus resection groups were 38.0 (34.5, 40.0) versus 10 (5.3, 14.0) [p < 0.0001]. Poor financial well-being was directly correlated with the cost of care [p < 0.0001]. Median psychosocial well-being scores were similar across both groups, however the cryoablation group had higher scores for physical [100 (100, 100) vs. 89 (79, 100); p = 0.0141], sexual [100 (91, 100) vs. 91 (87.5, 91); p = 0.0079], and cosmetic [100 (100, 100) vs. 88 (88, 100); p = 0.0171] outcomes., Conclusion: Cryoablation offers a cost-effective and quality-of-life advantage compared with resection for early-stage, low-risk breast cancer., (© 2022. Society of Surgical Oncology.)

Inflammation-related diseases are recognized as the major cause of morbidity around the globe. In this study, the anti-inflammatory potential of sericin, curcumin, and their mixture was investigated in vivo and in vitro. Edema was induced via 1% carrageenan and then sericin (0.03, 0.06, 0.09 mg/ml), curcumin (1%, 2%, 3%), and their mixture doses were applied topically. The paw circumference and thickness were measured after 1-, 2-, 3-, 4-, 5-, and 6-hour post-carrageenan injection. The levels of IL-4 and IL-10 were measured from the serum. In mice fibroblast cells, sericin (20, 40, 60 μg/ml), curcumin (5, 10, 20 μM), and mixture concentrations were applied and then stimulated with lipopolysaccharide (LPS). Afterward, the cells were used for the analysis of gene expression, and the supernatant was collected for protein expression of IL-1β, IL-4, and IL-10. Our results demonstrated that sericin and curcumin caused a dose-dependent reduction in edema, whereas the mixture-treated group reduced the paw thickness and circumference most significantly (p = .0001). Furthermore, the mixture treatment of carrageenan-inflicted group increased the levels of anti-inflammatory cytokines, IL-4 (650.87 pg/ml) and IL-10 (183.14 pg/ml), in comparison to the carrageenan control. The in vitro data revealed that among all the treatment doses, the mixture-treated group has effectively reduced the gene (1.13-fold) and protein (51.9 pg/ml) expression of IL-1β in comparison to McCoy cells stimulated with LPS. Moreover, mixture treatment elevated the expression of IL-4 and IL-10 at genes (4.3-fold and 3.7-fold, respectively) and protein levels (169.33 and 141.83 pg/ml, respectively). The current study reports the enhanced anti-inflammatory effects of the mixture of curcumin and sericin through modulating expressions of interleukins in vitro and in vivo. Thus, natural products (curcumin and sericin)-based formulations have greater potential for clinical investigations., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The development of digital technologies and the evolution of open innovation approaches have enabled the creation of diverse virtual organizations and enterprises coordinating their activities primarily online. The open innovation platform titled "International Natural Product Sciences Taskforce" (INPST) was established in 2018, to bring together in collaborative environment individuals and organizations interested in natural product scientific research, and to empower their interactions by using digital communication tools., Methods: In this work, we present a general overview of INPST activities and showcase the specific use of Twitter as a powerful networking tool that was used to host a one-week "2021 INPST Twitter Networking Event" (spanning from 31st May 2021 to 6th June 2021) based on the application of the Twitter hashtag #INPST., Results and Conclusion: The use of this hashtag during the networking event period was analyzed with Symplur Signals (https://www.symplur.com/), revealing a total of 6,036 tweets, shared by 686 users, which generated a total of 65,004,773 impressions (views of the respective tweets). This networking event's achieved high visibility and participation rate showcases a convincing example of how this social media platform can be used as a highly effective tool to host virtual Twitter-based international biomedical research events., Competing Interests: Conflict of Interest Authors Dr. Rajeev K. Singla and Shailja Singla have an honorary-based associations with the iGlobal Research and Publishing Foundation (iGRPF), New Delhi, India. Dr. Bernd Fiebich is associated with VivaCell Biotechnology GmbH. RKS, SS and BF along with the remaining authors, declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Given their role as Editor/Associate Editor/ Editorial board members, “Prof. Thomas Efferth”, “Ilkay Erdogan Orhan”, “Milen Georgiev”, “Davide Barreca”, “Maurizio Battino”, “Anupam Bishayee”, “Michael Heinrich”,and“Jianbo Xiao”had no involvement in the peer-review of this article and has no access to information regarding its peer-review., (Copyright © 2022 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

The morphology and composition of clasts have the potential to reveal the nature and extent of erosional processes acting in a region. Dense accumulations of granule- to pebble-sized clasts covering the ground throughout the Glen Torridon region of Gale crater on Mars were studied using data acquired by the Mars Science Laboratory Curiosity rover between sols 2300 and 2593. In this study, measurements of shape, size, texture, and elemental abundance of unconsolidated granules and pebbles within northern Glen Torridon were compiled. Nine primary clast types were identified through stepwise hierarchical clustering, all of which are sedimentary and can be compositionally linked to local bedrock, suggesting relatively short transport distances. Several clast types display features associated with fragmentation along bedding planes and existing cracks in bedrock. These results indicate that Glen Torridon clasts are primarily the product of in-situ physical weathering of local bedrock., (© 2022 Jet Propulsion Laboratory. California Institute of Technology. Government sponsorship acknowledged.)

To delineate the genetic bases of primary congenital glaucoma (PCG), we ascertained a large cohort consisting of 48 consanguineous families. Of these, we previously reported 26 families with mutations in CYP1B1 and six families with LTBP2, whereas the genetic bases responsible for PCG in 16 families remained elusive. We employed next-generation whole exome sequencing to delineate the genetic basis of PCG in four of these 16 familial cases. Exclusion of linkage to reported PCG loci was established followed by next-generation whole exome sequencing, which was performed on 10 affected individuals manifesting cardinal systems of PCG belonging to four unresolved families along with four control samples consisting of genomic DNAs of individuals harboring mutations in CYP1B1 and LTBP2. The analyses of sequencing datasets failed to identify potential causal alleles in the 10 exomes whereas c.1169G > A (p. Arg390His) in CYP1B1 and c.3427delC (p.Gln1143Argfs*35) in LTBP2 were identified in the control samples. Taken together, next-generation whole exome sequencing failed to delineate the genetic basis of PCG in familial cases excluded from mutations in CYP1B1 and LTBP2. These data strengthen the notion that compound heterozygous coding variants or non-coding variants might contribute to PCG., (© 2022. The Author(s).)

Here we report a consanguineous Pakistani family with multiple affected individuals with autosomal recessive congenital cataract (arCC). Exclusion analysis established linkage to chromosome 22q, and Sanger sequencing coupled with PCR-based chromosome walking identified a large homozygous genomic deletion. Our data suggest that this deletion leads to CRYBB2-CRYBB2P1 fusion, consisting of exons 1-5 of CRYBB2 and exon 6 of CRYBB2P1, the latter of which harbors the c.463 C > T (p.Gln155*) mutation, and is responsible for arCC., (© 2022. The Author(s).)

FYCO1 (FYVE and coiled-coil domain containing 1) is an adaptor protein, expressed ubiquitously and required for microtubule-dependent, plus-end-directed transport of macroautophagic/autophagic vesicles. We have previously shown that loss-of-function mutations in FYCO1 cause cataracts with no other ocular and/or extra-ocular phenotype. Here, we show fyco1 homozygous knockout ( fyco1 -/- ) mice recapitulate the cataract phenotype consistent with a critical role of FYCO1 and autophagy in lens morphogenesis. Transcriptome coupled with proteome and metabolome profiling identified many autophagy-associated genes, proteins, and lipids respectively perturbed in fyco1 -/- mice lenses. Flow cytometry of FYCO1 (c.2206C>T) knock-in (KI) human lens epithelial cells revealed a decrease in autophagic flux and autophagic vesicles resulting from the loss of FYCO1. Transmission electron microscopy showed cellular organelles accumulated in FYCO1 (c.2206C>T) KI lens-like organoid structures and in fyco1 -/- mice lenses. In summary, our data confirm the loss of FYCO1 function results in a diminished autophagic flux, impaired organelle removal, and cataractogenesis. Abbreviations: CC: congenital cataracts; DE: differentially expressed; ER: endoplasmic reticulum; FYCO1: FYVE and coiled-coil domain containing 1; hESC: human embryonic stem cell; KI: knock-in; OFZ: organelle-free zone; qRT-PCR: quantitative real-time PCR; PE: phosphatidylethanolamine; RNA-Seq: RNA sequencing; SD: standard deviation; sgRNA: single guide RNA; shRNA: shorthairpin RNA; TEM: transmission electron microscopy; WT: wild type.

Introduction: Caries in the deciduous dentition of children under six years of age is termed as early childhood caries (ECC). ECC is prevalent among Indian children and identifying modifiable risk factors is important for prevention. This systematic review was undertaken to describe the burden of ECC in India, its prevalence, associated risk factors along with its repercussions on childhood health., Materials and Methods: A search was conducted for published Indian studies on ECC through electronic databases and complemented with hand search. The protocol for the present systematic review was registered at PROSPERO (Ref No.CRD42022306234)Care was taken to include studies which could represent all parts of India- Central, North, South, East and West. Included papers were reviewed for prevalence of ECC and reported risk factors., Results: Overall 37 studies on ECC in India were identified relating to prevalence, 11 reported risk factors and two reported on the association between severe ECC and nutritional health and well-being. The prevalence of ECC in India in these studies varied from16% to 92.2%. This systematic review revealed that ECC is prevalent among Indian children and highlights the need of preventive intervention and early risk assessment by its own caries risk assessment (CRA) tool. Occurrence seems to be firmly connected with age, snacking frequency, feeding and oral hygiene habits and with social determinants of health including parental education level, low socioeconomic status and number of siblings., Competing Interests: All authors declare that there is no conflict on interest., (Copyright: © 2022 Journal of International Society of Preventive and Community Dentistry.)

Background: Morphological evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer is gaining momentum as an immunological biomarker. This experiment evaluates the role of TILs in distant tumors as a measure of abscopal effect from cryoablation of breast cancer., Methods: BALB/c mice underwent bilateral orthotopic transplant with 4T1-12B (triple-negative) cells. At 2 weeks, left tumors were treated by either resection (standard of care group) or cryoablation (intervention group) followed by resection of the distant right tumors 1 week posttreatment. TIL scores were calculated from hematoxylin and eosin-stained sections and phenotyped for cytotoxic T-lymphocyte (CTL) markers by immunofluorescence. Primarily resected tumors served as baseline (T baseline ), whereas resected distant right-sided served as the readout for abscopal effect (Abs Res or Abs Cryo ). Mice were monitored for tumor recurrence and metastasis., Results: The Abs Cryo had a significant mean (SD) increase in stromal (2.8 [1.1]%; p = 0.015) and invasive margin TILs (50 [12]%; p = 0.02) compared with T Baseline (1.0 [0]% and 31 [4.9]%, respectively). CTL phenotyping revealed a significant increase in mean (SD) CD8 + T cells (15.7 [12.1]; p = 0.02) and granzyme B (4.8 [3.6]; p = 0.048) for the Abs Cryo compared with T Baseline (5.2 [4.7] and 2.4 [0.9], respectively). Posttreatment, the cryoablation group had no recurrence or metastasis, whereas the resected group showed local recurrence and lung metastasis in 40% of the mice. Postprocedure increase in TIL score of distant tumors was associated with decrease in tumor relapse (p = 0.02)., Conclusions: Cryoablation induced a robust tumor-specific TIL response compared with resection, suggesting an abscopal effect leading to the prevention of cancer recurrence and metastasis., (© 2022. The Author(s).)

Background and Objectives: All medicine and healthcare undergraduates were encountered with terminations and delays of professional examinations. These alterations were on topmost of other tasks the COVID-19 pandemic carried out for instance not roaming, covered faces with masks and specifically segregation. This interruption of normal life was a major cause of mental health disaster and it is no surprise that medicine and healthcare undergraduate has had high rates of psychological effects including hopelessness, stress and suicidal thoughts. This study aimed to investigate the unmediated connection of anxiety and stress related mental health decline and suicide among medical and nonmedical undergraduates during the pandemic of covid-19., Methods: A multidiscipline online cross-sectional comparative study design was chosen for this study conducted from November 2020 to January 2021 with a pre-validated questionnaire to collect responses from sample size 1290. SPSS- 21 used for descriptive analysis of means, S.D, ANOVA and spearman's correlations. Forward step-wise model of linear regression applies for true significant bivariate relationship (p<.001)., Results: The result shows that all three cohorts were affected. Among the non-medical cohorts, B-Pharmacy students had the high level (p<.001) of anxiety with suicide ideation response (n=200; 39.2%), along with lowest level of envisions care (19.5%; p<.001) in pandemic. Control and independent variable had a strong negative effects on B-Pharmacy and medical students with p<.000., Conclusions: This study offered more data that the concerns, anxieties and uncertainties caused by pandemic COVID-19, don't roll out alone but remain as long-lasting problems demanding ongoing attention., Competing Interests: Declaration of conflict: The author and co-authors declare that they have no conflict of interests., (Copyright: © Pakistan Journal of Medical Sciences.)

Patients with inherited retinal dystrophies (IRDs) were recruited from two understudied populations: Mexico and Pakistan as well as a third well-studied population of European Americans to define the genetic architecture of IRD by performing whole-genome sequencing (WGS). Whole-genome analysis was performed on 409 individuals from 108 unrelated pedigrees with IRDs. All patients underwent an ophthalmic evaluation to establish the retinal phenotype. Although the 108 pedigrees in this study had previously been examined for mutations in known IRD genes using a wide range of methodologies including targeted gene(s) or mutation(s) screening, linkage analysis and exome sequencing, the gene mutations responsible for IRD in these 108 pedigrees were not determined. WGS was performed on these pedigrees using Illumina X10 at a minimum of 30X depth. The sequence reads were mapped against hg19 followed by variant calling using GATK. The genome variants were annotated using SnpEff, PolyPhen2, and CADD score; the structural variants (SVs) were called using GenomeSTRiP and LUMPY. We identified potential causative sequence alterations in 61 pedigrees (57%), including 39 novel and 54 reported variants in IRD genes. For 57 of these pedigrees the observed genotype was consistent with the initial clinical diagnosis, the remaining 4 had the clinical diagnosis reclassified based on our findings. In seven pedigrees (12%) we observed atypical causal variants, i.e. unexpected genotype(s), including 4 pedigrees with causal variants in more than one IRD gene within all affected family members, one pedigree with intrafamilial genetic heterogeneity (different affected family members carrying causal variants in different IRD genes), one pedigree carrying a dominant causative variant present in pseudo-recessive form due to consanguinity and one pedigree with a de-novo variant in the affected family member. Combined atypical and large structural variants contributed to about 20% of cases. Among the novel mutations, 75% were detected in Mexican and 50% found in European American pedigrees and have not been reported in any other population while only 20% were detected in Pakistani pedigrees and were not previously reported. The remaining novel IRD causative variants were listed in gnomAD but were found to be very rare and population specific. Mutations in known IRD associated genes contributed to pathology in 63% Mexican, 60% Pakistani and 45% European American pedigrees analyzed. Overall, contribution of known IRD gene variants to disease pathology in these three populations was similar to that observed in other populations worldwide. This study revealed a spectrum of mutations contributing to IRD in three populations, identified a large proportion of novel potentially causative variants that are specific to the corresponding population or not reported in gnomAD and shed light on the genetic architecture of IRD in these diverse global populations., Competing Interests: The authors have declared that no competing interests exist.

Here, we report a multi OMIC (transcriptome, proteome, and metabolome) approach to investigate molecular changes in lens fiber cells (FC) of mice exposed to cigarette smoke (CS). Pregnant mice were placed in a whole-body smoke chamber and a few days later pups were born, which were exposed to CS for 5 hours/day, 5 days/week for a total of 3½ months. We examined the mice exposed to CS for CS-related cataractogenesis after completion of the CS exposure but no cataracts were observed. Lenses of CS-exposed and age-matched, untreated control mice were extracted and lens FC were subjected to multi OMIC profiling. We identified 348 genes, 130 proteins, and 14 metabolites exhibiting significant (p < 0.05) differential levels in lens FC of mice exposed to CS, corresponding to 3.6%, 4.3%, and 5.0% of the total genes, protein, and metabolites, respectively identified in this study. Our multi OMIC approach confirmed that only a small fraction of the transcriptome, the proteome, and the metabolome was perturbed in the lens FC of mice exposed to CS, which suggests that exposure of CS had a minimal effect on the mouse lens. It is worth noting that while our results confirm that CS exposure does not have a substantial impact on the molecular landscape of the mouse lens FC, we cannot rule out that CS exposure for longer durations and/or in combination with other morbidities or environmental factors would have a more robust effect and/or result in cataractogenesis., (© 2021. The Author(s).)

Here, we evaluate the efficacy of cryopreserved human embryonic stem cell (hESC)-derived corneal endothelial cells (CECs) to form a functional monolayer of corneal endothelium (CE) in rabbits and monkeys. We injected cryopreserved hESC-derived CECs into the anterior chamber of rabbits and monkeys either immediately after mechanical scraping of the central CE or a few days later when corneal edema developed. All preclinical models developed deturgesced and clear corneas following the injection of cryopreserved hESC-derived CECs and remained comparable to the corneas of the untreated eye. Confocal scanning microscopy confirmed an intact structure of hexagonal/polygonal cells and immunohistochemical analysis illustrated a monolayer expressing barrier and pump function proteins in the regenerated CE. The necropsy examination confirmed no remarkable change in multiple tissues assessed for teratoma formation. In conclusion, our data demonstrate the efficacy of cryopreserved hESC-derived CECs to form a functional CE on the denuded Descemet's membrane., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the clinical efficacy of topical 0.1% lipid-based Thymoquinone (TQ) gel, as an antiplaque and antigingivitis agent., Materials and Methods: A randomized clinical trial was carried out in the Outpatient Department of Pediatric and Preventive Dentistry, Dr. Z.A. Dental College, India with a purposive sample of 60 healthy children of 12-18 years of age, having a gingival and plaque index ≥1; the children were divided into two groups by simple randomization. Group A (30 subjects) was advised to apply peanut amount of Chlorhexidine (CHX) gel, twice a day for 2min. Group B (30 subjects) was advised the same but with a peanut amount of 0.1% lipid-based TQ gel. The clinical parameters were the recording of plaque and gingival indices, prior to the treatment (baseline) and at the 14th and 28th day, respectively (post-treatment). The total duration of the study was 28 days with follow-up., Results: Data analysis was done by employing IBM Statistical Package for Social Sciences Windows software, version 20 (IBM Corp, Armonk, NY, USA). The 0.1% lipid-based TQ gel had a statistically significant reduction ( P < 0.001) in plaque index as compared with CHX gel during the 0-14th day and 0-28th day, respectively. Similarly, 0.1% lipid-based TQ gel showed a statistically significant reduction in gingival index ( P = 0.005) during the 0-14th day and a statistically significant reduction during the 0-28th day ( P < 0.001), as compared with CHX gel., Conclusions: Statistically significant reduction in plaque ( P < 0.001) and gingival index ( P < 0.001) with the usage of 0.1% lipid-based TQ gel., Competing Interests: The first author Dr. Saima Yunus Khan has no conflicts of interest. Coauthor Dr. Imran Ahmad is serving on the Board of Directors in several Pharma companies: 1. Jina Pharmaceuticals Inc., USA; 2. Novum Pharmaceutical Research Services, USA; 3. Accord Healthcare, USA; 4. Lambda Therapeutic Research Ltd., India; and 5. Head of Scientific Advisory Board at Intas Pharmaceuticals Ltd., India. The product that was tested in the current research belongs to Intas Pharmaceuticals Ltd., India, where there can be possible but not essential conflicts of interest. The reader should remain aware about the same., (Copyright: © 2021 Journal of International Society of Preventive and Community Dentistry.)

Peroxisomes, single-membrane intracellular organelles, play an important role in various metabolic pathways. The translocation of proteins from the cytosol to peroxisomes depends on peroxisome import receptor proteins and defects in peroxisome transport result in a wide spectrum of peroxisomal disorders. Here, we report a large consanguineous family with autosomal recessive congenital cataracts and developmental defects. Genome-wide linkage analysis localized the critical interval to chromosome 12p with a maximum two-point LOD score of 4.2 (θ = 0). Next-generation exome sequencing identified a novel homozygous missense variant (c.653 T > C; p.F218S) in peroxisomal biogenesis factor 5 (PEX5), a peroxisome import receptor protein. This missense mutation was confirmed by bidirectional Sanger sequencing. It segregated with the disease phenotype in the family and was absent in ethnically matched control chromosomes. The lens-specific knockout mice of Pex5 recapitulated the cataractous phenotype. In vitro import assays revealed a normal capacity of the mutant PEX5 to enter the peroxisomal Docking/Translocation Module (DTM) in the presence of peroxisome targeting signal 1 (PTS1) cargo protein, be monoubiquitinated and exported back into the cytosol. Importantly, the mutant PEX5 protein was unable to form a stable trimeric complex with peroxisomal biogenesis factor 7 (PEX7) and a peroxisome targeting signal 2 (PTS2) cargo protein and, therefore, failed to promote the import of PTS2 cargo proteins into peroxisomes. In conclusion, we report a novel missense mutation in PEX5 responsible for the defective import of PTS2 cargo proteins into peroxisomes resulting in congenital cataracts and developmental defects.

Purpose: To investigate changes at a molecular level in the mouse corneal endothelium (CE) exposed to chronic cigarette smoke (CS)., Methods: Pregnant mice (gestation days 18-20) were placed in a whole-body exposure smoking chamber, and a few days later pups were born. After 3.5 months of CS exposure, a ConfoScan4 scanning microscope was used to examine the corneal endothelial cells (CECs) of CS-exposed and control (Ct) mice. The CE was peeled under a microscope and maintained as four biological replicates (two male and two female) for CS-exposed and Ct mice; each replicate consisted of 16 CEs. The proteome of the CE was investigated through mass spectrometry., Results: The CE images of CS-exposed and Ct mice revealed a difference in the shape of CECs accompanied by a nearly 10% decrease in CEC density (P < 0.00003) following CS exposure. Proteome profiling identified a total of 524 proteins exhibiting statistically significant changes in CE from CS-exposed mice. Importantly, proteins associated with Descemet's membrane (DM), including COL4α1, COL4α2, COL4α3, COL4α4, COL4α5, COL4α6, COL8α1, COL8α2, and FN1, among others, exhibited diminished protein levels in the CE of CS-exposed mice., Conclusions: Our data confirm that exposure to CS results in reduced CEC density accompanied by diminished levels of multiple collagen and extracellular matrix proteins associated with DM.

Metabolomics is a study of the entire repertoire of metabolites in a cell at a particular time point. Here, we investigate the mouse lens at multiple embryonic and postnatal time points to establish the metabolome profile during early lens development. The lenses were isolated at six time points including embryonic day 15 (E15) and E18 and postnatal day 0 (P0), P3, P6, and P9. A total of four biological replicates of each time point, each consisting of 25 mg of lens tissue were preserved. Sample preparation was performed by protein precipitation followed by centrifugation to remove proteins and recover metabolites. The resulting extract was subjected to reverse phase/ultra-performance liquid chromatography-tandem mass spectrometry. Metabolome profiling identified a total of 353 metabolites in mouse lens, marked with an abundance of collagen, antioxidant, glycosaminoglycans, lipid, amino acid, and energy-related metabolites. A comparative metabolome analysis identified >200 metabolites exhibiting increased levels (p < 0.05) at latter time points relative to E15. Principal component analysis revealed distinct metabolomic signatures running from E15 to P9 while random forest analysis categorized lipid-, amino acid-, and nucleotide-related metabolites contributing significantly to the separation of the time points. To the best of our knowledge, this is the first report investigating the mouse lens metabolome at multiple embryonic and postnatal time points., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Here we report whole genome sequencing of four individuals (H3, H4, H5, and H6) from a family of Pakistani descent. Whole genome sequencing yielded 1084.92, 894.73, 1068.62, and 1005.77 million mapped reads corresponding to 162.73, 134.21, 160.29, and 150.86 Gb sequence data and 52.49x, 43.29x, 51.70x, and 48.66x average coverage for H3, H4, H5, and H6, respectively. We identified 3,529,659, 3,478,495, 3,407,895, and 3,426,862 variants in the genomes of H3, H4, H5, and H6, respectively, including 1,668,024 variants common in the four genomes. Further, we identified 42,422, 39,824, 28,599, and 35,206 novel variants in the genomes of H3, H4, H5, and H6, respectively. A major fraction of the variants identified in the four genomes reside within the intergenic regions of the genome. Single nucleotide polymorphism (SNP) genotype based comparative analysis with ethnic populations of 1000 Genomes database linked the ancestry of all four genomes with the South Asian populations, which was further supported by mitochondria based haplogroup analysis. In conclusion, we report whole genome sequencing of four individuals of Pakistani descent.

Here, we report proteome profiling of peripheral blood mononuclear cell (PBMC)-originated, induced pluripotent stem cell (iPSC)-derived, lens-like organoids termed lentoid bodies at two differentiation time points. A small aliquot of the blood sample was ascertained to collect PBMCs that were reprogrammed to iPSCs. The PBMC-originated, iPSCs were differentiated to lentoid bodies employing the "fried egg" method. Quantitative real-time PCR (qRT-PCR) analysis revealed increased expression levels of lens-associated markers in lentoid bodies while transmission electron microscopy identified closely packed lens epithelial- and differentiating fiber-like cells in lentoid bodies. Total cellular protein was extracted from lentoid bodies at differentiation day 25 and mass spectrometry identified a total of 9,473 proteins. The low counts of crystallin proteins at differentiation day 25 prompted us to re-examine the proteome at differentiation day 35 as we reasoned that 10 additional days of differentiation will increase the crystallin count. However, we did not detect any substantial increase in crystallin protein counts at differentiation day 35. In conclusion, we report generation and proteome profiles of PBMC-originated, iPSC-derived lentoid bodies at multiple differentiation time points., Competing Interests: Declaration of Competing Interest None, (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: This study was designed to identify the pathogenic variants in three consanguineous families with congenital cataracts segregating as a recessive trait., Methods: Consanguineous families with multiple individuals manifesting congenital cataracts were ascertained. All participating members underwent an ophthalmic examination. A small aliquot of the blood sample was collected from all participating individuals, and genomic DNAs were extracted. Homozygosity-based linkage analysis was performed using short tandem repeat (STR) markers. The haplotypes were constructed with alleles of the STR markers, and the two-point logarithm of odds (LOD) scores were calculated. The candidate gene was sequenced bidirectionally to identify the disease-causing mutations., Results: Linkage analysis localized the disease interval to chromosome 3p in three families. Subsequently, bidirectional Sanger sequencing identified two novel mutations-a single base deletion resulting in a frameshift (c.3196delC; p.His1066IlefsTer10) mutation and a single base substitution resulting in a nonsense (c.4270C>T; p.Arg1424Ter) mutation-and a known missense (c.4127T>C, p.Leu1376Pro) mutation in FYCO1 . All three mutations showed complete segregation with the disease phenotype and were absent in 96 ethnically matched control individuals., Conclusions: We report two novel mutations and a previously reported mutation in FYCO1 in three large consanguineous families. Taken together, mutations in  FYCO1 contribute nearly 15% to the total genetic load of autosomal recessive congenital cataracts in this cohort., (Copyright © 2020 Molecular Vision.)

Background: Effects of consanguineous marriage on human population are known. However, the inherited susceptibility to dental caries is unfortunately quite limited., Aim: This study aimed to assess the dental caries status (DMFT/deft [decayed-missed-filling teeth/decayed-extracted-filled teeth] index) in children born out of consanguineous and non-consanguineous marriages., Design: Household survey using a cross-sectional study design was planned, with a sample size of 2000 comprising (1600 non-consanguineous and 400 consanguineous) children, aged 6-9 years. Household survey was also planned using a systematic random sampling. Researcher conducted the study by visiting every 10th household of every 10th ward of Aligarh city, Uttar Pradesh, India. Information of risk factors for dental caries (sociodemographic, birth order, oral hygiene, feeding practices) was recorded on a pretested questionnaire with clinical examination of DMFT/deft index., Analysis: Student t test for equality of means and multivariate logistic regression were used., Results: By Student t test for equality of means, D component ( P = 0.003), d component ( P < 0.001), and deft score ( P < 0.001) were statistically significant in the consanguineous group. Multivariate logistic regression did not deduce any association of either of the study groups, but a significant association of risk factors with dental caries was observed., Conclusion: Dental caries that has multifactorial etiology, both environment and genetic factors, had an influence on the causation of dental caries in this study., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of International Society of Preventive and Community Dentistry.)

Purpose: Primary congenital glaucoma (PCG) is a genetically heterogeneous disorder caused by developmental defects in the anterior chamber and trabecular meshwork. This disease is an important cause of childhood blindness. In this study, we aim to identify the genetic determinants of PCG in three consanguineous families of Pakistani descent., Methods: Affected members of all three families underwent detailed ophthalmological examination including slit-lamp biomicroscopy. Blood samples were collected from affected and healthy members of all three families, and genomic DNA was extracted. Linkage analysis was performed for the known or reported loci of PCG to localize the disease interval, and logarithm of odds (LOD) scores were calculated. All protein-coding exons of the candidate gene, latent transforming growth factor-beta binding protein 2 ( LTBP2 ), were bidirectionally sequenced to identify the disease-causing mutation., Results: Short tandem repeat (STR) marker-based linkage analysis localized the critical interval to chromosome 14q with a maximum two-point LOD score of 2.86 (PKGL076), 2.8 (PKGL015), and 2.92 (PKGL042). Bidirectional Sanger sequencing of LTBP2 revealed three novel pathogenic variants, i.e., c.3028G>A (p.Asp1010Asn), c.3427delC (p.Gln1143Argfs*35), and c.5270G>A (p.Cys1757Tyr) in PKGL076, PKGL015, and PKGL042, respectively. All three mutations segregated with the disease phenotype in their respective families and were absent in 200 ethnically matched normal chromosomes., Conclusions: We identified three novel mutations, p.D1010N, p.Q1143Rfs*35, and p.C1757Y, in LTBP2 responsible for PCG., (Copyright © 2020 Molecular Vision.)

Purpose: To investigate the genetic basis of autosomal recessive congenital cataracts (arCC) in a large consanguineous Pakistani family., Methods: All participating members of family, PKCC074 underwent an ophthalmic examination. Slit-lamp photographs were ascertained for affected individuals that have not been operated for the removal of the cataractous lens. A small aliquot of the blood sample was collected from all participating individuals and genomic DNAs were extracted. A genome-wide scan was performed with polymorphic short tandem repeat (STR) markers and the logarithm of odds (LOD) scores were calculated. All coding exons and exon-intron boundaries of HSF4 were sequenced and expression of Hsf4 in mouse ocular lens was investigated. The C-terminal FLAG-tagged wild-type and mutant HSF4b constructs were prepared to examine the nuclear localization pattern of the mutant protein., Results: The ophthalmological examinations suggested that nuclear cataracts are present in affected individuals. Genome-wide linkage analyses localized the critical interval to a 10.95 cM (14.17 Mb) interval on chromosome 16q with a maximum two-point LOD score of 4.51 at θ = 0. Sanger sequencing identified a novel missense mutation: c.433G>C (p.Ala145Pro) that segregated with the disease phenotype in the family and was not present in ethnically matched controls. Real-time PCR analysis identified the expression of HSF4 in mouse lens as early as embryonic day 15 with a steady level of expression thereafter. The immunofluorescence tracking confirmed that both wild-type and mutant HSF4 (p.Ala145Pro) proteins localized to the nucleus., Conclusion: Here, we report a novel missense mutation in HSF4 associated with arCC in a familial case of Pakistani descent., Competing Interests: The authors have declared that no competing interests exist.

The ocular lens serves as an excellent system to investigate the intricate details of development and differentiation. Generation of lentoid bodies or lens-like structures using pluripotent stem cells is important for understanding the processes critical for lens morphogenesis and the mechanism of cataractogenesis. We previously reported the generation of peripheral blood mononuclear cell (PBMC)-originated, induced pluripotent stem cells (iPSCs). Here, we report generation of lentoid bodies from human embryonic stem cells (hESCs) and (PBMC)-originated, iPSCs employing the "fried egg" method with brief modifications. The ultrastructure analysis of hESC- and iPSC-derived lentoid bodies identified closely packed lens epithelial- and differentiating fiber-like cells. In addition, we performed RNA sequencing (RNA-Seq) based transcriptome profiling of hESC- and iPSC-derived lentoid bodies at differentiation day 25. Next-generation RNA sequencing (RNA-Seq) of hESC- and iPSC-derived lentoid bodies detected expression (≥0.659 RPKM) of 13,975 and 14,003 genes, respectively. Comparative transcriptome analysis of hESC- and iPSC-derived lentoid bodies revealed 13,563 (>96%) genes common in both datasets. Among the genes common in both transcriptome datasets, 12,856 (~95%) exhibited a quantitatively similar expression profile. Next, we compared the mouse lens epithelial and fiber cell transcriptomes with hESC- and iPSC-derived lentoid bodies transcriptomes and identified > 96% overlap with lentoid body transcriptomes. In conclusion, we report first-time comparative transcriptome analysis of hESC- and iPSC-derived lentoid bodies at differentiation day 25.

The present study was designed to record the effect of λ-cyhalothrin, Bifenthrin, and Glyphosate on the mortality, avoidance behavior, foraging activity, and activity of Acetylcholine esterase (AChE) and Carboxylesterase (CarE) in Neoscona theisi (Walckenaer, 1841). Highest mortality (70%) in N. theisi was recorded against λ-cyhalothrin. However, Glyphosate was found to be least toxic. Spider spent less time on insecticides/herbicide-treated surfaces. Insecticides/herbicide-treated N. theisi consumed less prey than untreated control spiders. Similarly, when N. theisi were offered insecticide/herbicide-treated prey, they consumed significantly less. Increased AChE and CarE activities were recorded in insecticides/herbicide-treated spiders as compared to control group. Total protein contents were less in insecticides/herbicide-treated spiders than control group. The results revealed that λ-cyhalothrin is more harmful to spiders as compared to Bifenthrin and Glyphosate. It is suggested that the effect of all pesticides used in agro-ecosystem on beneficial insects should be evaluated before using them in the fields., (© The Author(s) 2019. Published by Oxford University Press on behalf of Entomological Society of America.)

During chronic inflammation, neutrophils acting locally as effector cells not only activate antibacterial defense but also promote the inflammatory response. Interleukin 8 (IL-8), the main cytokine produced by activated neutrophils, positively correlates with the severity of respiratory tract diseases. By screening European plants traditionally used for treating respiratory tract diseases, we found that extracts of aerial parts of Eupatorium cannabinum inhibit IL-8 release from neutrophils. Using bioassay-guided fractionation, we identified five sesquiterpene lactones, eupatoriopicrin (1), 5'-deoxyeupatoriopicrin (2), hiyodorilactone A (3), 3-hydroxy-5'- O-acetyleupatoriopicrin = hiyodorilactone D (4), and hiyodorilactone B (5), that efficiently (IC 50 < 1 μM) inhibited IL-8 and TNF-α release in lipopolysaccharide (LPS)-stimulated human neutrophils. Moreover, all these sesquiterpene lactones suppressed the adhesion of human neutrophils to an endothelial monolayer by downregulating the expression of the β2 integrin CD11b/CD18 on the neutrophil surface. Furthermore, eupatoriopicrin efficiently suppressed LPS-induced phosphorylation of p38 MAPK and ERK and attenuated neutrophil infiltration in the thioglycolate-induced peritonitis model in mice. Altogether, these results demonstrate the potential of the sesquiterpene lactone eupatoriopicrin as a lead substance for targeting inflammation.

The corneal endothelium (CE), a monolayer of hexagonal cells constitutes the innermost layer of the cornea that is critical in maintaining clarity by mediating hydration through barrier and pump functions. Corneal endothelial cells (CECs) have limited proliferative potential and therefore generation of CECs has been undertaken by many groups. We previously reported generation of CECs from peripheral blood mononuclear cell (PBMC)-originated, induced pluripotent stem cells (iPSCs). In here, we extend our analysis through next-generation seqeuncing based transcriptome profiling of H9 human embryonic stem cell (hESC)- and human PBMC-originated, iPSC-derived CECs. The differentiating CECs on day 20 (D20) exhibited a tightly packed hexagonal/polygonal shape expressing zona occludens-1 (ZO-1) and N-cadherin at the cell boundaries. Next-generation RNA sequencing of hESC- and iPSC-derived CECs detected expression (≥0.659 RPKM) of 13,546 and 13,536 genes, respectively. Comparative transcriptome analysis of hESC- and iPSC-derived CECs revealed 13,208 (>96%) genes common in both transcriptomes. Among the 13,208 genes common in these transcriptomes, 12,580 (>95%) exhibited a quantitatively similar expression. To the best of our knowledge, this is the first report presenting comparative transcriptome analysis of hESC- and iPSC-derived CECs., (Copyright © 2018 Elsevier Ltd. All rights reserved.)