bluuebunny/crossref_metadata_2025_split huggingface dataset:
PCLAF induces bone marrow adipocyte senescence and contributes to skeletal aging
Authors: Xie Lingqi , Cheng Yalun , Hu Biao , Chen Xin , An Yuze , Xia Zhuying , Cai Guangping , Li Changjun , Peng Hui 
Published: July 2024

AbstractBone marrow adipocytes (BMAds) affect bone homeostasis, but the mechanism remains unclear. Here, we showed that exercise inhibited PCNA clamp-associated factor (PCLAF) secretion from the bone marrow macrophages to inhibit BMAds senescence and thus alleviated skeletal aging. The genetic deletion of PCLAF in macrophages inhibited BMAds senescence and delayed skeletal aging. In contrast, the transplantation of PCLAF-mediated senescent BMAds into the bone marrow of healthy mice suppressed bone turnover. Mechanistically, PCLAF bound to the ADGRL2 receptor to inhibit AKT/mTOR signaling that triggered BMAds senescence and subsequently spread senescence among osteogenic and osteoclastic cells. Of note, we developed a PCLAF-neutralizing antibody and showed its therapeutic effects on skeletal health in old mice. Together, these findings identify PCLAF as an inducer of BMAds senescence and provide a promising way to treat age-related osteoporosis.
ATR, CHK1 and WEE1 inhibitors cause homologous recombination repair deficiency to induce synthetic lethality with PARP inhibitors
Authors: Smith Hannah L. , Willmore Elaine , Prendergast Lisa , Curtin Nicola J. 
Published: July 2024

Abstract
Purpose
PARP inhibitors (PARPi) are effective in homologous recombination repair (HRR) defective (HRD) cancers. To (re)sensitise HRR proficient (HRP) tumours to PARPi combinations with other drugs are being explored. Our aim was to determine the mechanism underpinning the sensitisation to PARPi by inhibitors of cell cycle checkpoint kinases ATR, CHK1 and WEE1.

Experimental design
A panel of HRD and HRP cells (including matched BRCA1 or 2 mutant and corrected pairs) and ovarian cancer ascites cells were used. Rucaparib (PARPi) induced replication stress (RS) and HRR (immunofluorescence microscopy for γH2AX and RAD51 foci, respectively), cell cycle changes (flow cytometry), activation of ATR, CHK1 and WEE1 (Western Blot for pCHK1S345, pCHK1S296 and pCDK1Y15, respectively) and cytotoxicity (colony formation assay) was determined, followed by investigations of the impact on all of these parameters by inhibitors of ATR (VE-821, 1 µM), CHK1 (PF-477736, 50 nM) and WEE1 (MK-1775, 100 nM).

Results
Rucaparib induced RS (3 to10-fold), S-phase accumulation (2-fold) and ATR, CHK1 and WEE1 activation (up to 3-fold), and VE-821, PF-477736 and MK-1775 inhibited their targets and abrogated these rucaparib-induced cell cycle changes in HRP and HRD cells. Rucaparib activated HRR in HRP cells only and was (60-1,000x) more cytotoxic to HRD cells. VE-821, PF-477736 and MK-1775 blocked HRR and sensitised HRP but not HRD cells and primary ovarian ascites to rucaparib.

Conclusions
Our data indicate that, rather than acting via abrogation of cell cycle checkpoints, ATR, CHK1 and WEE1 inhibitors cause an HRD phenotype and hence “induced synthetic lethality” with PARPi.
Transposable elements-mediated recruitment of KDM1A epigenetically silences HNF4A expression to promote hepatocellular carcinoma
Authors: Jing Tiantian , Wei Dianhui , Xu Xiaoli , Wu Chengsi , Yuan Lili , Huang Yiwen , Liu Yizhen , Jiang Yanyi , Wang Boshi 
Published: July 2024

AbstractTransposable elements (TEs) contribute to gene expression regulation by acting as cis-regulatory elements that attract transcription factors and epigenetic regulators. This research aims to explore the functional and clinical implications of transposable element-related molecular events in hepatocellular carcinoma, focusing on the mechanism through which liver-specific accessible TEs (liver-TEs) regulate adjacent gene expression. Our findings reveal that the expression of HNF4A is inversely regulated by proximate liver-TEs, which facilitates liver cancer cell proliferation. Mechanistically, liver-TEs are predominantly occupied by the histone demethylase, KDM1A. KDM1A negatively influences the methylation of histone H3 Lys4 (H3K4) of liver-TEs, resulting in the epigenetic silencing of HNF4A expression. The suppression of HNF4A mediated by KDM1A promotes liver cancer cell proliferation. In conclusion, this study uncovers a liver-TE/KDM1A/HNF4A regulatory axis that promotes liver cancer growth and highlights KDM1A as a promising therapeutic target. Our findings provide insight into the transposable element-related molecular mechanisms underlying liver cancer progression.
Enantiopure trigonal bipyramidal coordination cages templated by in situ self-organized D2h-symmetric anions
Authors: Guo Shan , Zhan Wen-Wen , Yang Feng-Lei , Zhou Jie , Duan Yu-Hao , Zhang Dawei , Yang Yang 
Published: July 2024

AbstractThe control of a molecule’s geometry, chirality, and physical properties has long been a challenging pursuit. Our study introduces a dependable method for assembling D3-symmetric trigonal bipyramidal coordination cages. Specifically, D2h-symmetric anions, like oxalate and chloranilic anions, self-organize around a metal ion to form chiral-at-metal anionic complexes, which template the formation of D3-symmetric trigonal bipyramidal coordination cages. The chirality of the trigonal bipyramid is determined by the point chirality of chiral amines used in forming the ligands. Additionally, these cages exhibit chiral selectivity for the included chiral-at-metal anionic template. Our method is broadly applicable to various ligand systems, enabling the construction of larger cages when larger D2h-symmetric anions, like chloranilic anions, are employed. Furthermore, we successfully produce enantiopure trigonal bipyramidal cages with anthracene-containing backbones using this approach, which would be otherwise infeasible. These cages exhibit circularly polarized luminescence, which is modulable through the reversible photo-oxygenation of the anthracenes.
Unraveling the energy storage mechanism in graphene-based nonaqueous electrochemical capacitors by gap-enhanced Raman spectroscopy
Authors: Yin Xiao-Ting , You En-Ming , Zhou Ru-Yu , Zhu Li-Hong , Wang Wei-Wei , Li Kai-Xuan , Wu De-Yin , Gu Yu , Li Jian-Feng , Mao Bing-Wei , Yan Jia-Wei 
Published: July 2024

AbstractGraphene has been extensively utilized as an electrode material for nonaqueous electrochemical capacitors. However, a comprehensive understanding of the charging mechanism and ion arrangement at the graphene/electrolyte interface remain elusive. Herein, a gap-enhanced Raman spectroscopic strategy is designed to characterize the dynamic interfacial process of graphene with an adjustable number of layers, which is based on synergistic enhancement of localized surface plasmons from shell-isolated nanoparticles and a metal substrate. By employing such a strategy combined with complementary characterization techniques, we study the potential-dependent configuration of adsorbed ions and capacitance curves for graphene based on the number of layers. As the number of layers increases, the properties of graphene transform from a metalloid nature to graphite-like behavior. The charging mechanism shifts from co-ion desorption in single-layer graphene to ion exchange domination in few-layer graphene. The increase in area specific capacitance from 64 to 145 µF cm–2 is attributed to the influence on ion packing, thereby impacting the electrochemical performance. Furthermore, the potential-dependent coordination structure of lithium bis(fluorosulfonyl) imide in tetraglyme ([Li(G4)][FSI]) at graphene/electrolyte interface is revealed. This work adds to the understanding of graphene interfaces with distinct properties, offering insights for optimization of electrochemical capacitors.
SHP2 as a primordial epigenetic enzyme expunges histone H3 pTyr-54 to amend androgen receptor homeostasis
Authors: Chouhan Surbhi , Sridaran Dhivya , Weimholt Cody , Luo Jingqin , Li Tiandao , Hodgson Myles C. , Santos Luana N. , Le Sommer Samantha , Fang Bin , Koomen John M. , Seeliger Markus , Qu Cheng-Kui , Yart Armelle , Kontaridis Maria I. , Mahajan Kiran , Mahajan Nupam P. 
Published: July 2024

AbstractMutations that decrease or increase the activity of the tyrosine phosphatase, SHP2 (encoded by PTPN11), promotes developmental disorders and several malignancies by varying phosphatase activity. We uncovered that SHP2 is a distinct class of an epigenetic enzyme; upon phosphorylation by the kinase ACK1/TNK2, pSHP2 was escorted by androgen receptor (AR) to chromatin, erasing hitherto unidentified pY54-H3 (phosphorylation of histones H3 at Tyr54) epigenetic marks to trigger a transcriptional program of AR. Noonan Syndrome with Multiple Lentigines (NSML) patients, SHP2 knock-in mice, and ACK1 knockout mice presented dramatic increase in pY54-H3, leading to loss of AR transcriptome. In contrast, prostate tumors with high pSHP2 and pACK1 activity exhibited progressive downregulation of pY54-H3 levels and higher AR expression that correlated with disease severity. Overall, pSHP2/pY54-H3 signaling acts as a sentinel of AR homeostasis, explaining not only growth retardation, genital abnormalities and infertility among NSML patients, but also significant AR upregulation in prostate cancer patients.
Non-homologous end joining shapes the genomic rearrangement landscape of chromothripsis from mitotic errors
Authors: Hu Qing , Espejo Valle-Inclán Jose , Dahiya Rashmi , Guyer Alison , Mazzagatti Alice , Maurais Elizabeth G. , Engel Justin L. , Lu Huiming , Davis Anthony J. , Cortés-Ciriano Isidro , Ly Peter 
Published: July 2024

AbstractMitotic errors generate micronuclei entrapping mis-segregated chromosomes, which are susceptible to catastrophic fragmentation through chromothripsis. The reassembly of fragmented chromosomes by error-prone DNA double-strand break (DSB) repair generates diverse genomic rearrangements associated with human diseases. How specific repair pathways recognize and process these lesions remains poorly understood. Here we use CRISPR/Cas9 to systematically inactivate distinct DSB repair pathways and interrogate the rearrangement landscape of fragmented chromosomes. Deletion of canonical non-homologous end joining (NHEJ) components substantially reduces complex rearrangements and shifts the rearrangement landscape toward simple alterations without the characteristic patterns of chromothripsis. Following reincorporation into the nucleus, fragmented chromosomes localize within sub-nuclear micronuclei bodies (MN bodies) and undergo ligation by NHEJ within a single cell cycle. In the absence of NHEJ, chromosome fragments are rarely engaged by alternative end-joining or recombination-based mechanisms, resulting in delayed repair kinetics, persistent 53BP1-labeled MN bodies, and cell cycle arrest. Thus, we provide evidence supporting NHEJ as the exclusive DSB repair pathway generating complex rearrangements from mitotic errors.
Reducing nonradiative recombination for highly efficient inverted perovskite solar cells via a synergistic bimolecular interface
Authors: Xiong Shaobing , Tian Fuyu , Wang Feng , Cao Aiping , Chen Zeng , Jiang Sheng , Li Di , Xu Bin , Wu Hongbo , Zhang Yefan , Qiao Hongwei , Ma Zaifei , Tang Jianxin , Zhu Haiming , Yao Yefeng , Liu Xianjie , Zhang Lijun , Sun Zhenrong , Fahlman Mats , Chu Junhao , Gao Feng , Bao Qinye 
Published: July 2024

AbstractReducing interface nonradiative recombination is important for realizing highly efficient perovskite solar cells. In this work, we develop a synergistic bimolecular interlayer (SBI) strategy via 4-methoxyphenylphosphonic acid (MPA) and 2-phenylethylammonium iodide (PEAI) to functionalize the perovskite interface. MPA induces an in-situ chemical reaction at the perovskite surface via forming strong P-O-Pb covalent bonds that diminish the surface defect density and upshift the surface Fermi level. PEAI further creates an additional negative surface dipole so that a more n-type perovskite surface is constructed, which enhances electron extraction at the top interface. With this cooperative surface treatment, we greatly minimize interface nonradiative recombination through both enhanced defect passivation and improved energetics. The resulting p-i-n device achieves a stabilized power conversion efficiency of 25.53% and one of the smallest nonradiative recombination induced Voc loss of only 59 mV reported to date. We also obtain a certified efficiency of 25.05%. This work sheds light on the synergistic interface engineering for further improvement of perovskite solar cells.
Rethinking materials simulations: Blending direct numerical simulations with neural operators
Authors: Oommen Vivek , Shukla Khemraj , Desai Saaketh , Dingreville Rémi , Karniadakis George Em 
Published: July 2024

AbstractMaterials simulations based on direct numerical solvers are accurate but computationally expensive for predicting materials evolution across length- and time-scales, due to the complexity of the underlying evolution equations, the nature of multiscale spatiotemporal interactions, and the need to reach long-time integration. We develop a method that blends direct numerical solvers with neural operators to accelerate such simulations. This methodology is based on the integration of a community numerical solver with a U-Net neural operator, enhanced by a temporal-conditioning mechanism to enable accurate extrapolation and efficient time-to-solution predictions of the dynamics. We demonstrate the effectiveness of this hybrid framework on simulations of microstructure evolution via the phase-field method. Such simulations exhibit high spatial gradients and the co-evolution of different material phases with simultaneous slow and fast materials dynamics. We establish accurate extrapolation of the coupled solver with large speed-up compared to DNS depending on the hybrid strategy utilized. This methodology is generalizable to a broad range of materials simulations, from solid mechanics to fluid dynamics, geophysics, climate, and more.
Automated workflow for analyzing thermodynamic stability in polymorphic perovskite alloys
Authors: de Araujo Luis Octavio , Rêgo Celso R. C. , Wenzel Wolfgang , Piotrowski Maurício Jeomar , Dias Alexandre Cavalheiro , Guedes-Sobrinho Diego 
Published: July 2024

AbstractIn this first-principles investigation, we explore the polymorphic features of pseudo-cubic alloys, focusing on the impact of mixing organic and inorganic cations on their structural and electronic properties, configurational disorder, and thermodynamic stability. Employing an automated cluster expansion within the generalized quasichemical approximation (GQCA), our results reveal how the effective radius of the organic cation (rMA = 2.15 Å, rFA = 2.53 Å) and its dipole moment (μMA = 2.15 D, μFA = 0.25 D), influences Glazer’s rotations in the A1−xCsxPbI3 (A = MA, FA) sublattice, with MA-based alloy presenting a higher critical temperature (527 K) and being stable for x > 0.60 above 200 K, while its FA analog has a lower critical temperature (427.7 K) and is stable for x < 0.15 above 100 K. Additionally, polymorphic motifs magnify relativistic effects, impacting the thermodynamic behavior of the systems. Our methodology leverages the SimStack framework, an automated scientific workflow that enables the nuanced modeling of polymorphic alloys. This structured approach allows for comprehensive calculations of thermodynamic properties, phase diagrams, optoelectronic insights, and power conversion efficiencies while meticulously incorporating crucial relativistic effects like spin-orbit coupling (SOC) and quasi-particle corrections. Our findings advocate for the rational design of thermodynamically stable compositions in solar cell applications by calculating power conversion efficiencies using a spectroscopic limited maximum efficiency model, from which we obtained high efficiencies of about 28% (31–32%) for MA1−xCsxPbI3 with 0.50 < x < 1.00 (FA1−xCsxPbI3 with 0.0 < x < 0.20) as thermodynamically stable compositions at room temperature. The workflow’s significance is highlighted by a Colab-based notebook, which facilitates the analysis of raw data output, allowing users to delve into the physics of these complex systems. Our work underscores the pivotal role of composition and polymorphic degrees in determining the stability and optoelectronic properties of MHP alloys. It demonstrates the effectiveness of the SimStack workflow in advancing our understanding of these materials.
Phonon-mediated spin transport in quantum paraelectric metals
Authors: Kim Kyoung-Min , Chung Suk Bum 
Published: July 2024

AbstractThe concept of ferroelectricity is now often extended to include continuous inversion symmetry-breaking transitions in various metals and doped semiconductors. Paraelectric metals near ferroelectric quantum criticality, which we term ‘quantum paraelectric metals,’ possess soft transverse optical phonons which can have Rashba-type coupling to itinerant electrons in the presence of spin-orbit coupling. We find through the Kubo formula calculation that such Rashba electron-phonon coupling has a profound impact on electron spin transport. While the spin Hall effect arising from non-trivial electronic band structures has been studied extensively, we find here the presence of the Rashba electron-phonon coupling can give rise to spin current, including spin Hall current, in response to an inhomogeneous electric field even with a completely trivial band structure. Furthermore, this spin conductivity displays unconventional characteristics, such as quadrupolar symmetry associated with the wave vector of the electric field and a thermal activation behavior characterized by scaling laws dependent on the phonon frequency to temperature ratio. These findings shed light on exotic electronic transport phenomena originating from ferroelectric quantum criticality, highlighting the intricate interplay of charge and spin degrees of freedom.
A systematic review of structural and functional magnetic resonance imaging studies on the neurobiology of depressive symptoms in schizophrenia spectrum disorders
Authors: Gallucci Julia , Secara Maria T. , Chen Oliver , Oliver Lindsay D. , Jones Brett D. M. , Marawi Tulip , Foussias George , Voineskos Aristotle N. , Hawco Colin 
Published: July 2024

AbstractDepressive symptoms in Schizophrenia Spectrum Disorders (SSDs) negatively impact suicidality, prognosis, and quality of life. Despite this, efficacious treatments are limited, largely because the neural mechanisms underlying depressive symptoms in SSDs remain poorly understood. We conducted a systematic review to provide an overview of studies that investigated the neural correlates of depressive symptoms in SSDs using neuroimaging techniques. We searched MEDLINE, PsycINFO, EMBASE, Web of Science, and Cochrane Library databases from inception through June 19, 2023. Specifically, we focused on structural and functional magnetic resonance imaging (MRI), encompassing: (1) T1-weighted imaging measuring brain morphology; (2) diffusion-weighted imaging assessing white matter integrity; or (3) T2*-weighted imaging measures of brain function. Our search yielded 33 articles; 14 structural MRI studies, 18 functional (f)MRI studies, and 1 multimodal fMRI/MRI study. Reviewed studies indicate potential commonalities in the neurobiology of depressive symptoms between SSDs and major depressive disorders, particularly in subcortical and frontal brain regions, though confidence in this interpretation is limited. The review underscores a notable knowledge gap in our understanding of the neurobiology of depression in SSDs, marked by inconsistent approaches and few studies examining imaging metrics of depressive symptoms. Inconsistencies across studies’ findings emphasize the necessity for more direct and comprehensive research focusing on the neurobiology of depression in SSDs. Future studies should go beyond “total score” depression metrics and adopt more nuanced assessment approaches considering distinct subdomains. This could reveal unique neurobiological profiles and inform investigations of targeted treatments for depression in SSDs.
A novel technique for the single-port laparoscopic percutaneous extraperitoneal closure (SLPEC) of paediatric isolated giant inguinal hernias using double-modified hernia needles
Authors: Xu Long-Yao , Cui Xu , Huang Wen-Hua , Chen Liu , Zhou Chao-Ming 
Published: July 2024

AbstractThe objective was to explore the efficacy of single-port laparoscopic percutaneous extraperitoneal closure using double-modified hernia needles with hydrodissection (SLPEC group) and two-port laparoscopic percutaneous extraperitoneal closure (TLPEC group) for the treatment of giant indirect inguinal hernias in children. We performed a retrospective review of all children with giant indirect inguinal hernias (inner ring orifice diameter ≥ 1.5 cm) who underwent laparoscopic high ligation of the hernia sac at FuJian Children’s Hospital from January 2019 to December 2021. We collected data from the medical records of all the children and analysed their clinical characteristics and operation-related and follow-up information. Overall, this study included a cohort of 219 patients with isolated giant inguinal hernias who had complete clinical data and who had undergone laparoscopic high ligation of the hernia sac at our centre. All procedures were successfully performed for the 106 patients who underwent SLPEC and for the 113 patients who underwent TLPEC at our centre. There were no statistically significant differences in patient age, sex, body weight, follow-up time or the side of inguinal hernia between the SLPEC group and the TLPEC group (P = 0.123, 0.613, 0.121, 0.076 and 0.081, respectively). However, there were significant differences in the bleeding volume, visual analogue scale (VAS) score, and postoperative activity time between the two groups (P ≤ 0.001). The operation times in the TLPEC group were significantly longer than those in the SLPEC group (P = 0.048), but there were no significant differences in hospital length of stay or hospitalization costs between the two groups (P = 0.244 and 0.073, respectively). Incision scars were found in 2 patients in the SLPEC group and 9 patients in the TLPEC group, and there was a significant difference between the two groups (P = 0.04). However, the incidence of ipsilateral hernia recurrence, surgical site infection, suture-knot reactions and chronic inguinodynia did not significantly differ between the two groups (P = 0.332, 0.301, 0.332 and 0.599, respectively). Postoperative hydrocele occurred in only 1 male child in the SLPEC group and in no male children in the TLPEC group, and there was no difference between the two groups (P = 0.310). In this study, there were no cases of testicular atrophy or iatrogenic ascent of the testis. Compared with the TLPEC group, the SLPEC group had the advantages of a concealed incision, light scarring, minimal invasiveness, a reduced operation time, minimal bleeding, mild pain and rapid recovery. In conclusion, SLPEC using double-modified hernia needles with hydrodissection and high ligation of the hernia sac is a safe, effective and minimally invasive surgery. The cosmetic results are impressive, and the follow-up results are promising.