bluuebunny/crossref_metadata_2025 huggingface dataset:
PDZK1 suppresses TNBC development and sensitizes TNBC cells to erlotinib via the EGFR pathway
Authors: Ma Yuanzhen , Fang Zhiyu , Zhang Hongning , Qi Yijun , Mao Yuke , Zheng Junfang
Published: April 2024

Epidermal growth factor receptor (EGFR)-targeted drugs (erlotinib, etc.) are used to treat multiple types of tumours. EGFR is highly expressed in most triple-negative breast cancer (TNBC) patients. However, only a small proportion of TNBC patients benefit from EGFR-targeted drugs in clinical trials, and the resistance mechanism is unclear. Here, we found that PDZ domain containing 1 (PDZK1) is downregulated in erlotinib-resistant TNBC cells, suggesting that PDZK1 downregulation is related to erlotinib resistance in TNBC. PDZK1 binds to EGFR. Through this interaction, PDZK1 promotes EGFR degradation by enhancing the binding of EGFR to c-Cbl and inhibits EGFR phosphorylation by hindering EGFR dimerisation. We also found that PDZK1 is specifically downregulated in TNBC tissues and correlated with a poor prognosis in TNBC patients. In vitro and in vivo functional assays showed that PDZK1 suppressed TNBC development. Restoration of EGFR expression or kinase inhibitor treatment reversed the degree of cell malignancy induced by PDZK1 overexpression or knockdown, respectively. PDZK1 overexpression sensitised TNBC cells to erlotinib both in vitro and in vivo. In conclusion, PDZK1 is a significant prognostic factor for TNBC and a potential molecular therapeutic target for reversing erlotinib resistance in TNBC cells.
USP12 facilitates gastric cancer progression via stabilizing YAP
Authors: Zhang Peng , Liu Dongyi , Zang Yifeng , Wang Jinqing , Liu Ziping , Zhu Jian , Li Xin , Ding Yinlu
Published: April 2024

The dysregulation of Hippo signaling is a crucial factor driving the progression of gastric cancer, making the targeting of the Hippo pathway a promising therapeutic strategy. However, effective drugs targeting the Hippo/YAP axis remain unavailable. Thus, identifying potential therapeutic targets and mechanisms that inhibit the activity of the Hippo/YAP axis in gastric cancer is of paramount importance. The ubiquitination modification of the Hippo/YAP pathway plays a significant role in signaling transduction and cancer progression. In an effort to shed light on effective therapeutic targets, we conducted a screening using a deubiquitinase small interfering RNA library, leading to the identification of USP12 as an important deubiquitinase in the context of Hippo/YAP axis and the progression of gastric cancer. Our bioinformatic analysis further demonstrated a correlation between USP12 and poor survival, as well as a positive association with classical YAP target genes in gastric cancer samples. Notably, USP12 depletion was found to inhibit gastric cancer progression via the Hippo/YAP axis, whereas USP12 overexpression exhibited the opposite effect, promoting gastric cancer growth and enhancing YAP activity. Further studies through immuno-staining and immuno-precipitation assays indicated the nuclear localization of USP12 and its association with YAP to enhance YAP stability. Specifically, our findings revealed that USP12 could inhibit K48-linked poly-ubiquitination of YAP, predominantly at the K315 site. As a result, we have identified a novel regulatory mechanism involving USP12 and Hippo signaling in the progression of gastric cancer, with the potential for blockade of USP12 to materialize as a promising strategy for combating gastric cancer.
Structural basis for human Cav3.2 inhibition by selective antagonists
Authors: Huang Jian , Fan Xiao , Jin Xueqin , Lyu Chen , Guo Qinmeng , Liu Tao , Chen Jiaofeng , Davakan Amaël , Lory Philippe , Yan Nieng
Published: April 2024

The Cav3.2 subtype of T-type calcium channels has been targeted for developing analgesics and anti-epileptics for its role in pain and epilepsy. Here we present the cryo-EM structures of Cav3.2 alone and in complex with four T-type calcium channel selective antagonists with overall resolutions ranging from 2.8 Å to 3.2 Å. The four compounds display two binding poses. ACT-709478 and TTA-A2 both place their cyclopropylphenyl-containing ends in the central cavity to directly obstruct ion flow, meanwhile extending their polar tails into the IV-I fenestration. TTA-P2 and ML218 project their 3,5-dichlorobenzamide groups into the II-III fenestration and place their hydrophobic tails in the cavity to impede ion permeation. The fenestration-penetrating mode immediately affords an explanation for the state-dependent activities of these antagonists. Structure-guided mutational analysis identifies several key residues that determine the T-type preference of these drugs. The structures also suggest the role of an endogenous lipid in stabilizing drug binding in the central cavity.
Synthetic biology approaches for improving the specificity and efficacy of cancer immunotherapy
Authors: Zhu Bo , Yin Hang , Zhang Di , Zhang Meiling , Chao Xiaojuan , Scimeca Luca , Wu Ming-Ru
Published: April 2024

Immunotherapy has shown robust efficacy in treating a broad spectrum of hematological and solid cancers. Despite the transformative impact of immunotherapy on cancer treatment, several outstanding challenges remain. These challenges include on-target off-tumor toxicity, systemic toxicity, and the complexity of achieving potent and sustainable therapeutic efficacy. Synthetic biology has emerged as a promising approach to overcome these obstacles, offering innovative tools for engineering living cells with customized functions. This review provides an overview of the current landscape and future prospects of cancer immunotherapy, particularly emphasizing the role of synthetic biology in augmenting its specificity, controllability, and efficacy. We delineate and discuss two principal synthetic biology strategies: those targeting tumor surface antigens with engineered immune cells and those detecting intratumoral disease signatures with engineered gene circuits. This review concludes with a forward-looking perspective on the enduring challenges in cancer immunotherapy and the potential breakthroughs that synthetic biology may contribute to the field.
Beyond nothingness in the formation and functional relevance of voids in polymer films
Authors: Kalutantirige Falon C. , He Jinlong , Yao Lehan , Cotty Stephen , Zhou Shan , Smith John W. , Tajkhorshid Emad , Schroeder Charles M. , Moore Jeffrey S. , An Hyosung , Su Xiao , Li Ying , Chen Qian
Published: April 2024

Voids—the nothingness—broadly exist within nanomaterials and impact properties ranging from catalysis to mechanical response. However, understanding nanovoids is challenging due to lack of imaging methods with the needed penetration depth and spatial resolution. Here, we integrate electron tomography, morphometry, graph theory and coarse-grained molecular dynamics simulation to study the formation of interconnected nanovoids in polymer films and their impacts on permeance and nanomechanical behaviour. Using polyamide membranes for molecular separation as a representative system, three-dimensional electron tomography at nanometre resolution reveals nanovoid formation from coalescence of oligomers, supported by coarse-grained molecular dynamics simulations. Void analysis provides otherwise inaccessible inputs for accurate fittings of methanol permeance for polyamide membranes. Three-dimensional structural graphs accounting for the tortuous nanovoids within, measure higher apparent moduli with polyamide membranes of higher graph rigidity. Our study elucidates the significance of nanovoids beyond the nothingness, impacting the synthesis‒morphology‒function relationships of complex nanomaterials.
Pathogenic mutations of human phosphorylation sites affect protein–protein interactions
Authors: Rrustemi Trendelina , Meyer Katrina , Roske Yvette , Uyar Bora , Akalin Altuna , Imami Koshi , Ishihama Yasushi , Daumke Oliver , Selbach Matthias
Published: April 2024

Despite their lack of a defined 3D structure, intrinsically disordered regions (IDRs) of proteins play important biological roles. Many IDRs contain short linear motifs (SLiMs) that mediate protein-protein interactions (PPIs), which can be regulated by post-translational modifications like phosphorylation. 20% of pathogenic missense mutations are found in IDRs, and understanding how such mutations affect PPIs is essential for unraveling disease mechanisms. Here, we employ peptide-based interaction proteomics to investigate 36 disease-associated mutations affecting phosphorylation sites. Our results unveil significant differences in interactomes between phosphorylated and non-phosphorylated peptides, often due to disrupted phosphorylation-dependent SLiMs. We focused on a mutation of a serine phosphorylation site in the transcription factor GATAD1, which causes dilated cardiomyopathy. We find that this phosphorylation site mediates interaction with 14-3-3 family proteins. Follow-up experiments reveal the structural basis of this interaction and suggest that 14-3-3 binding affects GATAD1 nucleocytoplasmic transport by masking a nuclear localisation signal. Our results demonstrate that pathogenic mutations of human phosphorylation sites can significantly impact protein-protein interactions, offering insights into potential molecular mechanisms underlying pathogenesis.
Violation of emergent rotational symmetry in the hexagonal Kagome superconductor CsV3Sb5
Authors: Fukushima Kazumi , Obata Keito , Yamane Soichiro , Hu Yajian , Li Yongkai , Yao Yugui , Wang Zhiwei , Maeno Yoshiteru , Yonezawa Shingo
Published: April 2024

Superconductivity is caused by electron pairs that are canonically isotropic, whereas some exotic superconductors are known to exhibit non-trivial anisotropy stemming from unconventional pairings. However, superconductors with hexagonal symmetry, the highest rotational symmetry allowed in crystals, exceptionally have strong constraint that is called emergent rotational symmetry (ERS): anisotropic properties should be very weak especially near the critical temperature Tc even for unconventional pairings such as d-wave states. Here, we investigate superconducting anisotropy of the recently-found hexagonal Kagome superconductor CsV3Sb5, which is known to exhibit various intriguing phenomena originating from its undistorted Kagome lattice formed by vanadium atoms. Based on calorimetry performed under accurate two-axis field-direction control, we discover a combination of six- and two-fold anisotropies in the in-plane upper critical field. Both anisotropies, robust up to very close to Tc, are beyond predictions of standard theories. We infer that this clear ERS violation with nematicity is best explained by multi-component nematic superconducting order parameter in CsV3Sb5 intertwined with symmetry breakings caused by the underlying charge-density-wave order.
Amundsen Sea circulation controls bottom upwelling and Antarctic Pine Island and Thwaites ice shelf melting
Authors: Park Taewook , Nakayama Yoshihiro , Nam SungHyun
Published: April 2024

The Pine Island and Thwaites Ice Shelves (PIIS/TIS) in the Amundsen Sea are melting rapidly and impacting global sea levels. The thermocline depth (TD) variability, the interface between cold Winter Water and warm modified Circumpolar Deep Water (mCDW), at the PIIS/TIS front strongly correlates with basal melt rates, but the drivers of its interannual variability remain uncertain. Here, using an ocean model, we propose that the strength of the eastern Amundsen Sea on-shelf circulation primarily controls TD variability and consequent PIIS/TIS melt rates. The TD variability occurs because the on-shelf circulation meanders following the submarine glacial trough, creating vertical velocity through bottom Ekman dynamics. We suggest that a strong or weak ocean circulation, possibly linked to remote winds in the Bellingshausen Sea, generates corresponding changes in bottom Ekman convergence, which modulates mCDW upwelling and TD variability. We show that interannual variability of off-shelf zonal winds has a minor effect on ocean heat intrusion into PIIS/TIS cavities, contrary to the widely accepted concept.
Hydrophobic mismatch drives self-organization of designer proteins into synthetic membranes
Authors: Peruzzi Justin A. , Steinkühler Jan , Vu Timothy Q. , Gunnels Taylor F. , Hu Vivian T. , Lu Peilong , Baker David , Kamat Neha P.
Published: April 2024

The organization of membrane proteins between and within membrane-bound compartments is critical to cellular function. Yet we lack approaches to regulate this organization in a range of membrane-based materials, such as engineered cells, exosomes, and liposomes. Uncovering and leveraging biophysical drivers of membrane protein organization to design membrane systems could greatly enhance the functionality of these materials. Towards this goal, we use de novo protein design, molecular dynamic simulations, and cell-free systems to explore how membrane-protein hydrophobic mismatch could be used to tune protein cotranslational integration and organization in synthetic lipid membranes. We find that membranes must deform to accommodate membrane-protein hydrophobic mismatch, which reduces the expression and co-translational insertion of membrane proteins into synthetic membranes. We use this principle to sort proteins both between and within membranes, thereby achieving one-pot assembly of vesicles with distinct functions and controlled split-protein assembly, respectively. Our results shed light on protein organization in biological membranes and provide a framework to design self-organizing membrane-based materials with applications such as artificial cells, biosensors, and therapeutic nanoparticles.
Contrasting carbon cycle along tropical forest aridity gradients in West Africa and Amazonia
Authors: Zhang-Zheng Huanyuan , Adu-Bredu Stephen , Duah-Gyamfi Akwasi , Moore Sam , Addo-Danso Shalom D. , Amissah Lucy , Valentini Riccardo , Djagbletey Gloria , Anim-Adjei Kelvin , Quansah John , Sarpong Bernice , Owusu-Afriyie Kennedy , Gvozdevaite Agne , Tang Minxue , Ruiz-Jaen Maria C. , Ibrahim Forzia , Girardin Cécile A. J. , Rifai Sami , Dahlsjö Cecilia A. L. , Riutta Terhi , Deng Xiongjie , Sun Yuheng , Prentice Iain Colin , Oliveras Menor Imma , Malhi Yadvinder
Published: April 2024

Tropical forests cover large areas of equatorial Africa and play a substantial role in the global carbon cycle. However, there has been a lack of biometric measurements to understand the forests’ gross and net primary productivity (GPP, NPP) and their allocation. Here we present a detailed field assessment of the carbon budget of multiple forest sites in Africa, by monitoring 14 one-hectare plots along an aridity gradient in Ghana, West Africa. When compared with an equivalent aridity gradient in Amazonia, the studied West African forests generally had higher productivity and lower carbon use efficiency (CUE). The West African aridity gradient consistently shows the highest NPP, CUE, GPP, and autotrophic respiration at a medium-aridity site, Bobiri. Notably, NPP and GPP of the site are the highest yet reported anywhere for intact forests. Widely used data products substantially underestimate productivity when compared to biometric measurements in Amazonia and Africa. Our analysis suggests that the high productivity of the African forests is linked to their large GPP allocation to canopy and semi-deciduous characteristics.
Multisensory flicker modulates widespread brain networks and reduces interictal epileptiform discharges
Authors: Blanpain Lou T. , Cole Eric R. , Chen Emily , Park James K. , Walelign Michael Y. , Gross Robert E. , Cabaniss Brian T. , Willie Jon T. , Singer Annabelle C.
Published: April 2024

Modulating brain oscillations has strong therapeutic potential. Interventions that both non-invasively modulate deep brain structures and are practical for chronic daily home use are desirable for a variety of therapeutic applications. Repetitive audio-visual stimulation, or sensory flicker, is an accessible approach that modulates hippocampus in mice, but its effects in humans are poorly defined. We therefore quantified the neurophysiological effects of flicker with high spatiotemporal resolution in patients with focal epilepsy who underwent intracranial seizure monitoring. In this interventional trial (NCT04188834) with a cross-over design, subjects underwent different frequencies of flicker stimulation in the same recording session with the effect of sensory flicker exposure on local field potential (LFP) power and interictal epileptiform discharges (IEDs) as primary and secondary outcomes, respectively. Flicker focally modulated local field potentials in expected canonical sensory cortices but also in the medial temporal lobe and prefrontal cortex, likely via resonance of stimulated long-range circuits. Moreover, flicker decreased interictal epileptiform discharges, a pathological biomarker of epilepsy and degenerative diseases, most strongly in regions where potentials were flicker-modulated, especially the visual cortex and medial temporal lobe. This trial met the scientific goal and is now closed. Our findings reveal how multi-sensory stimulation may modulate cortical structures to mitigate pathological activity in humans.
Evolution of T cells in the cancer-resistant naked mole-rat
Authors: Lin Tzuhua D. , Rubinstein Nimrod D. , Fong Nicole L. , Smith Megan , Craft Wendy , Martin-McNulty Baby , Perry Rebecca , Delaney Martha A. , Roy Margaret A. , Buffenstein Rochelle
Published: April 2024

Naked mole-rats (NMRs) are best known for their extreme longevity and cancer resistance, suggesting that their immune system might have evolved to facilitate these phenotypes. Natural killer (NK) and T cells have evolved to detect and destroy cells infected with pathogens and to provide an early response to malignancies. While it is known that NMRs lack NK cells, likely lost during evolution, little is known about their T-cell subsets in terms of the evolution of the genes that regulate their function, their clonotypic diversity, and the thymus where they mature. Here we find, using single-cell transcriptomics, that NMRs have a large circulating population of γδT cells, which in mice and humans mostly reside in peripheral tissues and induce anti-cancer cytotoxicity. Using single-cell-T-cell-receptor sequencing, we find that a cytotoxic γδT-cell subset of NMRs harbors a dominant clonotype, and that their conventional CD8 αβT cells exhibit modest clonotypic diversity. Consistently, perinatal NMR thymuses are considerably smaller than those of mice yet follow similar involution progression. Our findings suggest that NMRs have evolved under a relaxed intracellular pathogenic selective pressure that may have allowed cancer resistance and longevity to become stronger targets of selection to which the immune system has responded by utilizing γδT cells.
Plasmids in the human gut reveal neutral dispersal and recombination that is overpowered by inflammatory diseases
Authors: Zorea Alvah , Pellow David , Levin Liron , Pilosof Shai , Friedman Jonathan , Shamir Ron , Mizrahi Itzhak
Published: April 2024

Plasmids are pivotal in driving bacterial evolution through horizontal gene transfer. Here, we investigated 3467 human gut microbiome samples across continents and disease states, analyzing 11,086 plasmids. Our analyses reveal that plasmid dispersal is predominantly stochastic, indicating neutral processes as the primary driver of their wide distribution. We find that only 20-25% of plasmid DNA is being selected in various disease states, constraining its distribution across hosts. Selective pressures shape specific plasmid segments with distinct ecological functions, influenced by plasmid mobilization lifestyle, antibiotic usage, and inflammatory gut diseases. Notably, these elements are more commonly shared within groups of individuals with similar health conditions, such as Inflammatory Bowel Disease (IBD), regardless of geographic location across continents. These segments contain essential genes such as iron transport mechanisms- a distinctive gut signature of IBD that impacts the severity of inflammation. Our findings shed light on mechanisms driving plasmid dispersal and selection in the human gut, highlighting their role as carriers of vital gene pools impacting bacterial hosts and ecosystem dynamics.
Two-dimensional lead halide perovskite lateral homojunctions enabled by phase pinning
Authors: Hong Huilong , Guo Songhao , Jin Leyang , Mao Yuhong , Chen Yuguang , Gu Jiazhen , Chen Shaochuang , Huang Xu , Guan Yan , Li Xiaotong , Li Yan , Lü Xujie , Fu Yongping
Published: April 2024

Two-dimensional organic-inorganic hybrid halide perovskites possess diverse structural polymorphs with versatile physical properties, which can be controlled by order-disorder transition of the spacer cation, making them attractive for constructing semiconductor homojunctions. Here, we demonstrate a space-cation-dopant-induced phase stabilization approach to creating a lateral homojunction composed of ordered and disordered phases within a two-dimensional perovskite. By doping a small quantity of pentylammonium into (butylammonium)2PbI4 or vice versa, we effectively suppress the ordering transition of the spacer cation and the associated out-of-plane octahedral tilting in the inorganic framework, resulting in phase pining of the disordered phase when decreasing temperature or increasing pressure. This enables epitaxial growth of a two-dimensional perovskite homojunction with tunable optical properties under temperature and pressure stimuli, as well as directional exciton diffusion across the interface. Our results demonstrate a previously unexplored strategy for constructing two-dimensional perovskite heterostructures by thermodynamic tuning and spacer cation doping.
Regulation by the RNA-binding protein Unkempt at its effector interface
Authors: Shah Kriti , He Shiyang , Turner David J. , Corbo Joshua , Rebbani Khadija , Dominguez Daniel , Bateman Joseph M. , Cheloufi Sihem , Igreja Cátia , Valkov Eugene , Murn Jernej
Published: April 2024

How RNA-binding proteins (RBPs) convey regulatory instructions to the core effectors of RNA processing is unclear. Here, we document the existence and functions of a multivalent RBP–effector interface. We show that the effector interface of a conserved RBP with an essential role in metazoan development, Unkempt, is mediated by a novel type of ‘dual-purpose’ peptide motifs that can contact two different surfaces of interacting proteins. Unexpectedly, we find that the multivalent contacts do not merely serve effector recruitment but are required for the accuracy of RNA recognition by Unkempt. Systems analyses reveal that multivalent RBP–effector contacts can repurpose the principal activity of an effector for a different function, as we demonstrate for the reuse of the central eukaryotic mRNA decay factor CCR4-NOT in translational control. Our study establishes the molecular assembly and functional principles of an RBP–effector interface.
Photonic-electronic integrated circuit-based coherent LiDAR engine
Authors: Lukashchuk Anton , Yildirim Halil Kerim , Bancora Andrea , Lihachev Grigory , Liu Yang , Qiu Zheru , Ji Xinru , Voloshin Andrey , Bhave Sunil A. , Charbon Edoardo , Kippenberg Tobias J.
Published: April 2024

Chip-scale integration is a key enabler for the deployment of photonic technologies. Coherent laser ranging or FMCW LiDAR, a perception technology that benefits from instantaneous velocity and distance detection, eye-safe operation, long-range, and immunity to interference. However, wafer-scale integration of these systems has been challenged by stringent requirements on laser coherence, frequency agility, and the necessity for optical amplifiers. Here, we demonstrate a photonic-electronic LiDAR source composed of a micro-electronic-based high-voltage arbitrary waveform generator, a hybrid photonic circuit-based tunable Vernier laser with piezoelectric actuators, and an erbium-doped waveguide amplifier. Importantly, all systems are realized in a wafer-scale manufacturing-compatible process comprising III-V semiconductors, silicon nitride photonic integrated circuits, and 130-nm SiGe bipolar complementary metal-oxide-semiconductor (CMOS) technology. We conducted ranging experiments at a 10-meter distance with a precision level of 10 cm and a 50 kHz acquisition rate. The laser source is turnkey and linearization-free, and it can be seamlessly integrated with existing focal plane and optical phased array LiDAR approaches.
Central role of d-band energy level in Cu-based intermetallic alloys
Authors: Zhao Jing , Xia Wenming , Zeng Zhi , Wang Xianlong
Published: April 2024

Cu-Au intermetallic alloys are classic paradigms in the history of alloy theory for studying order-disorder transition, phase stability, and so on. However, density functional theory with a generalized gradient approximation (GGA) fails to describe their formation energies and Au-rich ground states, e.g., calculated formation energies are nearly 40% smaller than experimental values. In this work, we found that these discrepancies, which are also common in other Cu-transition metal (TM) intermetallic alloys, are actually caused by the fact that GGA produces Cu-3d bands with a shallower energy level than the experimental results, leading to incorrect d-d hybridizations. By using the Hubbard U correction to adjust the d-bands to the correct position, the discrepancies in GGA calculations are eliminated. Our finding that the correct d-bands position is the key to characterize Cu-TMs, which can be achieved efficiently by applying the Hubbard U correction.
Predictors of stress resilience in Parkinson’s disease and associations with symptom progression
Authors: van der Heide Anouk , Dommershuijsen Lisanne J. , Puhlmann Lara M. C. , Kalisch Raffael , Bloem Bastiaan R. , Speckens Anne E. M. , Helmich Rick C.
Published: April 2024

People with Parkinson’s disease (PD) are sensitive to effects of long-term stress, but might differ in stress resilience, i.e. the ability to maintain mental health despite adversity. It is unclear whether stress resilience in PD is predominantly determined by dopamine deficiency, psychosocial factors, or both. In PD animal models, chronic stressors accelerate disease progression, but evidence in humans is lacking. Our objectives were to (1) distinguish stressor-reactive from resilient PD patients, (2) identify resilience factors, and (3) compare symptom progression between stressor-reactive and resilient patients. We conducted a longitudinal survey in Personalized Parkinson Project participants (N = 350 PD). We used the COVID-19 pandemic as a model of a stressor, aligned in time for the entire cohort. COVID-19-related stressors, perceived stress, and PD symptoms were assessed at 11 timepoints (April-October 2020). Both pre-COVID and in-COVID clinical assessments were available. We quantified stressor-reactivity as the residual between actual and predicted perceived stress relative to COVID-19-related stressors, and modeled trajectories of stressor-reactivity across timepoints. We explored pre-COVID predictors of 6-month average stressor-reactivity, and tested whether stressor-reactivity was prospectively associated with one-year clinical progression rates. Latent class trajectory models distinguished patients with high (N = 123) or low (N = 227) stressor-reactivity. Pre-existing anxiety, rumination and non-motor symptom severity predicted high stressor-reactivity (risk factors), whereas quality of life, social support, positive appraisal style and cognitive abilities predicted low stressor-reactivity (resilience factors). PD-specific factors, e.g. disease duration, motor severity, and levodopa use, did not predict stressor-reactivity. The COVID-19 pandemic did not accelerate disease progression, but worsened depressive symptoms in stressor-reactive PD patients.
Substantial cooling effect from aerosol-induced increase in tropical marine cloud cover
Authors: Chen Ying , Haywood Jim , Wang Yu , Malavelle Florent , Jordan George , Peace Amy , Partridge Daniel G. , Cho Nayeong , Oreopoulos Lazaros , Grosvenor Daniel , Field Paul , Allan Richard P. , Lohmann Ulrike
Published: April 2024

With global warming currently standing at approximately +1.2 °C since pre-industrial times, climate change is a pressing global issue. Marine cloud brightening is one proposed method to tackle warming through injecting aerosols into marine clouds to enhance their reflectivity and thereby planetary albedo. However, because it is unclear how aerosols influence clouds, especially cloud cover, both climate projections and the effectiveness of marine cloud brightening remain uncertain. Here we use satellite observations of volcanic eruptions in Hawaii to quantify the aerosol fingerprint on tropical marine clouds. We observe a large enhancement in reflected sunlight, mainly due to an aerosol-induced increase in cloud cover. This observed strong negative aerosol forcing suggests that the current level of global warming is driven by a weaker net radiative forcing than previously thought, arising from the competing effects of greenhouse gases and aerosols. This implies a greater sensitivity of Earth’s climate to radiative forcing and therefore a larger warming response to both rising greenhouse gas concentrations and reductions in atmospheric aerosols due to air quality measures. However, our findings also indicate that mitigation of global warming via marine cloud brightening is plausible and is most effective in humid and stable conditions in the tropics where solar radiation is strong.
Harnessing instability for work hardening in multi-principal element alloys
Authors: Xu Bowen , Duan Huichao , Chen Xuefei , Wang Jing , Ma Yan , Jiang Ping , Yuan Fuping , Wang Yandong , Ren Yang , Du Kui , Wei Yueguang , Wu Xiaolei
Published: April 2024

The strength–ductility trade-off has long been a Gordian knot in conventional metallic structural materials and it is no exception in multi-principal element alloys. In particular, at ultrahigh yield strengths, plastic instability, that is, necking, happens prematurely, because of which ductility almost entirely disappears. This is due to the growing difficulty in the production and accumulation of dislocations from the very beginning of tensile deformation that renders the conventional dislocation hardening insufficient. Here we propose that premature necking can be harnessed for work hardening in a VCoNi multi-principal element alloy. Lüders banding as an initial tensile response induces the ongoing localized necking at the band front to produce both triaxial stress and strain gradient, which enables the rapid multiplication of dislocations. This leads to forest dislocation hardening, plus extra work hardening due to the interaction of dislocations with the local-chemical-order regions. The dual work hardening combines to restrain and stabilize the premature necking in reverse as well as to facilitate uniform deformation. Consequently, a superior strength-and-ductility synergy is achieved with a ductility of ~20% and yield strength of 2 GPa during room-temperature and cryogenic deformation. These findings offer an instability-control paradigm for synergistic work hardening to conquer the strength–ductility paradox at ultrahigh yield strengths.
Single-molecule epitranscriptomic analysis of full-length HIV-1 RNAs reveals functional roles of site-specific m6As
Authors: Baek Alice , Lee Ga-Eun , Golconda Sarah , Rayhan Asif , Manganaris Anastasios A. , Chen Shuliang , Tirumuru Nagaraja , Yu Hannah , Kim Shihyoung , Kimmel Christopher , Zablocki Olivier , Sullivan Matthew B. , Addepalli Balasubrahmanyam , Wu Li , Kim Sanggu
Published: April 2024

Although the significance of chemical modifications on RNA is acknowledged, the evolutionary benefits and specific roles in human immunodeficiency virus (HIV-1) replication remain elusive. Most studies have provided only population-averaged values of modifications for fragmented RNAs at low resolution and have relied on indirect analyses of phenotypic effects by perturbing host effectors. Here we analysed chemical modifications on HIV-1 RNAs at the full-length, single RNA level and nucleotide resolution using direct RNA sequencing methods. Our data reveal an unexpectedly simple HIV-1 modification landscape, highlighting three predominant N6-methyladenosine (m6A) modifications near the 3′ end. More densely installed in spliced viral messenger RNAs than in genomic RNAs, these m6As play a crucial role in maintaining normal levels of HIV-1 RNA splicing and translation. HIV-1 generates diverse RNA subspecies with distinct m6A ensembles, and maintaining multiple of these m6As on its RNAs provides additional stability and resilience to HIV-1 replication, suggesting an unexplored viral RNA-level evolutionary strategy.
CT Cadaveric dataset for Radiomics features stability assessment in lumbar vertebrae
Authors: Levi Riccardo , Mollura Maximiliano , Savini Giovanni , Garoli Federico , Battaglia Massimiliano , Ammirabile Angela , Cappellini Luca A. , Superbi Simona , Grimaldi Marco , Barbieri Riccardo , Politi Letterio S.
Published: April 2024

Radiomics features (RFs) studies have showed limitations in the reproducibility of RFs in different acquisition settings. To date, reproducibility studies using CT images mainly rely on phantoms, due to the harness of patient exposure to X-rays. The provided CadAIver dataset has the aims of evaluating how CT scanner parameters effect radiomics features on cadaveric donor. The dataset comprises 112 unique CT acquisitions of a cadaveric truck acquired on 3 different CT scanners varying KV, mA, field-of-view, and reconstruction kernel settings. Technical validation of the CadAIver dataset comprises a comprehensive univariate and multivariate GLM approach to assess stability of each RFs extracted from lumbar vertebrae. The complete dataset is publicly available to be applied for future research in the RFs field, and could foster the creation of a collaborative open CT image database to increase the sample size, the range of available scanners, and the available body districts.
A global database on coral recovery following marine heatwaves
Authors: van Woesik Robert , Kratochwill Chelsey
Published: April 2024

Coral reefs support the world’s most diverse marine ecosystem and provide invaluable goods and services for millions of people worldwide. They are however experiencing frequent and intensive marine heatwaves that are causing coral bleaching and mortality. Coarse-grained climate models predict that few coral reefs will survive the 3 °C sea-surface temperature rise in the coming century. Yet, field studies show localized pockets of coral survival and recovery even under high-temperature conditions. Quantifying recovery from marine heatwaves is central to making accurate predictions of coral-reef trajectories into the near future. Here we introduce the world’s most comprehensive database on coral recovery following marine heatwaves and other disturbances, called Heatwaves and Coral-Recovery Database (HeatCRD) encompassing 29,205 data records spanning 44 years from 12,266 sites, 83 countries, and 160 data sources. These data provide essential information to coral-reef scientists and managers to best guide coral-reef conservation efforts at both local and regional scales.
Analyzing the dynamic patterns of COVID-19 through nonstandard finite difference scheme
Authors: Aljohani Abeer , Shokri Ali , Mukalazi Herbert
Published: April 2024

This paper presents a novel approach to analyzing the dynamics of COVID-19 using nonstandard finite difference (NSFD) schemes. Our model incorporates both asymptomatic and symptomatic infected individuals, allowing for a more comprehensive understanding of the epidemic's spread. We introduce an unconditionally stable NSFD system that eliminates the need for traditional Runge–Kutta methods, ensuring dynamical consistency and numerical accuracy. Through rigorous numerical analysis, we evaluate the performance of different NSFD strategies and validate our analytical findings. Our work demonstrates the benefits of using NSFD schemes for modeling infectious diseases, offering advantages in terms of stability and efficiency. We further illustrate the dynamic behavior of COVID-19 under various conditions using numerical simulations. The results from these simulations demonstrate the effectiveness of the proposed approach in capturing the epidemic's complex dynamics.
Emission of five OAM dispersive waves in dispersion-engineered double-ring core fiber
Authors: Geng Wenpu , Fang Yuxi , Bao Changjing , Pan Zhongqi , Yue Yang
Published: April 2024

Beams carrying orbital angular momentum (OAM) have exhibited significant potential across various fields, such as metrology, image coding, and optical communications. High-performance broadband coherent OAM sources are critical to the operation of optical systems. The emission of dispersive waves facilitates the efficient transfer of energy to distant spectral domains while preserving the coherence among the generated frequency components. Light sources that maintain consistency over a wide range can increase the efficiency of optical communication systems and improve the measurement accuracy in imaging and metrology. In this work, we propose a germanium-doped double ring-core fiber for five OAM dispersive waves (DWs) generation. The OAM1,1 mode supported in the fiber exhibits three zero-dispersion wavelengths (ZDWs) located at 1275, 1720 and 2325 nm. When pumped under normal dispersion, the output spectrum undergoes broadening and exhibits five DWs, situated around 955, 1120, 1450, 2795 and 2965 nm, respectively. Concomitant with blue-shifted and red-shifted dispersive waves, the spectrum spans from 895 to 3050 nm with high coherence. The effect of the fiber and input pulse parameters on DWs generation, as well as the underlying dynamics of the dispersive wave generation process, are discussed. As expected, the number and location of DWs generated in the output spectrum have agreement with the prediction of the phase-matching condition. Overall, this multiple DWs generation method in the proposed fiber paves the way for developing efficient and coherent OAM light sources in fiber-based optical systems.
Interpretable detection of epiretinal membrane from optical coherence tomography with deep neural networks
Authors: Ayhan Murat Seçkin , Neubauer Jonas , Uzel Mehmet Murat , Gelisken Faik , Berens Philipp
Published: April 2024

This study aimed to automatically detect epiretinal membranes (ERM) in various OCT-scans of the central and paracentral macula region and classify them by size using deep-neural-networks (DNNs). To this end, 11,061 OCT-images were included and graded according to the presence of an ERM and its size (small 100–1000 µm, large > 1000 µm). The data set was divided into training, validation and test sets (75%, 10%, 15% of the data, respectively). An ensemble of DNNs was trained and saliency maps were generated using Guided-Backprob. OCT-scans were also transformed into a one-dimensional-value using t-SNE analysis. The DNNs’ receiver-operating-characteristics on the test set showed a high performance for no-ERM, small-ERM and large-ERM cases (AUC: 0.99, 0.92, 0.99, respectively; 3-way accuracy: 89%), with small-ERMs being the most difficult ones to detect. t-SNE analysis sorted cases by size and, in particular, revealed increased classification uncertainty at the transitions between groups. Saliency maps reliably highlighted ERM, regardless of the presence of other OCT features (i.e. retinal-thickening, intraretinal pseudo-cysts, epiretinal-proliferation) and entities such as ERM-retinoschisis, macular-pseudohole and lamellar-macular-hole. This study showed therefore that DNNs can reliably detect and grade ERMs according to their size not only in the fovea but also in the paracentral region. This is also achieved in cases of hard-to-detect, small-ERMs. In addition, the generated saliency maps can be used to highlight small-ERMs that might otherwise be missed. The proposed model could be used for screening-programs or decision-support-systems in the future.
Content-illumination coupling guided low-light image enhancement network
Authors: Zhao Ruini , Xie Meilin , Feng Xubin , Su Xiuqin , Zhang Huiming , Yang Wei
Published: April 2024

Current low-light enhancement algorithms fail to suppress noise when enhancing brightness, and may introduces structural distortion and color distortion caused by halos or artifacts. This paper proposes a content-illumination coupling guided low-light image enhancement network (CICGNet), it develops a truss topology based on Retinex as backbone to decompose low-light image component in an end-to-end way. The preservation of content features and the enhancement of illumination features are carried out along with depth and width direction of the truss topology. Each submodule uses the same resolution input and output to avoid the introduction of noise. Illumination component prevents misestimation of global and local illumination by using pre- and post-activation features at different depth levels, this way could avoid possible halos and artifacts. The network progressively enhances the illumination component and maintains the content component stage-by-stage. The proposed algorithm demonstrates better performance compared with advanced attention-based low-light enhancement algorithms and state-of-the-art image restoration algorithms. We also perform extensive ablation studies and demonstrate the impact of low-light enhancement algorithm on the downstream task of computer vision. Code is available at: https://github.com/Ruini94/CICGNet.
Influence of circle of Willis modeling on hemodynamic parameters in anterior communicating artery aneurysms and recommendations for model selection
Authors: Yang Hyeondong , Cho Kwang-Chun , Hong Ineui , Kim Yeonwoo , Kim Yong Bae , Kim Jung-Jae , Oh Je Hoon
Published: April 2024

Computational fluid dynamics (CFD) has been utilized to calculate hemodynamic parameters in anterior communicating artery aneurysm (AComA), which is located at a junction between left and right A1 and A2 segments. However, complete or half circle of Willis (CoW) models are used indiscriminately. This study aims to suggest recommendations for determining suitable CoW model. Five patient-specific CoW models with AComA were used, and each model was divided into complete, left-half, and right-half models. After validating the CFD using a flow experiment, the hemodynamic parameters and flow patterns in five AComAs were compared. In four out of five cases, inflow from one A1 side had a dominant influence on the AComA, while both left and right A1 sides affected the AComA in the remaining case. Also, the average difference in time-averaged wall shear stress between the complete and half models for four cases was 4.6%, but it was 62% in the other case. The differences in the vascular resistances of left and right A1 and A2 segments greatly influenced the flow patterns in the AComA. These results may help to enhance clinicians’ understanding of blood flow in the brain, leading to improvements in diagnosis and treatment of cerebral aneurysms.
Digital inclusive finance, green technological innovation, and carbon emissions from a spatial perspective
Authors: Lu Yang , Xia Ziyi
Published: April 2024

Based on the panel data of 276 prefecture-level cities in China from 2011 to 2020, this study explores the impact of digital inclusive finance (DIF) on carbon emissions and the intrinsic mechanism of green technological innovation from a spatial perspective by constructing a spatial econometric model, a mediating effect model, and a threshold model. The results show that DIF significantly inhibits carbon emissions, exhibiting a spatial spillover effect. The transmission mechanism from a spatial perspective shows that green technological innovation plays a partial mediating role between DIF and carbon emissions, with the mediating effect accounting for approximately 59.47%. The heterogeneity analysis suggests that the impact of DIF on the reduction of carbon emissions is more pronounced in large and medium-sized cities and eastern regions. Further discussion reveals that the carbon reduction effect of DIF is also influenced by green technological innovation and industrial structure upgrading, showing threshold effects with marginal decreases and gradual increases, respectively.
Convolutional neural network algorithm trained on lumbar spine radiographs to predict outcomes of transforaminal epidural steroid injection for lumbosacral radicular pain from spinal stenosis
Authors: Kim Jeoung Kun , Chang Min Cheol
Published: April 2024

Little is known about the therapeutic outcomes of transforaminal epidural steroid injection (TFESI) in patients with lumbosacral radicular pain due to lumbar spinal stenosis (LSS). Using lumbar spine radiographs as input data, we trained a convolutional neural network (CNN) to predict therapeutic outcomes after lumbar TFESI in patients with lumbosacral radicular pain caused by LSS. We retrospectively recruited 193 patients for this study. The lumbar spine radiographs included anteroposterior, lateral, and bilateral (left and right) oblique views. We cut each lumbar spine radiograph image into a square shape that included the vertebra corresponding to the level at which the TFESI was performed and the vertebrae juxta below and above that level. Output data were divided into “favorable outcome” (≥ 50% reduction in the numeric rating scale [NRS] score at 2 months post-TFESI) and “poor outcome” (< 50% reduction in the NRS score at 2 months post-TFESI). Using these input and output data, we developed a CNN model for predicting TFESI outcomes. The area under the curve of our model was 0.920. Its accuracy was 87.2%. Our CNN model has an excellent capacity for predicting therapeutic outcomes after lumbar TFESI in patients with lumbosacral radicular pain induced by LSS.
Tunable magnetic confinement effect in a magnetic superlattice of graphene
Authors: Tosun Onur , Sarkar Preetha , Qian Chang , Gilbert Matthew , Chen Qian , Mason Nadya
Published: April 2024

Two-dimensional van der Waals materials such as graphene present an opportunity for band structure engineering using custom superlattice potentials. In this study, we demonstrate how self-assemblies of magnetic iron-oxide (Fe3O4) nanospheres stacked on monolayer graphene generate a proximity-induced magnetic superlattice in graphene and modify its band structure. Interactions between the nanospheres and the graphene layer generate superlattice Dirac points in addition to a gapped energy spectrum near the K and K′ valleys, resulting in magnetic confinement of quasiparticles around the nanospheres. This is evidenced by gate-dependent resistance oscillations, observed in our low temperature transport measurements, and confirmed by self-consistent tight binding calculations. Furthermore, we show that an external magnetic field can tune the magnetic superlattice potential created by the nanospheres, and thus the transport characteristics of the system. This technique for magnetic-field-tuned band structure engineering using magnetic nanostructures can be extended to a broader class of 2D van der Waals and topological materials.