bluuebunny/crossref_metadata_2025 huggingface dataset:
A different perspective for nonphotochemical quenching in plant antenna complexes
Authors: Cignoni Edoardo , Lapillo Margherita , Cupellini Lorenzo , Acosta-Gutiérrez Silvia , Gervasio Francesco Luigi , Mennucci Benedetta
Published: December 2021

Light-harvesting complexes of plants exert a dual function of light-harvesting (LH) and photoprotection through processes collectively called nonphotochemical quenching (NPQ). While LH processes are relatively well characterized, those involved in NPQ are less understood. Here, we characterize the quenching mechanisms of CP29, a minor LHC of plants, through the integration of two complementary enhanced-sampling techniques, dimensionality reduction schemes, electronic calculations and the analysis of cryo-EM data in the light of the predicted conformational ensemble. Our study reveals that the switch between LH and quenching state is more complex than previously thought. Several conformations of the lumenal side of the protein occur and differently affect the pigments’ relative geometries and interactions. Moreover, we show that a quenching mechanism localized on a single chlorophyll-carotenoid pair is not sufficient but many chlorophylls are simultaneously involved. In such a diffuse mechanism, short-range interactions between each carotenoid and different chlorophylls combined with a protein-mediated tuning of the carotenoid excitation energies have to be considered in addition to the commonly suggested Coulomb interactions.
Population-based estimates of breast cancer risk for carriers of pathogenic variants identified by gene-panel testing
Authors: Southey Melissa C. , Dowty James G. , Riaz Moeen , Steen Jason A. , Renault Anne-Laure , Tucker Katherine , Kirk Judy , James Paul , Winship Ingrid , Pachter Nicholas , Poplawski Nicola , Grist Scott , Park Daniel J. , Pope Bernard J. , Mahmood Khalid , Hammet Fleur , Mahmoodi Maryam , Tsimiklis Helen , Theys Derrick , Rewse Amanda , Willis Amanda , Morrow April , Speechly Catherine , Harris Rebecca , Sebra Robert , Schadt Eric , Lacaze Paul , McNeil John J. , Giles Graham G. , Milne Roger L. , Hopper John L. , Nguyen-Dumont Tú
Published: December 2021

Population-based estimates of breast cancer risk for carriers of pathogenic variants identified by gene-panel testing are urgently required. Most prior research has been based on women selected for high-risk features and more data is needed to make inference about breast cancer risk for women unselected for family history, an important consideration of population screening. We tested 1464 women diagnosed with breast cancer and 862 age-matched controls participating in the Australian Breast Cancer Family Study (ABCFS), and 6549 healthy, older Australian women enroled in the ASPirin in Reducing Events in the Elderly (ASPREE) study for rare germline variants using a 24-gene-panel. Odds ratios (ORs) were estimated using unconditional logistic regression adjusted for age and other potential confounders. We identified pathogenic variants in 11.1% of the ABCFS cases, 3.7% of the ABCFS controls and 2.2% of the ASPREE (control) participants. The estimated breast cancer OR [95% confidence interval] was 5.3 [2.1–16.2] for BRCA1, 4.0 [1.9–9.1] for BRCA2, 3.4 [1.4–8.4] for ATM and 4.3 [1.0–17.0] for PALB2. Our findings provide a population-based perspective to gene-panel testing for breast cancer predisposition and opportunities to improve predictors for identifying women who carry pathogenic variants in breast cancer predisposition genes.
Capillary flow of liquids in open microchannels: overview and recent advances
Authors: Kolliopoulos Panayiotis , Kumar Satish
Published: December 2021

Capillary flow is the spontaneous wicking of liquids in narrow spaces without the assistance of external forces. Examples of capillary flow can be found in numerous applications ranging from controlling and transporting fuel in spacecrafts to printed electronics manufacturing. Open rectangular microchannels often appear in these applications, with the lack of a top resulting in a complex free-surface morphology and evaporation. Here, we present a brief overview of this topic and discuss some recent advances.
Quasi-particle interference of the van Hove singularity in Sr2RuO4
Authors: Kreisel A. , Marques C. A. , Rhodes L. C. , Kong X. , Berlijn T. , Fittipaldi R. , Granata V. , Vecchione A. , Wahl P. , Hirschfeld P. J.
Published: December 2021

The single-layered ruthenate Sr2RuO4 is one of the most enigmatic unconventional superconductors. While for many years it was thought to be the best candidate for a chiral p-wave superconducting ground state, desirable for topological quantum computations, recent experiments suggest a singlet state, ruling out the original p-wave scenario. The superconductivity as well as the properties of the multi-layered compounds of the ruthenate perovskites are strongly influenced by a van Hove singularity in proximity of the Fermi energy. Tiny structural distortions move the van Hove singularity across the Fermi energy with dramatic consequences for the physical properties. Here, we determine the electronic structure of the van Hove singularity in the surface layer of Sr2RuO4 by quasi-particle interference imaging. We trace its dispersion and demonstrate from a model calculation accounting for the full vacuum overlap of the wave functions that its detection is facilitated through the octahedral rotations in the surface layer.
Education shapes the structure of semantic memory and impacts creative thinking
Authors: Denervaud Solange , Christensen Alexander P. , Kenett Yoed. N. , Beaty Roger E.
Published: December 2021

Education is central to the acquisition of knowledge, such as when children learn new concepts. It is unknown, however, whether educational differences impact not only what concepts children learn, but how those concepts come to be represented in semantic memory—a system that supports higher cognitive functions, such as creative thinking. Here we leverage computational network science tools to study hidden knowledge structures of 67 Swiss schoolchildren from two distinct educational backgrounds—Montessori and traditional, matched on socioeconomic factors and nonverbal intelligence—to examine how educational experience shape semantic memory and creative thinking. We find that children experiencing Montessori education show a more flexible semantic network structure (high connectivity/short paths between concepts, less modularity) alongside higher scores on creative thinking tests. The findings indicate that education impacts how children represent concepts in semantic memory and suggest that different educational experiences can affect higher cognitive functions, including creative thinking.
Identifying the essential nutritional requirements of the probiotic bacteria Bifidobacterium animalis and Bifidobacterium longum through genome-scale modeling
Authors: Schöpping Marie , Gaspar Paula , Neves Ana Rute , Franzén Carl Johan , Zeidan Ahmad A.
Published: December 2021

Although bifidobacteria are widely used as probiotics, their metabolism and physiology remain to be explored in depth. In this work, strain-specific genome-scale metabolic models were developed for two industrially and clinically relevant bifidobacteria, Bifidobacterium animalis subsp. lactis BB-12® and B. longum subsp. longum BB-46, and subjected to iterative cycles of manual curation and experimental validation. A constraint-based modeling framework was used to probe the metabolic landscape of the strains and identify their essential nutritional requirements. Both strains showed an absolute requirement for pantethine as a precursor for coenzyme A biosynthesis. Menaquinone-4 was found to be essential only for BB-46 growth, whereas nicotinic acid was only required by BB-12®. The model-generated insights were used to formulate a chemically defined medium that supports the growth of both strains to the same extent as a complex culture medium. Carbohydrate utilization profiles predicted by the models were experimentally validated. Furthermore, model predictions were quantitatively validated in the newly formulated medium in lab-scale batch fermentations. The models and the formulated medium represent valuable tools to further explore the metabolism and physiology of the two species, investigate the mechanisms underlying their health-promoting effects and guide the optimization of their industrial production processes.
Malaria transmission-blocking conjugate vaccine in ALFQ adjuvant induces durable functional immune responses in rhesus macaques
Authors: Scaria Puthupparampil V. , Anderson Charles , Muratova Olga , Alani Nada , Trinh Hung V. , Nadakal Steven T. , Zaidi Irfan , Lambert Lynn , Beck Zoltan , Barnafo Emma K. , Rausch Kelly M. , Rowe Chris , Chen Beth , Matyas Gary R. , Rao Mangala , Alving Carl R. , Narum David L. , Duffy Patrick E.
Published: December 2021

Malaria transmission-blocking vaccines candidates based on Pfs25 and Pfs230 have advanced to clinical studies. Exoprotein A (EPA) conjugate of Pfs25 in Alhydrogel® developed functional immunity in humans, with limited durability. Pfs230 conjugated to EPA (Pfs230D1-EPA) with liposomal adjuvant AS01 is currently in clinical trials in Mali. Studies with these conjugates revealed that non-human primates are better than mice to recapitulate the human immunogenicity and functional activity. Here, we evaluated the effect of ALFQ, a liposomal adjuvant consisting of TLR4 agonist and QS21, on the immunogenicity of Pfs25-EPA and Pfs230D1-EPA in Rhesus macaques. Both conjugates generated strong antibody responses and functional activity after two vaccinations though activity declined rapidly. A third vaccination of Pfs230D1-EPA induced functional activity lasting at least 9 months. Antibody avidity increased with each vaccination and correlated strongly with functional activity. IgG subclass analysis showed induction of Th1 and Th2 subclass antibody levels that correlated with activity.
Reactive oxygen species limit intestinal mucosa-bacteria homeostasis in vitro
Authors: Luchan Joshua , Choi Christian , Carrier Rebecca L.
Published: December 2021

Interactions between epithelial and immune cells with the gut microbiota have wide-ranging effects on many aspects of human health. Therefore, there is value in developing in vitro models capable of performing highly controlled studies of such interactions. However, several critical factors that enable long term homeostasis between bacterial and mammalian cultures have yet to be established. In this study, we explored a model consisting of epithelial and immune cells, as well as four different bacterial species (Bacteroides fragilis KLE1958, Escherichia coli MG1655, Lactobacillus rhamnosus KLE2101, or Ruminococcus gnavus KLE1940), over a 50 hour culture period. Interestingly, both obligate and facultative anaerobes grew to similar extents in aerobic culture environments during the co-culture period, likely due to measured microaerobic oxygen levels near the apical surface of the epithelia. It was demonstrated that bacteria elicited reactive oxygen species (ROS) production, and that the resulting oxidative damage heavily contributed to observed epithelial barrier damage in these static cultures. Introduction of a ROS scavenger significantly mitigated oxidative damage, improving cell monolayer integrity and reducing lipid peroxidation, although not to control (bacteria-free culture) levels. These results indicate that monitoring and mitigating ROS accumulation and oxidative damage can enable longer term bacteria-intestinal epithelial cultures, while also highlighting the significance of additional factors that impact homeostasis in mammalian cell-bacteria systems.
Circular RNA mediated gene regulation in chronic diabetic complications
Authors: Patil Nikhil S. , Feng Biao , Su Zhaoliang , Castellani Christina A. , Chakrabarti Subrata
Published: December 2021

Chronic diabetic complications affect multiple organs causing widespread organ damage. Although there are some commonalities, the phenotype of such changes show tissue specific variation. Given this, we examined whether differences in circular RNA (circRNA) mediated gene regulatory mechanisms contribute to changes in gene expression at the basal level and in diabetes. CircRNAs are single-stranded RNA with covalently closed loop structures and act as miRNA sponges, factors of RNA splicing, scaffolding for proteins, regulators of transcription, and modulators of the expression of parental genes, among other roles. We examined heart and retinal tissue from Streptozotocin-induced diabetic mice with established diabetes related tissue damage and tissue from non-diabetic controls. A custom array analysis was performed and the data were analysed. Two major circRNA mediated processes were uniquely upregulated in diabetic heart tissue, namely, positive regulation of endothelial cell migration and regulation of mitochondria: mitochondrial electron transport. In the retina, circRNAs regulating extracellular matrix protein production and endothelial to mesenchymal transition (EndMT) were found to be upregulated. The current study identified regulatory and potential pathogenetic roles of specific circRNA in diabetic retinopathy and cardiomyopathy. Understanding such novel mechanisms, may in the future, be useful to develop RNA based treatment strategies.
Mechanism of kinetin-induced death of Vicia faba ssp. minor root cortex cells
Authors: Kaźmierczak Andrzej , Kunikowska Anita , Doniak Magdalena , Kornaś Andrzej
Published: December 2021

Cell death (CD) may be induced by endogenous or exogenous factors and contributes to all the steps of plant development. This paper presents results related to the mechanism of CD regulation induced by kinetin (Kin) in the root cortex of Vicia faba ssp. minor. To explain the process, 6-(2-hydroxy-3-methylbenzylamino)purine (PI-55), adenine (Ad), 5′-amine-5′-deoxyadenosine (Ado) and N-(2-chloro-4-piridylo)-N′-phenylurea (CPPU) were applied to (i) block cytokinin receptors (CKs) and inhibit the activities of enzymes of CK metabolism, i.e., (ii) phosphoribosyltransferase, (iii) kinases, and (iv) oxidases, respectively. Moreover, ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid (EGTA), lanthanum chloride (LaCl3), ruthenium red (RRed) and cyclosporine A (CS-A) were applied to (i) chelate extracellular calcium ions (Ca2+) as well as blocks of (ii) plasma-, (iii) endoplasmic reticulum- (ER) membrane Ca2+ ion channels and (iv) mitochondria- (MIT) Ca2+ ions release by permeability transition por (PTP), respectively. The measured physiological effectiveness of these factors was the number of living and dying cortex cells estimated with orange acridine (OA) and ethidium bromide (EB), the amounts of cytosolic Ca2+ ions with chlortetracycline (CTC) staining and the intensity of chromatin and Ca2+-CTC complex fluorescence, respectively. Moreover, the role of sorafenib, an inhibitor of RAF kinase, on the vitality of cortex cells and ethylene levels as well as the activities of RAF-like kinase and MEK2 with Syntide-2 and Mek2 as substrates were studied. The results clarified the previously presented suggestion that Kin is converted to appropriate ribotides (5′-monophosphate ribonucleotides), which cooperate with the ethylene and Ca2+ ion signalling pathways to transduce the signal of kinetin-programmed cell death (Kin-PCD). Based on the present and previously published results related to Kin-PCD, the crosstalk between ethylene and MAP kinase signalling, as well as inhibitors of CK receptors and enzymes of their metabolism, is proposed.
High-throughput nanofluidic real-time PCR to discriminate Pneumococcal Conjugate Vaccine (PCV)-associated serogroups 6, 18, and 22 to serotypes using modified oligonucleotides
Authors: Downs S. L. , Madhi S. A. , Van der Merwe L. , Nunes M. C. , Olwagen C. P.
Published: December 2021

Current real-time high-throughput Polymerase Chain Reaction (qPCR) methods do not distinguish serotypes 6A from 6B, 18C from 18A/B and 22F from 22A. We established a nanofluidic real-time PCR (Fluidigm) for serotyping that included Dual-Priming-Oligonucleotides (DPO), a Locked-Nucleic-Acid (LNA) probe and TaqMan assay-sets for high-throughput serotyping. The designed assay-sets target capsular gene wciP in serogroup 6, wciX and wxcM in serogroup 18, and wcwA in serogroup 22. An algorithm combining results from published assay-sets (6A/B/C/D; 6C/D; 18A/B/C; 22A/F) and designed assay-sets for 6A/C; 18B/C/F; 18C/F, 18F and 22F was validated through blind analysis of 1973 archived clinical samples collected from South African children ≤ 5-years-old (2009–2011), previously serotyped with the culture-based Quellung method. All assay-sets were efficient (92–101%), had low variation between replicates (R2 > 0.98), and were able to detect targets at a limit of detection (LOD) of < 100 Colony-Forming-Units (CFU)/mL of sample. There was high concordance (Kappa = 0.73–0.92); sensitivity (85–100%) and specificity (96–100%) for Fluidigm compared with Quellung for serotyping 6A; 6B; 6C; 18C and 22F. Fluidigm distinguishes vaccine-serotypes 6A, 6B, 18C, next-generation PCV-serotype 22F and non-vaccine-serotypes 6C, 6D, 18A, 18B, 18F and 22A. Discriminating single serotypes is important for assessing serotype replacement and the impact of PCVs on vaccine- and non-vaccine serotypes.
Respiratory function modulated during execution, observation, and imagination of walking via SII
Authors: Pellicano Antonello , Mingoia Gianluca , Ritter Christoph , Buccino Giovanni , Binkofski Ferdinand
Published: December 2021

The Mirror Neurons System (MNS) consists of brain areas active during actions execution, as well as observation-imagination of the same actions. MNS represents a potential mechanism by which we understand other's action goals. We investigated MNS activation for legs actions, and its interaction with the autonomic nervous system. We performed a physiological and fMRI investigation on the common neural structures recruited during the execution, observation, and imagination of walking, and their effects on respiratory activity. Bilateral SMA were activated by all three tasks, suggesting that these areas are responsible for the core of the MNS effect for walking. Moreover, we observed in bilateral parietal opercula (OP1, secondary somatosensory cortex-SII) evidence of an MNS subtending walking execution-observation-imagination that also modulated the respiratory function. We suggest that SII, in modulating the vegetative response during motor activity but also during observation-imagination, consists of a re-enacting function which facilitates the understanding of motor actions.
Kinetics of DNA looping by Anabaena sensory rhodopsin transducer (ASRT) by using DNA cyclization assay
Authors: Lee Jae Jin , Kim Sung Hyun , Lee Keon Ah , Chuon Kimleng , Jung Kwang-Hwan , Kim Doseok
Published: December 2021

DNA cyclization assay together with single-molecule FRET was employed to monitor protein-mediated bending of a short dsDNA (~ 100 bp). This method provides a simple and easy way to monitor the structural change of DNA in real-time without necessitating prior knowledge of the molecular structures for the optimal dye-labeling. This assay was applied to study how Anabaena sensory rhodopsin transducer (ASRT) facilitates loop formation of DNA as a possible mechanism for gene regulation. The ASRT-induced DNA looping was maximized at 50 mM of Na+, while Mg2+ also played an essential role in the loop formation.
iTRAQ based protein profile analysis revealed key proteins involved in regulation of drought-tolerance during seed germination in Adzuki bean
Authors: Han Xuesong , Yang Fangwen , Zhao Yongguo , Chen Hongwei , Wan Zhenghuang , Li Li , Sun Longqing , Liu Liangjun , Jiao Chunhai , Liu Changyan , Sha Aihua
Published: December 2021

Adzuki bean is an important legume crop due to its high-quality protein, fiber, vitamins, minerals as well as rich bioactive substances. However, it is vulnerable to drought at the germination stage. However, little information is available about the genetic control of drought tolerance during seed germination in adzuki bean. In this study, some differential expression proteins (DEPs) were identified during seed germination between the drought-tolerant variety 17235 and drought-sensitive variety 17033 in adzuki bean using iTRAQ method. A total of 2834 proteins were identified in the germinating seeds of these two adzuki beans. Compared with the variety 17033, 87 and 80 DEPs were increased and decreased accumulation in variety 17235 under drought, respectively. Meanwhile, in the control group, a few DEPs, including 9 up-regulated and 21 down-regulated proteins, were detected in variety 17235, respectively. GO, KEGG, and PPI analysis revealed that the DEPs related to carbohydrate metabolism and energy production were significantly increased in response to drought stresses. To validate the proteomic function, the ectopic overexpression of V-ATPase in tobacco was performed and the result showed that V-ATPase upregulation could enhance the drought tolerance of tobacco. The results provide valuable insights into genetic response to drought stress in adzuki bean, and the DEPs could be applied to develop biomarkers related to drought tolerant in adzuki bean breeding projects.
C-reactive protein independently predicts survival in pancreatic neuroendocrine neoplasms
Authors: Nießen Anna , Schimmack Simon , Sandini Marta , Fliegner Dominik , Hinz Ulf , Lewosinska Magdalena , Hackert Thilo , Büchler Markus W. , Strobel Oliver
Published: December 2021

Pancreatic neuroendocrine neoplasms (pNEN) are highly variable in their postresection survival. Determination of preoperative risk factors is essential for treatment strategies. C-reactive protein (CRP) has been implicated in the pathogenesis of pNEN and shown to be associated with survival in different tumour entities. Patients undergoing surgery for pNEN were retrospectively analysed. Patients were divided into three subgroups according to preoperative CRP serum levels. Clinicopathological features, overall and disease-free survival were assessed. Uni- and multivariable survival analyses were performed. 517 surgically resected pNEN patients were analysed. CRP levels were significantly associated with relevant clinicopathological parameters and prognosis and were able to stratify subgroups with significant and clinically relevant differences in overall and disease-free survival. In univariable sensitivity analyses CRP was confirmed as a prognostic factor for overall survival in subgroups with G2 differentiation, T1/T2 and T3/T4 tumour stages, patients with node positive disease and with and without distant metastases. By multivariable analysis, preoperative CRP was confirmed as an independent predictor of postresection survival together with patient age and the established postoperative pathological predictors grading, T-stage and metastases. Preoperative serum CRP is a strong predictive biomarker for both overall and disease free survival of surgically resected pNEN. CRP is associated with prognosis independently of grading and tumour stage and may be of additional use for treatment decisions.
Stimulation efficiency of an actuator driven piston at the biological interface to the inner ear
Authors: Busch Susan , Ghoncheh Mohammad , Lenarz Thomas , Maier Hannes
Published: December 2021

Direct acoustic cochlear stimulation uses piston motion to substitute for stapes footplate (SFP) motion. The ratio of piston to stapes footplate motion amplitude, to generate the same loudness percept, is an indicator of stimulation efficiency. We determined the relationship between piston displacement to perceived loudness, the achieved maximum power output and investigated stapes fixation and obliteration as confounding factors. The electro-mechanical transfer function of the actuator was determined preoperatively on the bench and intraoperatively by laser Doppler vibrometry. Clinically, perceived loudness as a function of actuator input voltage was calculated from bone conduction thresholds and direct thresholds via the implant. The displacement of a 0.4 mm diameter piston required for a perception equivalent to 94 dB SPL at the tympanic membrane compared to normal SFP piston displacement was 27.6–35.9 dB larger, consistent with the hypothesis that the ratio between areas is responsible for stimulation efficiency. Actuator output was 110 ± 10 eq dB SPLFF @1Vrms ≤ 3 kHz and decreased to 100 eq dB SPLFF at 10 kHz. Output was significantly higher for mobile SFPs but independent from obliteration. Our findings from clinical data strongly support the assumption of a geometrical dependency on piston diameter at the biological interface to the cochlea.
Pharmacogenetics of induction therapy-related toxicities in childhood acute lymphoblastic leukemia patients treated with UKALL 2003 protocol
Authors: Aslam Sara , Ameer Sonia , Shabana N. A. , Ahmed Mehboob
Published: December 2021

Chemotherapy related toxicities have been the major factor limiting the success of acute lymphoblastic leukemia (ALL) induction therapy. Several factors, including the pharmacogenetics of asparaginase and anthracyclines, could contribute to difference in treatment outcome in ALL. We investigated the significance of variations in genes involved in hepatic and cardiac toxicity in acute lymphoblastic leukemia (ALL). Genotyping of SOD2 (rs4880), PNPL3 (rs738409) and ABCC1 (rs4148350), CBR1 (rs9024) and ABCG2 (rs2231142) was performed by Tetra-ARMS PCR-based technique to evaluate the genotype–phenotype correlation. Our results showed only minor allele G of SOD2 rs4880 increase the risk of hepatic toxicity [OR 2.63 (1.42–4.84), P =  < 0.05] while minor alleles of other SNPs showed protective impact. However, the genetic contrast analysis showed a recessive form of SOD2 rs4880 [OR 7.82 (3.86–15.85), P =  < 0.05] and PNPLA3 I148M [OR 5.82 (3.43–9.87), P =  < 0.05] variants whereas dominant genotype of ABCC1 rs4148350 [OR 2.52 (1.55–4.10), P =  < 0.05] significantly predisposes hepatotoxicity. Furthermore, heterozygous form of ABCG2 rs2231142 [OR 5.25 (1.84–14.95), P =  < 0.05] and recessive genotype of 3′UTR variant CBR1 rs9024 [OR 2.31 (1.31–4.07), P =  < 0.05] were strongly associated with cardiotoxicity. The information obtained from these genetic variations could offer biomarkers for individualization of therapeutic intervention in ALL.
Deep learning for anatomical interpretation of video bronchoscopy images
Authors: Yoo Ji Young , Kang Se Yoon , Park Jong Sun , Cho Young-Jae , Park Sung Yong , Yoon Ho Il , Park Sang Jun , Jeong Han-Gil , Kim Tackeun
Published: December 2021

Anesthesiologists commonly use video bronchoscopy to facilitate intubation or confirm the location of the endotracheal tube; however, depth and orientation in the bronchial tree can often be confused because anesthesiologists cannot trace the airway from the oropharynx when it is performed using an endotracheal tube. Moreover, the decubitus position is often used in certain surgeries. Although it occurs rarely, the misinterpretation of tube location can cause accidental extubation or endobronchial intubation, which can lead to hyperinflation. Thus, video bronchoscopy with a decision supporting system using artificial intelligence would be useful in the anesthesiologic process. In this study, we aimed to develop an artificial intelligence model robust to rotation and covering using video bronchoscopy images. We collected video bronchoscopic images from an institutional database. Collected images were automatically labeled by an optical character recognition engine as the carina and left/right main bronchus. Except 180 images for the evaluation dataset, 80% were randomly allocated to the training dataset. The remaining images were assigned to the validation and test datasets in a 7:3 ratio. Random image rotation and circular cropping were applied. Ten kinds of pretrained models with < 25 million parameters were trained on the training and validation datasets. The model showing the best prediction accuracy for the test dataset was selected as the final model. Six human experts reviewed the evaluation dataset for the inference of anatomical locations to compare its performance with that of the final model. In the experiments, 8688 images were prepared and assigned to the evaluation (180), training (6806), validation (1191), and test (511) datasets. The EfficientNetB1 model showed the highest accuracy (0.86) and was selected as the final model. For the evaluation dataset, the final model showed better performance (accuracy, 0.84) than almost all human experts (0.38, 0.44, 0.51, 0.68, and 0.63), and only the most-experienced pulmonologist showed performance comparable (0.82) with that of the final model. The performance of human experts was generally proportional to their experiences. The performance difference between anesthesiologists and pulmonologists was marked in discrimination of the right main bronchus. Using bronchoscopic images, our model could distinguish anatomical locations among the carina and both main bronchi under random rotation and covering. The performance was comparable with that of the most-experienced human expert. This model can be a basis for designing a clinical decision support system with video bronchoscopy.
Genome-wide association study and genomic heritabilities for blood protein levels in Lori-Bakhtiari sheep
Authors: Zamani P. , Mohammadi H. , Mirhoseini S. Z.
Published: December 2021

Serum protein levels are related to physiological and pathological status of animals and could be affected by both genetic and environmental factors. This study aimed to evaluate genetic variation of serum protein profile in sheep. Blood samples were randomly collected from 96 Lori-Bakhtiari ewes, a heavy meat-type breed. Total protein, albumin, globulin, α1, α2, β and γ globulins and IgG levels were measured in blood serum. The samples were genotyped using the Illumina OvineSNP50 BeadChip. The studied traits adjusted for age, birth type, birth season and estimate of breeding value for body weight were considered as pseudo-phenotypes in genome-wide association analysis. In the GWAS model, the first five principal components were fitted as covariates to correct the biases due to possible population stratification. The Plink, R and GCTA software were used for genome-wide association analysis, construction of Q-Q and Manhattan plots and estimation of genetic variances, respectively. Noticeable genomic heritabilities ± SE were estimated for total and γ globulins (0.868 ± 0.262 and 0.831 ± 0.364, respectively), but other protein fractions had zero or close to zero estimates. Based on the Bonferroni adjusted p values, four QTLs located on 181.7 Mbp of OAR3, 107.7 Mbp of OAR4, 86.3 Mbp of OAR7 and 83.0 Mbp of OAR8 were significantly associated with α1, β, β and γ globulins, respectively. The results showed that the PKP2, IGF2R, SLC22A1 and SLC22A2 genes could be considered as candidate genes for blood serum proteins. The present study showed significant genetic variations of some blood protein fractions.
The role of reactive oxygen species in the immunity induced by nano-pulse stimulation
Authors: Guo Siqi , Burcus Niculina I. , Scott Megan , Jing Yu , Semenov Iurii
Published: December 2021

Reactive oxygen species (ROS) are byproducts of tumor cells treated with Nano-Pulse Stimulation (NPS). Recently, ROS have been suggested as a contributing factor in immunogenic cell death and T cell-mediated immunity. This research further investigated the role of NPS induced ROS in antitumor immunity. ROS production in 4T1-luc breast cancer cells was characterized using three detection reagents, namely, Amplex Red, MitoSox Red, and Dihydroethidium. The efficiency of ROS quenching was evaluated in the presence or absence of ROS scavengers and/or antioxidants. The immunogenicity of NPS treated tumor cells was assessed by ex vivo dendritic cell activation, in vivo vaccination assay and in situ vaccination with NPS tumor ablation. We found that NPS treatment enhanced the immunogenicity of 4T1-luc mouse mammary tumor, resulted in a potent in situ vaccination protection and induced long-term T cell immunity. ROS production derived from NPS treated breast cancer cells was an electric pulse dose-dependent phenomenon. Noticeably, the dynamic pattern of hydrogen peroxide production was different from that of superoxide production. Interestingly, regardless of NPS treatment, different ROS scavengers could either block or promote ROS production and stimulate or inhibit tumor cell growth. The activation of dendritic cells was not influenced by blocking ROS generation. The results from in vivo vaccination with NPS treated cancer cells suggests that ROS generation was not a prerequisite for immune protection.
Lyl-1 regulates primitive macrophages and microglia development
Authors: Wang Shoutang , Ren Deshan , Arkoun Brahim , Kaushik Anna-Lila , Matherat Gabriel , Lécluse Yann , Filipp Dominik , Vainchenker William , Raslova Hana , Plo Isabelle , Godin Isabelle
Published: December 2021

During ontogeny, macrophage populations emerge in the Yolk Sac (YS) via two distinct progenitor waves, prior to hematopoietic stem cell development. Macrophage progenitors from the primitive/”early EMP” and transient-definitive/”late EMP” waves both contribute to various resident primitive macrophage populations in the developing embryonic organs. Identifying factors that modulates early stages of macrophage progenitor development may lead to a better understanding of defective function of specific resident macrophage subsets. Here we show that YS primitive macrophage progenitors express Lyl-1, a bHLH transcription factor related to SCL/Tal-1. Transcriptomic analysis of YS macrophage progenitors indicate that primitive macrophage progenitors present at embryonic day 9 are clearly distinct from those present at later stages. Disruption of Lyl-1 basic helix-loop-helix domain leads initially to an increased emergence of primitive macrophage progenitors, and later to their defective differentiation. These defects are associated with a disrupted expression of gene sets related to embryonic patterning and neurodevelopment. Lyl-1-deficiency also induce a reduced production of mature macrophages/microglia in the early brain, as well as a transient reduction of the microglia pool at midgestation and in the newborn. We thus identify Lyl-1 as a critical regulator of primitive macrophages and microglia development, which disruption may impair resident-macrophage function during organogenesis.
Nrf2 plays a critical role in the metabolic response during and after spaceflight
Authors: Uruno Akira , Saigusa Daisuke , Suzuki Takafumi , Yumoto Akane , Nakamura Tomohiro , Matsukawa Naomi , Yamazaki Takahiro , Saito Ristumi , Taguchi Keiko , Suzuki Mikiko , Suzuki Norio , Otsuki Akihito , Katsuoka Fumiki , Hishinuma Eiji , Okada Risa , Koshiba Seizo , Tomioka Yoshihisa , Shimizu Ritsuko , Shirakawa Masaki , Kensler Thomas W. , Shiba Dai , Yamamoto Masayuki
Published: December 2021

Space travel induces stresses that contribute to health problems, as well as inducing the expression of Nrf2 (NF-E2-related factor-2) target genes that mediate adaptive responses to oxidative and other stress responses. The volume of epididymal white adipose tissue (eWAT) in mice increases during spaceflight, a change that is attenuated by Nrf2 knockout. We conducted metabolome analyses of plasma from wild-type and Nrf2 knockout mice collected at pre-flight, in-flight and post-flight time points, as well as tissues collected post-flight to clarify the metabolic responses during and after spaceflight and the contribution of Nrf2 to these responses. Plasma glycerophospholipid and sphingolipid levels were elevated during spaceflight, whereas triacylglycerol levels were lower after spaceflight. In wild-type mouse eWAT, triacylglycerol levels were increased, but phosphatidylcholine levels were decreased, and these changes were attenuated in Nrf2 knockout mice. Transcriptome analyses revealed marked changes in the expression of lipid-related genes in the liver and eWAT after spaceflight and the effects of Nrf2 knockout on these changes. Based on these results, we concluded that space stress provokes significant responses in lipid metabolism during and after spaceflight; Nrf2 plays critical roles in these responses.
Pd-Catalysed oxidative carbonylation of α-amino amides to hydantoins under mild conditions
Authors: Voronov Aleksandr , Botla Vinayak , Montanari Luca , Carfagna Carla , Mancuso Raffaella , Gabriele Bartolo , Maestri Giovanni , Motti Elena , Della Ca Nicola
Published: December 2021

The common reaction pathway involving unprotected α-amino amides that leads to the formation of symmetrical urea under palladium-catalyzed carbonylative conditions is avoided here. Hydantoins are selectively obtained under mild and safe conditions.
Evidence of dynamical effects and critical field in a cobalt spin crossover complex
Authors: Ekanayaka Thilini K. , Wang Ping , Yazdani Saeed , Phillips Jared Paul , Mishra Esha , Dale Ashley S. , N’Diaye Alpha T. , Klewe Christoph , Shafer Padraic , Freeland John , Streubel Robert , Wampler James Paris , Zapf Vivien , Cheng Ruihua , Shatruk Michael , Dowben Peter A.
Published: December 2021

The spin crossover complex [Co(SQ)2(4-CN-py)2] exhibits a nonzero critical field for net alignment of the orbital magnetic moment and the net spin and orbital moments are sensitive to temperature.
A DNAzyme-based normalized fluorescence strategy for direct quantification of endogenous zinc in living cells
Authors: Zhang Xuanhao , Song Zhi-Ling , Chao Qiqi , Li Qian , Kong Rongmei , Fan Gao-Chao , Luo Xiliang
Published: December 2021

A reliable fluorescence strategy with normalized output signal is developed for the direct quantification of endogenous zinc in living cells.
Proton binding to humic nano particles: electrostatic interaction and the condensation approximation
Authors: Koopal Luuk , Xiong Juan , Tan Wenfeng , Saito Takumi , Avena Marcelo
Published: December 2021

Condensation approximation method applied to the charge density curves of a humic acid (left) and the calculated humic acid average electrostatic potentials, CA, corresponding with the Langmuir–Freundlich-soft-Poisson–Boltzmann-theory.
Nanostructuring and macroscopic behavior of type V deep eutectic solvents based on monoterpenoids
Authors: Zamora Lorena , Benito Cristina , Gutiérrez Alberto , Alcalde Rafael , Alomari Noor , Bodour Ahmad Al , Atilhan Mert , Aparicio Santiago
Published: December 2021

Type V natural deep eutectic solvents based on monoterpenoids (cineole, carvone, menthol, and thymol) are studied using a combined experimental and molecular modeling approach.
Insight into the characteristics of microbial communities in a single-stage anammox reactor under different oxygen conditions
Authors: Li Zhaoyang , Ge Zheng , Li Jialin , Yang Shenhua , Peng Yongzhen , Zhang Liang
Published: December 2021

Micro-aerobic conditions enhanced the stability of the PN/A system, which was associated with the high diversity and network complexity. Micro-aerobic conditions provided a more complex niche for both aerobic and anaerobic bacteria.
Atomically dispersed Co–N–C electrocatalysts synthesized by a low-speed ball milling method for proton exchange membrane fuel cells
Authors: Liu Tao , Sun Feng , Huang Meihua , Guan Lunhui
Published: December 2021

A green method of low-speed ball milling was applied to synthesize the precursor of Co–N–C catalysts with high performance.
Enhanced third harmonic generation in ultrathin free-standing β-Ga2O3 nanomembranes: study on surface and bulk contribution
Authors: Yi Gao , Jeon Sangheon , Kwon Young Woo , Park Jongkyoon , Nguyen Duy Anh , Suchand Sandeep C. S. , Hwang Wan Sik , Hong Suck Won , Kim Seungchul , Kim Young-Jin
Published: December 2021

Third harmonic generation from freestanding and glass-supported ultrathin β-Ga2O3 nanomembranes. The surface and bulk contributions of nonlinear optical harmonic generation.
Dimension switchable auto-fluorescent peptide-based 1D and 2D nano-assemblies and their self-influence on intracellular fate and drug delivery
Authors: Chibh Sonika , Kaur Komalpreet , Gautam Ujjal K. , Panda Jiban Jyoti
Published: December 2021

The production of dynamic, environment-responsive shape-tunable biomaterials marks a significant step forward in the construction of synthetic materials that can easily rival their natural counterparts.
Chiral carbon dots – a functional domain for tyrosinase Cu active site modulation via remote target interaction
Authors: Ma Yurong , Zhang Mengling , Deng Zhixiong , Wang Xiting , Huang Hui , Yang Kai , Yuan Bing , Liu Yang , Kang Zhenhui
Published: December 2021

LCDs-1/tyrosinase hybrid enzyme can serve as a new functional domain for tyrosinase Cu active site modulation via remote target interaction and efficiently inhibit oxidation of dopamine.
Discovery of gargantulides B and C, new 52-membered macrolactones from Amycolatopsis sp. Complete absolute stereochemistry of the gargantulide family
Authors: Carretero-Molina Daniel , Ortiz-López Francisco Javier , Gren Tetiana , Oves-Costales Daniel , Martín Jesús , Román-Hurtado Fernando , Sparholt Jørgensen Tue , de la Cruz Mercedes , Díaz Caridad , Vicente Francisca , Blin Kai , Reyes Fernando , Weber Tilmann , Genilloud Olga
Published: December 2021

Gargantulides B and C are among the most complex bacterial polyketides discovered so far. A combination of NMR and genome-based bioinformatics analyses allowed us to complete and revise the absolute stereochemistry of the entire gargantulide family.
Eutectic-based liposome as a potential delivery system of paeonol
Authors: Wu Jieyu , Yang Suqin , Yin Tianxiang , Wang Xiaoyong
Published: December 2021

A THEDES based on paeonol and lauric acid was constructed and showed potential applicability for the delivery of paeonol.
A novel strategy for sensitive and rapid detection of ascorbic acid via the Tyndall effect of cobalt hydroxide nanoflakes
Authors: Gao Qian , Wan Jing , Chen Xuejiang , Mo Xiaomei , Sun Yao , Zou Jianmei , Nie Jinfang , Zhang Yun
Published: December 2021

A novel colorimetric nanosensor was initially developed for the equipment-free sensitive detection of ascorbic acid based on the Tyndall effect of cobalt hydroxide nanoflakes.
The interplay between ternary molten carbonate and biomaterials during pressurized slow pyrolysis
Authors: Jalalabadi Tahereh , Moghtaderi Behdad , Allen Jessica
Published: December 2021

The effect of pressure on the thermochemical conversion of woody biomass and lignin in the presence of carbonate additives has been investigated at moderate temperatures (600 and 800 °C).
Transparent porous polymer sheets for efficient product separation in solar water splitting
Authors: Özen Ciler , Obata Keisuke , Bogdanoff Peter , Yulianto Nursidik , Wasisto Hutomo Suryo , Abdi Fatwa F.
Published: December 2021

The crossover and ohmic losses of porous polymer sheets used as transparent product separators in solar water splitting cells are evaluated using multiphysics simulation and validation experiments.
Argentophilic pyridinic nitrogen for embedding lithiophilic silver nanoparticles in a three-dimensional carbon scaffold for reversible lithium plating/stripping
Authors: Jeon Yuju , Kim Jonghak , Jang Haeseong , Lee Jeongin , Kim Min Gyu , Liu Nian , Song Hyun-Kon
Published: December 2021

Ten times heavy silver loading into a 3D scaffold via a strong Ag+–pN interaction between silver cations and argentophilic pyridinic nitrogen of melamine provides a strong lithiophilicity, largely improving lithium plating/stripping reversibility.
Designing ultratough, malleable and foldable biocomposites for robust green electronic devices
Authors: Hou Xunan , Liu Siqi , He Chaobin
Published: December 2021

Nanoscale domains and entangled interfaces create ultratough, malleable and foldable polymer blends from common biodegradable plastics, which find applications in green flexible electronic devices.
Triggering interfacial activity of the traditional La0.5Sr0.5MnO3 cathode with Co-doping for proton-conducting solid oxide fuel cells
Authors: Yin Yanru , Yu Shoufu , Dai Hailu , Bi Lei
Published: December 2021

Doping the Co element into the traditional La0.5Sr0.5MnO3−δ cathode material triggers the activity of the cathode/electrolyte interface in the composite cathode, leading to impressively high cell performance for proton-conducting solid oxide fuel cells.
Promoting high T2 contrast in Dy-doped MSNs through Curie effects
Authors: Ellis Connor M. , Pellico Juan , Young Liam A. J. , Miller Jack , Davis Jason J.
Published: December 2021

The dominant Curie effect underpinning relaxivity enhancements in T2 has been systematically tuned through paramagnetic loading density. This results in the optimisation of acquired MR image contrast, and facilitates effective high field imaging.
Multi-ligand modified PC@DOX-PA/EGCG micelles effectively inhibit the growth of ER+, PR+ or HER2+ breast cancer
Authors: Wang Xiaozhen , He Jiecheng , Jiang Siyuan , Gao Yifei , Zhang Ling-Kun , Yin Liang , You Rong , Guan Yan-Qing
Published: December 2021

Tumor heterogeneity is a large challenge to overcome in breast cancer therapy. In this study, we develop one multi-targeted drug delivery system, which could target to BT-474, MCF-7, EMT-6, and MDA-MB-231 cells, and inhibit their growth.
Targeting drug delivery and efficient lysosomal escape for chemo-photodynamic cancer therapy by a peptide/DNA nanocomplex
Authors: Wang Qiusheng , He Ziyun , Zhu Hai , Gao Wenxia , Zhang Nan , Li Jing , Yan Jianqin , He Bin , Ye Xueting
Published: December 2021

Our study demonstrated a biocompatible peptide/DNA composite nanoplatform for combinational cancer therapy via the targeted delivery of therapeutic agents and efficient lysosomal escape.
A mixed-dimensional WS2/GaSb heterojunction for high-performance p–n diodes and junction field-effect transistors
Authors: Cheng Zichao , Song Xiufeng , Jiang Lianfu , Wang Lude , Sun Jiamin , Yang Zaixing , Jian Yuxuan , Zhang Shengli , Chen Xiang , Zeng Haibo
Published: December 2021

High-performance WS2/GaSb junction field-effect transistor.
Hollow MOF-derived CoNi/C composites as effective electromagnetic absorbers in the X-band and Ku-band
Authors: Yu Yadi , Fang Yi , Hu Qi , Shang Xueni , Tang Chengchun , Meng Fanbin
Published: December 2021

This article reports the successful fabrication of a lightweight CoNi/C nanocomposite as an electromagnetic wave absorber, which has excellent microwave absorption performance in the X-band and Ku-band.