bluuebunny/crossref_metadata_2025 huggingface dataset:
Data-driven design of new chiral carboxylic acid for construction of indoles with C-central and C–N axial chirality via cobalt catalysis
Authors: Zhang Zi-Jing , Li Shu-Wen , Oliveira João C. A. , Li Yanjun , Chen Xinran , Zhang Shuo-Qing , Xu Li-Cheng , Rogge Torben , Hong Xin , Ackermann Lutz
Published: May 2023

Challenging enantio- and diastereoselective cobalt-catalyzed C–H alkylation has been realized by an innovative data-driven knowledge transfer strategy. Harnessing the statistics of a related transformation as the knowledge source, the designed machine learning (ML) model took advantage of delta learning and enabled accurate and extrapolative enantioselectivity predictions. Powered by the knowledge transfer model, the virtual screening of a broad scope of 360 chiral carboxylic acids led to the discovery of a new catalyst featuring an intriguing furyl moiety. Further experiments verified that the predicted chiral carboxylic acid can achieve excellent stereochemical control for the target C–H alkylation, which supported the expedient synthesis for a large library of substituted indoles withC-central and C–N axial chirality. The reported machine learning approach provides a powerful data engine to accelerate the discovery of molecular catalysis by harnessing the hidden value of the available structure-performance statistics.
Multi-omic features of oesophageal adenocarcinoma in patients treated with preoperative neoadjuvant therapy
Authors: M. Naeini Marjan , Newell Felicity , Aoude Lauren G. , Bonazzi Vanessa F. , Patel Kalpana , Lampe Guy , Koufariotis Lambros T. , Lakis Vanessa , Addala Venkateswar , Kondrashova Olga , Johnston Rebecca L. , Sharma Sowmya , Brosda Sandra , Holmes Oliver , Leonard Conrad , Wood Scott , Xu Qinying , Thomas Janine , Walpole Euan , Tao Mai G. , Ackland Stephen P. , Martin Jarad , Burge Matthew , Finch Robert , Karapetis Christos S. , Shannon Jenny , Nott Louise , Bohmer Robert , Wilson Kate , Barnes Elizabeth , Zalcberg John R. , Mark Smithers B. , Simes John , Price Timothy , Gebski Val , Nones Katia , Watson David I. , Pearson John V. , Barbour Andrew P. , Waddell Nicola
Published: May 2023

Oesophageal adenocarcinoma is a poor prognosis cancer and the molecular features underpinning response to treatment remain unclear. We investigate whole genome, transcriptomic and methylation data from 115 oesophageal adenocarcinoma patients mostly from the DOCTOR phase II clinical trial (Australian New Zealand Clinical Trials Registry-ACTRN12609000665235), with exploratory analysis pre-specified in the study protocol of the trial. We report genomic features associated with poorer overall survival, such as the APOBEC mutational and RS3-like rearrangement signatures. We also show that positron emission tomography non-responders have more sub-clonal genomic copy number alterations. Transcriptomic analysis categorises patients into four immune clusters correlated with survival. The immune suppressed cluster is associated with worse survival, enriched with myeloid-derived cells, and an epithelial-mesenchymal transition signature. The immune hot cluster is associated with better survival, enriched with lymphocytes, myeloid-derived cells, and an immune signature including CCL5, CD8A, and NKG7. The immune clusters highlight patients who may respond to immunotherapy and thus may guide future clinical trials.
The largest prehistoric mound in Europe is the Bronze-Age Hill of Udine (Italy) and legend linked its origin to Attila the Hun
Authors: Fontana A. , Vinci G. , Ronchi L. , Mocchiutti A. , Muscio G. , Visentini P. , Bassetti M. , Novellino M. D. , Badino F. , Musina G. , Bonomi S.
Published: May 2023

Prehistoric monuments often constitute evident landmarks and sometimes, after falling into disuse, fascinated local people enough to stimulate speculations about their origin over time. According to legend, the Hill of Udine (NE Italy) was built by Attila the Hun’s soldiers, but its origin (natural or anthropogenic) has been debated until now. Our research analyzed five new 40-m long stratigraphic cores, investigating for the first time the total thickness of the hill and compared the data with the available archaeological information. Moreover, we considered other hills and mounds in northern Italy and other European regions where folklore traditions relate their origin to Attila. The geoarchaeological and ethnographic data prove that the Hill of Udine is a Bronze Age anthropogenic mound erected between 1400 and 1150 BCE and that, later, folklore has transformed the ancestral memory of its origin into legend. By measuring 30 m in height and over 400,000 m3 in volume, the flat-topped hill is the largest prehistoric mound in Europe. This discovery reveals unprecedented skills in earth construction and confirms significant anthropogenic modifications of the environment during Bronze Age.
Visualization of the relationship between electrogustometry and whole mouth test using multidimensional scaling
Authors: Ha Jong-Gyun , Kim Bo-ra , Cho Ara , Jeong Yeonsu , Rha Min-Seok , Kang Ju-Wan , Cho Hyung-Ju , Yoon Joo-Heon , Kim Chang-Hoon
Published: May 2023

Interpreting the relationship between different taste function tests of different stimuli, such as chemical and electrical stimulation, is still poorly understood. This study aims to analyze visually as well as quantitatively how to interpret the relationship of results between taste function tests using different stimuli. Patients who underwent the whole mouth test and Electrogustometry (EGM) at a tertiary medical center between August 2018 and December 2018 were reviewed retrospectively with electronic medical records. Of the 110 patients, a total of 86 adults who self-reported that their taste function was normal through a questionnaire were enrolled. EGM measured the thresholds of the chorda tympani (CT) and glossopharyngeal nerve (GL) area of the tongue. The whole mouth test measured detection and recognition thresholds for sweet, salty, bitter, sour, and umami taste. Statistical analyses of Pearson’s, Spearman’s rank and polyserial correlation and multidimensional scaling (MDS) was performed. The EGM threshold for the average value of both CT regions and the recognition threshold of the whole mouth test were significantly correlated in sweet, salty, bitter, and sour taste (r = 0.244–0.398, P < 0.05), and the detection threshold was correlated only significant in sweet (r = 0.360, P = 0.007). In the MDS analysis results, the three-dimensional (D) solution was chosen over the 2-D solution because of the lower stress. Detection-, recognition threshold of whole mouth test and EGM thresholds of CT and GL area, those were standardized by Z-score, formed well-distinguished sections in the MDS analyses. The EGM threshold of the CT area was closer to the detection and recognition thresholds than the EGM threshold of the GL area. In general, the EGM threshold was closer to the recognition threshold than the detection threshold for each taste. Overall, visualization of the relationship of whole mouth test and EGM by MDS was in good agreement with quantitative analysis. EGM and whole mouth test seem to reflect different aspects of taste. However, when interpreting the EGM results, the EGM threshold of the CT area will show more similarity to the recognition threshold than the detection threshold for the whole mouth test.
Ensemble-based multi-tissue classification approach of colorectal cancer histology images using a novel hybrid deep learning framework
Authors: Khazaee Fadafen Masoud , Rezaee Khosro
Published: May 2023

Colorectal cancer (CRC) is the second leading cause of cancer death in the world, so digital pathology is essential for assessing prognosis. Due to the increasing resolution and quantity of whole slide images (WSIs), as well as the lack of annotated information, previous methodologies cannot be generalized as effective decision-making systems. Since deep learning (DL) methods can handle large-scale applications, they can provide a viable alternative to histopathology image (HI) analysis. DL architectures, however, may not be sufficient to classify CRC tissues based on anatomical histopathology data. A dilated ResNet (dResNet) structure and attention module are used to generate deep feature maps in order to classify multiple tissues in HIs. In addition, neighborhood component analysis (NCA) overcomes the constraint of computational complexity. Data is fed into a deep support vector machine (SVM) based on an ensemble learning algorithm called DeepSVM after the features have been selected. CRC-5000 and NCT-CRC-HE-100 K datasets were analyzed to validate and test the hybrid procedure. We demonstrate that the hybrid model achieves 98.75% and 99.76% accuracy on CRC datasets. The results showed that only pathologists' labels could successfully classify unseen WSIs. Furthermore, the hybrid deep learning method outperforms state-of-the-art approaches in terms of computational efficiency and time. Using the proposed mechanism for tissue analysis, it will be possible to correctly predict CRC based on accurate pathology image classification.
Pilot evaluation of a single oral fecal microbiota transplantation for canine atopic dermatitis
Authors: Sugita Koji , Shima Ayaka , Takahashi Kaho , Ishihara Genki , Kawano Koji , Ohmori Keitaro
Published: May 2023

The gut microbiota has been suggested to be involved in the pathogenesis of canine atopic dermatitis (cAD). However, the gut microbiota has not been well characterized in dogs with atopic dermatitis (AD). In addition, the efficacy of fecal microbiota transplantation (FMT) in dogs with AD remains unclear. This research, therefore, aimed to characterize the gut microbiota of dogs with AD and conduct pilot evaluation of the efficacy of a single oral FMT on clinical signs and the gut microbiota of dogs with AD. For these purposes, we used 12 dogs with AD and 20 healthy dogs. The 16S rRNA analysis of the fecal microbiota revealed significant differences between 12 dogs with AD and 20 healthy dogs. Next, a single oral FMT was performed in 12 dogs with AD as a single-arm, open-label clinical trial for 56 days. A single oral FMT significantly decreased Canine Atopic Dermatitis Extent and Severity Index (CADESI)-04 scores from day 0 (median score, 16.5) to day 56 (8) and Pruritus Visual Analog Scale (PVAS) scores from days 0 (median score, 3) to day 56 (1). Furthermore, a single oral FMT changed the composition of the fecal microbiota of dogs with AD at the phylum and genus levels. The number of common amplicon sequence variants in the fecal microbiota between donor dogs and dogs with AD was positively correlated with CADESI-04 and PVAS reduction ratios 56 days after FMT. Our findings suggest that the gut microbiota plays a pivotal role in the pathogenesis of cAD, and that oral FMT could be a new therapeutic approach targeting the gut microbiota in cAD.
Next-generation RNA sequencing elucidates transcriptomic signatures of pathophysiologic nerve regeneration
Authors: Warner Wesley S. , Stubben Christopher , Yeoh Stewart , Light Alan R. , Mahan Mark A.
Published: May 2023

The cellular and molecular underpinnings of Wallerian degeneration have been robustly explored in laboratory models of successful nerve regeneration. In contrast, there is limited interrogation of failed regeneration, which is the challenge facing clinical practice. Specifically, we lack insight on the pathophysiologic mechanisms that lead to the formation of neuromas-in-continuity (NIC). To address this knowledge gap, we have developed and validated a novel basic science model of rapid-stretch nerve injury, which provides a biofidelic injury with NIC development and incomplete neurologic recovery. In this study, we applied next-generation RNA sequencing to elucidate the temporal transcriptional landscape of pathophysiologic nerve regeneration. To corroborate genetic analysis, nerves were subject to immunofluorescent staining for transcripts representative of the prominent biological pathways identified. Pathophysiologic nerve regeneration produces substantially altered genetic profiles both temporally and in the mature neuroma microenvironment, in contrast to the coordinated genetic signatures of Wallerian degeneration and successful regeneration. To our knowledge, this study presents as the first transcriptional study of NIC pathophysiology and has identified cellular death, fibrosis, neurodegeneration, metabolism, and unresolved inflammatory signatures that diverge from pathways elaborated by traditional models of successful nerve regeneration.
Effects of two years of physically active lessons on cognitive indicators in children
Authors: Oliveira David N. , Silva Ellen Caroline M. , Barboza Luciana L. S. , Thuany Mabliny , Araújo Raphael Henrique O. , Silva Roberto Jerônimo S. , Gomes Thayse Natacha , Schmitz Heike , Tejada Julian , Silva Danilo R.
Published: May 2023

Our purpose was to evaluate the effect of physically active lessons (PAL) on the cognitive performance of children during two years of follow-up. Four classes (second grade of elementary school) were divided into two intervention classes (n = 34) and two control classes (n = 27). Evaluations were performed before the intervention (M1), after 3 (M2) and 9 (M3) months in the 1st year, and 14 (M4) and 18 (M5) months in the 2nd year. The intervention was based on PAL integrated with the curricular components, which stimulated the children to stand or move in the classroom. Cognitive performance was evaluated using three computerized tests for response inhibition, selective attention, and cognitive flexibility. The children in the intervention classes presented improved cognitive performance in the execution of all tasks along the two years follow-up, in both correct answers and time reactions, with exception of correct answers of visual search. For the intervention classes, in most of the tasks, the mean differences confidence interval of 95% did not include the 0 on the two last moments of evaluation, and in all cases, the mean differences of them between M1 versus M5 were significantly different with high values of effect size (cohen -d > 1). PAL promotes modest improvements in diverse cognitive functions in children.
Synergistic cytotoxic effects of an extremely low-frequency electromagnetic field with doxorubicin on MCF-7 cell line
Authors: Ramazi Shahin , Salimian Mani , Allahverdi Abdollah , Kianamiri Shahla , Abdolmaleki Parviz
Published: May 2023

Breast cancer is one of the leading causes of cancer deaths in women worldwide. Magnetic fields have shown anti-tumor effects in vitro and in vivo as a non-invasive therapy method that can affect cellular metabolism remotely. Doxorubicin (DOX) is one of the most commonly used drugs for treating breast cancer patients. It can be assumed that combining chemotherapy and magnetotherapy is one of the most effective treatments for breast cancer. This study aimed to investigate the potential cytotoxic effect of DOX at low concentrations in combination with extremely low-frequency electromagnetic fields (ELF–EMF; 50 Hz; 20 mT). The breast cancer cell line MCF-7 was examined for oxidative stress, cell cycle, and apoptosis. MCF-7 cells were treated with various concentrations of DOX as an apoptosis-inducing agent and ELF–EMF. Cytotoxicity was examined using the MTT colorimetric assay at 12, 24, and 48 h. Consequently, concentration- and time-dependent cytotoxicity was observed in MCF-7 cells for DOX within 24 h. The MTT assay results used showed that a 2 μM concentration of DOX reduced cell viability to 50% compared with control, and as well, the combination of ELF–EMF and DOX reduced cell viability to 50% compared with control at > 0.25 μM doses for 24 h. In MCF-7 cells, combining 0.25 μM DOX with ELF–EMF resulted in increased ROS levels and DOX-induced apoptosis. Flow cytometry analysis, on the other hand, revealed enhanced arrest of MCF-7 cells in the G0-G1 phase of the cell cycle, as well as inducing apoptotic cell death in MCF-7 cells, implying that the synergistic effects of 0.25 μM DOX and ELF–EMF may represent a novel and effective agent against breast cancer.
Panoramic dental tomosynthesis imaging by use of CBCT projection data
Authors: Kwon Taejin , Choi Da-in , Hwang Jaehong , Lee Taewon , Lee Inje , Cho Seungryong
Published: May 2023

Dental CBCT and panoramic images are important imaging modalities used in dental diagnosis and treatment planning. In order to acquire a panoramic image without an additional panoramic scan, in this study, we proposed a method of reconstructing a panoramic image by extracting panoramic projection data from dental CBCT projection data. After specifying the patient’s dental arch from the patient’s CBCT image, panoramic projection data are extracted from the CBCT projection data along the appropriate panoramic scan trajectory that fits the dental arch. A total of 40 clinical human datasets and one head phantom dataset were used to test the proposed method. The clinical human dataset used in this study includes cases in which it is difficult to reconstruct panoramic images from CBCT images, such as data with severe metal artifacts or data without teeth. As a result of applying the panoramic image reconstruction method proposed in this study, we were able to successfully acquire panoramic images from the CBCT projection data of various patients. The proposed method acquires a universally applicable panoramic image that is less affected by CBCT image quality and metal artifacts by extracting panoramic projection data from dental CBCT data and reconstructing a panoramic image.
Study of nasal mucosa histopathological changes in patients with hypersensitivity pneumonitis
Authors: Akl Yosri , Ibrahim Eman Kamal , Algarf Tareq Muhammad , Mostafa Rasha R. , Abdel-Hamid Hoda M. , Muhammed Asmaa Ibrahim
Published: May 2023

Hypersensitivity pneumonitis (HP) is an interstitial lung disease that develops after inhalation of a variety antigens in susceptible individuals. The nasal mucosa is constantly exposed to these antigens that can irritate the respiratory mucosa. So, the purpose of this study was to study nasal histopathological changes in order to identify any shared pathological changes between the upper airways and the well-known pathological features of HP. 40 HP patients diagnosed at the Chest Department, Kasr Alainy hospital following ATS/JRS/ALAT guidelines were included. Patients were subjected to thorough history, high-resolution computed tomography, spirometry, cough evaluation test (CET), sinonasal outcome test-22 (SNOT-22), sinonasal examination and nasal mucosal biopsy by an otolaryngologist under visualization by a rigid nasal endoscope. The mean age of the patients was 46.2 ± 13.5 (85% were females and 15% were males). 90% of patients presented with cough and the mean CET was 17.15 ± 5.59.77.5% of patients suffered from sinonasal symptoms and the mean SNOT-22 was 12.18 ± 3.8. There was a significant correlation between the burden of sinonasal symptoms represented by the SNOT-22 and the severity of the cough represented by CET (r 0.40, p 0.01). 87.5% of HP patients had chronic inflammation of the nasal mucosa with predominant lymphocytic infiltration in 72.5% of patients. 77.5% of HP patients had a high burden of sinonasal symptoms which is positively associated with cough severity. 72.5% of patients had predominately lymphocytic infiltration of the nasal mucosa.

Trial registration: retrospectively registered, registration number is NCT05723796, date of registration 13/02/2023.
Somatostatin-expressing interneurons modulate neocortical network through GABAb receptors in a synapse-specific manner
Authors: Kanigowski Dominik , Bogaj Karolina , Barth Alison L. , Urban-Ciecko Joanna
Published: May 2023

The firing activity of somatostatin-expressing inhibitory neurons (SST-INs) can suppress network activity via both GABAa and GABAb receptors (Rs). Although SST-INs do not receive GABAaR input from other SST-INs, it is possible that SST-IN-released GABA could suppress the activity of SST-INs themselves via GABAbRs, providing a negative feedback loop. Here we characterized the influence of GABAbR modulation on SST-IN activity in layer 2/3 of the somatosensory cortex in mice. We compared this to the effects of GABAbR activation on parvalbumin-expressing interneurons (PV-INs). Using in vitro whole-cell patch clamp recordings, pharmacological and optogenetic manipulations, we found that the firing activity of SST-INs suppresses excitatory drive to themselves via presynaptic GABAbRs. Postsynaptic GABAbRs did not influence SST-IN spontaneous activity or intrinsic excitability. Although GABAbRs at pre- and postsynaptic inputs to PV-INs are modestly activated during cortical network activity in vitro, the spontaneous firing of SST-INs was not the source of GABA driving this GABAbR activation. Thus, SST-IN firing regulates excitatory synaptic strength through presynaptic GABAbRs at connections between pyramidal neurons (Pyr-Pyr) and synapses between pyramidal neurons and SST-INs (Pyr-SST), but not Pyr-PV and PV-Pyr synapses. Our study indicates that two main types of neocortical inhibitory interneurons are differentially modulated by SST-IN-mediated GABA release.
Bismuth sulfoiodide (BiSI) nanorods: synthesis, characterization, and photodetector application
Authors: Mistewicz Krystian , Das Tushar Kanti , Nowacki Bartłomiej , Smalcerz Albert , Kim Hoe Joon , Hajra Sugato , Godzierz Marcin , Masiuchok Olha
Published: May 2023

The nanorods of bismuth sulfoiodide (BiSI) were synthesized at relatively low temperature (393 K) through a wet chemical method. The crystalline one-dimensional (1D) structure of the BiSI nanorods was confirmed using high resolution transmission microscopy (HRTEM). The morphology and chemical composition of the material were examined by applying scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS), respectively. The average diameter of 126(3) nm and length of 1.9(1) µm of the BiSI nanorods were determined. X-ray diffraction (XRD) revealed that prepared material consists of a major orthorhombic BiSI phase (87%) and a minor amount of hexagonal Bi13S18I2phase (13%) with no presence of other residual phases. The direct energy band gap of 1.67(1)  eV was determined for BiSI film using diffuse reflectance spectroscopy (DRS). Two types of photodetectors were constructed from BiSI nanorods. The first one was traditional photoconductive device based on BiSI film on stiff glass substrate equipped with Au electrodes. An influence of light intensity on photocurrent response to monochromatic light (λ = 488 nm) illumination was studied at a constant bias voltage. The novel flexible photo-chargeable device was the second type of prepared photodetectors. It consisted of BiSI film and gel electrolyte layer sandwiched between polyethylene terephthalate (PET) substrates coated with indium tin oxide (ITO) electrodes. The flexible self-powered BiSI photodetector exhibited open-circuit photovoltage of 68 mV and short-circuit photocurrent density of 0.11 nA/cm2under light illumination with intensity of 0.127 W/cm2. These results confirmed high potential of BiSI nanorods for use in self-powered photodetectors and photo-chargeable capacitors.
Predicting body mass index in early childhood using data from the first 1000 days
Authors: Cheng Erika R. , Cengiz Ahmet Yahya , Miled Zina Ben
Published: May 2023

Few existing efforts to predict childhood obesity have included risk factors across the prenatal and early infancy periods, despite evidence that the first 1000 days is critical for obesity prevention. In this study, we employed machine learning techniques to understand the influence of factors in the first 1000 days on body mass index (BMI) values during childhood. We used LASSO regression to identify 13 features in addition to historical weight, height, and BMI that were relevant to childhood obesity. We then developed prediction models based on support vector regression with fivefold cross validation, estimating BMI for three time periods: 30–36 (N = 4204), 36–42 (N = 4130), and 42–48 (N = 2880) months. Our models were developed using 80% of the patients from each period. When tested on the remaining 20% of the patients, the models predicted children’s BMI with high accuracy (mean average error [standard deviation] = 0.96[0.02] at 30–36 months, 0.98 [0.03] at 36–42 months, and 1.00 [0.02] at 42–48 months) and can be used to support clinical and public health efforts focused on obesity prevention in early life.
The impact of TLR2 and aging on the humoral immune response to Staphylococcus aureus bacteremia in mice
Authors: Gupta Priti , Hu Zhicheng , Kopparapu Pradeep Kumar , Deshmukh Meghshree , Sághy Tibor , Mohammad Majd , Jin Tao , Engdahl Cecilia
Published: May 2023

Aging alters immunoglobulin production, affecting the humoral immune response. Toll-like receptor 2 (TLR2) recognizes Staphylococcus aureus (S. aureus) which causes bacteremia with high mortality in the elderly. To understand how TLR2 and aging affect the humoral immune response in bacteremia, four groups of mice (wild type-young, wild type-old, TLR2−/−-young, and TLR2−/−-old) were used to analyze immunoglobulin levels in healthy conditions as well as 10 days after intravenous injection with S. aureus. We found that aging increased the levels of both IgM and IgG. Increased IgG in aged mice was controlled by TLR2. In bacteremia infection, aged mice failed to mount proper IgM response in both wild-type (WT) and TLR2−/− mice, whereas IgG response was impaired in both aged and TLR2−/− mice. Aged mice displayed reduced IgG1 and IgG2a response irrespective of TLR2 expression. However, impaired IgG2b response was only found in aged WT mice and not in TLR2−/− mice. Both aging and TLR2−/− increased the levels of anti-staphylococcal IgM in bacteremia. Aging increased sialylated IgG in WT mice but not in TLR2−/− mice. IgG sialylation was not affected by the infection in neither of the mice. In summary, aging increases all immunoglobulins except IgG1. However, aged mice fail to mount a proper antibody response to S. aureus bacteremia. TLR2 plays the regulatory role in IgG but not IgM response to infection.
Modulation of tumor immune microenvironment by TAS-115, a multi-receptor tyrosine kinase inhibitor, promotes antitumor immunity and contributes anti-PD-1 antibody therapy
Authors: Shibutani Toshihiro , Goto Risa , Miyazaki Isao , Hashimoto Akihiro , Suzuki Takamasa , Ishida Keiji , Haruma Tomonori , Osada Toshihiro , Harada Takafumi , Fujita Hidenori , Ohkubo Shuichi
Published: May 2023

TAS-115 is an oral multi-receptor tyrosine kinase inhibitor that strongly inhibits kinases implicated in antitumor immunity, such as colony stimulating factor 1 receptor and vascular endothelial growth factor receptor. Because these kinases are associated with the modulation of immune pathways, we investigated the immunomodulatory activity of TAS-115. An in vitro cytokine assay revealed that TAS-115 upregulated interferon γ (IFNγ) and interleukin-2 secretion by T cells, suggesting that TAS-115 activated T cells. Gene expression analysis suggested that TAS-115 promoted M1 macrophage differentiation. In in vivo experiments, although TAS-115 exerted a moderate antitumor effect in the MC38 mouse colorectal cancer model under immunodeficient conditions, this effect was enhanced under immunocompetent conditions. Furthermore, combination of TAS-115 and anti-PD-1 antibody exhibited greater antitumor activity than either treatment alone. Flow cytometry analysis showed the increase in IFNγ- and granzyme B (Gzmb)-secreting tumor-infiltrating T cells by TAS-115 treatment. The combination treatment further increased the percentage of Gzmb+CD8+ T cells and decreased the percentage of macrophages compared with either treatment alone. These results highlight the potential therapeutic effect of TAS-115 in combination with PD-1 blockade, mediated via activation of antitumor immunity by TAS-115.
Dietary Ulva lactuca and CAZyme supplementation improve serum biochemical profile and hepatic composition of weaned piglets
Authors: Ribeiro David M. , Lopes Paula A. , Pinto Rui M. A. , Pestana José M. , Costa Mónica M. , Alfaia Cristina M. , Mourato Miguel P. , de Almeida André M. , Freire João P. B. , Prates José A. M.
Published: May 2023

Ulva lactuca is a seaweed with antinutritional cell wall for monogastrics. Carbohydrate-Active enZymes (CAZymes) supplementation can potentially cause its disruption. This study evaluates four diets: Ctrl—control diet; UL—control + 7% U. lactuca (wild caught, powdered form); ULR—UL + 0.005% Rovabio® Excel AP; ULU—UL + 0.01% ulvan lyase on piglets’ haematologic and serologic profiles, hepatic lipids and minerals. White blood cells and lymphocytes reached the highest values in piglets fed UL compared to control, and to control and ULR; respectively (P < 0.05). IgG levels were boosted by seaweed incorporation compared to control (P = 0.015). The glycaemic homeostasis was assured by the seaweed inclusion. Dietary seaweed decreased serum lipids (P < 0.001), with the exception of ULU, due to HDL-cholesterol increase (P < 0.001). Cortisol was decreased in ULR and ULU (P < 0.001). No systemic inflammation was observed (P > 0.05). While hepatic n-3 PUFA increased in piglets fed with seaweed diets due to increment of beneficial 22:5n-3 and 22:6n-3 fatty acids (P < 0.05), the opposite occurred for n-6 PUFA, PUFA/SFA and n-6/n-3 ratios (P < 0.05). Hepatic pigments were unchanged (P > 0.05). ULR reduced α-tocopherol levels (P = 0.036) and increased serum potassium levels (P < 0.001) compared to control. Seaweed contributed to overcome piglets’ weaning stress, with some benefits of including CAZyme supplementation.
Discovery of an underground chamber to protect kings and queens during winter in temperate termites
Authors: Takata Mamoru , Konishi Takao , Nagai Shuya , Wu Yao , Nozaki Tomonari , Tasaki Eisuke , Matsuura Kenji
Published: May 2023

Overwintering is a critical part of the annual cycle for species that live in temperate, polar, and alpine regions. Consequently, low-temperature biology is a key determinant of temperate species distribution. Termites are distributed predominantly in tropical regions, and a limited number of species are found in the temperate zone. Here, in the termiteReticulitermes speratus, we report the discovery of an underground chamber that protects kings and queens to survive the winter, which is separate from the one they used during the warmer breeding season. In the spring, the royals inhabited decayed logs on the ground, then moved to their underground chamber located in the roots of stumps in the fall. The winter minimum temperature measured in the royal chamber was higher than that in the logs on the ground. In overwintering termites, the kings and queens had higher cold tolerance than workers and soldiers. Air temperatures dropped below the critical temperature multiple times, as evidenced from the past 140 years of weather records in Kyoto. These results demonstrated the survival strategies of reproductives to overcome the environment at the latitudinal limits. This study helps further the understanding of the termite’s seasonal phenology, long-term survivorship, and life cycle.
Profile of sleep disturbances in patients with recurrent depressive disorder or bipolar affective disorder in a tertiary sleep disorders service
Authors: Drakatos Panagis , O’Regan David , Liao Yingqi , Panayiotou Constantinos , Higgins Sean , Kabiljo Renata , Benson Joshua , Pool Norman , Tahmasian Masoud , Romigi Andrea , Nesbitt Alexander , Stokes Paul R. A. , Kumari Veena , Young Allan H. , Rosenzweig Ivana
Published: May 2023

Bidirectional relationship between sleep disturbances and affective disorders is increasingly recognised, but its underlying mechanisms are far from clear, and there is a scarcity of studies that report on sleep disturbances in recurrent depressive disorder (RDD) and bipolar affective disorder (BPAD). To address this, we conducted a retrospective study of polysomnographic and clinical records of patients presenting to a tertiary sleep disorders clinic with affective disorders. Sixty-three BPAD patients (32 female; mean age ± S.D.: 41.8 ± 12.4 years) and 126 age- and gender-matched RDD patients (62 female; 41.5 ± 12.8) were studied. Whilst no significant differences were observed in sleep macrostructure parameters between BPAD and RDD patients, major differences were observed in comorbid sleep and physical disorders, both of which were higher in BPAD patients. Two most prevalent sleep disorders, namely obstructive sleep apnoea (OSA) (BPAD 50.8.0% vs RDD 29.3%, P = 0.006) and insomnia (BPAD 34.9% vs RDD 15.0%, P = 0.005) were found to be strongly linked with BPAD. In summary, in our tertiary sleep clinic cohort, no overt differences in the sleep macrostructure between BPAD and RDD patients were demonstrated. However, OSA and insomnia, two most prevalent sleep disorders, were found significantly more prevalent in patients with BPAD, by comparison to RDD patients. Also, BPAD patients presented with significantly more severe OSA, and with higher overall physical co-morbidity. Thus, our findings suggest an unmet/hidden need for earlier diagnosis of those with BPAD.
Identification of photocrosslinking peptide ligands by mRNA display
Authors: Wu Yuteng , Bertran M. Teresa , Joshi Dhira , Maslen Sarah L. , Hurd Catherine , Walport Louise J.
Published: May 2023

Photoaffinity labelling is a promising method for studying protein-ligand interactions. However, obtaining a specific, efficient crosslinker can require significant optimisation. We report a modified mRNA display strategy, photocrosslinking-RaPID (XL-RaPID), and exploit its ability to accelerate the discovery of cyclic peptides that photocrosslink to a target of interest. As a proof of concept, we generated a benzophenone-containing library and applied XL-RaPID screening against a model target, the second bromodomain of BRD3. This crosslinking screening gave two optimal candidates that selectively labelled the target protein in cell lysate. Overall, this work introduces direct photocrosslinking screening as a versatile technique for identifying covalent peptide ligands from mRNA display libraries incorporating reactive warheads.
Environmental conditions are the dominant factor influencing stability of terrestrial ecosystems on the Tibetan plateau
Authors: Ren Liang , Huo Jiaxuan , Xiang Xiang , Pan Yingping , Li Yuanqiao , Wang Yuanyuan , Meng Dehui , Yu Cheng , Chen Yang , Xu Zichao , Huang Yongmei
Published: May 2023

Ecosystem stability is essential for the sustainable provision of diverse ecosystem services. However, the factors that maintain ecosystem stability and their relative importance on the Tibetan Plateau, a region sensitive to climate change, remain unclear. Here, we combined data from ground-based biodiversity surveys at 143 sites from 2019 to 2021 with the temporal stability of ecosystems derived from remote sensing data from 2000 to 2020 to disentangle mechanisms of diversity–stability relationships. We further quantified the impact of biodiversity (taxonomic, functional, and phylogenetic diversity) and environmental context (spatial location, climate, and soil conditions) on temporal stability. Our results show that the stability of a typical ecosystem on the Tibetan Plateau is mainly regulated by environmental factors, and the environmental context can directly affect the stability of the ecosystem rather than indirectly through biodiversity. These findings are critical for adaptation measures and prioritizing conservation areas for future climate change scenarios.
Gravity field changes reveal deep mass transfer before and after the 2013 Lushan earthquake
Authors: Wang Linhai , Chen Shi , Zhuang Jiancang , Zhang Bei , Shi Wen , Yang Jinling , Xu Weimin
Published: May 2023

The 2013 MS7.0 Lushan earthquake, Sichuan, China, occurred on a blind thrust fault in the southern Longmenshan fault belt. The terrestrial hybrid repeated gravity observation enables us to investigate the redistribution of both surface and deep mass. Here, we find a transient increase in the gravity field about 2 years before the earthquake and a drop after the mainshock. A Bayesian inversion method with spatiotemporal smoothness is employed to extract the apparent density changes. The increase of apparent density on the south of the focal zone is assumed to be related to crustal mass transfer. We introduce a disc-shaped equivalent source model with a homogeneous density to address this hypothesis, and estimate the model parameters by Markov Chain Monte Carlo simulations. As a fluid diffusion footprint is indicated by the seismicity migration in this region, with a fitted diffusion rate of 10 m2 s−1, we conclude that such deep crustal mass transfer may be caused by fluid diffusion.
Reduced selection for antibiotic resistance in community context is maintained despite pressure by additional antibiotics
Authors: Fang Peiju , Elena Alan Xavier , Kunath Maxi Antonia , Berendonk Thomas U , Klümper Uli
Published: May 2023

Selection for antibiotic resistance at very low antibiotic concentrations has been demonstrated for individual antibiotics in single species experiments. Furthermore, selection in these focal strains is reduced when taking place in complex microbial community context. However, in the environment, bacteria are rarely exposed to single, but rather complex mixtures of selective agents. Here, we explored how the presence of a second selective agent affects selection dynamics between isogenic pairs of focal E. coli strains, differing exclusively in a single resistance determinant, in the absence and presence of a model wastewater community across a gradient of antibiotics. An additional antibiotic that exclusively affects the model wastewater community, but to which the focal strains are resistant to, was chosen as the second selective agent. This allowed exploring how inhibition alters the community’s ability to reduce selection. In the presence of the community, the selection coefficient at specific antibiotic concentrations was consistently decreased compared to the absence of the community. While pressure through the second antibiotic significantly decreased the activity and diversity of the community, its ability to reduce selection was consistently maintained at levels comparable to those recorded in absence of the second antibiotic. This indicates that the observed effects of community context on selection dynamics are rather based on competitive or protective effects between the focal strains and a small proportion of bacteria within the community, than on general competition for nutrients. These findings have implications for our understanding of the evolution and selection for multi-drug resistant strains.
A SAR and QSAR study on cyclin dependent kinase 4 inhibitors using machine learning methods
Authors: Pang Xiaoyang , Zhao Yunyang , Li Guo , Liu Jianrong , Yan Aixia
Published: May 2023

Machine learning methods are used to predict the inhibitory activity of the compound targeting cyclin dependent kinase 4 (CDK4), and analyse fragment features of CDK4 inhibitors.
3D printed integrated nanoporous membranes for electroextraction of DNA
Authors: Kalathil Balakrishnan Hari , Lee Soo Min , Dumée Ludovic F. , Doeven Egan H. , Alexander Richard , Yuan Dan , Guijt Rosanne M.
Published: May 2023

3D printed functionally integrated device containing nanoporous membranes with properties tailored for the electroextraction of DNA.
A coumarin-pyrazole-based probe for the fluorescence detection of phosgene with high selectivity and sensitivity
Authors: Hu Qiang , Song Yu-Fei , Wu Wei-Na , Zhao Xiao-Lei , Wang Yuan , Fan Yun-Chang
Published: May 2023

In this study, we reported a coumarin-pyrazole-based probe for the fluorescence detection of phosgene. Probe 1 responded rapidly to phosgene with good selectivity and high sensitivity, especially for phosgene gas-phase detection.
Efficient and zero thermal quenching Sm3+-activated Li2LaTiTaO7 phosphor for white LEDs
Authors: Wang Qi , Wang Shangwei , Pang Ran , Tan Taixing , Wen He-rui , Zhang Su , You Hongpeng , Li Chengyu , Zhang Hongjie
Published: May 2023

A novel orange-red phosphor Li2La1−xTiTaO7:xSm3+ (abbreviated as LLTT:Sm3+) for white light-emitting diodes (w-LEDs) has been successfully synthesized and systematically investigated.
Current status and future prospects of bioactive molecules delivered through sustainable encapsulation techniques for food fortification
Authors: Dahiya Divakar , Terpou Antonia , Dasenaki Marilena , Nigam Poonam S.
Published: May 2023

In a world of growing population and changing climate, health and sustainable food production are nowadays considered the most pressing challenges.
A review of bioactive peptides as functional food ingredients: mechanisms of action and their applications in active packaging and food quality improvement
Authors: Najafian Leila
Published: May 2023

The creation of bioactive peptides (BPs) from dietary proteins holds considerable promise for the expansion of functional foods and nutraceuticals.
Cinchona-alkaloid-derived NN ligands for ruthenium catalyzed asymmetric hydrogenation of ketones
Authors: Sun Hao , Dai Pinli , Tian Jie , Xu Qian , Chen Qian , Li Linlin , Meng Xin , Zhang Lin , Li Chun
Published: May 2023

The asymmetric hydrogenation of ketones was catalyzed by ruthenium and cinchona-alkaloid-derived NN ligands bearing N–H moieties, producing the corresponding alcohols with up to 98.8% ee.
Carbohydrate recognition using metal–ligand assemblies
Authors: Ahamed Rafiq , Venkatesh Jayashree , Srithar Rakshantha , Gaikwad Sudhakar , Pramanik Susnata
Published: May 2023

This review summarises the recognition of carbohydrates using metal-ligand assemblies, including metallosupramolecules, macrocycles, and cages. It also highlights the challenges and future directions in the field.
Strain relaxation in monolayer MoS2 over flexible substrate
Authors: Basu Nilanjan , Kumar Ravindra , Manikandan D. , Ghosh Dastidar Madhura , Hedge Praveen , Nayak Pramoda K. , Bhallamudi Vidya Praveen
Published: May 2023

Strain relaxation in 1L MoS2 transpires through crack formation at around 4.5% of strain.
Selective hydrogenation of dimethyl terephthalate over a potassium-modified Ni/SiO2 catalyst
Authors: Xiao Han , Zhang Chao , Zhao Jiaojiao , Zheng Zhaohui , Li Yuehui
Published: May 2023

Selective hydrogenation of DMT to DMCD was achieved a using KF-modified Ni/SiO2 catalyst. Doping only 0.5 wt% of KF by post-impregnation significantly improves the reactivity and selectivity (41% vs 95% conversion; 83% vs 96% selectivity).
Characterization of cellulose-functionalized phillipsite biocomposite as an enhanced carrier of oxaliplatin drug during the treatment of colorectal cancer: loading, release, and cytotoxicity
Authors: Alfassam Haifa E. , Ashraf Menna-Tullah , Al Othman Sarah I. , Al-Waili Maha A. , Allam Ahmed A. , Abukhadra Mostafa R.
Published: May 2023

Natural phillipsite (N.Ph) was hybridized with cellulose fibers to produce a safe biocomposite (CF/N.Ph) as an enhanced delivery structure of traditional oxaliplatin (OXPN) chemotherapy during the treatment stages of colorectal cancer cells.
Substrate-derived Sortase A inhibitors: targeting an essential virulence factor of Gram-positive pathogenic bacteria
Authors: Abujubara Helal , Hintzen Jordi C. J. , Rahimi Shadi , Mijakovic Ivan , Tietze Daniel , Tietze Alesia A.
Published: May 2023

A series of peptidomimetic Sortase A inhibitors is reported. These compounds show inhibition activity of the Sortase A enzyme and efficiently prevent biofilm formation of S. aureus.
Progress in the chemistry of molecular actinide-nitride compounds
Authors: Keener Megan , Maria Leonor , Mazzanti Marinella
Published: May 2023

This review covers the rapid progress that was made over the past decade in the chemistry of actinide nitrides with a focus on uranium terminal and bridging nitrides, their synthesis and reactivity, and a few recent breakthroughs with thorium.
Potassium-modified bifunctional MgAl-SBA-15 for aldol condensation of furfural and acetone
Authors: Arumugam Mahashanon , Kikhtyanin Oleg , Osatiashtiani Amin , Kyselová Veronika , Fila Vlastimil , Paterova Iva , Wong Ka-Lun , Kubička David
Published: May 2023

Potassium modified acid–base bifunctionalized MgAl-SBA-15 for mild aldol condensation of furfural and acetone to high-quality jet-fuel range or chemical intermediates.
pH response of sequence-controlled polyampholyte brushes
Authors: Yuan Xin , Hatch Harold W. , Conrad Jacinta C. , Marciel Amanda B. , Palmer Jeremy C.
Published: May 2023

We use molecular simulation to investigate the pH response of sequence-controlled polyampholyte brushes (PABs) with polymer chains consisting of alternating blocks of weakly acidic and basic monomers.
Construction of micelles and hollow spheres via the self-assembly behavior of poly(styrene-alt-pHPMI) copolymers with poly(4-vinylpyridine) derivatives mediated by hydrogen bonding interactions
Authors: Ma Tzu-Ling , Du Wei-Ting , Kuo Shiao-Wei
Published: May 2023

H-bonding connected micelles were prepared using a P4VP-deriviate shell and a poly(S-alt-pHPMI) core in a selective solvent, then cross-linker was used to stabilize the PS-co-P4VP and dissolve the poly(S-alt-pHPMI) in DMF to obtain hollow spheres.
Safe-and-sustainable-by-design chemicals and advanced materials: a paradigm shift towards prevention-based risk governance is needed
Authors: Hristozov Danail , Zabeo Alex , Soeteman-Hernández Lya G. , Pizzol Lisa , Stoycheva Stella
Published: May 2023

We need a paradigm shift towards prevention-based risk governance of chemicals and advanced materials via a transition towards SSbD. Defining SSbD metrics and trade-offs should be a co-creative process and can benefit from applying digital tools.
Zincophilic multilayer graphene structures leveraging fast and ultrastable Zn-ion storage
Authors: Huang Qi , Jin Yaowei , Huang Lu , Cong Yao , Xu Zijie
Published: May 2023

Zincophilic multilayer graphene structurein situconstructed to glue more electroactive sites and opposite charge-carrier uptake entails alternate binding of Zn2+/CF3SO3−at active sites.
Differentiation of snake venom using Raman spectroscopic analysis
Authors: Mozhaeva Vera , Starkov Vladislav , Kudryavtsev Denis , Prokhorov Kirill , Garnov Sergey , Utkin Yuri
Published: May 2023

We have proposed an economical express method based on Raman spectroscopy, which with the help of mathematical processing allows the classification of snake venoms according to their composition and the determination of snake family or even genus.
An enhanced ultrasensitive solar-blind UV photodetector based on an asymmetric Schottky junction designed with graphene/β-Ga2O3/Ag
Authors: Qi Song , Liu Jiahang , Yue Jianying , Ji Xueqiang , Shen Jiaying , Yang Yongtao , Wang Jinjin , Li Shan , Wu Zhenping , Tang Weihua
Published: May 2023

The device has a dark current of 12.09 pA and achieves an outstanding responsivity of 44.09 A W−1, a high detectivity of 5.84 × 1012 Jones.
Ethereum phishing detection based on graph neural networks
Authors: Xiong Ao , Tong Yuanzheng , Jiang Chengling , Guo Shaoyong , Shao Sujie , Huang Jing , Wang Wei , Qi Baozhen
Published: May 2023

With the development of blockchain, cryptocurrencies are also showing a boom. However, due to the decentralized and anonymous nature of blockchain, cryptocurrencies have inevitably become a hotbed for fraudulent crimes. For example, phishing scams are frequent, which not only jeopardize the financial security of blockchain, but also hinder the promotion of blockchain technology. To solve this problem, this paper proposes a graph neural network‐based phishing detection method for Ethereum, and validates it using Ethereum datasets. Specifically, this paper proposes a feature learning algorithm named TransWalk, which consists of a random walk strategy for transaction networks and a multi‐scale feature extraction method for Ethereum. Then, an Ethereum phishing fraud detection framework is built based on TransWalk, and conduct extensive experiments on the Ethereum dataset to verify the effectiveness of this scheme in identifying Ethereum phishing detection.