bluuebunny/crossref_metadata_2025 huggingface dataset:
Microtubules regulate pancreatic β-cell heterogeneity via spatiotemporal control of insulin secretion hot spots
Authors: Trogden Kathryn P , Lee Justin , Bracey Kai M , Ho Kung-Hsien , McKinney Hudson , Zhu Xiaodong , Arpag Goker , Folland Thomas G , Osipovich Anna B , Magnuson Mark A , Zanic Marija , Gu Guoqiang , Holmes William R , Kaverina Irina
Published: November 2021

Heterogeneity of glucose-stimulated insulin secretion (GSIS) in pancreatic islets is physiologically important but poorly understood. Here, we utilize mouse islets to determine how microtubules (MTs) affect secretion toward the vascular extracellular matrix at single cell and subcellular levels. Our data indicate that MT stability in the β-cell population is heterogenous, and that GSIS is suppressed in cells with highly stable MTs. Consistently, MT hyper-stabilization prevents, and MT depolymerization promotes the capacity of single β-cell for GSIS. Analysis of spatiotemporal patterns of secretion events shows that MT depolymerization activates otherwise dormant β-cells via initiation of secretion clusters (hot spots). MT depolymerization also enhances secretion from individual cells, introducing both additional clusters and scattered events. Interestingly, without MTs, the timing of clustered secretion is dysregulated, extending the first phase of GSIS and causing oversecretion. In contrast, glucose-induced Ca2+ influx was not affected by MT depolymerization yet required for secretion under these conditions, indicating that MT-dependent regulation of secretion hot spots acts in parallel with Ca2+ signaling. Our findings uncover a novel MT function in tuning insulin secretion hot spots, which leads to accurately measured and timed response to glucose stimuli and promotes functional β-cell heterogeneity.
mTOR-dependent translation drives tumor infiltrating CD8+ effector and CD4+ Treg cells expansion
Authors: De Ponte Conti Benedetta , Miluzio Annarita , Grassi Fabio , Abrignani Sergio , Biffo Stefano , Ricciardi Sara
Published: November 2021

We performed a systematic analysis of the translation rate of tumor-infiltrating lymphocytes (TILs) and the microenvironment inputs affecting it, both in humans and in mice. Measurement of puromycin incorporation, a proxy of protein synthesis, revealed an increase of translating CD4+ and CD8+ cells in tumors, compared to normal tissues. High translation levels are associated with phospho-S6 labeling downstream of mTORC1 activation, whereas low levels correlate with hypoxic areas, in agreement with data showing that T cell receptor stimulation and hypoxia act as translation stimulators and inhibitors, respectively. Additional analyses revealed the specific phenotype of translating TILs. CD8+ translating cells have enriched expression of IFN-γ and CD-39, and reduced SLAMF6, pointing to a cytotoxic phenotype. CD4+ translating cells are mostly regulatory T cells (Tregs) with enriched levels of CTLA-4 and Ki67, suggesting an expanding immunosuppressive phenotype. In conclusion, the majority of translationally active TILs is represented by cytotoxic CD8+ and suppressive CD4+ Tregs, implying that other subsets may be largely composed by inactive bystanders.
Framework for rapid comparison of extracellular vesicle isolation methods
Authors: Ter-Ovanesyan Dmitry , Norman Maia , Lazarovits Roey , Trieu Wendy , Lee Ju-Hyun , Church George M , Walt David R
Published: November 2021

Extracellular vesicles (EVs) are released by all cells into biofluids and hold great promise as reservoirs of disease biomarkers. One of the main challenges in studying EVs is a lack of methods to quantify EVs that are sensitive enough and can differentiate EVs from similarly sized lipoproteins and protein aggregates. We demonstrate the use of ultrasensitive, single-molecule array (Simoa) assays for the quantification of EVs using three widely expressed transmembrane proteins: the tetraspanins CD9, CD63, and CD81. Using Simoa to measure these three EV markers, as well as albumin to measure protein contamination, we were able to compare the relative efficiency and purity of several commonly used EV isolation methods in plasma and cerebrospinal fluid (CSF): ultracentrifugation, precipitation, and size exclusion chromatography (SEC). We further used these assays, all on one platform, to improve SEC isolation from plasma and CSF. Our results highlight the utility of quantifying EV proteins using Simoa and provide a rapid framework for comparing and improving EV isolation methods from biofluids.
Differential adhesion regulates neurite placement via a retrograde zippering mechanism
Authors: Sengupta Titas , Koonce Noelle L , Vázquez-Martínez Nabor , Moyle Mark W , Duncan Leighton H , Emerson Sarah E , Han Xiaofei , Shao Lin , Wu Yicong , Santella Anthony , Fan Li , Bao Zhirong , Mohler William A , Shroff Hari , Colón-Ramos Daniel A
Published: November 2021

During development, neurites and synapses segregate into specific neighborhoods or layers within nerve bundles. The developmental programs guiding placement of neurites in specific layers, and hence their incorporation into specific circuits, are not well understood. We implement novel imaging methods and quantitative models to document the embryonic development of the C. elegans brain neuropil, and discover that differential adhesion mechanisms control precise placement of single neurites onto specific layers. Differential adhesion is orchestrated via developmentally regulated expression of the IgCAM SYG-1, and its partner ligand SYG-2. Changes in SYG-1 expression across neuropil layers result in changes in adhesive forces, which sort SYG-2-expressing neurons. Sorting to layers occurs, not via outgrowth from the neurite tip, but via an alternate mechanism of retrograde zippering, involving interactions between neurite shafts. Our study indicates that biophysical principles from differential adhesion govern neurite placement and synaptic specificity in vivo in developing neuropil bundles.
An Observational Study of Corneal Endothelial Alterations in Eyes with Unilateral Pseudoexfoliation
Authors: Thool Archana , Ramani Rashmi , Tidake Pravin
Published: November 2021

Introduction: Pseudoexfoliation (PXF) is an age-related generalised disorder of extracellular matrix primarily affecting eyes. It is characterised by deposition of pseudoexfoliative material in the anterior segment of eye. Also it is a bilateral condition but can have asymmetric presentation and can be clinically seen only in one eye. Alteration in endothelial cell morphology along with other alteration in anterior segment of the eye can compromise the surgical outcome. Aim: To evaluate the corneal endothelial cell density and morphology in patients with unilateral PXF. Materials and Methods: The present study was hospital-based cross-sectional observational study which included 55 patients with unilateral PXF, who came to the Department of Opthalmology, Acharya Vinoba Bhave Rural Hospital (AVBRH), Wardha, Maharashtra, India between June 2020 to November 2020. Specular microscopy was performed on all eyes to evaluate cell density and morphology, coefficient of variation in cell size and percentage of hexagonal cells in corneal endothelium and compared with fellow normal eye. Statistical analysis was done by using descriptive and inferential statistics using students unpaired t-test, p-value <0.05 was considered as level of significance. Results: The present study included 55 patients, of which 26 were males and 29 were females. Mean age of the patients was 63.85±7.05 years. Majority of patients were in the range of 61 to 70 years (56.36%). The mean corneal endothelial cell density in the PXF eye was 2299.54±84.95 cells/mm2, which was significantly lower as compared to fellow normal eye with p-value <0.001. Mean coefficient of variation of cell size in PXF eye was 35.49±4.62, p-value=0.064 and hexagonality was 51.12±4.91, p-value=0.13. Both the parameters were statistically non significant on comparison of two eyes. Central corneal thickness was thicker in pseudoexfoliative eye of 551.29±33.11 microns (μm), than fellow eye but was statistically non significant. Conclusion: Eyes with PXF had alteration in endothelial cell morphology with decrease in cell density as compared to eyes without PXF clinically.
Knowledge and Adoption of Commercial Vegetable Growers in District Budgam, J&K
Authors: Iqbal Badar , Ahmad Mushtaq , Nissar Roman , A. Bhat Raies , Badrudurez . , Islam Noor Ul , Rashid Zahida , Gani G.
Published: November 2021

The study was conducted on 250 vegetable growers selected from ten villages of Budgam district of Jammu and Kashmir. The basic objective of the study was to ascertain the knowledge possessed and adoption level of growers as well as the economic status of vegetable growers. The result revealed that 50.80 per cent of the respondents had medium level of knowledge, 48.40 per cent of respondents belonged to medium adoption category and majority of 60.80 per cent of the vegetable growers belong to the middle economic status group.
Skew Arcsine Distribution
Authors: Celik Nuri
Published: November 2021

The arcsine distribution is very important tool in statistics literature especially in Brownian motion studies. However, modelling real data sets, even when the potential underlying distribution is pre-defined, is very complicated and difficult in statistical modelling. For this reason, we desire some flexibility on the underlying distribution. In this study, we propose a new distribution obtained by arcsine distribution with Azzalini’s skewness procedure. The main characteristics of the proposed distribution are determined both with theoretically and simulation study.
Perceived Profitability of Agroforestry in Rural Multan of Pakistan
Authors: Zubair Muhammad , Atif Tasleem Syed Muhammad , Hussain Syed Bilal
Published: November 2021

Agroforestry remained a profitable venture across the globe if managed well spatially and temporarily. Farmlands are viable option to practice agroforestry in Pakistan for sustaining farmers’ livelihoods as well as to provide products and services for ever increasing population. This study focusses on how agroforestry is being perceived as profitable enterprise by the farmers in Multan, Punjab Pakistan. Rural areas of Multan were selected for this study and 200 farmers were selected randomly from 10 villages across 02 union councils using multi-stage sampling procedure. The results revealed that agroforestry remained the prime land use system as reported by the farmers (99%) belonging to agropastoral and agroforestry practice. Moreover, agroforestry perceived as high-income system providing variety of product (increased crop and fodder production, variety of products and income) and services (Carbon sequestration, climate amelioration, soil conservation). The study concluded the need for public-private partnership for the promotion of agroforestry in the region.
Bioassay Guided Screening of Cryptolepis Extracts for Onward Synthesis of Nano Ferrites
Authors: Murtaza Hafza , Sikander Aasia , Murtaza Umema , Masroor Ashir , Ghafoor Filza
Published: November 2021

A study was designed to investigate the presence of nanoferrites in Cryptolepis buchanani. In this study, various leaves and stem organic extracts were prepared separately using the solvents viz., n-hexane, ethyl acetate, ethanol and water. Different phytochemical tests for alkaloids, carbohydrates, oils, amino acids and others were performed to determine their presence in the extracts. These plant extracts were used for screening of sample via UV and HPLC techniques to compare the wavelength and absorbance, and retention time on chromatogram by extracts, respectively. The results showed the presence of alkaloids, carbohydrates and proteins in all the samples. However, other compounds were present randomly. Spectroscopy showed highest peaks with ethyl acetate extracts and the lowest with water. The surface properties and size of nickel-zinc nano ferrites were evaluated by Energy-dispersive X-ray spectroscopy (EDX) and Scanning Electron Microscopy (SEM). The former, showed the presence of nickel (Ni) and zinc (Zn) weighing 4.27⁒ of N ,6.89⁒ of C and 35.5⁒ of O in the sample which confirmed the presence of nano ferrites in leaves and stem of C. buchanani.
Brown and Yellow Rust of Wheat in India –Significance of Climate on It’s Races and Resistance
Authors: Srinivas Katravath , Rahman Shaik Moizur , Yadav Manu , Sharma Mamta
Published: November 2021

Wheat is one of the most important staple food crops having global economic significance. Grown globally around 215 million hectares area with production of more than 600 million tons. Wheat is constrained in its production due to several biotic factors, among them yellow rust of wheat, Puccinia striiformis Westend. f.sp. tritici Eriks and Henn. (Pst) and brown rust of wheat, Puccinia recondita f.sp. tritici (Eriks. and E. Henn.) D.M. Henderson (Ptr) continues to be a serious threat and dominant factor limiting its yield potential globally. The estimated yield losses range from 10-70%, while in a severe epidemic the grain damage can be as great as 100%. Pathogens are considered to be favoured by the cooler areas but current races are more adaptable to high temperatures causing significant yield reduction in wheat. In India, prevalent pathotypes for yellow rust include 46S119, 110S119, and 238S119. Yr5, Yr10, Yr15, YrSp, and YrSk genes are resistant to Pst pathotypes in Indian conditions, while in the case of leaf rust of wheat, prevalent pathotypes are 77-5, 77-9, and 104-2. Lr9, Lr19, Lr24, Lr25, Lr29, Lr32, Lr39, Lr45, and Lr47 are the genes having resistance to Ptr pathotypes in Indian conditions. This publication provides a comprehensive overview of the stripe and leaf rusts of wheat in India and their virulent races, types of host resistance and provides a tool for effective management of wheat rust disease.
Studies on the Growth Responses of Common Carp (Cyprinus carpio) Progenies Raised Using Different Starter Diets
Authors: Ed-Idoko J. O. , Solomon S. G. , Annune P. A. , Ikap S. I. , Iber B. T. , Torsabo D.
Published: November 2021

200 fry of carp obtained from induced breeding by stripping were fed three times daily ad libitum with Artemia (DT1), commercial starter diet (DT2), and dried egg yolk (DT3)for  8 weeks. Each  treatments were in triplicates in indoor hatchery. At the end of the experiment, the progenies mean weight gained (MWG) was highest in the treatments fed Artemia (3.490±0.015a) as compared to others with significant difference (P<0.05).Mean weight gained (MWG) was highest in the treatments fed Artemia. Percentage weight gain (%WG) and specific growth rate (SGR) had no significant differences (P<0.05). Feed conversion ratio (FCR) was highest (P<0.05) in treatment fed with smashed egg yolk. Feed conversion efficiency (FCE) was highest (P<0.05) in the treatment fed with composed feed. Mortality rate was highest in treatment fed with Artemia, and percentage survival was highest (P<0.05) in treatment fed with composed feed. Percentage jumpers per treatment were highest in Artemia diet. In conclusion, it is imperative that Artemia feed (amidst other starter diets researched on) is most preferable for the optimum growth and development of common carp fry.
The Effect of Using Biological Treatment on Microbial Growth during the Malting of Sorghum
Authors: Ayodeji Oluwatosin Charles , Titilayo Afolabi Folake , Musliu Abdulkadir , Oluwafemi Fasiku
Published: November 2021

Malting is an important industrial product with a huge market outlet. Sorghum grain carries a numerous and variable, microbial population that mainly consists of bacteria, yeasts, and filamentous fungi. Sorghum malt is heavily reliant on chemical control of moulds and coliforms. This research aimed at investigating ways of improving malt quality and safety, using starter cultures of lactic acid bacteria and yeast, during the steeping stage of malting. All the steep treatments contained a sizeable population of moulds, greater than 4logcfu/mL, at 0hrs of steeping. A 3Log decrease was recorded in the steep treatment containing only single culture of Lactobacillus plantarum All the steeping treatments achieved varying levels of anti-nutrient reduction. The Lactobacillus plantarum CLB8 steep reduced the phytate level by as much as 47% when compared to the phytate level in sorghum grain. The combined cultures of Lactobacillus plantarum CLB8 and Saccharomyces cerevisiaeCYT1 reduced the phytate content by as much as 40% when compared to the sorghum grain without treatment. When compared to the control steep, the Lactobacillus plantarum CLB8 steep improved the anti-nutrient degradation by 31%. The combined cultures of Lactobacillus plantarum CLB8 and Saccharomyces cerevisiae CYT1 reduced the phytate content by as much as 23% when compared with the control steep. The polyphenol content was reduced by about 46% in the Lactobacillus plantarum CLB8 steep and 29% in the combined cultures of Lactobacillus plantarum CLB8 and Saccharomyces cerevisiae CYT1 steep when compared to the polyphenol content in the whole sorghum grain. Only the Lactobacillus plantarum CLB8 steep had better polyphenol reduction than the control with a 9.6% reduction more than the control. It was concluded that lactic acid bacteria can be apply as a biological control organism in malting of grains.
Mitigation of Lead Neurotoxicity by Aqueous Fruit Extract of Adansonia digitata in Adult Wistar Rats
Authors: Otong Eduitem S. , Musa Sunday A. , Danborno Barnabas , Sambo Sohnap J.
Published: November 2021

Aim: The current study seeks to explore the neuroprotective benefits of Adansonia digitata against lead induced memory impairment, neurotransmitter/AChE activity imbalance, oxidative stress as well as brain damage.

Methodology: Thirty male adult rats weighing 160g-200g were divided randomly into six groups (I-V1) consisting of five (5) rats in each group. Group I served as control and were administered with distilled water (1 ml/kg) only while groups II -VI were treatment groups. Group II were administered 250 mg/kg of Adansonia digitata; group III were administered 30 mg/kg of lead; Group IV were administered 250 mg/kg of Adansonia digitata plus 30 mg/kg of lead; Group V were administered 500 mg/kg of Adansonia digitata plus 30 mg/kg of lead; Group VI were administered 30 mg/kg of lead plus 10 mg/kg of succimer. All administrations were carried out through oral gavage for a period of 28 days.

Results: Lead administration caused memory impairment, decreased dopamine concentration and AChE activity in brain, induced oxidative stress resulting in brain damage.  Adansonia digitata treatment significantly (P<.001) attenuated memory impairment, modulated dopamine concentration and AChE activity, prevented oxidative stress and ameliorated histopathological changes in the brain of Wistar rats.

Conclusion: The result showed that Adansonia digitata ameliorates lead-induced memory impairment in Wistar rats by improving memory index, controlling dopamine concentration and AChE activity, preventing oxidative stress and neuronal degeneration.
A Review of Indian Perceptions on Condom Use
Authors: Wankhede Pratibha , Wanjari Mayur
Published: November 2021

In the late 1960s, India's National Family Planning Programme introduced condoms as one of the family planning methods. Since its inception, the condom has been promoted as a method of family planning through social marketing. With the rising prevalence and incidence of sexually transmitted infections (STIs), such as HIV/AIDS, the condom has been promoted as a dual method of protection against both unintended pregnancies and sexually transmitted infections. Despite different initiatives at various levels, overall condom use among Indian couples remains low. In this paper, we examine the research on condom perception among Indian couples. The report specifically evaluates research and strategies designed to enhance condom usage among couples; predictors of condom use; reasons for not using a condom; and perception versus the experience of condom failure. Non-acceptance by partners, perceived ineffectiveness, reduced comfort, lack of sexual satisfaction, husband's alcohol usage, depression, and anxiety, and not being accessible at the time were among the reported condom-related issues. The importance of the media in promoting condom use was mentioned as a significant strategy to raise awareness and use. Acceptance of male condoms would be aided in a variety of ways.
2019-nCoV2: An Overview of Awareness about Emerging and Re-emerging Infectious Diseases and Sustainable Development: A Retrospective and Cross-sectional Study
Authors: Guetat Arbi , Alshrari Ahmed S. , Chebbi Taha , Abdelwahab Abdelrhman T. , Abdelfattah Marwa A. , Alenezi Ahmed S. , Al-Ghamdi Faraj
Published: November 2021

The doctrine of Sustainability is known to be a holistic approach and there is an increased recognition that Sustainable Development Goals (SDGs) are linked to one another. Within less than two decades, the present pandemic (COVID19) is the third emerged highly pathogenic and deadly human coronaviruses. Hence, risk of emerging infectious diseases (EIDs) is a key component of the sustainable development approach.  In order to determine knowledge, awareness and attitude, an online questionnaire-based survey was conducted in a total of 114 members of Saudi Arabian’s staff. Results about knowledge and awareness varied between 98.2 % and 38.59%. About 77.21% (Mean value) of the participants are well awarded about the subject of the study. The constant collation of the showed that the majorities of the correlation between variables were very strong (20.87%) or strong (38.46%). Synthetically, themes such as human impact on the environment, human health and global stability, SDGs and pandemics, human susceptibility for diseases and uses of drugs were found to be interdepend in the perception of the academic staff in the Saudi Arabian universities. It is suggested that there is a need to introduce time-oriented policy, and implement awareness plans in the country for the future generation.
The Relationship of Perceived Body Image, Body Mass Index and Physical Activity with Weight Status among Students at King Abdulaziz University Hospital
Authors: Alobiri Futoon S. , Alharbi Roaa A. , Algethami Mohammed R. , Ateeq Raghdah H. , Badurayq Aseel M. , Almuhyawi Razan A. , Jamal Wisam H.
Published: November 2021

Aim: Identify the relation between poor esteem for body image and weight-related behaviors. The results will help increase awareness and improve students’ lifestyles to have a better body image and achieve ideal body weight.

Methods: A cross-sectional study was conducted among King Abdulaziz University medical students (n= 460) between July to the end of August 2019. Data was collected using the International physical activity questionnaire (IPAQ), figure rating scale (FRS) and analyzed using SPSS software.

Result: The results showed that the average Body Mass Index (BMI) was 24.80 ± 11.89. Participant sex was an important factor influencing the prevalence of obesity; male students were more obese than female students with a significant difference (p<0.001). The level of body satisfaction was also affected by gender. Students in preclinical years were more likely to gain weight more than clinical years students.

Conclusion: The results show a significant relationship between body satisfaction and gender (P<0.0001) despite having diverse BMIs. Overweight and obese males and females' participants had the lowest body satisfaction. Females who were too thin and had low BMIs described themselves as normal, while males describe themselves as too thin. Conversely, females with high BMIs described themselves as too fat, while males described themselves as normal. This could be due to different factors. Also, underweight females and males have high body satisfaction, which can lead to dangerous behaviors to maintain low body weight which cause negative health consequences.
Folklore Herbal Plants as a Safe and Natural Hair Depilatories
Authors: Shanker Kalakotla , Shaik Shamshe , Vijayanandhan V. , Sunilkumar Reddy Tamatam , S. M. N. Mydin Rabiatul Basria , Dhanabal S. P.
Published: November 2021

Hair is one of the distinguishing characteristics of mammals, and it serves a variety of functions including protection from external forces, production of sebum, apocrine sweat, and pheromones. However, the unwanted hair growth is always a worrying aspect among teenage girls and women. The present study is the need of selecting herbal depilatories over chemical depilatories due to its high efficacy, safety and lesser side effects. The various types of hair removal process, herbs showing depilatory action and their composition for herbal cream are studied. According to statistics, the use of depilatories has been steadily expanding, and the global hair removal products market was valued at USO 2.2 billion in 2018, with a CAGR of 5.5 percent predicted from 2019 to 2025. Depilatories are the cosmetic preparation which is used to remove the hair from skin, in chemical depilatories the main active ingredients are salts of thioglycolic acids, sulphides and stannites which can produce rashes and side effects on long time usage, whereas herbal depilatories include active ingredients like Turmeric, Indian neetle, Neem, Tanner’s cassia, Apple cider vinegar, Paw-paw extract etc. which are tremendously safe to use. Hence in this study we have been discussed about importance of few folklore herbal medicine and preparation methods of both chemical and herbal depilatories.
A Study on Prevalence of Anemia among Pregnant Women Attending Antenatal Clinic at Rural Health Centre (RHC) and Hospital, Jabalpur City, M.P.
Authors: Tiwari Jyoti , Linson C. C.
Published: November 2021

Weakness is a wholesome lack issue, and 56 percent of the women living in developing countries are pallid (World Health Organization). Iron deficiency is the second leading cause of maternal death in India, accounting for 20% of all maternal deaths. To focus on the incidence of sickliness in pastoral expecting women and investigate the factors coupled with paleness. The review focused on pregnant women, who visited the Maternity Clinic of the Rural Health Preparation Center and saw a clinic in India. The study will last one year, beginning on September 1, 2021, and ending on September 7, 2021. According to World Health Organization guidelines, iron insufficiency was designated. The total number of participants was 269, as determined by a pre-planned and pre-tested survey. The review subjects ranged in age from 20 to 30 and above 30. We've also found iron deficiency in the first, second, and third trimesters. Continuous renal sickness and postpartum drain were restricted as of late blood bonded. The conclusion of iron deficiency was attempted using a fringe blood smear analysis and a conventional haemoglobin analysis using Shale's approach. The prevalence of iron insufficiency is 58.36 percent across 269 individuals, including mild, moderate, and severe weakness. The mother's age, education, socioeconomic standing, equality, and food preferences were discovered to be profoundly important determinants. Family structure, size, and menarche completion were not found to be significant predictors of illness. The significant incidence of iron deficiency (58.36 percent) indicates that the National Nutrition Anemia Prophylaxis Program is not being implemented properly.
SAMHSA keeps $75/$15 CM limits despite methamphetamine epidemic, OIG ruling
Authors: Knopf Alison
Published: November 2021

The rule that patients can only get $75 a year as part of contingency management (CM) treatment is, in fact, nonexistent, as of last year's ruling by the Department of Health and Human Services Office of Inspector General (OIG) (see “CM for stimulant use disorder: No limit imposed by OIG,” ADAW Nov. 8; https://onlinelibrary.wiley.com/doi/full/10.1002/adaw.33255). However, the Substance Abuse and Mental Health Services Administration (SAMHSA) still has that rule for all of its funding.
Former acting director of ONDCP calls for more treatment
Authors: Knopf Alison
Published: November 2021

Regina LaBelle, then acting director of the Office of National Drug Control Policy (ONDCP), spoke at a Georgetown University conference in September on model opioid litigation. She referred to how the opioid overdose epidemic began — with prescription overdoses. One small town in West Virginia, Kermit, was flooded with opioids. It turns out they were coming from a pill mill in Florida, where a doctor would come in for an hour a day dispensing pain pills, and the buyers would fly back to West Virginia with them. “These doctors were not treating pain; they were operating a criminal enterprise,” said LaBelle.
Customizing New Titanium Dioxide Nanoparticles with Controlled Particle Size and Shape Distribution: A Feasibility Study Toward Reference Materials for Quality Assurance of Nonspherical Nanoparticle Characterization
Authors: Pellegrino Francesco , Ortel Erik , Mielke Johannes , Schmidt Roland , Maurino Valter , Hodoroaba Vasile-Dan
Published: November 2021

An overview is given on the synthesis of TiO2 nanoparticles with well‐defined nonspherical shapes (platelet like, bipyramidal, and elongated), with the focus on controlled, reproducible synthesis, as a key requirement for the production of reference materials with homogeneous and stable properties. Particularly with regard to the nanoparticle shapes, there is a high need of certified materials, solely one material of this type being commercially available since a few months (elongated TiO2). Further, measurement approaches with electron microscopy as the golden method to tackle the nanoparticle shape are developed to determine accurately the size and shape distribution for such nonspherical particles. A prerequisite for accurate and easy (i.e., automated) image analysis is the sample preparation, which ideally must ensure a deposition of the nanoparticles from liquid suspension onto a substrate such that the particles do not overlap, are solvent‐free, and have a high deposition density. Challenges in the synthesis of perfectly monodispersed and solvent‐free TiO2 nanoparticles of platelet and acicular shapes are highlighted as well as successful measurement approaches on how to extract from 2D projection electron micrographs the most accurate spatial information, that is, true 3D size, for example, of the bipyramidal nanoparticles with different geometrical orientations on a substrate.
Roadmap for Ferroelectric Domain Wall Nanoelectronics
Authors: Sharma Pankaj , Moise Theodore S. , Colombo Luigi , Seidel Jan
Published: November 2021

Ferroelectric domain walls naturally form at nanoscale interfaces of polar order leading to electronic properties distinct from the bulk that can also be electrically programmed. These nanoscale features currently are being actively explored for the development of agile, low‐energy electronics for applications in memory, logic, and brain‐inspired neuromorphic computing. In this article, the authors review the state of the art, the latest developments, and outline key device and material challenges, emerging opportunities, and new directions for the accelerated engineering and commercialization of domain wall technology.
Extracellular Vesicles Generated Using Bioreactors and their Therapeutic Effect on the Acute Kidney Injury Model
Authors: Kang Hyejin , Bae Yeon‐hee , Kwon Yongmin , Kim Sejoong , Park Jaesung
Published: November 2021

Extracellular vesicles (EVs) are nano‐sized vesicles secreted by cells, having beneficial effects for various types of regenerative processes. Although EVs have shown promising effects as therapeutic agents, these effects are difficult to research due to the limitations of EV production. In this study, an EV production method based on a flat‐plate bioreactor is introduced. The bioreactor produces approximately seven times more mesenchymal stem cell‐derived EVs than static culture conditions. The mechanism underlying the increased production of EVs in a flat‐plate bioreactor and its application to acute kidney injury is investigated. This study describes the mechanism of EV production by demonstrating the link between EV biogenesis and increased calcium ion concentration under flow conditions. EVs secreted by cells cultured in the bioreactor have therapeutic efficacy in terms of improving kidney damage, resulting in tissue regeneration in a cisplatin‐induced acute kidney injury model. This method will help overcome the limitations of EV production, and the analysis of the application of EVs will increase their reliability as well as the understanding of the use of bioreactor‐derived EVs as therapeutic agents.
Growth Media Conditions Influence the Secretion Route and Release Levels of Engineered Extracellular Vesicles
Authors: Bost Jeremy P. , Saher Osama , Hagey Daniel , Mamand Doste R. , Liang Xiuming , Zheng Wenyi , Corso Giulia , Gustafsson Oskar , Görgens André , Smith CI Edvard , Zain Rula , El Andaloussi Samir , Gupta Dhanu
Published: November 2021

Extracellular vesicles (EVs) are nanosized cell‐derived vesicles produced by all cells, which provide a route of intercellular communication by transmitting biological cargo. While EVs offer promise as therapeutic agents, the molecular mechanisms of EV biogenesis are not yet fully elucidated, in part due to the concurrence of numerous interwoven pathways which give rise to heterogenous EV populations in vitro. The equilibrium between the EV‐producing pathways is heavily influenced by factors in the extracellular environment, in such a way that can be taken advantage of to boost production of engineered EVs. In this study, a quantifiable EV‐engineering approach is used to investigate how different cell media conditions alter EV production. The presence of serum, exogenous EVs, and other signaling factors in cell media alters EV production at the physical, molecular, and transcriptional levels. Further, it is demonstrated that the ceramide‐dependent EV biogenesis route is the major pathway to production of engineered EVs during optimized EV‐production. These findings suggest a novel understanding to the mechanisms underlying EV production in cell culture which can be applied to develop advanced EV production methods.
A Comparison of Charge Carrier Dynamics in Organic and Perovskite Solar Cells
Authors: Wu Jiaying , Cha Hyojung , Du Tian , Dong Yifan , Xu Weidong , Lin Chieh‐Ting , Durrant James R.
Published: November 2021

The charge carrier dynamics in organic solar cells and organic–inorganic hybrid metal halide perovskite solar cells, two leading technologies in thin‐film photovoltaics, are compared. The similarities and differences in charge generation, charge separation, charge transport, charge collection, and charge recombination in these two technologies are discussed, linking these back to the intrinsic material properties of organic and perovskite semiconductors, and how these factors impact on photovoltaic device performance is elucidated. In particular, the impact of exciton binding energy, charge transfer states, bimolecular recombination, charge carrier transport, sub‐bandgap tail states, and surface recombination is evaluated, and the lessons learned from transient optical and optoelectronic measurements are discussed. This perspective thus highlights the key factors limiting device performance and rationalizes similarities and differences in design requirements between organic and perovskite solar cells.
Chlorination Enabling a Low‐Cost Benzodithiophene‐Based Wide‐Bandgap Donor Polymer with an Efficiency of over 17%
Authors: Wang Hang , Lu Hao , Chen Ya‐Nan , Ran Guangliu , Zhang Andong , Li Dawei , Yu Na , Zhang Zhe , Liu Yahui , Xu Xinjun , Zhang Wenkai , Bao Qinye , Tang Zheng , Bo Zhishan
Published: November 2021

Three regioregular benzodithiophene‐based donor–donor (D–D)‐type polymers (PBDTT, PBDTT1Cl, and PBDTT2Cl) are designed, synthesized, and used as donor materials in organic solar cells (OSCs). Because of the weak intramolecular charge‐transfer effect, these polymers exhibit large optical bandgaps (>2.0 eV). Among these three polymers, PBDTT1Cl exhibits more ordered and closer molecular stacking, and its devices demonstrate higher and more balanced charge mobilities and a longer charge‐separated state lifetime. As a result of these comprehensive benefits, PBDTT1Cl‐based OSCs give a very impressive power conversion efficiency (PCE) of 17.10% with a low nonradiative energy loss (0.19 eV). Moreover, PBDTT1Cl also possesses a low figure‐of‐merit value and good universality to match with different acceptors. This work provides a simply and efficient strategy to design low‐cost high‐performance polymer donor materials.
Cell Sheet‐Like Soft Nanoreactor Arrays
Authors: Shi Qianqian , Yong Zijun , Uddin Md Hemayet , Fu Runfang , Sikdar Debabrata , Yap Lim Wei , Fan Bo , Liu Yiyi , Dong Dashen , Cheng Wenlong
Published: November 2021

Tissues, which consist of groups of closely packed cell arrays, are essentially sheet‐like biosynthesis plants. In tissues, individual cells are discrete microreactors working under highly viscous and confined environments. Herein, soft polystyrene‐encased nanoframe (PEN) reactor arrays, as analogous nanoscale “sheet‐like chemosynthesis plants”, for the controlled synthesis of novel nanocrystals, are reported. Although the soft polystyrene (PS) is only 3 nm thick, it is elastic, robust, and permeable to aqueous solutes, while significantly slowing down their diffusion. PEN‐associated palladium (Pd) crystallization follows a diffusion‐controlled zero‐order kinetics rather than a reaction‐controlled first‐order kinetics in bulk solution. Each individual PEN reactor has a volume in the zeptoliter range, which offers a unique confined environment, enabling a directional inward crystallization, in contrast to the conventional outward nucleation/growth that occurs in an unconfined bulk solution. This strategy makes it possible to generate a set of mono‐, bi‐, and trimetallic, and even semiconductor nanocrystals with tunable interior structures, which are difficult to achieve with normal systems based on bulk solutions.
Bioinks and Bioprinting Strategies for Skeletal Muscle Tissue Engineering
Authors: Samandari Mohamadmahdi , Quint Jacob , Rodríguez‐delaRosa Alejandra , Sinha Indranil , Pourquié Olivier , Tamayol Ali
Published: November 2021

Skeletal muscles play important roles in critical body functions and their injury or disease can lead to limitation of mobility and loss of independence. Current treatments result in variable functional recovery, while reconstructive surgery, as the gold‐standard approach, is limited due to donor shortage, donor‐site morbidity, and limited functional recovery. Skeletal muscle tissue engineering (SMTE) has generated enthusiasm as an alternative solution for treatment of injured tissue and serves as a functional disease model. Recently, bioprinting has emerged as a promising tool for recapitulating the complex and highly organized architecture of skeletal muscles at clinically relevant sizes. Here, skeletal muscle physiology, muscle regeneration following injury, and current treatments following muscle loss are discussed, and then bioprinting strategies implemented for SMTE are critically reviewed. Subsequently, recent advancements that have led to improvement of bioprinting strategies to construct large muscle structures, boost myogenesis in vitro and in vivo, and enhance tissue integration are discussed. Bioinks for muscle bioprinting, as an essential part of any bioprinting strategy, are discussed, and their benefits, limitations, and areas to be improved are highlighted. Finally, the directions the field should expand to make bioprinting strategies more translational and overcome the clinical unmet needs are discussed.
High Miscibility Compatible with Ordered Molecular Packing Enables an Excellent Efficiency of 16.2% in All‐Small‐Molecule Organic Solar Cells
Authors: Zhang Lili , Zhu Xiangwei , Deng Dan , Wang Zhen , Zhang Ziqi , Li Yi , Zhang Jianqi , Lv Kun , Liu Lixuan , Zhang Xuning , Zhou Huiqiong , Ade Harald , Wei Zhixiang
Published: November 2021

In all‐small‐molecule organic solar cells (ASM‐OSCs), a high short‐circuit current (Jsc) usually needs a small phase separation, while a high fill factor (FF) is generally realized in a highly ordered packing system. However, small domain and ordered packing always conflicted each other in ASM‐OSCs, leading to a mutually restricted Jsc and FF. In this study, alleviation of the previous dilemma by the strategy of obtaining simultaneous good miscibility and ordered packing through modulating homo‐ and heteromolecular interactions is proposed. By moving the alkyl‐thiolation side chains from the para‐ to the meta‐position in the small‐molecule donor, the surface tension and molecular planarity are synchronously enhanced, resulting in compatible properties of good miscibility with acceptor BTP‐eC9 and strong self‐assembly ability. As a result, an optimized morphology with multi‐length‐scale domains and highly ordered packing is realized. The device exhibits a long carrier lifetime (39.8 μs) and fast charge collection (15.5 ns). A record efficiency of 16.2% with a high FF of 75.6% and a Jsc of 25.4 mA cm−2 in the ASM‐OSCs is obtained. These results demonstrate that the strategy of simultaneously obtaining good miscibility with high crystallinity could be an efficient photovoltaic material design principle for high‐performance ASM‐OSCs.
Coordination Polymer‐Coated CaCO3 Reinforces Radiotherapy by Reprogramming the Immunosuppressive Metabolic Microenvironment
Authors: Wang Chunjie , Dong Ziliang , Hao Yu , Zhu Yujie , Ni Jing , Li Quguang , Liu Bo , Han Yikai , Yang Zhijuan , Wan Jianmei , Yang Kai , Liu Zhuang , Feng Liangzhu
Published: November 2021

Radiotherapy is widely exploited for the treatment of a large range of cancers in clinic, but its therapeutic effectiveness is seriously crippled by the tumor immunosuppression, mainly driven by the altered metabolism of cancer cells. Here, a pH‐responsive nanomedicine is prepared by coating calcium carbonate (CaCO3) nanoparticles with 4‐phenylimidazole (4PI), an inhibitor against indoleamine 2,3‐dioxygenase 1 (IDO‐1), together with zinc ions via the coordination reaction, aiming at reinforcing the treatment outcome of radiotherapy. The obtained pH‐responsive nanomedicine, coined as acidity‐IDO1‐modulation nanoparticles (AIM NPs), is able to instantly neutralize protons, and release 4PI to suppress the IDO1‐mediated production of kynurenine (Kyn) upon tumor accumulation. As a result, treatment with AIM NPs can remarkably enhance the therapeutic efficacy of radiotherapy against both murine CT26 and 4T1 tumors by eliciting potent antitumor immunity. Furthermore, it is shown that such combination treatment can effectively suppress the growth of untreated distant tumors via the abscopal effect, and result in immune memory responses to reject rechallenged tumors. This work highlights a novel strategy of simultaneous tumor acidity neutralization and IDO1 inhibition to potentiate radiotherapy, with great promises to suppress tumor metastasis and recurrence by eliciting robust antitumor immunity.
Sodium‐Doped Titania Self‐Rectifying Memristors for Crossbar Array Neuromorphic Architectures
Authors: Kim Sung‐Eun , Lee Jin‐Gyu , Ling Leo , Liu Stephanie E. , Lim Hyung‐Kyu , Sangwan Vinod K. , Hersam Mark C. , Lee Hong‐Sub
Published: November 2021

Memristors integrated into a crossbar‐array architecture (CAA) are promising candidates for nonvolatile memory elements in artificial neural networks. However, the relatively low reliability of memristors coupled with crosstalk and sneak currents in CAAs have limited the realization of the full potential of this technology. Here, high‐reliability Na‐doped TiO2 memristors grown in situ by atomic layer deposition (ALD) are demonstrated, where reversible Na migration underlies the resistive‐switching mechanism. By employing ALD growth with an aqueous NaOH reactant in deionized water, uniform implantation of Na dopants is achieved in the crystallized TiO2 thin films at 250 °C without post‐annealing. The resulting Na‐doped TiO2 memristors show electroforming‐free and self‐rectifying resistive‐switching behavior, and they are ideally suited for selectorless CAAs. Effective addressing of selectorless nodes is demonstrated via electrical measurement of individual memristors in a 6 × 6 crossbar using a read current of less than 1 µA with negligible sneak current at or below the noise level of ≈100 pA. Finally, the long‐term potentiation and depression synaptic behavior from these Na‐doped TiO2 memristors achieves greater than 99.1% accuracy for image‐recognition tasks using a convolutional neural network based on the selectorless of crossbar arrays.
A Flexible and Wavelength‐Designable Polymer Light‐Emitting Diode Employing Sandwich‐Encapsulation for Wearable Skin Rejuvenation Photomedicine
Authors: Kim Hyuncheol , Choi Hye‐Ryung , Park Yongjin , Jeon Yongmin , Lee Ho Seung , Jeong Eun Gyo , Park Kyoung‐Chan , Choi Kyung Cheol
Published: November 2021

Organic light‐emitting diodes (OLEDs) and polymer light‐emitting diodes (PLEDs) are considered promising devices in that they are not limited to conventional display devices and can provide versatile functions in photomedicine. Many attempts to replace rigid photomedicine devices with wearable light‐emitting devices are in progress, and OLEDs have shown feasibility with respect to device conformality and photo‐medical efficiency. This paper presents a newly designed flexible optoelectronic device utilizing a wavelength‐designable PLED as an option for realizing disposable photomedicine devices. An optical design based on a multilayer electrode and an additional injection unit is proposed; it allows control of the device peak wavelength without any deterioration of charge injection. Furthermore, a sandwich structure utilizing transferable thin‐film encapsulation enables the PLED to achieve mechanical flexibility, low device heat generation, and sufficient operational lifetime (>8 h). When fibroblasts are irradiated by the wavelength‐designable PLED with a 630 nm peak, cell proliferation and production of type‐I procollagen increase by 25% and 36%, respectively. The change of matrix metalloproteinase‐1 is also evaluated, and it is found to decrease by 23%. Based on these results, the wavelength‐designable PLED induces distinct changes of biological factors.
Recent Advances in Bio‐Compatible Oxygen Singlet Generation and Its Tumor Treatment
Authors: Jin Zheng Yang , Fatima Hira , Zhang Yue , Shao Zongping , Chen Xiang Jian
Published: November 2021

Light‐dependent singlet oxygen (1O2) produced in photodynamic therapy (PDT), is a biologically compatible reactive oxygen species showing the potential to kill tumor cells with fewer side effects on nearby normal healthy cells. The development of a high 1O2 generating photosensitizer is a particularly demanding research areas. Based on Jablonski's diagram, the photophysical factors influencing the generation of 1O2 are intersystem crossing, triplet quantum yield and life, and the singlet‐triplet energy gap. Moreover, nanocarriers are also an emerging research topic with enhanced/localized delivery of photosensitizers to improve the dosage of light and enriched production of 1O2. In this review, the production principle of 1O2 in PDT and its killing mechanism with respect to tumor cells are reviewed. In addition, the progress of PDT has been supplemented in clinical applications in recent years and the emergent preclinical tactics for prospective solutions to these challenges are discussed to improve the effectiveness and usefulness of these procedures. Moreover, the remaining research gaps and future work is outlined. This review is anticipated to heighten the research for developing new strategies for modulating the photophysical properties and improved the delivery of photosensitizers.