bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery of the dendrophylliid scleractinian Heteropsammia cochlea (Spengler, 1781) in Halimeda bioherms of the Northern Great Barrier Reef
Authors: Borghi Stefano , Clements Matthew , Webb Monique , Bostock Helen , Webster Jody M. , McNeil Mardi , Nothdurft Luke , Byrne Maria
Published: June 2023

Halimedabioherms on the Northern Great Barrier Reef (GBR) extend for over 6000 km2. To explore the ecological and biogeographical importance of these bioherms was one of the aims of a recent voyage on the Research Vessel (RV)Investigator. Through the use of underwater images and habitat sampling, we found populations ofHeteropsammia cochlea(Spengler, 1781) living in the bioherms. The scleractinian coral genusHeteropsammia(Dendrophylliidae) is a group of solitary, apozooxanthellate, single-polyp corals with a widespread distribution in tropical and sub-tropical regions. Populations ofH. cochleawere observed with individuals dispersed on open-sand habitat and among patches ofHalimedaat 30–40 m water depth in mean densities of 89 and 29 corals per m2, respectively. Fluorescence microscopy was used to assess the presence of zooxanthellae, indicating that they are actively photosynthesising at these depths. These are the first observations ofH. cochleain association with theHalimedabioherms on the Northern GBR.
Possible therapeutic targets for NLRP3 inflammasome-induced breast cancer
Authors: Wang Xixi , Lin Junyi , Wang Zhe , Li Zhi , Wang Minghua
Published: June 2023

Inflammation plays a major role in the development and progression of breast cancer(BC). Proliferation, invasion, angiogenesis, and metastasis are all linked to inflammation and tumorigenesis. Furthermore, tumor microenvironment (TME) inflammation-mediated cytokine releases play a critical role in these processes. By recruiting caspase-1 through an adaptor apoptosis-related spot protein, inflammatory caspases are activated by the triggering of pattern recognition receptors on the surface of immune cells. Toll-like receptors, NOD-like receptors, and melanoma-like receptors are not triggered. It activates the proinflammatory cytokines interleukin (IL)-1β and IL-18 and is involved in different biological processes that exert their effects. The Nod-Like Receptor Protein 3 (NLRP3) inflammasome regulates inflammation by mediating the secretion of proinflammatory cytokines and interacting with other cellular compartments through the inflammasome's central role in innate immunity. NLRP3 inflammasome activation mechanisms have received much attention in recent years. Inflammatory diseases including enteritis, tumors, gout, neurodegenerative diseases, diabetes, and obesity are associated with abnormal activation of the NLRP3 inflammasome. Different cancer diseases have been linked to NLRP3 and its role in tumorigenesis may be the opposite. Tumors can be suppressed by it, as has been seen primarily in the context of colorectal cancer associated with colitis. However, cancers such as gastric and skin can also be promoted by it. The inflammasome NLRP3 is associated with breast cancer, but there are few specific reviews. This review focuses on the structure, biological characteristics and mechanism of inflammasome, the relationship between NLRP3 in breast cancer Non-Coding RNAs, MicroRNAs and breast cancer microenvironment, especially the role of NLRP3 in triple-negative breast cancer (TNBC). And the potential strategies of using NLRP3 inflammasome to target breast cancer, such as NLRP3-based nanoparticle technology and gene target therapy, are reviewed.
Hypocoercivity for non-linear infinite-dimensional degenerate stochastic differential equations
Authors: Eisenhuth Benedikt , Grothaus Martin
Published: June 2023

The aim of this article is to construct solutions to second order in time stochastic partial differential equations and to show hypocoercivity of the corresponding transition semigroups. More generally, we analyze non-linear infinite-dimensional degenerate stochastic differential equations in terms of their infinitesimal generators. In the first part of this article we use resolvent methods developed by Beznea, Boboc and Röckner to construct diffusion processes with infinite lifetime and explicit invariant measures. The processes provide weak solutions to infinite-dimensional Langevin dynamics. The second part deals with a general abstract Hilbert space hypocoercivity method, developed by Dolbeaut, Mouhot and Schmeiser. In order to treat stochastic (partial) differential equations, Grothaus and Stilgenbauer translated these concepts to the Kolmogorov backwards setting taking domain issues into account. To apply these concepts in the context of infinite-dimensional Langevin dynamics we use an essential m-dissipativity result for infinite-dimensional Ornstein–Uhlenbeck operators, perturbed by the gradient of a potential. We allow unbounded diffusion operators as coefficients and apply corresponding regularity estimates. Furthermore, essential m-dissipativity of a non-sectorial Kolmogorov backward operator associated to the dynamic is needed. Poincaré inequalities for measures with densities w.r.t. infinite-dimensional non-degenerate Gaussian measures are studied. Deriving a stochastic representation of the semigroup generated by the Kolmogorov backward operator as the transition semigroup of a diffusion process enables us to show an $$L^2$$

L
2

-exponential ergodicity result for the weak solution. Finally, we apply our results to explicit infinite-dimensional degenerate diffusion equations.
Computing $$\mathbb {A}^1$$-Euler numbers with Macaulay2
Authors: Pauli Sabrina
Published: June 2023

We use Macaulay2 for several enriched counts in $${\text {GW}}(k)$$

GW
(
k
)

. First, we compute the count of lines on a general cubic surface using Macaulay2 over $$\mathbb {F}_p$$

F
p

in $${\text {GW}}(\mathbb {F}_p)$$

GW
(

F
p

)

for p a prime number and over $$\mathbb {Q}$$
Q
in $${\text {GW}}(\mathbb {Q})$$

GW
(
Q
)

. This gives a new proof for the fact that the $$\mathbb {A}^1$$

A

1

-Euler number of $${\text {Sym}}^3\mathcal {S}^*\rightarrow {\text {Gr}}(2,4)$$

Sym

3

S

∗

→
Gr

(
2
,
4
)

is $$15\langle 1\rangle +12\langle -1\rangle $$

15
⟨
1
⟩
+
12
⟨
-
1
⟩

. Then, we compute the count of lines in $$\mathbb {P}^3$$

P

3

meeting 4 general lines, the count of lines on a quadratic surface meeting one general line and the count of singular elements in a pencil of degree d-surfaces. Finally, we provide code to compute the EKL-form and compute several $$\mathbb {A}^1$$

A

1

-Milnor numbers.
Cement kiln dust in CIMENCAM Figuil (North Cameroon): characteristics and recycling as additives for blended cement production
Authors: Hamadou Toumba , Kanouo Nguo Sylvestre , Dikwa Jerome , Tchamba Arlin Bruno , Duna Linda Lekuna
Published: June 2023

This work presents the manufacture of CKD-blended cement from raw materials such as clinker, gypsum, marble and cement kiln dust (CKD) obtained from CIMENCAM Figuil, North Region of Cameroon. The raw materials were first characterized through XRF chemical analyses. Chemical tests (proportion of free lime, loss on ignition, sulfate, and insoluble residues), physical tests (fineness, consistency, setting time, and expansion), and compressive strength tests were carried out on manufactured CKD-blended cements and mortars. Clinker is composed of CaO (65.30%) and SiO2 (21.13%), with significant MgO (2.71%), Na2O + K2O (1.29%), SO3 (0.81%) and lime saturation factor of (97.9); which make this clinker good for cement production. Gypsum is composed of SO3 (36.32%) and CaO (33.92%) but contains very low proportion of impurities; it is therefore classified as low-impurities gypsum suitable for cement productions. The marble is dominantly composed of CaO (37.09%) with significant SiO2 (7.26%), SO3(2.40%), (2.36%), Fe2O3 (1.82%) and MgO (0.18%); it is classified as low-CaO calcitic-aluminosilicate and ferrosilicate bearing marble. The CKD is dominantly made up of CaO (46.0%) and SiO2 (11.62%) with significantly low Na2O + K2O (1.02%), and SO3(2.16%); this classifies it as low alkalies-sulfate cement kiln dust. The proportion of free lime, SO3, loss on ignition, and insoluble residues in the manufactured CKD-blended cements increase with an increase in the proportion of CKD. The blaine specific surface area (BSSA) (4797–6346 cm2/g) and the sieved residues (26.14–30.36%) show an increase with the proportion of used CKD. The compressive strength tests carried out on the prepared brick-shape hardened CKD-cement mortars (at 2, 7, and 28 days) show that, the resistance depends on the proportion of the used CKD (0% control, 5%, 10%, 15%, 20%… up to 50%). Pressures of 17.5 to 11.6 MPa was obtained in 2 days, 28.9 to 20.0 MPa in 7 days, and 35.5–23.3 MPa in 28 days.
Protecting Data and Queries in Cloud-Based Scenarios
Authors: De Capitani di Vimercati Sabrina , Foresti Sara , Samarati Pierangela
Published: June 2023

The availability of cloud services offered by different providers brings several advantages to users and companies, facilitating the storage, sharing, and processing of data. At the same time, the adoption of cloud services brings new security and privacy risks and challenges. As a matter of fact when leveraging cloud-based services for data storage and processing, data owners loose direct control on their data. Data and queries over them could then be at risk for both potentially improper exposure, compromising their confidentiality, or tampering, compromising their integrity. In this paper, we discuss the main issues to be addressed for guaranteeing data security and privacy in cloud-based storage and processing. We illustrate the different challenges to be considered and the research directions toward their solutions.
Reliability Estimation and Optimization of a Smart Meter Architecture Using a Monte Carlo Simulation
Authors: Altenburg Tobias , Staegemann Daniel , Volk Matthias , Turowski Klaus
Published: June 2023

The technological evolution is dominating the social change. There is a constant increase in the number of networked devices and the use of smart meters has become more relevant. A required feature of smart meter architectures is reliability, which ensures the continuous provision of the services of the system. In this article, the research question “How can a low-fault smart metering architecture be achieved based on constructive methods?” is answered with the objective of designing a low-fault smart meter architecture. By implementing optimization methods, an improvement in reliability can be achieved. A structured approach to reliability optimization using topological modifications to the architecture is described, along with evaluation of the improved reliability. For this purpose, reliability block diagrams are combined with Monte Carlo simulation to calculate the most realistic approximation of system reliability. Finally, the results of the individual reliability analyses are summarized and compared to show the optimization potential.
How to make continental reconstructions: the importance of the knowledge of high strain along former plate boundaries
Authors: Şengör A. M. Celâl , Natal’in Boris A. , Lom Nalan , Zabcı Cengiz , Sunal Gürsel
Published: June 2023

Continental reconstructions became a geological problem after the rise of continental drift. With plate tectonics, it became easy to make reconstructions once ocean-floor magnetic anomaly stripes became available. However, for times before the medial Jurassic, continental reconstructions must depend on palaeomagnetism, palaeoclimatology and palaeobiogeography. All three methods give rough latitudinal control, whereas obtaining longitudinal control has proved elusive. We here show that a detailed knowledge of strain history, i.e. careful mapping and integrating change of shape in rock bodies and the displacements implead by them in orogenic belts between formerly separate continental rafts may also provide longitudinal control of relative continental positions and thus enable the geologist to generate displacement paths during the drift histories of continents before the early Jurassic. We present below two examples of continental reconstructions, in which strain histories of rock packages between two cratons play a predominant role, namely the Altaids, mainly in the Phanerozoic, and the Saharides, mainly in the Neoproterozoic.
A Stochastic Dynamical Model of Slope Creep and Failure
Authors: Lei Qinghua , Sornette Didier
Published: June 2023

We propose a stochastic dynamical model to simulate slope secondary and tertiary creep phenomena. The slope secondary creep is represented by the Kesten process defined as a stochastic affine auto‐regressive process involving both multiplicative and additive random variables. The Kesten process can realistically capture the co‐existence of a background deformation and intermittent displacement bursts, which are together well characterized by an inverse gamma velocity distribution. The slope tertiary creep is modeled by a nonlinear stochastic dynamical equation embodying a nonlinear feedback mechanism and a nonlinear random effect, which can mimic the development of slow or catastrophic landslides. For catastrophic landslides, the probability density function of slope velocities tends to deviate from the inverse gamma distribution by populating the “dragon‐king” regime, although sometimes they may grow undetectably in the “black‐swan” regime. Our model provides a quantitative framework to understand, simulate, and interpret complex landslide displacement time series.
A Deep‐Learning Ensemble Method to Detect Atmospheric Rivers and Its Application to Projected Changes in Precipitation Regime
Authors: Tian Yuan , Zhao Yang , Son Seok‐Woo , Luo Jing‐Jia , Oh Seok‐Geun , Wang Yinjun
Published: June 2023

This study aims to detect atmospheric rivers (ARs) around the world by developing a deep‐learning ensemble method using AR catalogs of the ClimateNet data set. The ensemble method, based on 20 semantic segmentation algorithms, notably reduces the bias of the testing data set, with its intersection over union score being 1.7%–10.1% higher than that of individual algorithms. This method is then applied to the Coupled Model Intercomparison Project Phase 6 (CMIP6) datasets to quantify AR frequency and its related precipitation in the historical period (1985–2014) and future period (2070–2099) under the Shared Socioeconomic Pathways 5–8.5 warming scenario. The six key regions, which are distributed in different continents of the globe and greatly influenced by ARs, are particularly highlighted. The results show that CMIP6 multi‐model mean with the deep‐learning ensemble method reasonably reproduces the observed AR frequency. In most key regions, both heavy precipitation (90–99 percentile) and extremely heavy precipitation (>99 percentile) are projected to increase in a warming climate mainly due to the increased AR‐related precipitation. The AR contributions to future heavy and extremely heavy precipitation increase range from 145.1% to 280.5% and from 36.2% to 213.5%, respectively, indicating that ARs should be taken into account to better understand the future extreme precipitation changes.
Molecular Characterization of Brown Carbon Chromophores in Atmospherically Relevant Samples and Their Gas‐Particle Distribution and Diurnal Variation in the Atmosphere
Authors: Xing Chong , Wan Yibei , Wang Qiongqiong , Kong Shaofei , Huang Xiangpeng , Ge Xinlei , Xie Mingjie , Yu Huan
Published: June 2023

By developing a nontarget tandem mass spectrometry experiment workflow, we identified the most probable structures of 100 brown carbon (BrC) chromophores in five types of atmospherically relevant samples including ambient aerosols, biomass burning aerosols, road tunnel aerosols, toluene secondary organic aerosol and rainwater. These chromophores were classified into nine groups, that is, 31 nitrophenols, 12 benzoic acids, 11 oxygenated polycyclic aromatic hydrocarbons, 10 phenols, 10 aryl amides/amines, 9 phenylpropene derivatives, 9 coumarins and flavonoids, 5 pyridines, and 3 nitrobenzoic acids. Among them, aryl amides/amine chromophores, which were mostly found in rainwater, were reported for the first time. The identified chromophores accounted for 20.9%–83.5% of total light absorption over 300–400 nm wavelength or total ion intensity in the 5 types of samples. We identified the characteristic chromophore groups in each sample type and identical chromophores among different sample types, especially between the source samples and ambient aerosols. Gas‐particle distribution and diurnal variation of 13 BrC compounds in the atmosphere were measured by an online high‐resolution chemical ionization mass spectrometer equipped with a Filter Inlet for Gases and Aerosols. It was found that gas‐particle distribution of BrC compounds was dictated by their functional group, oxygen and carbon atom numbers. The BrC compounds containing nitro‐group had higher nighttime concentrations, while those without nitro‐group had higher daytime concentrations.
Aggressive and psychopathic traits are linked to the acquisition of stable but imprecise hostile expectations
Authors: Buades-Rotger Macià , Smeijers Danique , Gallardo-Pujol David , Krämer Ulrike M. , Brazil Inti A.
Published: June 2023

Individuals with hostile expectations (HEX) anticipate harm from seemingly neutral or ambiguous stimuli. However, it is unclear how HEX are acquired, and whether specific components of HEX learning can predict antisocial thought, conduct, and personality. In an online sample of healthy young individuals (n = 256, 69% women), we administered a virtual shooting task and applied computational modelling of behaviour to investigate HEX learning and its constellation of correlates. HEX acquisition was best explained by a hierarchical reinforcement learning mechanism. Crucially, we found that individuals with relatively higher self-reported aggressiveness and psychopathy developed stronger and less accurate hostile beliefs as well as larger prediction errors. Moreover, aggressive and psychopathic traits were associated with more temporally stable hostility representations. Our study thus shows that aggressiveness and psychopathy are linked with the acquisition of robust yet imprecise hostile beliefs through reinforcement learning.
Effects of risperidone/paliperidone versus placebo on cognitive functioning over the first 6 months of treatment for psychotic disorder: secondary analysis of a triple-blind randomised clinical trial
Authors: Allott Kelly , Yuen Hok Pan , Baldwin Lara , O’Donoghue Brian , Fornito Alex , Chopra Sidhant , Nelson Barnaby , Graham Jessica , Kerr Melissa J. , Proffitt Tina-Marie , Ratheesh Aswin , Alvarez-Jimenez Mario , Harrigan Susy , Brown Ellie , Thompson Andrew D. , Pantelis Christos , Berk Michael , McGorry Patrick D. , Francey Shona M. , Wood Stephen J.
Published: June 2023

The drivers of cognitive change following first-episode psychosis remain poorly understood. Evidence regarding the role of antipsychotic medication is primarily based on naturalistic studies or clinical trials without a placebo arm, making it difficult to disentangle illness from medication effects. A secondary analysis of a randomised, triple-blind, placebo-controlled trial, where antipsychotic-naive patients with first-episode psychotic disorder were allocated to receive risperidone/paliperidone or matched placebo plus intensive psychosocial therapy for 6 months was conducted. A healthy control group was also recruited. A cognitive battery was administered at baseline and 6 months. Intention-to-treat analysis involved 76 patients (antipsychotic medication group: 37; 18.6Mage [2.9] years; 21 women; placebo group: 39; 18.3Mage [2.7]; 22 women); and 42 healthy controls (19.2Mage [3.0] years; 28 women). Cognitive performance predominantly remained stable (working memory, verbal fluency) or improved (attention, processing speed, cognitive control), with no group-by-time interaction evident. However, a significant group-by-time interaction was observed for immediate recall (p = 0.023), verbal learning (p = 0.024) and delayed recall (p = 0.005). The medication group declined whereas the placebo group improved on each measure (immediate recall: p = 0.024; ηp2 = 0.062; verbal learning: p = 0.015; ηp2 = 0.072 both medium effects; delayed recall: p = 0.001; ηp2 = 0.123 large effect). The rate of change for the placebo and healthy control groups was similar. Per protocol analysis (placebo n = 16, medication n = 11) produced similar findings. Risperidone/paliperidone may worsen verbal learning and memory in the early months of psychosis treatment. Replication of this finding and examination of various antipsychotic agents are needed in confirmatory trials. Antipsychotic effects should be considered in longitudinal studies of cognition in psychosis.

Trial registration: Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au/; ACTRN12607000608460).
Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality
Authors: Oddsson Asmundur , Sulem Patrick , Sveinbjornsson Gardar , Arnadottir Gudny A. , Steinthorsdottir Valgerdur , Halldorsson Gisli H. , Atlason Bjarni A. , Oskarsson Gudjon R. , Helgason Hannes , Nielsen Henriette Svarre , Westergaard David , Karjalainen Juha M. , Katrinardottir Hildigunnur , Fridriksdottir Run , Jensson Brynjar O. , Tragante Vinicius , Ferkingstad Egil , Jonsson Hakon , Gudjonsson Sigurjon A. , Beyter Doruk , Moore Kristjan H. S. , Thordardottir Helga B. , Kristmundsdottir Snaedis , Stefansson Olafur A. , Rantapää-Dahlqvist Solbritt , Sonderby Ida Elken , Didriksen Maria , Stridh Pernilla , Haavik Jan , Tryggvadottir Laufey , Frei Oleksandr , Walters G. Bragi , Kockum Ingrid , Hjalgrim Henrik , Olafsdottir Thorunn A. , Selbaek Geir , Nyegaard Mette , Erikstrup Christian , Brodersen Thorsten , Saevarsdottir Saedis , Olsson Tomas , Nielsen Kaspar Rene , Haraldsson Asgeir , Bruun Mie Topholm , Hansen Thomas Folkmann ,   DBDS Genomic Consortium, Brunak Søren , Nielsen Kasper Rene , Brun Mie Topholm , Stefánsson Hreinn , Þorsteinsdóttir Unnur , Steingrimsdottir Thora , Jacobsen Rikke Louise , Lie Rolv T. , Djurovic Srdjan , Alfredsson Lars , Lopez de Lapuente Portilla Aitzkoa , Brunak Soren , Melsted Pall , Halldorsson Bjarni V. , Saemundsdottir Jona , Magnusson Olafur Th. , Padyukov Leonid , Banasik Karina , Rafnar Thorunn , Askling Johan , Klareskog Lars , Pedersen Ole Birger , Masson Gisli , Havdahl Alexandra , Nilsson Bjorn , Andreassen Ole A. , Daly Mark , Ostrowski Sisse Rye , Jonsdottir Ingileif , Stefansson Hreinn , Holm Hilma , Helgason Agnar , Thorsteinsdottir Unnur , Stefansson Kari , Gudbjartsson Daniel F.
Published: June 2023

Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. To explore genetic causes of recessive lethality, we searched for sequence variants with deficit of homozygosity among 1.52 million individuals from six European populations. In this study, we identified 25 genes harboring protein-altering sequence variants with a strong deficit of homozygosity (10% or less of predicted homozygotes). Sequence variants in 12 of the genes cause Mendelian disease under a recessive mode of inheritance, two under a dominant mode, but variants in the remaining 11 have not been reported to cause disease. Sequence variants with a strong deficit of homozygosity are over-represented among genes essential for growth of human cell lines and genes orthologous to mouse genes known to affect viability. The function of these genes gives insight into the genetics of intrauterine lethality. We also identified 1077 genes with homozygous predicted loss-of-function genotypes not previously described, bringing the total set of genes completely knocked out in humans to 4785.
Allosteric activation of cell wall synthesis during bacterial growth
Authors: Shlosman Irina , Fivenson Elayne M. , Gilman Morgan S. A. , Sisley Tyler A. , Walker Suzanne , Bernhardt Thomas G. , Kruse Andrew C. , Loparo Joseph J.
Published: June 2023

The peptidoglycan (PG) cell wall protects bacteria against osmotic lysis and determines cell shape, making this structure a key antibiotic target. Peptidoglycan is a polymer of glycan chains connected by peptide crosslinks, and its synthesis requires precise spatiotemporal coordination between glycan polymerization and crosslinking. However, the molecular mechanism by which these reactions are initiated and coupled is unclear. Here we use single-molecule FRET and cryo-EM to show that an essential PG synthase (RodA-PBP2) responsible for bacterial elongation undergoes dynamic exchange between closed and open states. Structural opening couples the activation of polymerization and crosslinking and is essential in vivo. Given the high conservation of this family of synthases, the opening motion that we uncovered likely represents a conserved regulatory mechanism that controls the activation of PG synthesis during other cellular processes, including cell division.
Trichalcogenasupersumanenes and its concave-convex supramolecular assembly with fullerenes
Authors: Sun Yixun , Wang Xin , Yang Bo , Chen Muhua , Guo Ziyi , Wang Yiting , Li Ji , Xu Mingyu , Zhang Yunjie , Sun Huaming , Dang Jingshuang , Fan Juan , Li Jing , Wei Junfa
Published: June 2023

Synthesis of buckybowls have stayed highly challenging due to the large structural strain caused by curvedπsurface. In this paper, we report the synthesis and properties of two trichalcogenasupersumanenes which three chalcogen (sulfur or selenium) atoms and three methylene groups bridge at the bay regions of hexa-peri-hexabenzocoronene. These trichalcogenasupersumanenes are synthesized quickly in three steps using an Aldol cyclotrimerization, a Scholl oxidative cyclization, and a Stille type reaction. X-ray crystallography analysis reveals that they encompass bowl diameters of 11.06 Å and 11.35 Å and bowl depths of 2.29 Å and 2.16 Å for the trithiasupersumanene and triselenosupersumanene, respectively. Furthermore, trithiasupersumanene derivative with methyl chains can form host-guest complexes with C60or C70, which are driven by concave-convexπ ⋯ πinteractions and multiple C–H ⋯ πinteractions between bowl and fullerenes.
Vaccine-induced protection against SARS-CoV-2 requires IFN-γ-driven cellular immune response
Authors: Wang Xiaolei , Yuen Terrence Tsz-Tai , Dou Ying , Hu Jingchu , Li Renhao , Zeng Zheng , Lin Xuansheng , Gong Huarui , Chan Celia Hoi-Ching , Yoon Chaemin , Shuai Huiping , Ho Deborah Tip-Yin , Hung Ivan Fan-Ngai , Zhang Bao-Zhong , Chu Hin , Huang Jian-Dong
Published: June 2023

The overall success of worldwide mass vaccination in limiting the negative effect of the COVID-19 pandemics is inevitable, however, recent SARS-CoV-2 variants of concern, especially Omicron and its sub-lineages, efficiently evade humoral immunity mounted upon vaccination or previous infection. Thus, it is an important question whether these variants, or vaccines against them, induce anti-viral cellular immunity. Here we show that the mRNA vaccine BNT162b2 induces robust protective immunity in K18-hACE2 transgenic B-cell deficient (μMT) mice. We further demonstrate that the protection is attributed to cellular immunity depending on robust IFN-γ production. Viral challenge with SARS-CoV-2 Omicron BA.1 and BA.5.2 sub-variants induce boosted cellular responses in vaccinated μMT mice, which highlights the significance of cellular immunity against the ever-emerging SARS-CoV-2 variants evading antibody-mediated immunity. Our work, by providing evidence that BNT162b2 can induce significant protective immunity in mice that are unable to produce antibodies, thus highlights the importance of cellular immunity in the protection against SARS-CoV-2.
Discovery of senolytics using machine learning
Authors: Smer-Barreto Vanessa , Quintanilla Andrea , Elliott Richard J. R. , Dawson John C. , Sun Jiugeng , Campa Víctor M. , Lorente-Macías Álvaro , Unciti-Broceta Asier , Carragher Neil O. , Acosta Juan Carlos , Oyarzún Diego A.
Published: June 2023

Cellular senescence is a stress response involved in ageing and diverse disease processes including cancer, type-2 diabetes, osteoarthritis and viral infection. Despite growing interest in targeted elimination of senescent cells, only few senolytics are known due to the lack of well-characterised molecular targets. Here, we report the discovery of three senolytics using cost-effective machine learning algorithms trained solely on published data. We computationally screened various chemical libraries and validated the senolytic action of ginkgetin, periplocin and oleandrin in human cell lines under various modalities of senescence. The compounds have potency comparable to known senolytics, and we show that oleandrin has improved potency over its target as compared to best-in-class alternatives. Our approach led to several hundred-fold reduction in drug screening costs and demonstrates that artificial intelligence can take maximum advantage of small and heterogeneous drug screening data, paving the way for new open science approaches to early-stage drug discovery.
Analysis and modeling of cancer drug responses using cell cycle phase-specific rate effects
Authors: Gross Sean M. , Mohammadi Farnaz , Sanchez-Aguila Crystal , Zhan Paulina J. , Liby Tiera A. , Dane Mark A. , Meyer Aaron S. , Heiser Laura M.
Published: June 2023

Identifying effective therapeutic treatment strategies is a major challenge to improving outcomes for patients with breast cancer. To gain a comprehensive understanding of how clinically relevant anti-cancer agents modulate cell cycle progression, here we use genetically engineered breast cancer cell lines to track drug-induced changes in cell number and cell cycle phase to reveal drug-specific cell cycle effects that vary across time. We use a linear chain trick (LCT) computational model, which faithfully captures drug-induced dynamic responses, correctly infers drug effects, and reproduces influences on specific cell cycle phases. We use the LCT model to predict the effects of unseen drug combinations and confirm these in independent validation experiments. Our integrated experimental and modeling approach opens avenues to assess drug responses, predict effective drug combinations, and identify optimal drug sequencing strategies.
Scarless wound healing programmed by core-shell microneedles
Authors: Zhang Ying , Wang Shenqiang , Yang Yinxian , Zhao Sheng , You Jiahuan , Wang Junxia , Cai Jingwei , Wang Hao , Wang Jie , Zhang Wei , Yu Jicheng , Han Chunmao , Zhang Yuqi , Gu Zhen
Published: June 2023

Effective reprogramming of chronic wound healing remains challenging due to the limited drug delivery efficacy hindered by physiological barriers, as well as the inappropriate dosing timing in distinct healing stages. Herein, a core-shell structured microneedle array patch with programmed functions (PF-MNs) is designed to dynamically modulate the wound immune microenvironment according to the varied healing phases. Specifically, PF-MNs combat multidrug-resistant bacterial biofilm at the early stage via generating reactive oxygen species (ROS) under laser irradiation. Subsequently, the ROS-sensitive MN shell gradually degrades to expose the MN core component, which neutralizes various inflammatory factors and promotes the phase transition from inflammation to proliferation. In addition, the released verteporfin inhibits scar formation by blocking Engrailed-1 (En1) activation in fibroblasts. Our experiments demonstrate that PF-MNs promote scarless wound repair in mouse models of both acute and chronic wounds, and inhibit the formation of hypertrophic scar in rabbit ear models.
Revealing proteome-level functional redundancy in the human gut microbiome using ultra-deep metaproteomics
Authors: Li Leyuan , Wang Tong , Ning Zhibin , Zhang Xu , Butcher James , Serrana Joeselle M. , Simopoulos Caitlin M. A. , Mayne Janice , Stintzi Alain , Mack David R. , Liu Yang-Yu , Figeys Daniel
Published: June 2023

Functional redundancy is a key ecosystem property representing the fact that different taxa contribute to an ecosystem in similar ways through the expression of redundant functions. The redundancy of potential functions (or genome-level functional redundancy $${{{{{{\rm{FR}}}}}}}_{g}$$

FR

g

) of human microbiomes has been recently quantified using metagenomics data. Yet, the redundancy of expressed functions in the human microbiome has never been quantitatively explored. Here, we present an approach to quantify the proteome-level functional redundancy $${{{{{{\rm{FR}}}}}}}_{p}$$

FR

p

in the human gut microbiome using metaproteomics. Ultra-deep metaproteomics reveals high proteome-level functional redundancy and high nestedness in the human gut proteomic content networks (i.e., the bipartite graphs connecting taxa to functions). We find that the nested topology of proteomic content networks and relatively small functional distances between proteomes of certain pairs of taxa together contribute to high $${{{{{{\rm{FR}}}}}}}_{p}$$

FR

p

in the human gut microbiome. As a metric comprehensively incorporating the factors of presence/absence of each function, protein abundances of each function and biomass of each taxon, $${{{{{{\rm{FR}}}}}}}_{p}$$

FR

p

outcompetes diversity indices in detecting significant microbiome responses to environmental factors, including individuality, biogeography, xenobiotics, and disease. We show that gut inflammation and exposure to specific xenobiotics can significantly diminish the $${{{{{{\rm{FR}}}}}}}_{p}$$

FR

p

with no significant change in taxonomic diversity.
Impaired histone inheritance promotes tumor progression
Authors: Tian Congcong , Zhou Jiaqi , Li Xinran , Gao Yuan , Wen Qing , Kang Xing , Wang Nan , Yao Yuan , Jiang Jiuhang , Song Guibing , Zhang Tianjun , Hu Suili , Liao JingYi , Yu Chuanhe , Wang Zhiquan , Liu Xiangyu , Pei Xinhai , Chan Kuiming , Liu Zichuan , Gan Haiyun
Published: June 2023

Faithful inheritance of parental histones is essential to maintain epigenetic information and cellular identity during cell division. Parental histones are evenly deposited onto the replicating DNA of sister chromatids in a process dependent on the MCM2 subunit of DNA helicase. However, the impact of aberrant parental histone partition on human disease such as cancer is largely unknown. In this study, we construct a model of impaired histone inheritance by introducing MCM2-2A mutation (defective in parental histone binding) in MCF-7 breast cancer cells. The resulting impaired histone inheritance reprograms the histone modification landscapes of progeny cells, especially the repressive histone mark H3K27me3. Lower H3K27me3 levels derepress the expression of genes associated with development, cell proliferation, and epithelial to mesenchymal transition. These epigenetic changes confer fitness advantages to some newly emerged subclones and consequently promote tumor growth and metastasis after orthotopic implantation. In summary, our results indicate that impaired inheritance of parental histones can drive tumor progression.
Vection underwater illustrates the limitations of neutral buoyancy as a microgravity analog
Authors: Bury Nils-Alexander , Jenkin Michael , Allison Robert S. , Herpers Rainer , Harris Laurence R.
Published: June 2023

Neutral buoyancy has been used as an analog for microgravity from the earliest days of human spaceflight. Compared to other options on Earth, neutral buoyancy is relatively inexpensive and presents little danger to astronauts while simulating some aspects of microgravity. Neutral buoyancy removes somatosensory cues to the direction of gravity but leaves vestibular cues intact. Removal of both somatosensory and direction of gravity cues while floating in microgravity or using virtual reality to establish conflicts between them has been shown to affect the perception of distance traveled in response to visual motion (vection) and the perception of distance. Does removal of somatosensory cues alone by neutral buoyancy similarly impact these perceptions? During neutral buoyancy we found no significant difference in either perceived distance traveled nor perceived size relative to Earth-normal conditions. This contrasts with differences in linear vection reported between short- and long-duration microgravity and Earth-normal conditions. These results indicate that neutral buoyancy is not an effective analog for microgravity for these perceptual effects.
The one-step fabrication of porous hASC-laden GelMa constructs using a handheld printing system
Authors: Jo SeoYul , Lee JiUn , Lee Hyeongjin , Ryu Dongryeol , Kim GeunHyung
Published: June 2023

The fabrication of highly porous cell-loaded structures in tissue engineering applications has been a challenging issue because non-porous cell-laden struts can cause severe cell necrosis in the middle region owing to poor transport of nutrients and oxygen. In this study, we propose a versatile handheld 3D printer for the effective fabrication of porous cell-laden methacrylated gelatin (GelMa) with high porosity (≈97%) by air injection and a bubble-making system using mesh filters through which a mixture of air/GelMa bioink is passed. In particular, the pore size and foamability of the cell constructs could be manipulated using various processing parameters (rheological properties of GelMa, filter size and number, and air-bioink volume ratio). To demonstrate the feasibility of the cell construct as a tissue engineering substitute for muscle regeneration, in vitro cellular activities and in vivo regeneration ability of human adipose stem cells were assessed. The in vitro results demonstrated that the human adipose stem cells (hASCs) fabricated using the handheld 3D printer were alive and well-proliferated. Furthermore, the in vivo results showed that the hASCs-constructs directly printed from the handheld 3D printer showed significant restoration of functionality and efficient muscle regeneration in the volumetric muscle loss model of mice. Based on these results, the fabrication method of the porous cell-laden construct could be a promising tool for regenerating muscle tissues.
Transcriptom and miRNA data of PUFA-enriched stimulated murine macrophage and human endothelial cell lines
Authors: Roessler Claudia , Schumann Julia
Published: June 2023

Inflammation is associated with the adaptation of macrophages and endothelial cells, and the dysregulation of these differentiation processes has been directly linked to both acute and chronic disease states. As cells in constant contact with blood, macrophages and endothelial cells are also under the direct influence of immunomodulatory dietary components such as polyunsaturated fatty acids (PUFA). RNA sequencing analyses allow us to understand the global changes in gene expression occurring during cell differentiation, including both transcriptional (transcriptome) and post-transcriptional (miRNAs) levels. We generated a comprehensive RNA sequencing dataset of parallel transcriptome and miRNA profiles of PUFA-enriched and pro-inflammatory stimulated macrophages and endothelial cells aiming to uncover the underlying molecular mechanisms. PUFA concentrations and duration of supplementation were based on dietary ranges, allowing for metabolism and plasma membrane uptake of fatty acids. The dataset may serve as a resource to study transcriptional and post-transcriptional changes associated with macrophage polarisation and endothelial dysfunction in inflammatory settings and their modulation by omega-3 and omega-6 fatty acids.
Racial and ethnic difference in the risk of fractures in the United States: a systematic review and meta-analysis
Authors: Bao Yueyang , Xu Yingke , Li Zhuowei , Wu Qing
Published: June 2023

This systematic review and meta-analysis examined the association between race and ethnicity and fracture risk in the United States. We identified relevant studies by searching PubMed and EMBASE for studies published from the databases’ inception date to December 23, 2022. Only observational studies conducted in the US population that reported the effect size of racial-ethnic minority groups versus white people were included. Two investigators independently conducted literature searches, study selection, risk of bias assessment, and data abstraction; discrepancies were resolved by consensus or consultation of a third investigator. Twenty-five studies met the inclusion criteria, and the random-effects model was used to calculate the pooled effect size due to heterogeneity between the studies. Using white people as the reference group, we found that people of other races and ethnic groups had a significantly lower fracture risk. In Black people, the pooled relative risk (RR) was 0.46 (95% confidence interval (CI), 0.43–0.48, p < 0.0001). In Hispanics, the pooled RR was 0.66 (95% CI, 0.55–0.79, p < 0.0001). In Asian Americans, the pooled RR was 0.55 (95% CI, 0.45–0.66, p < 0.0001). In American Indians, the pooled RR was 0.80 (95% CI, 0.41–1.58, p = 0.3436). Subgroup analysis by sex in Black people revealed the strength of association was greater in men (RR = 0.57, 95% CI = 0.51–0.63, p < 0.0001) than in women (RR = 0.43, 95% CI = 0.39–0.47, p < 0.0001). Our findings suggest that people of other races and ethnic groups have a lower fracture risk than white people.
Maternal exposure to benzophenone derivatives and their impacts on offspring's birth outcomes in a Middle Eastern population
Authors: Teiri Hakimeh , Samaei Mohammad Reza , Dehghani Mansooreh , Azhdarpoor Abooalfazl , Mohammadi Farzaneh , Kelishadi Roya , Hajizadeh Yaghoub
Published: June 2023

Widespread use of benzophenones (BPs), a group of environmental phenolic compounds, is suspected of interfering with human health. The association of prenatal exposure to benzophenone derivatives with birth outcomes including birth weight and length, head, arm and thoracic circumference, abnormalities, corpulence index and anterior fontanelle diameter (AFD) was investigated. Mother-infant pairs of 166 within PERSIAN cohort population in Isfahan, Iran, in the 1st and 3rd trimesters of pregnancy were assessed. Four common benzophenone metabolites including 2,4-dihydroxy benzophenone (BP-1), 2-hydroxy-4-methoxy benzophenone (BP-3), 4-hydroxy benzophenone (4-OH-BP) and 2,2′-dihydroxy-4-methoxy benzophenone (BP-8) were measured in maternal urine samples. The median concentration of 4-OH-BP, BP-3, BP-1 and BP-8 were 3.15, 16.98, 9.95 and 1.04 µg/g Cr, respectively. In the 1st trimester, 4-OH-BP showed a significant correlation with AFD in total infants, decreasing 0.034 cm AFD per a log unit increase of 4-OH-BP. Within the male neonates, 4-OH-BP in the 1st and BP-8 in the 3rd trimester were significantly associated with head circumference and AFD increase, respectively. Among female neonates in the 3rd trimester, increasing 4-OH-BP and BP-3 concentration was correlated with a decrease in birth weight and AFD, respectively. This study demonstrated that all the target BP derivatives can influence normal fetal growth at any age of the pregnancy, nevertheless, to support these findings further studies are needed in a large and different group population.
Synthesis of new hybrid pyridines catalyzed by Fe3O4@SiO2@urea-riched ligand/Ch-Cl
Authors: Zarei Narges , Zolfigol Mohammad Ali , Torabi Morteza , Yarie Meysam
Published: June 2023

Herein, a new heterogeneous catalytic system through modification of urea functionalized magnetic nanoparticles with choline chloride [Fe3O4@SiO2@urea-riched ligand/Ch-Cl] was designed and synthesized. Then, the synthesized Fe3O4@SiO2@urea-riched ligand/Ch-Cl was characterized by using FT-IR spectroscopy, FESEM, TEM, EDS-Mapping, TGA/DTG and VSM techniques. After that, the catalytic usage of Fe3O4@SiO2@urea-riched ligand/Ch-Cl was investigated for the synthesis of hybrid pyridines with sulfonate and/or indole moieties. Delightfully, the outcome was satisfactory and the applied strategy represents several advantages such as short reaction times, convenience of operation and relatively good yields of obtained products. Moreover, the catalytic behavior of several formal homogeneous DESs was investigated for the synthesis of target product. In addition, a cooperative vinylogous anomeric-based oxidation pathway was suggested as rational mechanism for the synthesis of new hybrid pyridines.
A single-center experience of over 300 cases of single-incision robotic cholecystectomy comparing the da Vinci SP with the Si/Xi systems
Authors: Choi Yoo Jin , Sang Nguyen Thanh , Jo Hye-Sung , Kim Dong-Sik , Yu Young-Dong
Published: June 2023

Minimally invasive surgery is usually more beneficial than open surgeries in various fields of surgery. With the newly developed Single-Port (SP) robotic surgical system, even single-site surgery has become easier to access. We compared single-incision robotic cholecystectomy between the Si/Xi and SP systems. This retrospective single-center study enrolled patients who underwent single-incision robotic cholecystectomy between July 2014 and July 2021. The clinical outcomes of the da Vinci Si/Xi and SP systems were compared. In total, 334 patients underwent single-incision robotic cholecystectomy (118 Si/Xi vs. 216 SP). The SP group had more chronic or acute cholecystitis than the Si/Xi group did. There was more bile spillage in the Si/Xi group during the surgery. The total operative and docking times were significantly shorter in the SP group. There was no difference in the postoperative outcomes. The SP system is safe and feasible regarding comparable postoperative complication rates and is more convenient regarding docking and techniques.
Flow rate resonance of actively deforming particles
Authors: Parisi Daniel R. , Wiebke Lucas E. , Mandl Judith N. , Textor Johannes
Published: June 2023

Lymphoid organs are unusual multicellular tissues: they are densely packed, but the lymphocytes trafficking through them are actively moving. We hypothesize that the intriguing ability of lymphocytes to avoid jamming and clogging is in part attributable to the dynamic shape changes that cells undergo when they move. In this work, we test this hypothesis by investigating an idealized system, namely, the flow of self-propelled, oscillating particles passing through a narrow constriction in two dimensions (2D), using numerical simulations. We found that deformation allows particles with these properties to flow through a narrow constriction in conditions when non-deformable particles would not be able to do so. Such a flowing state requires the amplitude and frequency of oscillations to exceed threshold values. Moreover, a resonance leading to the maximum flow rate was found when the oscillation frequency matched the natural frequency of the particle related to its elastic stiffness. To our knowledge, this phenomenon has not been described previously. Our findings could have important implications for understanding and controlling flow in a variety of systems in addition to lymphoid organs, such as granular flows subjected to vibration.
Fuzzy random evaluation of creep model of frozen soft soil in metro tunnel construction using artificial ground freezing technique
Authors: Yao Yafeng , Zhu Yan , Shen Dejian , Zhang Zhemei , Wang Wei
Published: June 2023

Mastering the creep characteristics of artificial frozen soil and scientifically evaluating the creep model is an important guarantee for the safety of subway tunnel freezing construction. Base on the construction of Nantong metro tunnel, the uniaxial compressive strength tests of the artificially frozen soft soil were carried out to obtain the influence law of temperature on the uniaxial compressive strength, and the uniaxial creep tests were carried out to obtain the influence law of temperature and stress grade on creep, at − 5, − 10 and − 15 °C. The experimental results show that the creep characteristics of frozen soft soil specimens have obvious fuzzy randomness. The traditional ant colony algorithm is improved by optimizing the pheromone fuzzification coefficient, which improves the search efficiency and avoids the local optimum effectively. Subsequently, the improved fuzzy ant colony algorithm is used to invert the flexibility parameters of commonly used permafrost creep models. The fuzzy weight of evaluation index and the fuzzy random evaluation matrix were determined to evaluate the optimal creep model under three different stress levels of frozen soft soil. Finally, the reliability of the fuzzy random evaluation method was verified by engineering measured data.