bluuebunny/crossref_metadata_2025 huggingface dataset:
Dihydroquinazolinones as adaptative C(sp3) handles in arylations and alkylations via dual catalytic C–C bond-functionalization
Authors: Lv Xin-Yang , Abrams Roman , Martin Ruben
Published: May 2022

C–C bond forming cross-couplings are convenient technologies for the construction of functional molecules. Consequently, there is continual interest in approaches that can render traditionally inert functionality as cross-coupling partners, included in this are ketones which are widely-available commodity chemicals and easy to install synthetic handles. Herein, we describe a dual catalytic strategy that utilizes dihydroquinazolinones derived from ketone congeners as adaptative one-electron handles for forging C(sp3) architectures via α C–C cleavage with aryl and alkyl bromides. Our approach is achieved by combining the flexibility and modularity of nickel catalysis with the propensity of photoredox events for generating open-shell reaction intermediates. This method is distinguished by its wide scope and broad application profile––including chemical diversification of advanced intermediates––, providing a catalytic technique complementary to existing C(sp3) cross-coupling reactions that operates within the C–C bond-functionalization arena.
IRF4 drives clonal evolution and lineage choice in a zebrafish model of T-cell lymphoma
Authors: Amanda Stella , Tan Tze King , Ong Jolynn Zu Lin , Theardy Madelaine Skolastika , Wong Regina Wan Ju , Huang Xiao Zi , Ali Muhammad Zulfaqar , Li Yan , Gong Zhiyuan , Inagaki Hiroshi , Foo Ee Yong , Pang Brendan , Tan Soo Yong , Iida Shinsuke , Sanda Takaomi
Published: May 2022

IRF4 is a master regulator of immunity and is also frequently overexpressed in mature lymphoid neoplasms. Here, we demonstrate the oncogenicity of IRF4 in vivo, its potential effects on T-cell development and clonal evolution using a zebrafish model. IRF4-transgenic zebrafish develop aggressive tumors with massive infiltration of abnormal lymphocytes that spread to distal organs. Many late-stage tumors are mono- or oligoclonal, and tumor cells can expand in recipient animals after transplantation, demonstrating their malignancy. Mutation ofp53accelerates tumor onset, increases penetrance, and results in tumor heterogeneity. Surprisingly, single-cell RNA-sequencing reveals that the majority of tumor cells are double-negative T-cells, many of which expresstcr-γ that became dominant as the tumors progress, whereas double-positive T-cells are largely diminished. Gene expression and epigenetic profiling demonstrates thatgata3, mycb, lrrn1, patl1andpsip1are specifically activated in tumors, while genes responsible for T-cell differentiation includingid3are repressed.IRF4-driven tumors are sensitive to the BRD inhibitor.
TH17 cells promote CNS inflammation by sensing danger signals via Mincle
Authors: Zhang Quanri , Liu Weiwei , Wang Han , Zhou Hao , Bulek Katarzyna , Chen Xing , Zhang Cun-Jin , Zhao Junjie , Zhang Renliang , Liu Caini , Kang Zizhen , Bermel Robert A. , Dubyak George , Abbott Derek W. , Xiao Tsan Sam , Nagy Laura E. , Li Xiaoxia
Published: May 2022

The C-type lectin receptor Mincle is known for its important role in innate immune cells in recognizing pathogen and damage associated molecular patterns. Here we report a T cell–intrinsic role for Mincle in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). Genomic deletion of Mincle in T cells impairs TH17, but not TH1 cell-mediated EAE, in alignment with significantly higher expression of Mincle in TH17 cells than in TH1 cells. Mechanistically, dying cells release β-glucosylceramide during inflammation, which serves as natural ligand for Mincle. Ligand engagement induces activation of the ASC-NLRP3 inflammasome, which leads to Caspase8-dependent IL-1β production and consequentially TH17 cell proliferation via an autocrine regulatory loop. Chemical inhibition of β-glucosylceramide synthesis greatly reduces inflammatory CD4+ T cells in the central nervous system and inhibits EAE progression in mice. Taken together, this study indicates that sensing of danger signals by Mincle on TH17 cells plays a critical role in promoting CNS inflammation.
CNPY4 inhibits the Hedgehog pathway by modulating membrane sterol lipids
Authors: Lo Megan , Sharir Amnon , Paul Michael D. , Torosyan Hayarpi , Agnew Christopher , Li Amy , Neben Cynthia , Marangoni Pauline , Xu Libin , Raleigh David R. , Jura Natalia , Klein Ophir D.
Published: May 2022

The Hedgehog (HH) pathway is critical for development and adult tissue homeostasis. Aberrant HH signaling can lead to congenital malformations and diseases including cancer. Although cholesterol and several oxysterol lipids have been shown to play crucial roles in HH activation, the molecular mechanisms governing their regulation remain unresolved. Here, we identify Canopy4 (CNPY4), a Saposin-like protein, as a regulator of the HH pathway that modulates levels of membrane sterol lipids. Cnpy4–/– embryos exhibit multiple defects consistent with HH signaling perturbations, most notably changes in digit number. Knockdown of Cnpy4 hyperactivates the HH pathway in vitro and elevates membrane levels of accessible sterol lipids, such as cholesterol, an endogenous ligand involved in HH activation. Our data demonstrate that CNPY4 is a negative regulator that fine-tunes HH signal transduction, revealing a previously undescribed facet of HH pathway regulation that operates through control of membrane composition.
Expanding the positivity offset theory of anhedonia to the psychosis continuum
Authors: Riehle Marcel , Pillny Matthias , Lincoln Tania M.
Published: May 2022

People with schizophrenia and negative symptoms show diminished net positive emotion in low-arousing contexts (diminished positivity offset) and co-activate positive and negative emotion more frequently (increased ambivalence). Here, we investigated whether diminished positivity offset and increased ambivalence covary with negative symptoms along the continuum of psychotic symptoms. We conducted an online-study in an ad-hoc community sample (N = 261). Participants self-reported on psychotic symptoms (negative symptoms, depression, positive symptoms, anhedonia) and rated positivity, negativity, and arousal elicited by pleasant, unpleasant, and neutral stimuli. The data were analyzed with multilevel linear models. Increasing levels of all assessed symptom areas showed significant associations with diminished positivity offset. Increased ambivalence was related only to positive symptoms. Our results show that the diminished positivity offset is associated with psychotic symptoms in a community sample, including, but not limited to, negative symptoms. Ecological validity and symptom specificity require further investigation.
Quantification of salt stress in wheat leaves by Raman spectroscopy and machine learning
Authors: Kecoglu Ibrahim , Sirkeci Merve , Unlu Mehmet Burcin , Sen Ayse , Parlatan Ugur , Guzelcimen Feyza
Published: May 2022

The salinity level of the growing medium has diverse effects on the development of plants, including both physical and biochemical changes. To determine the salt stress level of a plant endures, one can measure these structural and chemical changes. Raman spectroscopy and biochemical analysis are some of the most common techniques in the literature. Here, we present a combination of machine learning and Raman spectroscopy with which we can both find out the biochemical change that occurs while the medium salt concentration changes and predict the level of salt stress a wheat sample experiences accurately using our trained regression models. In addition, by applying different machine learning algorithms, we compare the level of success for different algorithms and determine the best method to use in this application. Production units can take actions based on the quantitative information they get from the trained machine learning models related to salt stress, which can potentially increase efficiency and avoid the loss of crops.
Spatiotemporal neural network with attention mechanism for El Niño forecasts
Authors: Kim Jinah , Kwon Minho , Kim Sung-Dae , Kug Jong-Seong , Ryu Joon-Gyu , Kim Jaeil
Published: May 2022

To learn spatiotemporal representations and anomaly predictions from geophysical data, we propose STANet, a spatiotemporal neural network with a trainable attention mechanism, and apply it to El Niño predictions for long-lead forecasts. The STANet makes two critical architectural improvements: it learns spatial features globally by expanding the network’s receptive field and encodes long-term sequential features with visual attention using a stateful long-short term memory network. The STANet conducts multitask learning of Nino3.4 index prediction and calendar month classification for predicted indices. In a comparison of the proposed STANet performance with the state-of-the-art model, the accuracy of the 12-month forecast lead correlation coefficient was improved by 5.8% and 13% for Nino3.4 index prediction and corresponding temporal classification, respectively. Furthermore, the spatially attentive regions for the strong El Niño events displayed spatial relationships consistent with the revealed precursor for El Niño occurrence, indicating that the proposed STANet provides good understanding of the spatiotemporal behavior of global sea surface temperature and oceanic heat content for El Niño evolution.
Dynamics of parasympathetic activity in violent incarcerated offenders before, during, and in recovery from an emotional inhibition task
Authors: Palix Julie , Gillespie Steven M. , Abbiati Milena , Abu-Akel Ahmad
Published: May 2022

Dynamics of the autonomic nervous system (ANS) are hypothesized to play a role in the emergence of interpersonal violence. In the present study, we examined continuous activities of the inhibitory parasympathetic pathway of the ANS through the root mean square of successive differences between normal heartbeats (RMSSD) in 22 male offenders who committed interpersonal violence and 24 matched controls from the general population across three successive phases: resting baseline, while performing an emotional Go/No-Go task, and post-task recovery. Results showed that across the three phases, the offender group presented lower RMSSD at baseline (pFDR = .003; Cohen’s d =  − 1.11), but similar levels during the task, attributed to a significant increase in their RMSSD level (pFDR = .027, Cohen’s d =  − 1.26). During recovery, while no distinction between the two groups was found, both groups showed signs of recovering toward baseline values. These findings suggest that violent incarcerated offenders can flexibly engage parasympathetic resources to meet environmental challenges. This underscores the necessity of considering parasympathetic dynamics and its respective mobilization/flexibility to better understand ANS profiles underlying interpersonal violence as well as its potential utility in designing more tailored interventions.
Clinical prediction model of pathological response following neoadjuvant chemoradiotherapy for rectal cancer
Authors: Shin Jung Kyong , Huh Jung Wook , Lee Woo Yong , Yun Seong Hyeon , Kim Hee Cheol , Cho Yong Beom , Park Yoon Ah
Published: May 2022

Patients with pathologic complete response (pCR) achievement can consider local excision or “watch and wait” strategy instead of a radical surgery. This study analyzed the predictive factors of pCR in rectal cancer patients who underwent radical operation after neoadjuvant chemoradiotherapy (nCRT). This study also analyzed the recurrence patterns in patients who achieved pCR and the oncologic outcomes and prognostic factors by ypStage. Between 2000 and 2013, 1,089 consecutive rectal cancer patients who underwent radical resection after nCRT were analyzed. These patients were classified into two groups according to pCR. The clinicopathologic and oncologic outcomes were analyzed and compared between the two groups. Multivariate analysis was conducted on factors related to pCR. The proportion of patients achieving pCR was 18.2% (n = 198). The pCR group demonstrated earlier clinical T and N stages, smaller tumor size, better differentiation, and a lower percentage of circumferential resection margin (CRM) involvement than did the non-pCR group. The prognostic factors associated with poorer disease-free survival were high preoperative carcinoembryonic antigen levels, non-pCR, poor histology, lymphatic/perineural invasion, and involvement of CRM. Multivariate analysis revealed that clinical node negativity, tumor size < 4 cm, and well differentiation were significant independent clinical predictors for achieving pCR. Patients with pCR displayed better long-term outcomes than those with non-pCR. The pCR-prediction model, based on predictive factors, is potentially useful for prognosis and for prescribing a treatment strategy in patients with advanced rectal cancer who need nCRT.
Predictive value of clinical and 18F-FDG-PET/CT derived imaging parameters in patients undergoing neoadjuvant chemoradiation for esophageal squamous cell carcinoma
Authors: Marr Lisa , Haller Bernhard , Pyka Thomas , Peeken Jan C. , Jesinghaus Moritz , Scheidhauer Klemens , Friess Helmut , Combs Stephanie E. , Münch Stefan
Published: May 2022

Aim of this study was to validate the prognostic impact of clinical parameters and baseline 18F-FDG-PET/CT derived textural features to predict histopathologic response and survival in patients with esophageal squamous cell carcinoma undergoing neoadjuvant chemoradiation (nCRT) and surgery. Between 2005 and 2014, 38 ESCC were treated with nCRT and surgery. For all patients, the 18F-FDG-PET-derived parameters metabolic tumor volume (MTV), SUVmax, contrast and busyness were calculated for the primary tumor using a SUV-threshold of 3. The parameter uniformity was calculated using contrast-enhanced computed tomography. Based on histopathological response to nCRT, patients were classified as good responders (< 10% residual tumor) (R) or non-responders (≥ 10% residual tumor) (NR). Regression analyses were used to analyse the association of clinical parameters and imaging parameters with treatment response and overall survival (OS). Good response to nCRT was seen in 27 patients (71.1%) and non-response was seen in 11 patients (28.9%). Grading was the only parameter predicting response to nCRT (Odds Ratio (OR) = 0.188, 95% CI: 0.040–0.883; p = 0.034). No association with histopathologic treatment response was seen for any of the evaluated imaging parameters including SUVmax, MTV, busyness, contrast and uniformity. Using multivariate Cox-regression analysis, the heterogeneity parameters busyness (Hazard Ratio (HR) = 1.424, 95% CI: 1.044–1.943; p = 0.026) and contrast (HR = 6.678, 95% CI: 1.969–22.643;p = 0.002) were independently associated with OS, while no independent association with OS was seen for SUVmax and MTV. In patients with ESCC undergoing nCRT and surgery, baseline 18F-FDG-PET/CT derived parameters could not predict histopathologic response to nCRT. However, the PET/CT derived features busyness and contrast were independently associated with OS and should be further investigated.
A human pancreatic ECM hydrogel optimized for 3-D modeling of the islet microenvironment
Authors: Tremmel Daniel M. , Sackett Sara Dutton , Feeney Austin K. , Mitchell Samantha A. , Schaid Michael D. , Polyak Erzsebet , Chlebeck Peter J. , Gupta Sakar , Kimple Michelle E. , Fernandez Luis A. , Odorico Jon S.
Published: May 2022

Extracellular matrix (ECM) plays a multitude of roles, including supporting cells through structural and biochemical interactions. ECM is damaged in the process of isolating human islets for clinical transplantation and basic research. A platform in which islets can be cultured in contact with natural pancreatic ECM is desirable to better understand and support islet health, and to recapitulate the native islet environment. Our study demonstrates the derivation of a practical and durable hydrogel from decellularized human pancreas that supports human islet survival and function. Islets embedded in this hydrogel show increased glucose- and KCl-stimulated insulin secretion, and improved mitochondrial function compared to islets cultured without pancreatic matrix. In extended culture, hydrogel co-culture significantly reduced levels of apoptosis compared to suspension culture and preserved controlled glucose-responsive function. Isolated islets displayed altered endocrine and non-endocrine cell arrangement compared to in situ islets; hydrogel preserved an islet architecture more similar to that observed in situ. RNA sequencing confirmed that gene expression differences between islets cultured in suspension and hydrogel largely fell within gene ontology terms related to extracellular signaling and adhesion. Natural pancreatic ECM improves the survival and physiology of isolated human islets.
Tillage, green manure and residue retention improves aggregate-associated phosphorus fractions under rice–wheat cropping
Authors: Sharma Sandeep , Kaur Sukhjinder , Parkash Choudhary Om , Singh Manpreet , Al-Huqail Asma A. , Ali Hayssam M. , Kumar Ritesh , Siddiqui Manzer H.
Published: May 2022

The sustainability of the rice–wheat system is threatened due to the deterioration of soil health and emergence of new challenges of climate change caused by low nutrient use efficiency and large scale burning of crop residues. The conservation agriculture based on tillage intensity, crop residue retention and raising green manuring (GM) crops during the intervening period between wheat harvest and rice establishment offers opportunities for restoration of phosphorus (P) dynamics and stimulate phosphatase activities within the macro-and micro-aggregates. Phosphorus and phosphatase activities in the soil aggregates affected by different residue management practices remain poorly understood. Thus, soil samples were obtained after a five-year field experiment to identify the effect of tillage, green manure and residue management on aggregate-associated phosphorus fractions. Four main plot treatments in rice included combination of wheat straw and GM were conventional till puddled transplanted rice (PTR) with no wheat straw (PTRW0), PTR with 25% wheat stubbles retained (PTRW25), PTR without wheat straw and GM (PTRW0 + GM), and PTR with wheat stubbles and GM (PTRW25 + GM). Three sub-plots treatments in the successive wheat crop were conventional tillage (CT) with rice straw removed (CTWR0), zero tillage (ZT) with rice straw removed (ZTWR0) and ZT with rice straw retained as surface mulch (ZTWR100). Results of the present study revealed significantly higher phosphorus fractions (HCl-P, NaHCO3-Piand NaOH-Po) in treatment PTRW25 + GM and ZTWR100compared with PTRW0/CTWR0within both macro- and micro-aggregates. The total phosphorus (P), available P, alkaline phosphatase and phytin-P were significantly higher under ZTWR100than CTWR0. The principal component analysis identified NaOH-Po, NaHCO3-Piand HCl-P as the dominant and reliable indicators for evaluating P transformation within aggregates under conservation agriculture-based practices.
Time-dependent effect of desensitization with wasp venom on selected parameters of the immune system
Authors: Szymański Łukasz , Urbańska Weronika , Ciepielak Martyna , Cios Aleksandra , Stankiewicz Wanda , Stelmasiak Marta , Rzeszotarska Agnieszka , Korsak Jolanta , Lewicki Sławomir , Chciałowski Andrzej
Published: May 2022

The emergence of tolerance during Hymenoptera venom immunotherapy (VIT) is a complex process. The main goal of VIT is to induce a change from proinflammatory Th2 response to the Th1 response. However, the immune mechanism of acquiring rapid tolerance during VIT has not yet been fully understood. Therefore, we have analyzed (in 4-time points: 0, 2, 6, and 24 weeks after the initiation phase of VIT) the concentration of complement C3, C4, and C5 components, lymphocyte subpopulations (flow cytometry), as well as histamine and tryptase serum concentrations of 43 patients with wasp venom allergy (III and IV Müller grade) classified to ultra-rush treatment and 18 volunteers as the control group (CG). We observed that VIT affected the immune system by inducing changes in the complement system (decreased C3 and C4 compartment protein concentrations) and "normalized" the percentage of lymphocytes and neutrophils in the peripheral blood. Moreover, a significant increase in the percentage of nTreg in the blood of patients treated with VIT was observed. On the other hand, there were no changes in histamine or tryptase concentrations in the blood. Increased percentage of nTreg cells is a well-known mechanism by which VIT affects the immune system. Finally, VIT also modulated the concentrations of the complement components, which may be a previously unknown VIT mechanism of action.
TPMS-based membrane lung with locally-modified permeabilities for optimal flow distribution
Authors: Hesselmann Felix , Halwes Michael , Bongartz Patrick , Wessling Matthias , Cornelissen Christian , Schmitz-Rode Thomas , Steinseifer Ulrich , Jansen Sebastian Victor , Arens Jutta
Published: May 2022

Membrane lungs consist of thousands of hollow fiber membranes packed together as a bundle. The devices often suffer from complications because of non-uniform flow through the membrane bundle, including regions of both excessively high flow and stagnant flow. Here, we present a proof-of-concept design for a membrane lung containing a membrane module based on triply periodic minimal surfaces (TPMS). By warping the original TPMS geometries, the local permeability within any region of the module could be raised or lowered, allowing for the tailoring of the blood flow distribution through the device. By creating an iterative optimization scheme for determining the distribution of streamwise permeability inside a computational porous domain, the desired form of a lattice of TPMS elements was determined via simulation. This desired form was translated into a computer-aided design (CAD) model for a prototype device. The device was then produced via additive manufacturing in order to test the novel design against an industry-standard predicate device. Flow distribution was verifiably homogenized and residence time reduced, promising a more efficient performance and increased resistance to thrombosis. This work shows the promising extent to which TPMS can serve as a new building block for exchange processes in medical devices.
CRISPR-Cas9 mediated generation of a conditional poly(A) binding protein nuclear 1 (Pabpn1) mouse model reveals an essential role for hematopoietic stem cells
Authors: Sommerkamp Pia , Sommerkamp Alexander C. , Zeisberger Petra , Eiben Paula Leonie , Narr Andreas , Korkmaz Aylin , Przybylla Adriana , Sohn Markus , van der Hoeven Franciscus , Schönig Kai , Trumpp Andreas
Published: May 2022

Poly(A) binding protein nuclear 1 (PABPN1) is known for its role in poly(A) tail addition and regulation of poly(A) tail length. In addition, it has been shown to be involved in alternative polyadenylation (APA). APA is a process regulating differential selection of polyadenylation sites, thereby influencing protein isoform expression and 3ʹ-UTR make-up. In this study, we generated an inducible Pabpn1flox/flox mouse model using crRNA-tracrRNA:Cas9 complexes targeting upstream and downstream genomic regions, respectively, in combination with a long single-stranded DNA (ssDNA) template. We performed extensive in vitro testing of various guide RNAs (gRNAs) to optimize recombination efficiency for in vivo application. Pabpn1flox/flox mice were generated and crossed to MxCre mice for validation experiments, allowing the induction of Cre expression in the bone marrow (BM) by poly(I:C) (pIC) injections. Validation experiments revealed successful deletion of Pabpn1 and absence of PABPN1 protein. Functionally, knockout (KO) of Pabpn1 led to a rapid and robust depletion of hematopoietic stem and progenitor cells (HSPCs) as well as myeloid cells, suggesting an essential role of Pabpn1 in the hematopoietic lineage. Overall, the mouse model allows an inducible in-depth in vivo analysis of the role of PABPN1 and APA regulation in different tissues and disease settings.
Mechanistic insights of ABC importer HutCD involved in heme internalization by Vibrio cholerae
Authors: Saha Indrila , Chakraborty Shrestha , Agarwal Shubhangi , Mukherjee Peeali , Ghosh Biplab , Dasgupta Jhimli
Published: May 2022

Heme internalization by pathogenic bacteria inside a human host to accomplish the requirement of iron for important cellular processes is of paramount importance. Despite this, the mechanism of heme import by the ATP-binding-cassette (ABC) transporter HutCD inVibrio choleraeremains unexplored. We have performed biochemical studies on ATPase HutD and its mutants, along with molecular modelling, docking and unbiased all-atom MD simulations on lipid-solvated models of permease-ATPase complex HutCD. The results demonstrated mechanisms of ATP binding/hydrolysis and trapped transient and global conformational changes in HutCD, necessary for heme internalization. ATPase HutD forms a dimer, independent of the permease HutC. Each HutD monomer canonically binds ATP in a 1:1 stoichiometry. MD simulations demonstrated that a rotational motion of HutC dimer occurs synchronously with the inter-dimeric D-loop interactions of HutDs. F151 of TM4–TM5 loop of HutC, packs with ATP and Y15 of HutD, initiating ‘cytoplasmic gate opening’ which mimics an ‘outward-facing’ to ‘inward-facing’ conformational switching upon ATP hydrolysis. The simulation on ‘inward-facing’ HutCD culminates to an ‘occluded’ state. The simulation on heme-docked HutCD indicated that the event of heme release occurs in ATP-free ‘inward-facing’ state. Gradual conformational changes of the TM5 helices of HutC towards the ‘occluded’ state facilitate ejection of heme.
Between-hospital variations in 3-year survival among patients with newly diagnosed gastric, colorectal, and lung cancer
Authors: Morishima Toshitaka , Okawa Sumiyo , Koyama Shihoko , Nakata Kayo , Tabuchi Takahiro , Miyashiro Isao
Published: May 2022

Due to increases in cancer survivability, quality assessments of cancer care must include long-term outcomes. This multicenter retrospective cohort study evaluated between-hospital variations in the 3-year survival rates of patients with gastric, colorectal, and lung cancer irrespective of treatment modality. We linked cancer registry data and administrative data from patients aged 18–99 years who were diagnosed with gastric, colorectal, or lung cancer between 2013 and 2015 in Osaka Prefecture, Japan. The 3-year survival rates were adjusted for potential prognostic factors using multilevel logistic regression models. Between-hospital variations were visually evaluated using funnel plots. We analyzed 10,296 gastric cancer patients from 30 hospitals, 9276 colorectal cancer patients from 30 hospitals, and 7978 lung cancer patients from 28 hospitals. The 3-year survival rate was 70.2%, 75.2%, and 45.0% for gastric, colorectal, and lung cancer, respectively. In the funnel plots, the adjusted survival rates of gastric and colorectal cancer for all hospitals lay between the lower and upper control limits of two standard deviations of the average survival rates. However, the adjusted survival rates of lung cancer for four hospitals lay below the lower limit while that for two hospitals lay above the upper limit. Older age, men, advanced cancer stage, comorbidities, functional disability, emergency admission, current/ex-smokers, and underweight were independently associated with poorer survival. In conclusion, there were between-hospital variations in 3-year survival for lung cancer even after adjusting for case mix. Quality improvement initiatives may be needed to raise the consistency of care.
Juvenile handling rescues autism-related effects of prenatal exposure to valproic acid
Authors: Seiffe Araceli , Ramírez Mauro Federico , Sempé Lucas , Depino Amaicha Mara
Published: May 2022

Environmental factors acting on young animals affect neurodevelopmental trajectories and impact adult brain function and behavior. Psychiatric disorders may be caused or worsen by environmental factors, but early interventions can improve performance. Understanding the possible mechanisms acting upon the developing brain could help identify etiological factors of psychiatric disorders and enable advancement of effective therapies. Research has focused on the long-lasting effects of environmental factors acting during the perinatal period, therefore little is known about the impact of these factors at later ages when neurodevelopmental pathologies such as autism spectrum disorder (ASD) are usually diagnosed. Here we show that handling mice during the juvenile period can rescue a range of behavioral and cellular effects of prenatal valproic acid (VPA) exposure. VPA-exposed animals show reduced sociability and increased repetitive behaviors, along with other autism-related endophenotypes such as increased immobility in the forced swim test and increased neuronal activity in the piriform cortex (Pir). Our results demonstrate that briefly handling mice every other day between postnatal days 22 and 34 can largely rescue these phenotypes. This effect can also be observed when animals are analyzed across tests using an “autism” factor, which also discriminates between animals with high and low Pir neuron activity. Thus, we identified a juvenile developmental window when environmental factors can determine adult autism-related behavior. In addition, our results have broader implications on behavioral neuroscience, as they highlight the importance of adequate experimental design and control of behavioral experiments involving treating or testing young animals.
Prognostic value of coronary artery calcium scores from 1.5 mm slice reconstructions of electrocardiogram-gated computed tomography scans in asymptomatic individuals
Authors: Kim Suh Young , Suh Young Joo , Lee Hye-Jeong , Kim Young Jin
Published: May 2022

It is unknown whether the thinner slice reconstruction has added value relative to 3 mm reconstructions in predicting major adverse cardiac events (MACEs). This retrospective study included 550 asymptomatic individuals who underwent cardiac CT. Coronary artery calcium (CAC) scores and severity categories were assessed from 1.5 and 3 mm scans. CAC scores obtained from 1.5 and 3 mm scans were compared using Wilcoxon signed-rank tests. Cox proportional hazard models were developed to predict MACEs based on the degree of coronary artery stenosis on coronary CT angiography and the presence of CAC on both scans. Model performances were compared using the time-dependent ROC curve and integrated area under the curve (iAUC) methods. The CAC scores obtained from 1.5 mm scans were significantly higher than those from 3 mm scans (median, interquartile range 4.5[0–71] vs. 0[0–48.4]; p < 0.001). Models showed no difference in predictive accuracy of the presence of CAC between 1.5 and 3 mm scans (iAUC, 0.625 vs. 0.672). In conclusion, CAC scores obtained from 1.5 mm scans are significantly higher than those from 3 mm scans, but do not provide added prognostic value relative to 3 mm scans.
Role of post-CCSD(T) corrections in predicting the energetics and kinetics of the OH˙ + O3 reaction
Authors: Rai Philips Kumar , Kumar Pradeep
Published: May 2022

The present work investigates the OH˙ + O3 reaction by means of chemical kinetics and quantum chemical calculations.
Spatial confinement toward creating artificial living systems
Authors: Shang Luoran , Ye Fangfu , Li Ming , Zhao Yuanjin
Published: May 2022

Spatial confinement is an important factor mediating both biological behaviors and artificial living systems. This review discusses spatial confinement as a design criterion for molecular reactors, artificial cells, tissue constructs, and organoids.
3D-printed hydrogel scaffold-loaded granulocyte colony-stimulating factor sustained-release microspheres and their effect on endometrial regeneration
Authors: Wen Jiaming , Hou Bo , Lin Weige , Guo Fang , Cheng Mi , Zheng Jie , He Ping , Ji Wanqing
Published: May 2022

3D-printed hydrogel scaffold-loaded G-CSF sustained-release microspheres significantly reduced the adhesion of the endometrium after injury in the IUA rat model and promoted endometrial structural and functional reconstruction.
Hard–soft chemistry guides the adaptable charge transport in lysine-doped heptapeptide junctions
Authors: Li Ying , Li Xiaobing , Qi Pan , Guo Cunlan
Published: May 2022

This work for the first time introduces hard–soft acid base theory to analyze the counterion-modulated peptide charge transport and rationalizes the enhancement of peptide charge transport by the peptide-counterion interactions.
Aggregation-induced emission by sequence-selective assembly of cyanolated distyrylbenzene in supramolecular DNA architectures
Authors: Ucar Hülya , Wagenknecht Hans-Achim
Published: May 2022

Cyanolated distyrylbenzene conjugated to 2′-deoxyuridine is a new building block for supramolecular DNA architectures combining aggregation-induced emission and sequence-selective binding.
Formaldehyde recognition through aminal formation in a luminescent metal–organic framework
Authors: Li Jia-Li , Xiong Xiao , Luo Dong , Wei Yu-Bai , Lu Weigang , Li Dan
Published: May 2022

Reticular synthesis of a pillar-layer metal–organic framework with a diamino-functionalized dicarboxylate as a pillar linker, realizing an exclusive luminescence response toward formaldehyde through aminal formation.
Sniffing out camphor: the fine balance between hydrogen bonding and London dispersion in the chirality recognition with α-fenchol
Authors: Quesada-Moreno María Mar , Fatima Mariyam , Medel Robert , Pérez Cristóbal , Schnell Melanie
Published: May 2022

Complexes between the chiral monoterpenoids camphor and α-fenchol were explored with vibrational and rotational jet spectroscopy as well as density functional theory to explore how chirality can influence the binding preferences in the gas phase.
1D Colloidal chains: recent progress from formation to emergent properties and applications
Authors: Fan Xinlong , Walther Andreas
Published: May 2022

This review discusses the assembly of 0D nanoparticles into hierarchical 1D superstructures with different levels of complexity, their emergent properties and use in functional materials.
Phosphorus or nitrogen – the first phosphatriptycene in coordination polymer chemistry
Authors: Gildenast Hans , Gruszien Lukas , Friedt Felix , Englert Ulli
Published: May 2022

We report the new heteroditopic ligand TRIP-Py which selectively binds metal cations of different Pearson character. We demonstrate this both in discrete complexes on either coordination site as well as in heterobimetallic coordination polymers.
Chiral (phosphine)-(imidazoline) PCN pincer palladium(ii) complexes: synthesis and application in asymmetric hydrophosphination of 2-alkenoylpyridines with diphenylphosphine
Authors: Huang Jun-Jian , Zhang Xiao-Qi , Yang Jing-Jing , Gong Jun-Fang , Song Mao-Ping
Published: May 2022

Twelve new chiral PCN pincer Pd(ii) complexes with varied chiral imidazoline moieties have been synthesized, structurally characterized and used as catalysts for enantioselective hydrophosphination of 2-alkenoylpyridines with diphenylphosphine.
C–H heteroarylation of aromatics via catalyst free SN2′ coupling cycloaromatization
Authors: Lu Qixing , Wang Tao , Wu Qian , Cheng Lijing , Luo Han , Liu Lei , Chu Guobiao , Wang Lufeng , Li Baosheng
Published: May 2022

We have developed C–H heteroarylation of aromatics via a catalyst free SN2′ coupling heterocycloaromatization that could realize the late-stage modification of various marketed pharmaceuticals or functional materials.
A practical and cost-effective approach to polysubstituted pyrimidine derivativesviaDBU mediated redox isomerization of propargyl alcohol and subsequent N–C–N fragment condensation
Authors: De Rimpa , Sengupta Utsav , Savarimuthu Antony , Misra Souvik , Nanda Jayanta , Bera Mrinal K.
Published: May 2022

A straightforward, efficient yet effortless approach for the synthesis of structurally important triarylated pyrimidine derivatives has been successfully developed using secondary propargyl alcohol and commercially available amidines under mild basic conditions.
Persulfate assisted photocatalytic degradation of tetracycline by bismuth titanate under visible light irradiation
Authors: Liu Wenwen , Wei Changqing , Peng Renfu , Chu Runfen , Sun Hao , Zhang Xiaoming , Xie Fang
Published: May 2022

A Bi2Ti2O7/persulfate system is constructed to degrade tetracycline and it shows enhanced degradation activity.
Computational studies on the possible formation of glycine via open shell gas-phase chemistry in the interstellar medium
Authors: Thripati Sorakayala
Published: May 2022

The possible formation of glycine in interstellar medium: step 1: HO-CO (radical) + CH2NH → NHCH2COOH (radical) and step 2a: NHCH2COOH (radical) + H2 → glycine + H (radical).
Application of DMSO as a methylthiolating reagent in organic synthesis
Authors: Li Xuemin , Wang Xi , Li Yadong , Xiao Jiaxi , Du Yunfei
Published: May 2022

This review mainly focuses on the research progress achieved in the synthesis of methylthiolated products using the cheap and environmentally friendly DMSO as an SMe source.
Flavin catalyzed desulfurization of peptides and proteins in aqueous media
Authors: Wan Chuan , Yang Dongyan , Qin Xuan , Xue Ziyi , Guo Xiaochun , Hou Zhanfeng , Jiang Chenran , Yin Feng , Wang Rui , Li Zigang
Published: May 2022

A biomimetic method has been established for the chemo-selective desulfurization of cysteinyl peptides and proteins in aqueous media.
Development of antioxidant-rich edible active films and coatings incorporated with de-oiled ethanolic green algae extract: a candidate for prolonging the shelf life of fresh produce
Authors: Mondal Kona , Bhattacharjee Sayan Kumar , Mudenur Chethana , Ghosh Tabli , Goud Vaibhav V. , Katiyar Vimal
Published: May 2022

The developed CS/CAEE edible active films possess UV-Vis light blocking property with ∼27% enhanced antioxidant activity and ∼60% reduced WVP. The edible coatings are nontoxic and extended the shelf life of green chillies at room temperature.
Preparation of a quartz microbalance sensor based on molecularly imprinted polymers and its application in formaldehyde detection
Authors: Liu Junbo , Zhao Wensi , Liu Jin , Cai Xuhong , Liang Dadong , Tang Shanshan , Xu Bao
Published: May 2022

A QCM electrode was modified with HCHO-MIPs. The detection conditions of sensor were optimized, and its selectivity was discussed. It was applied to detect the HCHO content in fresh shrimp samples.
Anin silicopredictive method to select multi-monomer combinations for peptide imprinting
Authors: Rajpal Soumya , Mizaikoff Boris
Published: May 2022

Single monomer Virtual screeningvs.Multi-monomer simultaneous docking for combinatorial screening and synthesis.
Surface passivation engineering approach to fluoroacrylate-incorporated polytetrafluoroethylene for highly reliable a-IGZO TFTs
Authors: Shan Fei , Zhao Han-Lin , Wang Xiao-Lin , Lee Jae-Yun , Kim Sung-Jin
Published: May 2022

A fluoroacrylate-incorporated polytetrafluoroethylene as a new material for passivation layers of a-IGZO TFTs is a potential technology to enhance stability by reducing the adsorption behavior of H2O and O2.
The crystallinity and piezoelectric properties of spray-coated films of P(VDF70-TrFE30): effects of film thickness and spin-crossover nanofillers
Authors: Angulo-Cervera José Elías , Piedrahita-Bello Mario , Martin Baptiste , Dantras Eric , Nicu Liviu , Leichle Thierry , Dalla Francesca Kevin , Da Costa Antonio , Ferri Anthony , Desfeux Rachel , Salmon Lionel , Molnár Gábor , Bousseksou Azzedine
Published: May 2022

Large-area, conformal films of P(VDF-TrFE) and its spin-crossover composites were spray-coated. The films exhibit good crystallinity and attractive electromechanical properties over a thickness range of more than two decades.
Divergent binding mode for a protozoan BRC repeat to RAD51
Authors: Pantelejevs Teodors , Hyvönen Marko
Published: May 2022

Interaction of BRCA2 through ca. 30 amino acid residue motifs, BRC repeats, with RAD51 is a conserved feature of the double-strand DNA break repair by homologous recombination in eukaryotes. In humans the binding of the eight BRC repeats is defined by two sequence motifs, FxxA and LFDE, interacting with distinct sites on RAD51. Little is known of the interaction of BRC repeats in other species, especially in protozoans, where variable number of BRC repeats are found in BRCA2 proteins. Here, we have studied in detail the interactions of the two BRC repeats in Leishmania infantum BRCA2 with RAD51. We show LiBRC1 is a high-affinity repeat and determine the crystal structure of its complex with LiRAD51. Using truncation mutagenesis of the LiBRC1 repeat, we demonstrate that high affinity binding is maintained in the absence of an LFDE-like motif and suggest compensatory structural features. These observations point towards a divergent evolution of BRC repeats, where a common FxxA-binding ancestor evolved additional contacts for affinity maturation and fine-tuning.
Activated brown adipose tissue releases exosomes containing mitochondrial methylene tetrahydrofolate dehydrogenase (NADP dependent) 1-like protein (MTHFD1L)
Authors: Leow Melvin Khee-Shing , Rengaraj Anantharaj , Narasimhan Kothandaraman , Verma Sanjay K. , Yaligar Jadegoud , Thu Giang Le Thi , Sun Lijuan , Goh Hui Jen , Govindharajulu Priya , Sadananthan Suresh Anand , Michael Navin , Meng Wei , Gallart-Palau Xavier , Sun Lei , Karnani Neerja , Sze Newman Siu Kwan , Velan S. Sendhil
Published: May 2022

Brown adipose tissue (BAT) is a promising weapon to combat obesity and metabolic disease. BAT is thermogenic and consumes substantial amounts of glucose and fatty acids as fuel for thermogenesis and energy expenditure. To study BAT function in large human longitudinal cohorts, safe and precise detection methodologies are needed. Although regarded a gold standard, the foray of PET-CT into BAT research and clinical applications is limited by its high ionizing radiation doses. Here, we show that brown adipocytes release exosomes in blood plasma that can be utilized to assess BAT activity. In the present study, we investigated circulating protein biomarkers that can accurately and reliably reflect BAT activation triggered by cold exposure, capsinoids ingestion and thyroid hormone excess in humans. We discovered an exosomal protein, methylene tetrahydrofolate dehydrogenase (NADP+ dependent) 1-like (MTHFD1L), to be overexpressed and detectable in plasma for all three modes of BAT activation in human subjects. This mitochondrial protein is packaged as a cargo within multivesicular bodies of the endosomal compartment and secreted as exosomes via exocytosis from activated brown adipocytes into the circulation. To support MTHFD1L as a conserved BAT activation response in other vertebrates, we examined a rodent model and also proved its presence in blood of rats following BAT activation by cold exposure. Plasma concentration of exosomal MTHFD1L correlated with human BAT activity as confirmed by PET-MR in humans and supported by data from rats. Thus, we deduce that MTHFD1L appears to be overexpressed in activated BAT compared to BAT in the basal nonstimulated state.
Genome-wide survey and genetic characteristics of Ophichthus evermanni based on Illumina sequencing platform
Authors: Yang Tianyan , Ning Zijun , Liu Yuping , Zhang Shufei , Gao Tianxiang
Published: May 2022

Ophichthidae fishes limit to continental shelf of all tropical and subtropical oceans and contain more than 350 species, representing the greatest specialization diversity in the order Anguiliformes. In the present study, we conducted a genome survey sequencing (GSS) analysis of Ophichthus evermanni by Illumina sequencing platform to briefly reveal its genomic characteristics and phylogenetic relationship. The first de novo assembled 1.97 Gb draft genome of O. evermanni was predicted based on K-mer analysis without obvious nucleotide bias. The heterozygosity ratio was 0.70%, and the sequence repeat ratio was calculated to be 43.30%. A total of 9016 putative coding genes were successfully predicted, in which 3587 unigenes were identified by gene ontology (GO) analysis and 4375 unigenes were classified into cluster of orthologous groups for enkaryotic complete genomes (KOG) functional categories. About 2,812,813 microsatellite motifs including mono-, di-, tri-, tetra-, penta- and hexanucleotide motifs were identified, with an occurrence frequency of 23.32%. The most abundant type was dinucleotide repeat motifs, accounting for 49.19% of the total repeat types. The mitochondrial genome, as a byproduct of GSS, was assembled to investigate the evolutionary relationships between O. evermanni and its relatives. Bayesian inference (BI) phylogenetic tree inferring from concatenated 12 protein-coding genes (PCGs) showed complicated relationships among Ophichthidae species, indicating a polyphyletic origin of the family. The results would achieve more thorough genetic information of snake eels and provide a theoretical basis and reference for further genome-wide analysis of O. evermanni.
Backoff‐toleration‐based opportunistic MAC protocol for underwater acoustic sensor networks
Authors: Chen Keyu
Published: May 2022

With the development of underwater internet, Underwater Acoustic Sensor Networks (UASNs) have become an important method for collecting marine parameters and data. The Medium Access Control (MAC) protocol is the underlying infrastructure of UASNs. It directly affects the utilization of the underwater acoustic channel and the overall performance of the network. The ALOHA protocol is the basis of the random accessing protocols. It freely accesses the channel, so the collision between data packets is very serious. To this end, this paper proposes a Backoff‐Toleration‐Based Opportunistic (BTBO) protocol. In this protocol, each sensor node opportunistically learns by backoffing tolerantly, and finds the optimal transmission time respectively to transmit the data packet. Simulation results show that the BTBO protocol has better throughput and average end‐to‐end delay. At the same time, the authors added adaptive design to the dynamic topology networks in the UASNs. The simulation results show that the protocol can effectively alleviate these problems and improve performance.
Method for predicting the remaining mileage of electric vehicles based on dimension expansion and model fusion
Authors: Tian Sheng , Li Chengwei , Lv Qing , Li Jia
Published: May 2022

Accurately predicting the remaining mileage of electric vehicles (EVs) can effectively alleviate user's mileage anxiety and develop refinement of energy management strategy. However, traditional prediction methods not only consume time and resources, but also accumulate errors and lack interpretability. In this paper, we proposed a model based on dimension expansion and model fusion strategy, which uses the extreme gradient boosting (XGBoost) algorithm to directly predict the remaining mileage of EVs. After pre‐processing the real running data of EVs, we constructed the field of remaining driving range and analyzed the relationship between features and remaining driving range, and then directly predicted the remaining driving mileage. Compared with other machine learning methods, XGBoost model has the highest accuracy. Then dimensional extended data set was obtained based on prior knowledge and symbol conversion, which improved the model performance. Finally, the model fusion strategy was adopted to further improve the generalization ability and stability of the model. The experimental results show that the Bootstrap aggregating (Bagging) fusion model has the highest predictive performance on the test set and outperformed other methods. The maximum RAE is not more than 3.5%, RMSE is less than 3km and MAE is about 2 km.