bluuebunny/crossref_metadata_2025 huggingface dataset:
Africa and the Domestic Implementation of the Geneva Conventions and Additional Protocols: Problems and Solutions
Authors: Balarabe Kasim
Published: April 2022

The Geneva Conventions have achieved universal ratification, and Additional Protocols I and II are binding on all African states except Eritrea and Somalia; however, their observance in African conflicts is flawed and inconsistent. From deliberate attacks on civilian populations to abduction and hostage-taking, humanitarian rules are openly flouted. Through an extensive assessment of the domestic measures required to implement the Geneva Conventions and Protocols in Africa, this article identifies the current level of implementation, existing gaps and possible non-legal factors that impact respect for the instruments in African conflicts. Violations are often associated with historical, political, religious and social factors that tainted the instruments’ lofty provisions and bequeathed a legacy that challenges the obligation to respect. Additionally, continuous political and religious struggles and the search for identity and relevance have displaced the ideals of the instruments’ humanitarian provisions. Reversing this trend requires an approach that appeals to and engages the continent beyond the traditional argument of obligation to respect.
Effectiveness of screened ceilings over the current best practice in reducing malaria prevalence in western Kenya: a cluster randomized-controlled trial
Authors: Minakawa Noboru , Kawada Hitoshi , Kongere James O. , Sonye George O. , Lutiali Peter A. , Awuor Beatrice , Isozumi Rie , Futami Kyoko
Published: April 2022

Increases in bed net coverage and antimalarial treatment have reduced the risk of malaria in sub-Saharan Africa. However, the pace of reduction has slowed, and new tools are needed to reverse this trend. We evaluated houses screened with insecticide-treated ceiling nets using a cluster randomized-controlled trial in western Kenya. The primary endpoints were Plasmodium falciparum PCR-positive prevalence (PCRPfPR) of children from 7 months to 10 years old and anopheline density. Ceiling nets and bed nets were provided to 1073 houses, and 1162 houses were provided with bed nets only. The treatment and control arms each had four clusters. We conducted three epidemiological and entomological post-intervention surveys over the course of a year and a half. Each epidemiological survey targeted 150 children per cluster, and entomological surveys targeted 25 houses. When the three surveys were combined, the median PCRPfPRs were 23% (IQR 8%) in the intervention arm and 42% (IQR 12%) in the control arm. The adjusted risk ratio (RR) was 0.53 [95% confidence interval (CI) 0.41–0.71; P = 0.029]. The median anopheline densities were 0.4 (IQR 0.4) and 2.0 (IQR 1.4), respectively. The adjusted RR was 0.41 (95% CI 0.29–0.90; P = 0.029). The present study indicates additional protection from insecticide-screened ceilings over the current best practice.
Respiratory viral infections are prevalent but uncomplicated in single ventricle CHD
Authors: Calley Brandon J. , Zhang Liyun , Pan Amy Y. , Ginde Salil , Kindel Steven J. , Spearman Andrew D.
Published: April 2022

Background:

Patients with single ventricle CHD have significant morbidity and healthcare utilisation throughout their lifetime, including non-cardiac hospital admissions. Respiratory viral infections are the main cause of hospitalisation in children, but few data exist for single ventricle patients. We sought to identify how respiratory viral infections impact patients with single ventricle CHD and potential differences between Glenn and Fontan circulation.

Methods:

We conducted a retrospective study of patients seen from 01/01/2011–12/31/2020. We identified patients with a history of single ventricle CHD and Glenn palliation, and a normoxic control group with isolated atrial septal defect requiring surgical closure. We compared viral-related clinical presentations, admissions, and admission characteristics.

Results:

A total of 312 patients were included (182 single ventricle, 130 atrial septal defect). Single ventricle patients were more likely than children with isolated atrial septal defect to be admitted with a respiratory virus (odds ratio 4.15 [2.30–7.46]), but there was no difference in mechanical ventilation or hospital length of stay (p = 0.4709). Single ventricle patients with Glenn circulation were more likely than those with Fontan circulation to present and be admitted (odds ratio 3.25 [1.62–6.52]), but there was no difference in ICU admission, mechanical ventilation, or hospital length of stay (p = 0.1516).

Conclusions:

Respiratory viral infections are prevalent but uncomplicated in patients with single ventricle CHD. Viral-related presentations and admissions are more prevalent during the period of Glenn circulation compared to Fontan circulation; however, rate of mechanical ventilation and hospital length of stay are similar.
Morphometric Analysis of Lysosomes in the Renal Tubule in Monoclonal Gammopathy Using Transmission Electron Microscopy: “Mottled Appearance” and Beyond
Authors: Jung Minsun , Lee Hajeong , Moon Kyung Chul
Published: April 2022

Lysosomal “mottled appearance”, or uneven electron-dense content related to monoclonal gammopathy (MG), has been mainly described in light chain proximal tubulopathy (LCPT). We aimed to determine the ultrastructural characteristics of lysosomal mottled appearance in kidney biopsies and its association with LCPT and MG. Seventy-seven biopsies were grouped into LCPT (n = 5), MG conditions other than LCPT (n = 43), and non-MG conditions (n = 29). The mottled lysosomes in the renal tubules were evaluated using transmission electron microscopy and morphometric analysis. Mottled lysosomes were more prevalent (% of present cases) and frequent (no. of mottled lysosomes/20,000× ultramicroscopic field) in the LCPT group (100% and 8.20 ± 4.15/field) than in the MG (41.9% and 1.13 ± 2.05/field) and non-MG (37.9% and 0.80 ± 1.44/field) groups. In morphometric analysis of all mottled lysosomes (n = 520) detected from the 34 biopsies (5 LCPT, 18 MG, and 11 non-MG), we found that mottled lysosomes were larger, more irregular, and more electron-dense for the LCPT group than for the MG and non-MG groups. Therefore, mottled lysosomes can be present in disorders other than LCPT or even without MG. The morphological characteristics of mottled lysosomes could provide objective guidance for the diagnosis of LCPT.
Solar Flux Dependence of Post‐Sunset Enhancement in Vertical Total Electron Content Over the Crest Region of Equatorial Ionization Anomaly
Authors: Kumar A. , Chakrabarty D. , Pandey K. , Yadav A. K.
Published: April 2022

Based on 10 years' of vertical total electron content (VTEC) data in solar cycle 24 from Ahmedabad (23.0°N, 72.6°E, dip angle 35.2°), a station under the crest region of equatorial ionization anomaly (EIA), it is shown that both the integrated residual and total post‐sunset enhancements in VTEC are conspicuous during Equinox and December solstice when solar flux level exceeds 110 solar flux unit (sfu) with the exception of the year 2012–2013. The post‐sunset enhancements are absent in June solstice at this local time even if the solar flux level exceeds 110 sfu. The integrated residual and total VTEC enhancements during post‐sunset hours are found to be linearly correlated with the solar flux level in Equinox and December solstice. It is noted that a parabolic fit works better for the integrated total VTEC enhancement during December solstice suggesting a possible saturation of VTEC enhancements at high solar flux levels. Based on these observations and Thermosphere Ionosphere Electrodynamics‐General circulation model (TIE‐GCM) outputs, it is argued that the pre‐reversal enhancement (PRE) in the equatorial F region zonal electric field works in tandem with latitudinal gradient in the F region plasma density to determine the degree of VTEC enhancement over the EIA crest region during post‐sunset hours. These results highlight the solar flux dependence of the post‐sunset enhancement of VTEC over the crest region and show that sudden stratospheric warming events in 2012–2013 suppressed these enhancements in December solstice even if solar flux levels exceeded 110 sfu.
MFG-E8 alleviates intervertebral disc degeneration by suppressing pyroptosis and extracellular matrix degradation in nucleus pulposus cells via Nrf2/TXNIP/NLRP3 axis
Authors: Ma Haiwei , Xie Chenglong , Chen Zhengtai , He Gaolu , Dai Zihan , Cai Hanchen , Zhang Haojie , Lu Hongwei , Wu Hongqiang , Hu Xinli , Zhou Kailiang , Zheng Gang , Xu Huazi , Xu Cong
Published: April 2022

Intervertebral disc degeneration (IVDD) is a chronic age-related degenerative disease accompanied by complex pathophysiological mechanisms. Increasing evidence indicates that NLRP3 inflammasome mediated pyroptosis of nucleus pulposus (NP) cells displays an important role in the pathological progression of IVDD. Milk fat globule-EGF factor-8 (MFG-E8) is an endogenously secreted glycoprotein with beneficial effects of anti-inflammatory, antioxidant, and modulation of NLRP3 inflammasome. However, the effect of MFG-E8 on IVDD remains unclear. In this study, our purpose is to clarify the expression changes of MFG-E8 in the IVDD process and explore the role and mechanism of MFG-E8. We found that MFG-E8’s expression was reduced in degraded nucleus pulposus tissues of humans and rats as well as hydrogen peroxide (H2O2)-treated NP cells. Exogenous supplementation of MFG-E8 could rescue H2O2-induced oxidative stress, mitochondrial dysfunction, and NLRP3 inflammasome activation and protect NP cells from pyroptosis and extracellular matrix (ECM) degradation. Mechanistically, Nrf2/TXNIP/NLRP3 axis plays a crucial role in MFG-E8-mediated suppression of the above-pathological events. In vivo, we established a rat intervertebral disc acupuncture model and found that MFG-E8 administration effectively alleviated IVDD development by imageological and histomorphological evaluation. Overall, our findings revealed the internal mechanisms underlying MFG-E8 regulation in NP cells and its intrinsic value for IVDD therapy.
Cell-in-cell structure mediates in-cell killing suppressed by CD44
Authors: Su Yan , Huang Hongyan , Luo Tianzhi , Zheng You , Fan Jie , Ren He , Tang Meng , Niu Zubiao , Wang Chenxi , Wang Yuqi , Zhang Zhengrong , Liang Jianqing , Ruan Banzhan , Gao Lihua , Chen Zhaolie , Melino Gerry , Wang Xiaoning , Sun Qiang
Published: April 2022

Penetration of immune cells into tumor cells was believed to be immune-suppressive via cell-in-cell (CIC) mediated death of the internalized immune cells. We unexpectedly found that CIC formation largely led to the death of the host tumor cells, but not the internalized immune cells, manifesting typical features of death executed by NK cells; we named this “in-cell killing” which displays the efficacy superior to the canonical way of “kiss-killing” from outside. By profiling isogenic cells, CD44 on tumor cells was identified as a negative regulator of “in-cell killing” via inhibiting CIC formation. CD44 functions to antagonize NK cell internalization by reducing N-cadherin-mediated intercellular adhesion and by enhancing Rho GTPase-regulated cellular stiffness as well. Remarkably, antibody-mediated blockade of CD44 signaling potentiated the suppressive effects of NK cells on tumor growth associated with increased heterotypic CIC formation. Together, we identified CIC-mediated “in-cell killing” as a promising strategy for cancer immunotherapy.
A Maluku Sea intermediate western boundary current connecting Pacific Ocean circulation to the Indonesian Throughflow
Authors: Yuan Dongliang , Yin Xueli , Li Xiang , Corvianawatie Corry , Wang Zheng , Li Yao , Yang Ya , Hu Xiaoyue , Wang Jing , Tan Shuwen , Surinati Dewi , Purwandana Adi , Wardana Adhitya Kusuma , Ismail Mochamad Furqon Azis , Budiman Asep Sandra , Bayhaqi Ahmad , Avianto Praditya , Santoso Priyadi Dwi , Kusmanto Edi , Dirhamsyah  , Arifin Zainal , Pratt Larry J.
Published: April 2022

The Indonesian Throughflow plays an important role in the global ocean circulation and climate. Existing studies of the Indonesian Throughflow have focused on the Makassar Strait and the exit straits, where the upper thermocline currents carry North Pacific waters to the Indian Ocean. Here we show, using mooring observations, that a previous unknown intermediate western boundary current (with the core at ~1000 m depth) exists in the Maluku Sea, which transports intermediate waters (primarily the Antarctic Intermediate Water) from the Pacific into the Seram-Banda Seas through the Lifamatola Passage above the bottom overflow. Our results suggest the importance of the western boundary current in global ocean intermediate circulation and overturn. We anticipate that our study is the beginning of more extensive investigations of the intermediate circulation of the Indo-Pacific ocean in global overturn, which shall improve our understanding of ocean heat and CO2storages significantly.
Extreme rainstorms drive exceptional organic carbon export from forested humid-tropical rivers in Puerto Rico
Authors: Clark K. E. , Stallard R. F. , Murphy S. F. , Scholl M. A. , González G. , Plante A. F. , McDowell W. H.
Published: April 2022

Extreme rainfall events in the humid-tropical Luquillo Mountains, Puerto Rico export the bulk of suspended sediment and particulate organic carbon. Using 25 years of river carbon and suspended sediment data, which targeted hurricanes and other large rainstorms, we estimated biogenic particulate organic carbon yields of 65 ± 16 tC km−2 yr−1 for the Icacos and 17.7 ± 5.1 tC km−2 yr−1 for the Mameyes rivers. These granitic and volcaniclastic catchments function as substantial atmospheric carbon-dioxide sinks, largely through export of river biogenic particulate organic carbon during extreme rainstorms. Compared to other regions, these high biogenic particulate organic carbon yields are accompanied by lower suspended sediment yields. Accordingly, particulate organic carbon export from these catchments is underpredicted by previous yield relationships, which are derived mainly from catchments with easily erodible sedimentary rocks. Therefore, rivers that drain petrogenic-carbon-poor bedrock require separate accounting to estimate their contributions to the geological carbon cycle.
Field-based tree mortality constraint reduces estimates of model-projected forest carbon sinks
Authors: Yu Kailiang , Ciais Philippe , Seneviratne Sonia I. , Liu Zhihua , Chen Han Y. H. , Barichivich Jonathan , Allen Craig D. , Yang Hui , Huang Yuanyuan , Ballantyne Ashley P.
Published: April 2022

Considerable uncertainty and debate exist in projecting the future capacity of forests to sequester atmospheric CO2. Here we estimate spatially explicit patterns of biomass loss by tree mortality (LOSS) from largely unmanaged forest plots to constrain projected (2015–2099) net primary productivity (NPP), heterotrophic respiration (HR) and net carbon sink in six dynamic global vegetation models (DGVMs) across continents. This approach relies on a strong relationship among LOSS, NPP, and HR at continental or biome scales. The DGVMs overestimated historical LOSS, particularly in tropical regions and eastern North America by as much as 5 Mg ha−1 y−1. The modeled spread of DGVM-projected NPP and HR uncertainties was substantially reduced in tropical regions after incorporating the field-based mortality constraint. The observation-constrained models show a decrease in the tropical forest carbon sink by the end of the century, particularly across South America (from 2 to 1.4 PgC y−1), and an increase in the sink in North America (from 0.8 to 1.1 PgC y−1). These results highlight the feasibility of using forest demographic data to empirically constrain forest carbon sink projections and the potential overestimation of projected tropical forest carbon sinks.
An intermetallic molecular nanomagnet with the lanthanide coordinated only by transition metals
Authors: Magott Michał , Brzozowska Maria , Baran Stanisław , Vieru Veacheslav , Pinkowicz Dawid
Published: April 2022

Magnetic molecules known as molecular nanomagnets (MNMs) may be the key to ultra-high density data storage. Thus, novel strategies on how to design MNMs are desirable. Here, inspired by the hexagonal structure of the hardest intermetallic magnet SmCo5, we have synthesized a nanomagnetic molecule where the central lanthanide (Ln) ErIII is coordinated solely by three transition metal ions (TM) in a perfectly trigonal planar fashion. This intermetallic molecule [ErIII(ReICp2)3] (ErRe3) starts a family of molecular nanomagnets (MNM) with unsupported Ln-TM bonds and paves the way towards molecular intermetallics with strong direct magnetic exchange interactions—a promising route towards high-performance single-molecule magnets.
Antiphased dust deposition and productivity in the Antarctic Zone over 1.5 million years
Authors: Weber Michael E. , Bailey Ian , Hemming Sidney R. , Martos Yasmina M. , Reilly Brendan T. , Ronge Thomas A. , Brachfeld Stefanie , Williams Trevor , Raymo Maureen , Belt Simon T. , Smik Lukas , Vogel Hendrik , Peck Victoria L. , Armbrecht Linda , Cage Alix , Cardillo Fabricio G. , Du Zhiheng , Fauth Gerson , Fogwill Christopher J. , Garcia Marga , Garnsworthy Marlo , Glüder Anna , Guitard Michelle , Gutjahr Marcus , Hernández-Almeida Iván , Hoem Frida S. , Hwang Ji-Hwan , Iizuka Mutsumi , Kato Yuji , Kenlee Bridget , OConnell Suzanne , Pérez Lara F. , Seki Osamu , Stevens Lee , Tauxe Lisa , Tripathi Shubham , Warnock Jonathan , Zheng Xufeng
Published: April 2022

The Southern Ocean paleoceanography provides key insights into how iron fertilization and oceanic productivity developed through Pleistocene ice-ages and their role in influencing the carbon cycle. We report a high-resolution record of dust deposition and ocean productivity for the Antarctic Zone, close to the main dust source, Patagonia. Our deep-ocean records cover the last 1.5 Ma, thus doubling that from Antarctic ice-cores. We find a 5 to 15-fold increase in dust deposition during glacials and a 2 to 5-fold increase in biogenic silica deposition, reflecting higher ocean productivity during interglacials. This antiphasing persisted throughout the last 25 glacial cycles. Dust deposition became more pronounced across the Mid-Pleistocene Transition (MPT) in the Southern Hemisphere, with an abrupt shift suggesting more severe glaciations since ~0.9 Ma. Productivity was intermediate pre-MPT, lowest during the MPT and highest since 0.4 Ma. Generally, glacials experienced extended sea-ice cover, reduced bottom-water export and Weddell Gyre dynamics, which helped lower atmospheric CO2 levels.
Intracavity Raman scattering couples soliton molecules with terahertz phonons
Authors: Völkel Alexandra , Nimmesgern Luca , Mielnik-Pyszczorski Adam , Wirth Timo , Herink Georg
Published: April 2022

Ultrafast atomic vibrations mediate heat transport, serve as fingerprints for chemical bonds and drive phase transitions in condensed matter systems. Light pulses shorter than the atomic oscillation period can not only probe, but even stimulate and control collective excitations. In general, such interactions are performed with free-propagating pulses. Here, we demonstrate intra-cavity excitation and time-domain sampling of coherent optical phonons inside an active laser oscillator. Employing real-time spectral interferometry, we reveal that Terahertz beats of Raman-active optical phonons are the origin of soliton bound-states – also termed “Soliton molecules” – and we resolve a coherent coupling mechanism of phonon and intra-cavity soliton motion. Concurring electronic and nuclear refractive nonlinearities generate distinct soliton trajectories and, effectively, enhance the time-domain Raman signal. We utilize the intrinsic soliton motion to automatically perform highspeed Raman spectroscopy of the intra-cavity crystal. Our results pinpoint the impact of Raman-induced soliton interactions in crystalline laser media and microresonators, and offer unique perspectives toward ultrafast nonlinear phononics by exploiting the coupling of atomic motion and solitons inside a cavity.
Chiral photochemistry of achiral molecules
Authors: Raucci Umberto , Weir Hayley , Bannwarth Christoph , Sanchez David M. , Martínez Todd J.
Published: April 2022

Chirality is a molecular property governed by the topography of the potential energy surface (PES). Thermally achiral molecules interconvert rapidly when the interconversion barrier between the two enantiomers is comparable to or lower than the thermal energy, in contrast to thermally stable chiral configurations. In principle, a change in the PES topography on the excited electronic state may diminish interconversion, leading to electronically prochiral molecules that can be converted from achiral to chiral by electronic excitation. Here we report that this is the case for two prototypical examples – cis-stilbene and cis-stiff stilbene. Both systems exhibit unidirectional photoisomerization for each enantiomer as a result of their electronic prochirality. We simulate an experiment to demonstrate this effect in cis-stilbene based on its interaction with circularly polarized light. Our results highlight the drastic change in chiral behavior upon electronic excitation, opening up the possibility for asymmetric photochemistry from an effectively nonchiral starting point.
Genomic distances reveal relationships of wild and cultivated beets
Authors: Sandell Felix L. , Stralis-Pavese Nancy , McGrath J. Mitchell , Schulz Britta , Himmelbauer Heinz , Dohm Juliane C.
Published: April 2022

Cultivated beets (Beta vulgaris ssp. vulgaris), including sugar beet, rank among the most important crops. The wild ancestor of beet crops is the sea beet Beta vulgaris ssp. maritima. Species and subspecies of wild beets are readily crossable with cultivated beets and are thus available for crop improvement. To study genomic relationships in the genus Beta, we sequence and analyse 606 beet genomes, encompassing sugar beet, sea beet, B. v. adanensis, B. macrocarpa, and B. patula. We observe two genetically distinct groups of sea beets, one from the Atlantic coast and the other from the Mediterranean area. Genomic comparisons based on k-mers identify sea beets from Greece as the closest wild relatives of sugar beet, suggesting that domestication of the ancestors of sugar beet may be traced to this area. Our work provides comprehensive insight into the phylogeny of wild and cultivated beets and establishes a framework for classification of further accessions of unknown (sub-)species assignment.
Structural insights into the peptide selectivity and activation of human neuromedin U receptors
Authors: You Chongzhao , Zhang Yumu , Xu Peiyu , Huang Sijie , Yin Wanchao , Eric Xu H. , Jiang Yi
Published: April 2022

Neuromedin U receptors (NMURs), including NMUR1 and NMUR2, are a group of Gq/11-coupled G protein-coupled receptors (GPCRs). NMUR1 and NMUR2 play distinct, pleiotropic physiological functions in peripheral tissues and in the central nervous system (CNS), respectively, according to their distinct tissue distributions. These receptors are stimulated by two endogenous neuropeptides, neuromedin U and S (NMU and NMS) with similar binding affinities. NMURs have gathered attention as potential drug targets for obesity and inflammatory disorders. Specifically, selective agonists for NMUR2 in peripheral tissue show promising long-term anti-obesity effects with fewer CNS-related side effects. However, the mechanisms of peptide binding specificity and receptor activation remain elusive. Here, we report four cryo-electron microscopy structures of Gq chimera-coupled NMUR1 and NMUR2 in complexes with NMU and NMS. These structures reveal the conserved overall peptide-binding mode and the mechanism of peptide selectivity for specific NMURs, as well as the common activation mechanism of the NMUR subfamily. Together, these findings provide insights into the molecular basis of the peptide recognition and offer an opportunity for the design of the selective drugs targeting NMURs.
Mapping the energy level alignment at donor/acceptor interfaces in non-fullerene organic solar cells
Authors: Li Xian’e , Zhang Qilun , Yu Jianwei , Xu Ye , Zhang Rui , Wang Chuanfei , Zhang Huotian , Fabiano Simone , Liu Xianjie , Hou Jianhui , Gao Feng , Fahlman Mats
Published: April 2022

Energy level alignment (ELA) at donor (D) -acceptor (A) heterojunctions is essential for understanding the charge generation and recombination process in organic photovoltaic devices. However, the ELA at the D-A interfaces is largely underdetermined, resulting in debates on the fundamental operating mechanisms of high-efficiency non-fullerene organic solar cells. Here, we systematically investigate ELA and its depth-dependent variation of a range of donor/non-fullerene-acceptor interfaces by fabricating and characterizing D-A quasi bilayers and planar bilayers. In contrast to previous assumptions, we observe significant vacuum level (VL) shifts existing at the D-A interfaces, which are demonstrated to be abrupt, extending over only 1–2 layers at the heterojunctions, and are attributed to interface dipoles induced by D-A electrostatic potential differences. The VL shifts result in reduced interfacial energetic offsets and increased charge transfer (CT) state energies which reconcile the conflicting observations of large energy level offsets inferred from neat films and large CT energies of donor - non-fullerene-acceptor systems.
Distinct and additive effects of calorie restriction and rapamycin in aging skeletal muscle
Authors: Ham Daniel J. , Börsch Anastasiya , Chojnowska Kathrin , Lin Shuo , Leuchtmann Aurel B. , Ham Alexander S. , Thürkauf Marco , Delezie Julien , Furrer Regula , Burri Dominik , Sinnreich Michael , Handschin Christoph , Tintignac Lionel A. , Zavolan Mihaela , Mittal Nitish , Rüegg Markus A.
Published: April 2022

Preserving skeletal muscle function is essential to maintain life quality at high age. Calorie restriction (CR) potently extends health and lifespan, but is largely unachievable in humans, making “CR mimetics” of great interest. CR targets nutrient-sensing pathways centering on mTORC1. The mTORC1 inhibitor, rapamycin, is considered a potential CR mimetic and is proven to counteract age-related muscle loss. Therefore, we tested whether rapamycin acts via similar mechanisms as CR to slow muscle aging. Here we show that long-term CR and rapamycin unexpectedly display distinct gene expression profiles in geriatric mouse skeletal muscle, despite both benefiting aging muscles. Furthermore, CR improves muscle integrity in mice with nutrient-insensitive, sustained muscle mTORC1 activity and rapamycin provides additive benefits to CR in naturally aging mouse muscles. We conclude that rapamycin and CR exert distinct, compounding effects in aging skeletal muscle, thus opening the possibility of parallel interventions to counteract muscle aging.
TNF is a potential therapeutic target to suppress prostatic inflammation and hyperplasia in autoimmune disease
Authors: Vickman Renee E. , Aaron-Brooks LaTayia , Zhang Renyuan , Lanman Nadia A. , Lapin Brittany , Gil Victoria , Greenberg Max , Sasaki Takeshi , Cresswell Gregory M. , Broman Meaghan M. , Paez J. Sebastian , Petkewicz Jacqueline , Talaty Pooja , Helfand Brian T. , Glaser Alexander P. , Wang Chi-Hsiung , Franco Omar E. , Ratliff Timothy L. , Nastiuk Kent L. , Crawford Susan E. , Hayward Simon W.
Published: April 2022

Autoimmune (AI) diseases can affect many organs; however, the prostate has not been considered to be a primary target of these systemic inflammatory processes. Here, we utilize medical record data, patient samples, and in vivo models to evaluate the impact of inflammation, as seen in AI diseases, on prostate tissue. Human and mouse tissues are used to examine whether systemic targeting of inflammation limits prostatic inflammation and hyperplasia. Evaluation of 112,152 medical records indicates that benign prostatic hyperplasia (BPH) prevalence is significantly higher among patients with AI diseases. Furthermore, treating these patients with tumor necrosis factor (TNF)-antagonists significantly decreases BPH incidence. Single-cell RNA-seq and in vitro assays suggest that macrophage-derived TNF stimulates BPH-derived fibroblast proliferation. TNF blockade significantly reduces epithelial hyperplasia, NFκB activation, and macrophage-mediated inflammation within prostate tissues. Together, these studies show that patients with AI diseases have a heightened susceptibility to BPH and that reducing inflammation with a therapeutic agent can suppress BPH.
Cooperative interaction between ERα and the EMT-inducer ZEB1 reprograms breast cancer cells for bone metastasis
Authors: Mohammadi Ghahhari Nastaran , Sznurkowska Magdalena K. , Hulo Nicolas , Bernasconi Lilia , Aceto Nicola , Picard Didier
Published: April 2022

The epithelial to mesenchymal transition (EMT) has been proposed to contribute to the metastatic spread of breast cancer cells. EMT-promoting transcription factors determine a continuum of different EMT states. In contrast, estrogen receptor α (ERα) helps to maintain the epithelial phenotype of breast cancer cells and its expression is crucial for effective endocrine therapies. Determining whether and how EMT-associated transcription factors such as ZEB1 modulate ERα signaling during early stages of EMT could promote the discovery of therapeutic approaches to suppress metastasis. Here we show that, shortly after induction of EMT and while cells are still epithelial, ZEB1 modulates ERα-mediated transcription induced by estrogen or cAMP signaling in breast cancer cells. Based on these findings and our ex vivo and xenograft results, we suggest that the functional interaction between ZEB1 and ERα may alter the tissue tropism of metastatic breast cancer cells towards bone.
Thermally boosted upconversion and downshifting luminescence in Sc2(MoO4)3:Yb/Er with two-dimensional negative thermal expansion
Authors: Liao Jinsheng , Wang Minghua , Lin Fulin , Han Zhuo , Fu Biao , Tu Datao , Chen Xueyuan , Qiu Bao , Wen He-Rui
Published: April 2022

Rare earth (RE3+)-doped phosphors generally suffer from thermal quenching, in which their photoluminescence (PL) intensities decrease at high temperatures. Herein, we report a class of unique two-dimensional negative-thermal-expansion phosphor of Sc2(MoO4)3:Yb/Er. By virtue of the reduced distances between sensitizers and emitters as well as confined energy migration with increasing the temperature, a 45-fold enhancement of green upconversion (UC) luminescence and a 450-fold enhancement of near-infrared downshifting (DS) luminescence of Er3+ are achieved upon raising the temperature from 298 to 773 K. The thermally boosted UC and DS luminescence mechanism is systematically investigated through in situ temperature-dependent Raman spectroscopy, synchrotron X-ray diffraction and PL dynamics. Moreover, the luminescence lifetime of 4I13/2 of Er3+ in Sc2(MoO4)3:Yb/Er displays a strong temperature dependence, enabling luminescence thermometry with the highest relative sensitivity of 12.3%/K at 298 K and low temperature uncertainty of 0.11 K at 623 K. These findings may gain a vital insight into the design of negative-thermal-expansion RE3+-doped phosphors for versatile applications.
Bound states at partial dislocation defects in multipole higher-order topological insulators
Authors: Yamada Sasha S. , Li Tianhe , Lin Mao , Peterson Christopher W. , Hughes Taylor L. , Bahl Gaurav
Published: April 2022

The bulk-boundary correspondence, which links a bulk topological property of a material to the existence of robust boundary states, is a hallmark of topological insulators. However, in crystalline topological materials the presence of boundary states in the insulating gap is not always necessary since they can be hidden in the bulk energy bands, obscured by boundary artifacts of non-topological origin, or, in the case of higher-order topology, they can be gapped altogether. Recently, exotic defects of translation symmetry called partial dislocations have been proposed to trap gapless topological modes in some materials. Here we present experimental observations of partial-dislocation-induced topological modes in 2D and 3D insulators. We particularly focus on multipole higher-order topological insulators built from circuit-based resonator arrays, since crucially they are not sensitive to full dislocation defects, and they have a sublattice structure allowing for stacking faults and partial dislocations.
Bipartite network models to design combination therapies in acute myeloid leukaemia
Authors: Jafari Mohieddin , Mirzaie Mehdi , Bao Jie , Barneh Farnaz , Zheng Shuyu , Eriksson Johanna , Heckman Caroline A. , Tang Jing
Published: April 2022

Combination therapy is preferred over single-targeted monotherapies for cancer treatment due to its efficiency and safety. However, identifying effective drug combinations costs time and resources. We propose a method for identifying potential drug combinations by bipartite network modelling of patient-related drug response data, specifically the Beat AML dataset. The median of cell viability is used as a drug potency measurement to reconstruct a weighted bipartite network, model drug-biological sample interactions, and find the clusters of nodes inside two projected networks. Then, the clustering results are leveraged to discover effective multi-targeted drug combinations, which are also supported by more evidence using GDSC and ALMANAC databases. The potency and synergy levels of selective drug combinations are corroborated against monotherapy in three cell lines for acute myeloid leukaemia in vitro. In this study, we introduce a nominal data mining approach to improving acute myeloid leukaemia treatment through combinatorial therapy.
Using automated synthesis to understand the role of side chains on molecular charge transport
Authors: Li Songsong , Jira Edward R. , Angello Nicholas H. , Li Jialing , Yu Hao , Moore Jeffrey S. , Diao Ying , Burke Martin D. , Schroeder Charles M.
Published: April 2022

The development of next-generation organic electronic materials critically relies on understanding structure-function relationships in conjugated polymers. However, unlocking the full potential of organic materials requires access to their vast chemical space while efficiently managing the large synthetic workload to survey new materials. In this work, we use automated synthesis to prepare a library of conjugated oligomers with systematically varied side chain composition followed by single-molecule characterization of charge transport. Our results show that molecular junctions with long alkyl side chains exhibit a concentration-dependent bimodal conductance with an unexpectedly high conductance state that arises due to surface adsorption and backbone planarization, which is supported by a series of control experiments using asymmetric, planarized, and sterically hindered molecules. Density functional theory simulations and experiments using different anchors and alkoxy side chains highlight the role of side chain chemistry on charge transport. Overall, this work opens new avenues for using automated synthesis for the development and understanding of organic electronic materials.
The stability of covalent dative bond significantly increases with increasing solvent polarity
Authors: Lo Rabindranath , Manna Debashree , Lamanec Maximilián , Dračínský Martin , Bouř Petr , Wu Tao , Bastien Guillaume , Kaleta Jiří , Miriyala Vijay Madhav , Špirko Vladimír , Mašínová Anna , Nachtigallová Dana , Hobza Pavel
Published: April 2022

It is generally expected that a solvent has only marginal effect on the stability of a covalent bond. In this work, we present a combined computational and experimental study showing a surprising stabilization of the covalent/dative bond in Me3NBH3 complex with increasing solvent polarity. The results show that for a given complex, its stability correlates with the strength of the bond. Notably, the trends in calculated changes of binding (free) energies, observed with increasing solvent polarity, match the differences in the solvation energies (ΔEsolv) of the complex and isolated fragments. Furthermore, the studies performed on the set of the dative complexes, with different atoms involved in the bond, show a linear correlation between the changes of binding free energies and ΔEsolv. The observed data indicate that the ionic part of the combined ionic-covalent character of the bond is responsible for the stabilizing effects of solvents.
Extra plasticity governed by shear band deflection in gradient metallic glasses
Authors: Tang Yao , Zhou Haofei , Lu Haiming , Wang Xiaodong , Cao Qingping , Zhang Dongxian , Yang Wei , Jiang Jian-Zhong
Published: April 2022

Inspired by gradient materials in nature, advanced engineering components with controlled structural gradients have attracted substantial research interests due to their exceptional combinations of properties. However, it remains challenging to generate structural gradients that penetrate through bulk materials, which is essential for achieving enhanced mechanical properties in metallic materials. Here, we report practical strategies to design controllable structural gradients in bulk metallic glasses (BMGs). By adjusting processing conditions, including holding time and/or controlling temperatures, of cryogenic thermal cycling and fast cooling, two different types of gradient metallic glasses (GMGs) with spatially gradient-distributed free volume contents can be synthesized. Both mechanical testing and atomistic simulations demonstrate that the spatial gradient can endow GMGs with extra plasticity. Such an enhanced mechanical property is governed by the gradient-induced deflection of shear deformation that fundamentally suppresses the unlimited shear localization on a straight plane that would be expected in BMGs without such a gradient.
A loss-of-adhesion CRISPR-Cas9 screening platform to identify cell adhesion-regulatory proteins and signaling pathways
Authors: de Rooij Martin F. M. , Thus Yvonne J. , Swier Nathalie , Beijersbergen Roderick L. , Pals Steven T. , Spaargaren Marcel
Published: April 2022

The clinical introduction of the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib, which targets B-cell antigen-receptor (BCR)-controlled integrin-mediated retention of malignant B cells in their growth-supportive lymphoid organ microenvironment, provided a major breakthrough in lymphoma and leukemia treatment. Unfortunately, a significant subset of patients is intrinsically resistant or acquires resistance against ibrutinib. Here, to discover novel therapeutic targets, we present an unbiased loss-of-adhesion CRISPR-Cas9 knockout screening method to identify proteins involved in BCR-controlled integrin-mediated adhesion. Illustrating the validity of our approach, several kinases with an established role in BCR-controlled adhesion, including BTK and PI3K, both targets for clinically applied inhibitors, are among the top hits of our screen. We anticipate that pharmacological inhibitors of the identified targets, e.g. PAK2 and PTK2B/PYK2, may have great clinical potential as therapy for lymphoma and leukemia patients. Furthermore, this screening platform is highly flexible and can be easily adapted to identify cell adhesion-regulatory proteins and signaling pathways for other stimuli, adhesion molecules, and cell types.
Finding predictive models for singlet fission by machine learning
Authors: Liu Xingyu , Wang Xiaopeng , Gao Siyu , Chang Vincent , Tom Rithwik , Yu Maituo , Ghiringhelli Luca M. , Marom Noa
Published: April 2022

Singlet fission (SF), the conversion of one singlet exciton into two triplet excitons, could significantly enhance solar cell efficiency. Molecular crystals that undergo SF are scarce. Computational exploration may accelerate the discovery of SF materials. However, many-body perturbation theory (MBPT) calculations of the excitonic properties of molecular crystals are impractical for large-scale materials screening. We use the sure-independence-screening-and-sparsifying-operator (SISSO) machine-learning algorithm to generate computationally efficient models that can predict the MBPT thermodynamic driving force for SF for a dataset of 101 polycyclic aromatic hydrocarbons (PAH101). SISSO generates models by iteratively combining physical primary features. The best models are selected by linear regression with cross-validation. The SISSO models successfully predict the SF driving force with errors below 0.2 eV. Based on the cost, accuracy, and classification performance of SISSO models, we propose a hierarchical materials screening workflow. Three potential SF candidates are found in the PAH101 set.
Drastic enhancement of magnetic critical temperature and amorphization in topological magnet EuSn2P2 under pressure
Authors: Bi Wenli , Culverhouse Trenton , Nix Zachary , Xie Weiwei , Tien Hung-Ju , Chang Tay-Rong , Dutta Utpal , Zhao Jiyong , Lavina Barbara , Alp Esen E. , Zhang Dongzhou , Xu Jingui , Xiao Yuming , Vohra Yogesh K.
Published: April 2022

High pressure is an effective tool to induce exotic quantum phenomena in magnetic topological insulators by controlling the interplay of magnetic order and topological state. This work presents a comprehensive high-pressure study of the crystal structure and magnetic ground state up to 62 GPa in an intrinsic topological magnet EuSn2P2. With a combination of high resolution X-ray diffraction, 151Eu synchrotron Mössbauer spectroscopy, X-ray absorption spectroscopy, molecular orbital calculations, and electronic band structure calculations, it has been revealed that pressure drives EuSn2P2 from a rhombohedral crystal to an amorphous phase at 36 GPa accompanied by a fourfold enhancement of magnetic ordering temperature. In the pressure-induced amorphous phase, Eu ions take an intermediate valence state. The drastic enhancement of magnetic ordering temperature from 30 K at ambient pressure to 130 K at 41.2 GPa resulting from Ruderman–Kittel–Kasuya–Yosida (RKKY) interactions likely attributes to the stronger Eu–Sn interaction at high pressure. These rich results demonstrate that EuSn2P2 is an ideal platform to study the correlation of the enhanced RKKY interactions, disordered lattice, intermediate valence, and topological state.
Selective removal of Na+ by NaTi2(PO4)3-MWCNT composite hollow-fiber membrane electrode in capacitive deionization
Authors: Park Joosung , Lee Mi-Young , Han Seungyeob , Lee Keun-Young , Kang Seoktae
Published: April 2022

In this study, NaTi2(PO4)3 (NTP) nanoparticles were incorporated into a carbon nanotube hollow-fiber (CHF) electrode for the selective removal of Na+ during the capacitive deionization (CDI) of salty water. Due to the Na+-selective electro-sorption of NTP nanoparticles, NTP-CHF achieved 1.5 ~2 times higher Na+ adsorption capacity than that of CHF only electrodes at a range of 1.7 mM~17.1 mM (100 mg L−1~1000 mg L−1) NaCl solution. Moreover NTP-CHF sustained the Na+ adsorption capacity even at the presence of Ca2+ ions, whereas the dramatic decrease in Na+ removal was observed in CHF with an increase of Ca2+ concentration. As the result, NTP-CHF can retain 52% of the initial Na+ removal capacity after three times of capture and release cycles at the presence of Ca2+, while CHF showed <10% of the initial Na+ removal capacity due to the irreversible adsorption of Ca2+ ions onto the MWCNT surface. Thus, the incorporation of NTP into the conductive carbon nanomaterial network can greatly improve both the adsorption capacity and selectivity of Na+ compared to the conventional carbon-based electrode during the CDI of salty water containing multivalent cations such as Ca2+.
Structural equation modeling reveals decoupling of ecological and self-perceived outcomes in a garden box social-ecological system
Authors: Tuominen Laura S. , Helle Samuli , Helanterä Heikki , Karell Patrik , Rapeli Lauri , Richmond Douglas , Vuorisalo Timo , Brommer Jon E.
Published: April 2022

It is well known that green urban commons enhance mental and physical well-being and improve local biodiversity. We aim to investigate how these outcomes are related in an urban system and which variables are associated with better outcomes. We model the outcomes of an urban common—box gardening—by applying the Social-Ecological Systems (SES) framework. We expand the SES framework by analyzing it from the perspective of social evolution theory. The system was studied empirically through field inventories and questionnaires and modeled quantitatively by Structural Equation Modeling (SEM). This method offers powerful statistical models of complex social-ecological systems. Our results show that objectively evaluated ecological outcomes and self-perceived outcomes are decoupled: gardening groups that successfully govern the natural resource ecologically do not necessarily report many social, ecological, or individual benefits, and vice versa. Social capital, box location, gardener concerns, and starting year influenced the changes in the outcomes. In addition, the positive association of frequent interactions with higher self-perceived outcomes, and lack of such association with relatedness of group members suggests that reciprocity rather than kin selection explains cooperation. Our findings exemplify the importance of understanding natural resource systems at a very low “grassroot” level.
A novel 2-phase residual U-net algorithm combined with optimal mass transportation for 3D brain tumor detection and segmentation
Authors: Lin Wen-Wei , Lin Jia-Wei , Huang Tsung-Ming , Li Tiexiang , Yueh Mei-Heng , Yau Shing-Tung
Published: April 2022

Utilizing the optimal mass transportation (OMT) technique to convert an irregular 3D brain image into a cube, a required input format for a U-net algorithm, is a brand new idea for medical imaging research. We develop a cubic volume-measure-preserving OMT (V-OMT) model for the implementation of this conversion. The contrast-enhanced histogram equalization grayscale of fluid-attenuated inversion recovery (FLAIR) in a brain image creates the corresponding density function. We then propose an effective two-phase residual U-net algorithm combined with the V-OMT algorithm for training and validation. First, we use the residual U-net and V-OMT algorithms to precisely predict the whole tumor (WT) region. Second, we expand this predicted WT region with dilation and create a smooth function by convolving the step-like function associated with the WT region in the brain image with a $$5\times 5\times 5$$

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blur tensor. Then, a new V-OMT algorithm with mesh refinement is constructed to allow the residual U-net algorithm to effectively train Net1–Net3 models. Finally, we propose ensemble voting postprocessing to validate the final labels of brain images. We randomly chose 1000 and 251 brain samples from the Brain Tumor Segmentation (BraTS) 2021 training dataset, which contains 1251 samples, for training and validation, respectively. The Dice scores of the WT, tumor core (TC) and enhanced tumor (ET) regions for validation computed by Net1–Net3 were 0.93705, 0.90617 and 0.87470, respectively. A significant improvement in brain tumor detection and segmentation with higher accuracy is achieved.