bluuebunny/crossref_metadata_2025 huggingface dataset:
Palmitoylation targets the calcineurin phosphatase to the phosphatidylinositol 4-kinase complex at the plasma membrane
Authors: Ulengin-Talkish Idil , Parson Matthew A. H. , Jenkins Meredith L. , Roy Jagoree , Shih Alexis Z. L. , St-Denis Nicole , Gulyas Gergo , Balla Tamas , Gingras Anne-Claude , Várnai Péter , Conibear Elizabeth , Burke John E. , Cyert Martha S.
Published: October 2021

Calcineurin, the conserved protein phosphatase and target of immunosuppressants, is a critical mediator of Ca2+signaling. Here, to discover calcineurin-regulated processes we examined an understudied isoform, CNAβ1. We show that unlike canonical cytosolic calcineurin, CNAβ1 localizes to the plasma membrane and Golgi due to palmitoylation of its divergent C-terminal tail, which is reversed by the ABHD17A depalmitoylase. Palmitoylation targets CNAβ1 to a distinct set of membrane-associated interactors including the phosphatidylinositol 4-kinase (PI4KA) complex containing EFR3B, PI4KA, TTC7B and FAM126A. Hydrogen-deuterium exchange reveals multiple calcineurin-PI4KA complex contacts, including a calcineurin-binding peptide motif in the disordered tail of FAM126A, which we establish as a calcineurin substrate. Calcineurin inhibitors decrease PI4P production during Gq-coupled GPCR signaling, suggesting that calcineurin dephosphorylates and promotes PI4KA complex activity. In sum, this work discovers a calcineurin-regulated signaling pathway which highlights the PI4KA complex as a regulatory target and reveals that dynamic palmitoylation confers unique localization, substrate specificity and regulation to CNAβ1.
Single-cell transcriptomic analysis of the tumor ecosystems underlying initiation and progression of papillary thyroid carcinoma
Authors: Pu Weilin , Shi Xiao , Yu Pengcheng , Zhang Meiying , Liu Zhiyan , Tan Licheng , Han Peizhen , Wang Yu , Ji Dongmei , Gan Hualei , Wei Wenjun , Lu Zhongwu , Qu Ning , Hu Jiaqian , Hu Xiaohua , Luo Zaili , Li Huajun , Ji Qinghai , Wang Jiucun , Zhang Xiaoming , Wang Yu-Long
Published: October 2021

The tumor ecosystem of papillary thyroid carcinoma (PTC) is poorly characterized. Using single-cell RNA sequencing, we profile transcriptomes of 158,577 cells from 11 patients’ paratumors, localized/advanced tumors, initially-treated/recurrent lymph nodes and radioactive iodine (RAI)-refractory distant metastases, covering comprehensive clinical courses of PTC. Our data identifies a “cancer-primed” premalignant thyrocyte population with normal morphology but altered transcriptomes. Along the developmental trajectory, we also discover three phenotypes of malignant thyrocytes (follicular-like, partial-epithelial-mesenchymal-transition-like, dedifferentiation-like), whose composition shapes bulk molecular subtypes, tumor characteristics and RAI responses. Furthermore, we uncover a distinct BRAF-like-B subtype with predominant dedifferentiation-like thyrocytes, enriched cancer-associated fibroblasts, worse prognosis and promising prospect of immunotherapy. Moreover, potential vascular-immune crosstalk in PTC provides theoretical basis for combined anti-angiogenic and immunotherapy. Together, our findings provide insight into the PTC ecosystem that suggests potential prognostic and therapeutic implications.
Cellular crosstalk regulates the aqueous humor outflow pathway and provides new targets for glaucoma therapies
Authors: Thomson Benjamin R. , Liu Pan , Onay Tuncer , Du Jing , Tompson Stuart W. , Misener Sol , Purohit Raj R. , Young Terri L. , Jin Jing , Quaggin Susan E.
Published: October 2021

Primary congenital glaucoma (PCG) is a severe disease characterized by developmental defects in the trabecular meshwork (TM) and Schlemm’s canal (SC), comprising the conventional aqueous humor outflow pathway of the eye. Recently, heterozygous loss of function variants in TEK and ANGPT1 or compound variants in TEK/SVEP1 were identified in children with PCG. Moreover, common variants in ANGPT1and SVEP1 have been identified as risk alleles for primary open angle glaucoma (POAG) in GWAS studies. Here, we show tissue-specific deletion of Angpt1 or Svep1 from the TM causes PCG in mice with severe defects in the adjacent SC. Single-cell transcriptomic analysis of normal and glaucomatous Angpt1 deficient eyes allowed us to identify distinct TM and SC cell populations and discover additional TM-SC signaling pathways. Furthermore, confirming the importance of angiopoietin signaling in SC, delivery of a recombinant ANGPT1-mimetic promotes developmental SC expansion in healthy and Angpt1 deficient eyes, blunts intraocular pressure (IOP) elevation and RGC loss in a mouse model of PCG and lowers IOP in healthy adult mice. Our data highlight the central role of ANGPT1-TEK signaling and TM-SC crosstalk in IOP homeostasis and provide new candidates for SC-targeted glaucoma therapy.
Dysregulation of TFH-B-TRM lymphocyte cooperation is associated with unfavorable anti-PD-1 responses in EGFR-mutant lung cancer
Authors: Cho Jae-Won , Park Seyeon , Kim Gamin , Han Heonjong , Shim Hyo Sup , Shin Sunhye , Bae Yong-Soo , Park Seong Yong , Ha Sang-Jun , Lee Insuk , Kim Hye Ryun
Published: October 2021

Patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations exhibit an unfavorable response to PD-1 inhibitor through unclear mechanisms. Hypothesizing thatEGFRmutations alter tumor-immune interactions, we compare tumor-infiltrating lymphocytes between EGFR mutant (EGFR-MT) and wild type (EGFR-WT) tumors through single-cell transcriptomic analysis. We find that B cells, CXCL13-producing follicular helper CD4+T (TFH)-like cells, and tissue-resident memory CD8+T (TRM)-like cells decreased in EGFR-MT tumors. The NOTCH-RBPJ regulatory network, which is vital for persistence of TRMstate, is perturbed, and the interactions between TFHand B cells through the CXCL13-CXCR5 axis disappear in EGFR-MT tumors. Notably, the proportion of TRM-like cells is predictive for anti-PD-1 response in NSCLC. Our findings suggest that the impairment of TFH-B-TRMcooperation in tertiary lymphoid structure formation, accompanied by the dysregulation of TRMhomeostasis and the loss of TFH-B crosstalk, underlies unfavorable anti-PD-1 response in EGFR-MT lung tumors.
A gravity-driven sintering method to fabricate geometrically complex compact piezoceramics
Authors: Shan Yao , Liu Shiyuan , Wang Biao , Hong Ying , Zhang Chao , Lim C. W. , Zhang Guangzu , Yang Zhengbao
Published: October 2021

Highly compact and geometrically complex piezoceramics are required by a variety of electromechanical devices owing to their outstanding piezoelectricity, mechanical stability and extended application scenarios. 3D printing is currently the mainstream technology for fabricating geometrically complex piezoceramic components. However, it is hard to print piezoceramics in a curve shape while also keeping its compactness due to restrictions on the ceramic loading and the viscosity of feedstocks. Here, we report a gravity-driven sintering (GDS) process to directly fabricate curved and compact piezoceramics by exploiting gravitational force and high-temperature viscous behavior of sintering ceramic specimens. The sintered lead zirconate titanate (PZT) ceramics possess curve geometries that can be facilely tuned via the initial mechanical boundary design, and exhibit high piezoelectric properties comparable to those of conventional-sintered compact PZT (d33 = 595 pC/N). In contrast to 3D printing technology, our GDS process is suitable for scale-up production and low-cost production of piezoceramics with diverse curved surfaces. Our GDS strategy is an universal and facile route to fabricate curved piezoceramics and other functional ceramics with no compromise of their functionalities.
Rapid digital light 3D printing enabled by a soft and deformable hydrogel separation interface
Authors: Wu Jingjun , Guo Jing , Linghu Changhong , Lu Yahui , Song Jizhou , Xie Tao , Zhao Qian
Published: October 2021

The low productivity of typical 3D printing is a major hurdle for its utilization in large-scale manufacturing. Innovative techniques have been developed to break the limitation of printing speed, however, sophisticated facilities or costly consumables are required, which still substantially restricts the economic efficiency. Here we report that a common stereolithographic 3D printing facility can achieve a very high printing speed (400 mm/h) using a green and inexpensive hydrogel as a separation interface against the cured part. In sharp contrast to other techniques, the unique separation mechanism relies on the large recoverable deformation along the thickness direction of the hydrogel interface during the layer-wise printing. The hydrogel needs to be extraordinarily soft and unusually thick to remarkably reduce the adhesion force which is a key factor for achieving rapid 3D printing. This technique shows excellent printing stability even for fabricating large continuous solid structures, which is extremely challenging for other rapid 3D printing techniques. The printing process is highly robust for fabricating diversified materials with various functions. With the advantages mentioned above, the presented technique is believed to make a large impact on large-scale manufacturing.
Technology agnostic frequency characterization methodology for memristors
Authors: Manouras Vasileios , Stathopoulos Spyros , Serb Alex , Prodromakis Themis
Published: October 2021

Over the past decade, memristors have been extensively studied for a number of applications, almost exclusively with DC characterization techniques. Studies of memristors in AC circuits are sparse, with only a few examples found in the literature, and characterization methods with an AC input are also sparingly used. However, publications concerning the usage of memristors in this working regime are currently on the rise. Here we propose a "technology agnostic" methodology for memristor testing in certain frequency bands. A measurement process is initially proposed, with specific instructions on sample preparation, followed by an equipment calibration and measurement protocol. This article is structured in a way which aims to facilitate the usage of any available measurement equipment and it can be applied on any type of memristive technology. The second half of this work is centered around the representation of data received from following this process. Bode plot and Nyquist plot representations are considered and the information received from them is evaluated. Finally, examples of expected behaviors are given, characterizing simulated scenarios which represent different internal device models and different switching behaviors, such as capacitive or inductive switching. This study aims at providing a cohesive way for memristor characterization, to be used as a good starting point for frequency applications, and for understanding physical processes inside the devices, by streamlining the measuring process and providing a frame in which data representation and comparison will be facilitated.
Risk factors associated with the severity of COVID-19 in a region of the Brazilian Amazon
Authors: Sardinha Daniele Melo , do Socorro Pompeu de Loiola Rosane , Ferreira Ana Lúcia da Silva , de Sá Carmem Aliandra Freire , Rodrigues Yan Corrêa , Lima Karla Valéria Batista , e Guimarães Ricardo José de Paula Souza , Lima Luana Nepomuceno Gondim Costa
Published: October 2021

The Brazilian Northern region registered a high incidence of COVID-19 cases, particularly in the state of Pará. The present study investigated the risk factors associated with the severity of COVID-19 in a Brazilian Amazon region of 100,819 cases. An epidemiological, cross-sectional, analytical and demographic study, analyzing data on confirmed cases for COVID-19 available at the Brazilian Ministry of Health's surveillance platform, was conducted. Variables such as, municipalities of residence, age, gender, signs and symptoms, comorbidities were included and associated with COVID-19 cases and outcomes. The spatial distribution was performed using the ArcGIS program. A total of 100,819 cases were evaluated. Overall, patients had the mean age of 42.3 years, were female (51.2%) and with lethality reaching 4.79% of cases. Main symptoms included fever (66.5%), cough (61.9%) and sore throat (39.8%). Regarding comorbidities, most of the patients presented cardiovascular disease (5.1%) and diabetes (4.2%). Neurological disease increased risk of death by nearly 15 times, followed by obesity (5.16 times) and immunodeficiency (5.09 time). The municipalities with the highest incidence rate were Parauapebas, Canaã dos Carajás and Jacareacanga. Similarity between the Lower Amazon, Marajó and Southwest mesoregions of Pará state were observed concerning the highest morbidity rates. The obtained data demonstrated that the majority of cases occurred among young adults, females, with the classic influenza symptoms and chronic diseases. Finally, data suggest that the highest incidences were no longer in the metropolitan region of the state. The higher lethality rate than in Brazil may be associated with the greater impacts of the disease in this Amazonian population, or factors associated with fragile epidemiological surveillance in the notification of cases of cure.
Modelling infectious diseases with herd immunity in a randomly mixed population
Authors: Law Kian Boon , M. Peariasamy Kalaiarasu , Mohd Ibrahim Hishamshah , Abdullah Noor Hisham
Published: October 2021

The conventional susceptible-infectious-recovered (SIR) model tends to magnify the transmission dynamics of infectious diseases, and thus the estimated total infections and immunized population may be higher than the threshold required for infection control and eradication. The study developed a new SIR framework that allows the transmission rate of infectious diseases to decline along with the reduced risk of contact infection to overcome the limitations of the conventional SIR model. Two new SIR models were formulated to mimic the declining transmission rate of infectious diseases at different stages of transmission. Model A utilized the declining transmission rate along with the reduced risk of contact infection following infection, while Model B incorporated the declining transmission rate following recovery. Both new models and the conventional SIR model were then used to simulate an infectious disease with a basic reproduction number (r0) of 3.0 and a herd immunity threshold (HIT) of 0.667 with and without vaccination. Outcomes of simulations were assessed at the time when the total immunized population reached the level predicted by the HIT, and at the end of simulations. Further, all three models were used to simulate the transmission dynamics of seasonal influenza in the United States and disease burdens were projected and compared with estimates from the Centers for Disease Control and Prevention. For the simulated infectious disease, in the initial phase of the outbreak, all three models performed expectedly when the sizes of infectious and recovered populations were relatively small. As the infectious population increased, the conventional SIR model appeared to overestimate the infections even when the HIT was achieved in all scenarios with and without vaccination. For the same scenario, Model A appeared to attain the level predicted by the HIT and in comparison, Model B projected the infectious disease to be controlled at the level predicted by the HIT only at high vaccination rates. For infectious diseases with high r0, and at low vaccination rates, the level at which the infectious disease was controlled cannot be accurately predicted by the current theorem. Transmission dynamics of infectious diseases with herd immunity can be accurately modelled by allowing the transmission rate of infectious diseases to decline along with the reduction of contact infection risk after recovery or vaccination. Model B provides a credible framework for modelling infectious diseases with herd immunity in a randomly mixed population.
The effects of an object’s height and weight on force calibration and kinematics when post-stroke and healthy individuals reach and grasp
Authors: Feingold-Polak Ronit , Yelkin Anna , Edelman Shmil , Shapiro Amir , Levy-Tzedek Shelly
Published: October 2021

Impairment in force regulation and motor control impedes the independence of individuals with stroke by limiting their ability to perform daily activities. There is, at present, incomplete information about how individuals with stroke regulate the application of force and control their movement when reaching, grasping, and lifting objects of different weights, located at different heights. In this study, we assess force regulation and kinematics when reaching, grasping, and lifting a cup of two different weights (empty and full), located at three different heights, in a total of 46 participants: 30 sub-acute stroke participants, and 16 healthy individuals. We found that the height of the reached target affects both force calibration and kinematics, while its weight affects only the force calibration when post-stroke and healthy individuals perform a reach-to-grasp task. There was no difference between the two groups in the mean and peak force values. The individuals with stroke had slower, jerkier, less efficient, and more variable movements compared to the control group. This difference was more pronounced with increasing stroke severity. With increasing stroke severity, post-stroke individuals demonstrated altered anticipation and preparation for lifting, which was evident for either cortical lesion side.
Aronia melanocarpa polysaccharide ameliorates inflammation and aging in mice by modulating the AMPK/SIRT1/NF-κB signaling pathway and gut microbiota
Authors: Zhao Yingchun , Liu Xinglong , Zheng Yinan , Liu Wencong , Ding Chuanbo
Published: October 2021

Aronia melanocarpais a natural medicinal plant that has a variety of biological activities, its fruit is often used for food and medicine.Aronia melanocarpapolysaccharide (AMP) is the main component of theAronia melanocarpafruit. This research evaluated the delay and protection of AMP obtained fromAronia melanocarpafruit on aging mice byd-Galactose (D-Gal) induction and explored the effect of supplementing AMP on the metabolism of the intestinal flora of aging mice. The aging model was established by intraperitoneal injection of D-Gal (200 mg/kg to 1000 mg/kg) once per 3 days for 12 weeks. AMP (100 and 200 mg/kg) was given daily by oral gavage after 6 weeks of D-Gal-induced. The results showed that AMP treatment significantly improved the spatial learning and memory impairment of aging mice determined by the eight-arm maze test. H&E staining showed that AMP significantly reversed brain tissue pathological damage and structural disorders. AMP alleviated inflammation and oxidative stress injury in aging brain tissue by regulating the AMPK/SIRT1/NF-κB and Nrf2/HO-1 signaling pathways. Particularly, AMP reduced brain cell apoptosis and neurological deficits by activating the PI3K/AKT/mTOR signaling pathway and its downstream apoptotic protein family. Importantly, 16S rDNA analysis indicated the AMP treatment significantly retarded the aging process by improving the composition of intestinal flora and abundance of beneficial bacteria. In summary, this study found that AMP delayed brain aging in mice by inhibiting inflammation and regulating intestinal microbes, which providing the possibility for the amelioration and treatment of aging and related metabolic diseases.
A modeling method for the development of a bioprocess to optimally produce umqombothi (a South African traditional beer)
Authors: Hlangwani Edwin , Doorsamy Wesley , Adebiyi Janet Adeyinka , Fajimi Lanrewaju Ibrahim , Adebo Oluwafemi Ayodeji
Published: October 2021

Bioprocess development for umqombothi (a South African traditional beer) as with other traditional beer products can be complex. As a result, beverage bioprocess development is shifting towards new systematic protocols of experimentation. Traditional optimization methods such as response surface methodology (RSM) require further comparison with a relevant machine learning system. Artificial neural network (ANN) is an effective non-linear multivariate tool in bioprocessing, with enormous generalization, prediction, and validation capabilities. ANN bioprocess development and optimization of umqombothi were done using RSM and ANN. The optimum condition values were 1.1 h, 29.3 °C, and 25.9 h for cooking time, fermentation temperature, and fermentation time, respectively. RSM was an effective tool for the optimization of umqombothi’s bioprocessing parameters shown by the coefficient of determination (R2) closer to 1. RSM significant parameters: alcohol content, total soluble solids (TSS), and pH had R2 values of 0.94, 0.93, and 0.99 respectively while the constructed ANN significant parameters: alcohol content, TSS, and viscosity had R2 values of 0.96, 0.96, and 0.92 respectively. The correlation between experimental and predicted values suggested that both RSM and ANN were suitable bioprocess development and optimization tools.
The time-fractional kinetic equation for the non-equilibrium processes
Authors: Aydiner Ekrem
Published: October 2021

In this study, we consider the non-Markovian dynamics of the generic non-equilibrium kinetic process. We summarize the generalized master equation, the continuous and discrete forms of the time-fractional diffusion equation. Using path integral formulation, we generalized the solutions of the Markovian system to the non-Markovian for the non-equilibrium kinetic processes. Then, we obtain the time-fractional kinetic equation for the non-equilibrium systems in terms of free energy. Finally, we introduce a time-fractional equation to analyse time evolution of the open probability for the deformed voltage-gated ion-channel system as an example.
Psychometric properties testing of a Cantonese version of the Life-Space Assessment in people with stroke
Authors: Ho Lily Y. W. , Lai Claudia K. Y. , Ng Shamay S. M.
Published: October 2021

The Life-Space Assessment (LSA) advances measurements of mobility by determining the extent of the spatial area in which a person moves in real life. Yet there is no Cantonese version of the LSA. This study aimed to translate and culturally adapt the LSA into Cantonese (C-LSA) and examine its psychometric properties in people with stroke. Psychometric properties were examined in 112 people with stroke. The life-space of stroke survivors was compared with that of healthy older people with and without depressive symptoms. The content validity of the C-LSA was good. The Cronbach’s α was 0.73. The test–retest reliability was 0.95. The standard error of measurement was 4.21 and the minimal detectable change was 11.66, without any ceiling or floor effects in the C-LSA composite score. The composite score correlated significantly with the Fugl-Meyer Assessment of lower extremities score (rs = 0.31), the Five Times Sit-To-Stand time (rs =  − 0.43), and the Frenchay Activities Index score (rs = 0.48). People with stroke had significantly lower C-LSA composite scores than healthy older people. Depressive symptoms worsened the composite and assisted life-space scores only of people with stroke. The C-LSA is a reliable and valid tool for measuring life-space in stroke populations.
Asymptomatic COVID-19 Adult Outpatients identified as Significant Viable SARS-CoV-2 Shedders
Authors: Glenet Marie , Lebreil Anne-Laure , Heng Laetitia , N’Guyen Yohan , Meyer Ittah , Andreoletti Laurent
Published: October 2021

Differential kinetics of RNA loads and infectious viral levels in the upper respiratory tract between asymptomatic and symptomatic SARS-CoV-2 infected adult outpatients remain unclear limiting recommendations that may guide clinical management, infection control measures and occupational health decisions. In the present investigation, 496 (2.8%) of 17,911 French adult outpatients were positive for an upper respiratory tract SARS-CoV-2 RNA detection by a quantitative RT-PCR assay, of which 180 (36.3%) were COVID-19 asymptomatic. Of these adult asymptomatic viral shedders, 75% had mean to high RNA viral loads (Ct values < 30) which median value was significantly higher than that observed in symptomatic subjects (P = 0.029), and 50.6% were positive by cell culture assays of their upper respiratory tract specimens. Our findings indicate that COVID-19 asymptomatic adult outpatients are significant viable SARS-CoV-2 shedders in their upper respiratory tract playing a major potential role as SARS-CoV-2 transmitters in various epidemiological transmission chains, promoting COVID-19 resurgence in populations.
A simple detection method for the serum sFLT1 protein in preeclampsia
Authors: Shibuya Masabumi , Matsui Haruka , Sasagawa Tadashi , Nagamatsu Takeshi
Published: October 2021

In normal pregnancy, the soluble form of FMS-like tyrosine kinase-1 (sFLT1)/ vascular endothelial growth factor receptor-1 (sVEGFR-1), a VEGF-trapping protein, is expressed in trophoblasts of the placenta, suggesting that it plays an important role in the physiological barrier between fetal and maternal angiogenesis, when stimulated with VEGF-A. In pathological conditions such as preeclampsia (PE), sFLT1 protein is abnormally overexpressed in trophoblasts and secreted into the serum, which could cause hypertension and proteinuria on the maternal side and growth retardation on the fetal side. Detection of an abnormal increase in serum sFLT1 during the early to middle stages of PE is essential for proper initiation of medical care. To carry out this screening for sFLT1, we developed an easier and relatively low-cost sandwich-type ELISA method using a single mixture of human serum sample with an anti-FLT1 antibody and heparin-beads, namely heparin-beads-coupled ELISA (HB-ELISA). This method takes only about 2 h, and the sFLT1 values were similar levels with commercially available recent ELISA kits: the serum sFLT1 protein was approximately 4.3-fold increased in severe PE compared with those in normal pregnancy.
Hip fracture in patients with non-dialysis chronic kidney disease stage 5
Authors: Tang Chao-Hsiun , Chou Che-Yi
Published: October 2021

Hip fracture is a significant health problem and is associated with increased mortality. Patients with chronic kidney disease (CKD) are more at risk of hip fracture than the general population, but the hip fracture risk is not evident among non-dialysis CKD stage 5 patients. This study aims to assess the risk of hip fracture in patients with non-dialysis CKD stage 5 comparing to those with CKD stages 1–4. Patients with non-dialysis CKD stage 5 and CKD stages 1–4 were retrieved from Taiwan longitudinal health insurance database 2011–2014. All patients were followed to the end of 2018 for the development of hip fractures. We analyze the risk of hip fracture of propensity score-matched patients with CKD stage 5 compared to patients with CKD stages 1–4 using stepwise Cox regression and competing risks regression. We analyzed 5649 propensity score-matched non-dialysis CKD 1–4 patients and non-dialysis CKD 5 patients between 2011 and 2014. All patients were followed to the end of 2018, 229 (4.1%) of CKD 1–4 patients in 21,899 patient-year, and 290 (5.1%) of CKD 5 patients had hip fractures in 18,137 patient-year. CKD 5 patients had a higher risk of hip fracture than patients with CKD stages 1–4. The adjusted HR was 1.53 (95% CI 1.08–1.54) in the Cox regression with adjustments for age, gender, comorbidity, and history of fracture. In the competing risks regression, the subdistribution hazard ratio was 1.29 (95% CI 1.08–1.54). Female gender, age, history of fractures, and Charlson–Deyo comorbidity index were independently associated with increased hip fracture risks. Non-dialysis CKD 5 patients had a higher risk of hip fracture than patients with CKD stages 1–4. This association is independent of patients’ age, female gender, history of fractures, and comorbidities.
Public toilets with insufficient ventilation present high cross infection risk
Authors: Lee M. C. Jeffrey , Tham K. W.
Published: October 2021

Due to insufficient ventilation, public toilets present high risks for cross-infection. The study investigated 61 public toilets to identify the causes and locations of biological contaminated sources. Airborne and surface bacterial contamination, carbon dioxide concentration, and surface ammonia levels were measured. Both bacterial contamination and CO2 are higher in non-ventilated toilets compared to their ventilated counterparts. Bacteria colony forming units (CFUs) in a public toilet with poor ventilation can reach 5 times the number of CFUs outside of the toilet. This suggests that non-ventilated public toilets present a higher risk of cross-infection. Areas near all kinds of sanitary equipment (toilet bowls, squat toilets and urinals) were highly contaminated, indicating that enhanced cleaning regimes are necessary. Further, lidless trash bins present a higher risk as contaminated matter within the trash bins is not inhibited from being released into the environment. Ventilation and cleaning need to be improved to mitigate the risk of cross-infection in public toilets.
Delicate balance among thermal stability, binding affinity, and conformational space explored by single-domain VHH antibodies
Authors: Ikeuchi Emina , Kuroda Daisuke , Nakakido Makoto , Murakami Akikazu , Tsumoto Kouhei
Published: October 2021

The high binding affinities and specificities of antibodies have led to their use as drugs and biosensors. Single-domain VHH antibodies exhibit high specificity and affinity but have higher stability and solubility than conventional antibodies as they are single-domain proteins. In this work, based on physicochemical measurements and molecular dynamics (MD) simulations, we have gained insight that will facilitate rational design of single-chain VHH antibodies. We first assessed two homologous VHH antibodies by differential scanning calorimetry (DSC); one had a high (64.8 °C) and the other a low (58.6 °C) melting temperature. We then generated a series of the variants of the low stability antibody and analyzed their thermal stabilities by DSC and characterized their structures through MD simulations. We found that a single mutation that resulted in 8.2 °C improvement in melting temperature resulted in binding affinity an order of magnitude lower than the parent antibody, likely due to a shift of conformational space explored by the single-chain VHH antibody. These results suggest that the delicate balance among conformational stability, binding capability, and conformational space explored by antibodies must be considered in design of fully functional single-chain VHH antibodies.
Diurnal changes in the murine small intestine are disrupted by obesogenic Western Diet feeding and microbial dysbiosis
Authors: Martchenko Sarah E. , Prescott David , Martchenko Alexandre , Sweeney Maegan E. , Philpott Dana J. , Brubaker Patricia L.
Published: October 2021

Intestinal functions demonstrate circadian rhythms thought to be entrained, in part, by an organisms’ intrinsic feeding and fasting periods as well as by the intestinal microbiome. Circadian disruption as a result of ill-timed nutrient exposure and obesogenic feeding poses an increased risk to disease. As such, the aim of this study was to assess the relationships between dietary timing, composition, and the microbiome with regard to rhythmic small intestinal structure and mucosal immunity. Rodent chow (RC)-mice exhibited time-dependent increases in small intestinal weight, villus height, and crypt depth as well as an increased proportion of CD8αα+ cells and concomitant decrease in CD8αβ+ cells at the onset of the feeding period (p < 0.05–0.001). Western diet (WD)-animals displayed disrupted time-dependent patterns in intestinal structure and lymphocyte populations (p < 0.05–0.01). Antibiotic-induced microbial depletion abrogated the time- and diet-dependent patterns in both RC- and WD-mice (p < 0.05–0.001). However, although germ-free-mice displayed altered rhythms, fecal microbial transfer from RC-mice was generally unsuccessful in restoring structural and immune changes in these animals. This study shows that adaptive changes in the small intestine at the onset of the feeding and fasting periods are disrupted by WD-feeding, and that these changes are dependent, in part, on the intestinal microbiome.
Electronic and optical properties of bulk and surface of CsPbBr3 inorganic halide perovskite a first principles DFT 1/2 approach
Authors: Ezzeldien Mohammed , Al-Qaisi Samah , Alrowaili Z. A. , Alzaid Meshal , Maskar E. , Es-Smairi A. , Vu Tuan V. , Rai D. P.
Published: October 2021

This work aims to test the effectiveness of newly developed DFT-1/2 functional in calculating the electronic and optical properties of inorganic lead halide perovskites CsPbBr3. Herein, from DFT-1/2 we have obtained the direct band gap of 2.36 eV and 3.82 eV for orthorhombic bulk and 001-surface, respectively. The calculated energy band gap is in qualitative agreement with the experimental findings. The bandgap of ultra-thin film of CsPbBr3 is found to be 3.82 eV, which is more than the expected range 1.23-3.10 eV. However, we have found that the bandgap can be reduced by increasing the surface thickness. Thus, the system under investigation looks promising for optoelectronic and photocatalysis applications, due to the bandgap matching and high optical absorption in UV–Vis (Ultra violet and visible spectrum) range of electro-magnetic(em) radiation.
Tailoring plasmon excitations in $$\alpha -{\mathcal {T}}_3$$ armchair nanoribbons
Authors: Iurov Andrii , Zhemchuzhna Liubov , Gumbs Godfrey , Huang Danhong , Fekete Paula , Anwar Farhana , Dahal Dipendra , Weekes Nicholas
Published: October 2021

We have calculated and investigated the electronic states, dynamical polarization function and the plasmon excitations for $$\alpha -{\mathcal {T}}_3$$

α
-

T
3

nanoribbons with armchair-edge termination. The obtained plasmon dispersions are found to depend significantly on the number of atomic rows across the ribbon and the energy gap which is also determined by the nanoribbon geometry. The bandgap appears to have the strongest effect on both the plasmon dispersions and their Landau damping. We have determined the conditions when relative hopping parameter $$\alpha $$
α
of an $$\alpha -{\mathcal {T}}_3$$

α
-

T
3

lattice has a strong effect on the plasmons which makes our material distinguished from graphene nanoribbons. Our results for the electronic and collective properties of $$\alpha -{\mathcal {T}}_3$$

α
-

T
3

nanoribbons are expected to find numerous applications in the development of the next-generation electronic, nano-optical and plasmonic devices.
Ventricular arrhythmias in mouse models of diabetic kidney disease
Authors: Laurita Kenneth R. , Khan Shenaz , McMahon Tracy , Dennis Adrienne T. , Li Vincent , Gaivin Robert , Sapa Hima , Fu Ji-dong , Schelling Jeffrey R.
Published: October 2021

Chronic kidney disease (CKD) affects more than 20 million people in the US, and it is associated with a significantly increased risk of sudden cardiac death (SCD). Despite the significance, the mechanistic relationship between SCD and CKD is not clear and there are few effective therapies. Using optical mapping techniques, we tested the hypothesis that mouse models of progressive diabetic kidney disease (DKD) exhibit enhanced ventricular arrhythmia incidence and underlying arrhythmia substrates. Compared to wild-type mice, both Leprdb/db eNOS−/− (2KO) and high fat diet plus low dose streptozotocin (HFD + STZ) mouse models of DKD experienced sudden death and greater arrhythmia inducibility, which was more common with isoproterenol than programmed electrical stimulation. 2KO mice demonstrated slowed conduction velocity, prolonged action potential duration (APD), and myocardial fibrosis; both 2KO and HFD + STZ mice exhibited arrhythmias and calcium dysregulation with isoproterenol challenge. Finally, circulating concentrations of the uremic toxin asymmetric dimethylarginine (ADMA) were elevated in 2KO mice. Incubation of human cardiac myocytes with ADMA prolonged APD, as also observed in 2KO mice hearts ex vivo. The present study elucidates an arrhythmia-associated mechanism of sudden death associated with DKD, which may lead to more effective treatments in the vulnerable DKD patient population.
Visible blue light inhibits infection and replication of SARS-CoV-2 at doses that are well-tolerated by human respiratory tissue
Authors: Stasko Nathan , Kocher Jacob F. , Annas Abigail , Henson Ibrahim , Seitz Theresa S. , Miller Joy M. , Arwood Leslee , Roberts Rachel C. , Womble Thomas M. , Keller Emily G. , Emerson Soren , Bergmann Michael , Sheesley Ashley N. Y. , Strong Rebecca J. , Hurst Brett L. , Emerson David , Tarbet E. Bart , Bradrick Shelton S. , Cockrell Adam S.
Published: October 2021

The delivery of safe, visible wavelengths of light can be an effective, pathogen-agnostic, countermeasure that would expand the current portfolio of SARS-CoV-2 intervention strategies beyond the conventional approaches of vaccine, antibody, and antiviral therapeutics. Employing custom biological light units, that incorporate optically engineered light-emitting diode (LED) arrays, we harnessed monochromatic wavelengths of light for uniform delivery across biological surfaces. We demonstrated that primary 3D human tracheal/bronchial-derived epithelial tissues tolerated high doses of a narrow spectral band of visible light centered at a peak wavelength of 425 nm. We extended these studies to Vero E6 cells to understand how light may influence the viability of a mammalian cell line conventionally used for assaying SARS-CoV-2. The exposure of single-cell monolayers of Vero E6 cells to similar doses of 425 nm blue light resulted in viabilities that were dependent on dose and cell density. Doses of 425 nm blue light that are well-tolerated by Vero E6 cells also inhibited infection and replication of cell-associated SARS-CoV-2 by > 99% 24 h post-infection after a single five-minute light exposure. Moreover, the 425 nm blue light inactivated cell-free betacoronaviruses including SARS-CoV-1, MERS-CoV, and SARS-CoV-2 up to 99.99% in a dose-dependent manner. Importantly, clinically applicable doses of 425 nm blue light dramatically inhibited SARS-CoV-2 infection and replication in primary human 3D tracheal/bronchial tissue. Safe doses of visible light should be considered part of the strategic portfolio for the development of SARS-CoV-2 therapeutic countermeasures to mitigate coronavirus disease 2019 (COVID-19).
Ventilatory responses during and following hypercapnic gas challenge are impaired in male but not female endothelial NOS knock-out mice
Authors: Getsy Paulina M. , Sundararajan Sripriya , May Walter J. , von Schill Graham C. , McLaughlin Dylan K. , Palmer Lisa A. , Lewis Stephen J.
Published: October 2021

The roles of endothelial nitric oxide synthase (eNOS) in the ventilatory responses during and after a hypercapnic gas challenge (HCC, 5% CO2, 21% O2, 74% N2) were assessed in freely-moving female and male wild-type (WT) C57BL6 mice and eNOS knock-out (eNOS-/-) mice of C57BL6 background using whole body plethysmography. HCC elicited an array of ventilatory responses that were similar in male and female WT mice, such as increases in breathing frequency (with falls in inspiratory and expiratory times), and increases in tidal volume, minute ventilation, peak inspiratory and expiratory flows, and inspiratory and expiratory drives. eNOS-/- male mice had smaller increases in minute ventilation, peak inspiratory flow and inspiratory drive, and smaller decreases in inspiratory time than WT males. Ventilatory responses in female eNOS-/- mice were similar to those in female WT mice. The ventilatory excitatory phase upon return to room-air was similar in both male and female WT mice. However, the post-HCC increases in frequency of breathing (with decreases in inspiratory times), and increases in tidal volume, minute ventilation, inspiratory drive (i.e., tidal volume/inspiratory time) and expiratory drive (i.e., tidal volume/expiratory time), and peak inspiratory and expiratory flows in male eNOS-/- mice were smaller than in male WT mice. In contrast, the post-HCC responses in female eNOS-/- mice were equal to those of the female WT mice. These findings provide the first evidence that the loss of eNOS affects the ventilatory responses during and after HCC in male C57BL6 mice, whereas female C57BL6 mice can compensate for the loss of eNOS, at least in respect to triggering ventilatory responses to HCC.
A small molecule screen identifies novel inhibitors of mechanosensory nematocyst discharge in Hydra
Authors: Hofmann Diana , Garg Niharika , Grässle Simone , Vanderheiden Sylvia , Bergheim Bruno Gideon , Bräse Stefan , Jung Nicole , Özbek Suat
Published: October 2021

Cnidarians are characterized by the possession of stinging organelles, called nematocysts, which they use for prey capture and defense. Nematocyst discharge is controlled by a mechanosensory apparatus with analogies to vertebrate hair cells. Members of the transient receptor potential (TRPN) ion channel family are supposed to be involved in the transduction of the mechanical stimulus. A small molecule screen was performed to identify compounds that affect nematocyst discharge in Hydra. We identified several [2.2]paracyclophanes that cause inhibition of nematocyst discharge in the low micro-molar range. Further structure–activity analyses within the compound class of [2.2]paracyclophanes showed common features that are required for the inhibitory activity of the [2.2]paracyclophane core motif. This study demonstrates that Hydra can serve as a model for small molecule screens targeting the mechanosensory apparatus in native tissues.
Substitutional synthesis of sub-nanometer InGaN/GaN quantum wells with high indium content
Authors: Vasileiadis I. G. , Lymperakis L. , Adikimenakis A. , Gkotinakos A. , Devulapalli V. , Liebscher C. H. , Androulidaki M. , Hübner R. , Karakostas Th. , Georgakilas A. , Komninou Ph. , Dimakis E. , Dimitrakopulos G. P.
Published: October 2021

InGaN/GaN quantum wells (QWs) with sub-nanometer thickness can be employed in short-period superlattices for bandgap engineering of efficient optoelectronic devices, as well as for exploiting topological insulator behavior in III-nitride semiconductors. However, it had been argued that the highest indium content in such ultra-thin QWs is kinetically limited to a maximum of 33%, narrowing down the potential range of applications. Here, it is demonstrated that quasi two-dimensional (quasi-2D) QWs with thickness of one atomic monolayer can be deposited with indium contents far exceeding this limit, under certain growth conditions. Multi-QW heterostructures were grown by plasma-assisted molecular beam epitaxy, and their composition and strain were determined with monolayer-scale spatial resolution using quantitative scanning transmission electron microscopy in combination with atomistic calculations. Key findings such as the self-limited QW thickness and the non-monotonic dependence of the QW composition on the growth temperature under metal-rich growth conditions suggest the existence of a substitutional synthesis mechanism, involving the exchange between indium and gallium atoms at surface sites. The highest indium content in this work approached 50%, in agreement with photoluminescence measurements, surpassing by far the previously regarded compositional limit. The proposed synthesis mechanism can guide growth efforts towards binary InN/GaN quasi-2D QWs.
Fitness consequences of targeted gene flow to counter impacts of drying climates on terrestrial-breeding frogs
Authors: Rudin-Bitterli Tabitha S. , Evans Jonathan P. , Mitchell Nicola J.
Published: October 2021

Targeted gene flow (TGF) could bolster the adaptive potential of isolated populations threatened by climate change, but could also lead to outbreeding depression. Here, we explore these possibilities by creating mixed- and within-population crosses in a terrestrial-breeding frog species threatened by a drying climate. We reared embryos of the crawling frog (Pseudophryne guentheri) on wet and dry soils and quantified fitness-related traits upon hatching. TGF produced mixed outcomes in hybrids, which depended on crossing direction (origin of gametes from each sex). North-south crosses led to low embryonic survival if eggs were of a southern origin, and high malformation rates when eggs were from a northern population. Conversely, east-west crosses led to one instance of hybrid vigour, evident by increased fitness and desiccation tolerance of hybrid offspring relative to offspring produced from within-population crosses. These contrasting results highlight the need to experimentally evaluate the outcomes of TGF for focal species across generations prior to implementing management actions.
Two Zr-based heterometal–organic frameworks for efficient CO2 reduction under visible light
Authors: Wang Ying , Fu Yaomei , You Siqi , Li Xuexin , Zhao Liang , Qin Chao , Wang Xinlong
Published: October 2021

Two novel zirconium-based heterometal–organic framework catalysts can effectively improve photocatalytic activities for CO2 photoreduction under visible light.
A comparison of methods for the estimation of the enthalpy of formation of rare earth compounds
Authors: Sanchez-Segado Sergio , Lectez Sebastien , Jha Animesh , Stackhouse Stephen
Published: October 2021

The accuracy of a suite of methods including a linear relationship developed by the authors, has been evaluated for the estimation of the enthalpy of formation of a selected group of rare earth compounds.
Phenalenyls as tunable excellent molecular conductors and switchable spin filters
Authors: Smeu Manuel , Monti Oliver L. A. , McGrath Dominic
Published: October 2021

Phenalenyls can be tuned by heteroatom substitution to perform as excellent electron conductors or spin filters.
Unlocking the potential of biofuels via reaction pathways in van Krevelen diagrams
Authors: Palacio Lozano Diana Catalina , Jones Hugh E. , Ramirez Reina Tomas , Volpe Roberto , Barrow Mark P.
Published: October 2021

Graphical representation of bio-oil compositions in van Krevelen diagrams reveals reaction pathways to infer upgrading routes that can improve the economic potential of biofuels.
Visible-light-driven electron donor–acceptor complex induced sulfonylation of diazonium salts with sulfinates
Authors: Liang Xin , Li Yufei , Xia Qing , Cheng Lan , Guo Jianbo , Zhang Pei , Zhang Weihua , Wang Qingmin
Published: October 2021

An efficient metal, catalyst, and oxidant free sulfonylation reaction, enabled by a visible-light-driven electron donor–acceptor (EDA) complex induced radical coupling reaction has been reported.
High throughput production of microcapsules using microfluidics for self-healing of cementitious materials
Authors: Ribeiro de Souza Lívia , Al-Tabbaa Abir
Published: October 2021

Parallel junctions on a modular chip were used to produce high throughput monodisperse microcapsules for self-healing in cementitious materials.
Blood apheresis technologies – a critical review on challenges towards efficient blood separation and treatment
Authors: Bacal Christine Jurene O. , Maina James W. , Nandurkar Harshal H. , Khaleel Maryam , Guijt Rosanne , Chang Yung , Dwyer Karen M. , Dumée Ludovic F.
Published: October 2021

This review article critically assesses materials engineering advances across blood separation technologies which addresses operating challenges such as surface fouling and material biocompatibility.
High-performance triboelectric nanogenerators based on the organic semiconductor copper phthalocyanine
Authors: You Zhongyuan , Chang Jiawei , Li Zezhong , Lu Tianyu , Wang Shuting , Wang Fang , Hu Bingxi , Wang Hai , Li Lian , Fang Weihai , Liu Ying
Published: October 2021

Triboelectric nanogenerators were fabricated using organic semiconductor CuPc. With 10 wt% iodine doping, the devices showed an excellent performance with a voltage output of 300 V, a current density of 110 mA m−2, and a power density of 8.68 W m−2.
Tuning the current rectification behavior of Rh2-based molecular junctions by varying their supramolecular structures
Authors: Bu Donglei , Huang Changgeng , Sha Pengzhan , Chen Shangxian , Bu Duocheng , Huang Shaoming
Published: October 2021

It is found that both the bridging ligands and the number of repeating units in the Rh2-based molecular junctions are critical to their current rectification behaviors.