bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of K-Solutions of Rectangular Flaw With Semi-Elliptical Flaw for PWSCC Growth Analysis
Authors: Hojo Kiminobu , Rudland David
Published: November 2024

The JSME Codes and Standards has a Code Case of K-solutions of a rectangular flaw for primary water stress corrosion cracking (PWSCC) growth analysis. The shape of axial PWSCC flaws in a dissimilar material weld (DMW) joint is relatively rectangular rather than semi-elliptical. This flaw will propagate selectively in the weld metal, which makes it a deep, short flaw. The K-solutions of the JSME Code Case have been provided considering the features of the PWSCC flaw conservatively. The same K-solutions for a Code Case of ASME Section XI were proposed and have been discussed in a Working Group of the ASME Sec. XI Standard Committee. In the Working Group, sample problems were proposed to confirm necessity of introduction of K-solutions for a rectangular flaw into the ASME Code, and the appropriateness of the code description of a draft Code Case based on the JSME Code Case. Especially, there was a discussion to avoid over-conservatism of the K-solution. In the sample problems, the K-solutions, that is Gi coefficients, of a rectangular flaw and a semi-elliptical flaw were compared for various flaws with a different flaw depth and length. The deeper and the narrower the flaw, the larger the difference of the Gi coefficients between a rectangular flaw and a semielliptical flaw, up to the ratio of 0.5 to 0.6. Also, PWSCC propagation calculations of both types of the flaws assumed in a DMW joint of a primary coolant pipe with double V groove, a hot leg with single V groove and a surge line with single V groove were performed by using the K-solutions of a rectangular flaw and a semi-elliptical flaw. These Code basis calculation results were compared with the result of the advanced FE (AFEA) analyses which simulated actual axial flaw growth behavior. In the sample problems, the initial flaw was a semi-circular flaw within a weld width or a rectangular flaw with a length of the weld width. The initial semi-circular flaw grew with a semi-elliptical shape and the initial rectangular flaw grew with a rectangular shape. As a result, the calculation results of semi-elliptical flaws were quite similar to those of AFEA. The condition of a rectangular flaw with the initial flaw length of the weld width was too conservative, which was in the code description of the first draft Code Case. If the initial semi-circular flaw reached the weld boundary at the surface point and changed to a rectangular flaw, the PWSCC propagation behaviors were reasonably conservative. Based on the results of the sample problems, the code description of the Code Case was revised.
Research on the Application of Risk-Managed Technical Specifications in Passive Nuclear Power Plants
Authors: Yan Zhen , Wang Jiajian , Ma Gang , Sun Jianwen , Wang Zhenqi , Liu Dalin , Wang Shuting , Zhu Sheng
Published: November 2024

The Technical Specification is the top-level document for the operation of a nuclear power plant and is an important basis for action to safeguard and realize the safety of a nuclear power plant. Risk-managed technical specifications use risk-informed technology to optimize traditional technical specifications. By introducing risk-informed completion times instead of completion times for limiting conditions for operation, it enhances the flexibility of nuclear power plant operation and maintenance, avoids potential risks caused by unnecessary unplanned shutdowns and mode switching, and provides an effective way for power plants to control and reduce the risks of maintenance activities. Based on the design characteristics of passive nuclear power plants, this paper takes a passive nuclear power plant as the research object to carry out the research on the application of risk-managed technical specifications in passive nuclear power plants, which includes: determining the applicable plant operation modes by considering the purpose of the application of risk-managed technical specifications and the operation modes characteristics of the units; determining the risk management thresholds in terms of balancing the risks and the flexibility of operation and maintenance; and formulating the LCO actions screening criteria applicable to risk-managed technical specifications in light of the characteristics of passive nuclear power plants; and conducting a comprehensive screening of actions related to the limiting conditions for operation in the technical specification of the plant in light of the feedback from the operation of the plant; and finally in order to support the application of risk-managed technical specifications in operating power plants, providing development recommendations for the management and implementation process of the nuclear power plant.
Molten Salt Reactor Simulation by a MOOSE-Based Application Suanni
Authors: Zhang Ao , Dai Ming , Xia Shaopeng , Chen Jingen , Cai Xiangzhou
Published: November 2024

Liquid fueled Molten Salt Reactors use homogeneously mixed fuel and have less heterogeneity than traditional solid fueled reactors. The two-step method successfully applied for Light Water Reactors is expected to obtain good accuracy and efficiency in MSR simulations. This paper implements a two-step procedure into a newly developed code Suanni based on the Multi-physcis Object Oriented Simulation Environment (MOOSE) framework. Suanni utilizes an open-source Monte Carlo code OpenMC for producing few-group cross sections and providing high-fidelity solutions to calculate super homogenization (SPH) factors. A diffusion solver with continuous finite element method is implemented in Suanni for the second step core simulation with SPH corrected cross sections. A Molten Salt Thermal Reactor (MSTR) core is used for the verification of the newly developed code, and the reference results come from continuous-energy OpenMC calculations. The keff and power errors are relatively large when no SPH correction is used. These errors can be significantly reduced with 4-group SPH corrected cross sections, where kes error is less than 300 pcm and relative power errors range from −2.4% to −0.35% for 3D rod-in MSTR simulation.
Numerical Investigation of High-Temperature Heat Pipes With Different Wick Structures Under Non-Uniform Heating Boundary Conditions
Authors: Guo Kailun , Sun Qishi , Sun Hao , Wang Chenlong , Chen Kang , Tian Wenxi , Su Guanghui , Qiu Suizheng
Published: November 2024

High-temperature heat pipe is an ideal technical solution for microreactors applied for space missions, planet surface, and the small electricity markets on the ground. However, the internal fluid flow state and the effects of key parameters such as permeability, porosity, and capillary force of wick structure on the distribution of working fluid inside the heat pipe are difficult to measure experimentally. In this study, a general CFD model for heat pipe with wick structure that can predict the thermal behavior at different steady-state conditions was carried out. The thermal conduction through heat pipe shell, liquid film on the inner surface, and the formation of liquid reservoir at the bottom of heat pipe were considered in this model. A high-temperature heat pipe model considering the flow of liquid working fluid inside the wick structure was developed based on the Star-CCM+ numerical simulation software. The model used a combination of the liquid film model and the Volume of Fluid (VOF) model to simulate the effects of fluid flow and collection behavior inside the wick structure on the heat transfer characteristics of the heat pipe. The method included models for flow resistance and capillary driving force under steady-state conditions, centrifugal force and time-varying gravitational field under motion conditions, and mixed convective heat transfer caused by motion conditions. The accuracy of the numerical simulation was validated using typical potassium high-temperature heat pipe experiments. The effects of different permeability and capillary force characteristics of the wick structure on heat transfer and internal fluid distribution in the heat pipe were studied. Based on the current method, high-temperature heat pipes with different inclinations (0°, 90 °and 45°) were investigated. Additionally, non-uniform heating boundary conditions were added to the high-temperature heat pipe evaporator section to investigate its heat transfer performance under real reactor axial power input. This investigation lays the foundation for the design and analysis of the heat transfer characteristics of high-temperature heat pipes.
Fast Solution of Schrödinger Equation Based on Complex One-Dimensional Potential Wells
Authors: Liu Zihao , Wang Xiang
Published: November 2024

The Schrödinger equation (SE) is a fundamental equation in quantum mechanics that describes the behavior of quantum systems. Solving the SE is crucial for understanding quantum phenomena, but it is a challenging task, particularly for complex potential wells, which require significant computational resources to obtain high accuracy by using traditional numerical methods. Recently, deep neural networks, such as Fourier neural operator (FNO), have made significant breakthroughs in solving partial differential equations. This paper explores solving the one-dimensional SE with diversified but classified potential wells using FNO. Gaussian random fields are used to generate the potential function, and then FNO is used to learn the mapping relationship between different potential functions and the solutions to the SE. The results show that the trained FNO can accurately output the solution to the SE under the corresponding potential function in a very short time, and the output results are completely consistent with expectations. Moreover, using FNO to solve the SE is significantly faster than traditional solvers, especially when the grid size is large. Therefore, in the future, FNO will provide a new solving method in complex, high-dimensional cases, such as two-dimensional, three-dimensional, and time-dependent SEs.
Research on Diffusion and Mitigation of Severe Accident Source Terms in Floating Nuclear Power Plant
Authors: Xu Tao , Wang Junlong , Zhang Bin , Li Jishen , Liu Jiajia , Xia Mingming , Ma Haifu , Wu Yirui
Published: November 2024

ACP100S is a modular floating nuclear power plant independently developed by China National Nuclear Corporation (CNNC) with broad application prospects. At present, research on the source terms of severe accidents in floating nuclear power plants is not sufficient, and research is needed on the migration and distribution of source terms under severe accident conditions, as well as mitigation measures for source terms. Focusing on ACP100S, a severe accident source term analysis model for floating nuclear power plant reactor is established using the ISAA code in this paper. The accident process, release and migration of the source terms after the accident are studied. At the same time, the mitigation effect of containment spray on severe accident source terms is studied, as well. The results show that after the accident, the total amount of noble gases is about 99.7% in the containment and 0.254% in the primary circuit. The fraction of Cs is 80.1% in the containment, 19.1% in the primary circuit and 0.637% in the reactor cavity. And the share of CsI is 85.8% in the containment, 2.73% in primary circuit and 9.13% in reactor cavity. In addition, spray can reduce the concentration of Cs and CsI in the containment by about 52.48% and 73.44%, which has a significant effect on the mitigation of source terms.
Measurement of ocean currents by seafloor distributed optical-fiber acoustic sensing
Authors: Lin Jianmin , He Runjing , Tang Qunshu , Zhang Lei , Xu Wen
Published: November 2024

Ocean current measurements play a crucial role in aiding our understanding of ocean dynamics and circulation systems. Traditional methods, such as drifters and ocean buoys, are sparsely distributed and of limited effectiveness due to the nature of the marine environment and high operating expenses. Distributed acoustic sensing (DAS) is an emerging technology using submarine optical-fiber (OF) cables as dense seismo-acoustic arrays, offering a new perspective for ocean observations. Here, in situ observations of ocean surface gravity waves (OSGWs) and ocean currents by DAS were made along a pre-existing 33.6 km seafloor OF cable. The average current velocity and water depth along the cable were determined from observed OSGW-induced seafloor noise (0.05–0.2 Hz) using ambient-noise interferometry and frequency-domain beamforming. Variations in current velocity were derived at high spatiotemporal resolution using the frequency-domain waveform-stretching method. The inverted current velocity was verified by nearby ocean buoy observations and forecasting results. The observations demonstrate the effectiveness of DAS-instrumented OF cables in monitoring ocean currents.
Pathogenic mitochondrial DNA mutations inhibit melanoma metastasis
Authors: Shelton Spencer D. , House Sara , Martins Nascentes Melo Luiza , Ramesh Vijayashree , Chen Zhenkang , Wei Tao , Wang Xun , Llamas Claire B. , Venigalla Siva Sai Krishna , Menezes Cameron J. , Allies Gabriele , Krystkiewicz Jonathan , Rösler Jonas , Meckelmann Sven W. , Zhao Peihua , Rambow Florian , Schadendorf Dirk , Zhao Zhiyu , Gill Jennifer G. , DeBerardinis Ralph J. , Morrison Sean J. , Tasdogan Alpaslan , Mishra Prashant
Published: November 2024

Mitochondrial DNA (mtDNA) mutations are frequent in cancer, yet their precise role in cancer progression remains debated. To functionally evaluate the impact of mtDNA variants on tumor growth and metastasis, we developed an enhanced cytoplasmic hybrid (cybrid) generation protocol and established isogenic human melanoma cybrid lines with wild-type mtDNA or pathogenic mtDNA mutations with partial or complete loss of mitochondrial oxidative function. Cybrids with homoplasmic levels of pathogenic mtDNA reliably established tumors despite dysfunctional oxidative phosphorylation. However, these mtDNA variants disrupted spontaneous metastasis from primary tumors and reduced the abundance of circulating tumor cells. Migration and invasion of tumor cells were reduced, indicating that entry into circulation is a bottleneck for metastasis amid mtDNA dysfunction. Pathogenic mtDNA did not inhibit organ colonization following intravenous injection. In heteroplasmic cybrid tumors, single-cell analyses revealed selection against pathogenic mtDNA during melanoma growth. Collectively, these findings experimentally demonstrate that functional mtDNA is favored during melanoma growth and supports metastatic entry into the blood.
Spatial multiplex analysis of lung cancer reveals that regulatory T cells attenuate KRAS-G12C inhibitor–induced immune responses
Authors: Cole Megan , Anastasiou Panayiotis , Lee Claudia , Yu Xiaofei , de Castro Andrea , Roelink Jannes , Moore Chris , Mugarza Edurne , Jones Martin , Valand Karishma , Rana Sareena , Colliver Emma , Angelova Mihaela , Enfield Katey S. S. , Magness Alastair , Mullokandov Asher , Kelly Gavin , de Gruijl Tanja D. , Molina-Arcas Miriam , Swanton Charles , Downward Julian , van Maldegem Febe
Published: November 2024

Kirsten rat sarcoma virus (KRAS)–G12C inhibition causes remodeling of the lung tumor immune microenvironment and synergistic responses to anti–PD-1 treatment, but only in T cell infiltrated tumors. To investigate mechanisms that restrain combination immunotherapy sensitivity in immune-excluded tumors, we used imaging mass cytometry to explore cellular distribution in an immune-evasive KRAS mutant lung cancer model. Cellular spatial pattern characterization revealed a community where CD4
+
and CD8
+
T cells and dendritic cells were gathered, suggesting localized T cell activation. KRAS-G12C inhibition led to increased PD-1 expression, proliferation, and cytotoxicity of CD8
+
T cells, and CXCL9 expression by dendritic cells, indicating an effector response. However, suppressive regulatory T cells (T
regs
) were also found in frequent contact with effector T cells within this community. Lung adenocarcinoma clinical samples showed similar communities. Depleting T
regs
led to enhanced tumor control in combination with anti–PD-1 and KRAS-G12C inhibitor. Combining T
reg
depletion with KRAS inhibition shows therapeutic potential for increasing antitumoral immune responses.
A dual role for PSIP1/LEDGF in T cell acute lymphoblastic leukemia
Authors: Demoen Lisa , Matthijssens Filip , Reunes Lindy , Palhais Bruno , Lintermans Béatrice , T’Sas Sara , Fijalkowski Igor , Taminau Joachim , Akele Muluembet Z. , Van Belle Siska , Taghon Tom , Deforce Dieter , Van Nieuwerburgh Filip , Berx Geert , Ntziachristos Panagiotis , Debyser Zeger , Durinck Kaat , Pieters Tim , Goossens Steven , Van Vlierberghe Pieter
Published: November 2024

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy. Current intensified therapeutic protocols coincide with severe side effects, and no salvage therapy is available for primary therapy-resistant or relapsed patients. This highlights the need to identify new therapeutic targets in T-ALL. PSIP1, dispensable for normal hematopoiesis, is a dependency factor in
KMT2A
-rearranged myeloid leukemia. Nonetheless, loss-of-function mutations suggest a tumor suppressor role for PSIP1 in T-ALL. Here, we demonstrate that the loss of
Psip1
accelerates T-ALL initiation in mice which we correlated with reduced H3K27me3 binding. Contrastingly, loss of PSIP1 impaired cell proliferation in several T-ALL cell lines. In cell lines, PSIP1 down-regulation leads to a reduction of COX20, an assembly factor of the cytochrome c oxidase in the mitochondria, and to a reduction in mitochondrial respiration. This indicates that PSIP1 can exert a dual role in the context of T-ALL, either as a tumor suppressor gene during tumor initiation or as a dependency factor in tumor maintenance.
Suppression of non-muscle myosin II boosts T cell cytotoxicity against tumors
Authors: Yang Yingyun , Wen Dahan , Lin Feng , Song Xiaowei , Pang Ruiyang , Sun Weihao , Yu Donglin , Zhang Ziyi , Yu Tao , Kong Jie , Zhang Lei , Cao Xinyuan , Liao Wanying , Wang Dingding , Yang Qianyi , Liang Junbo , Zhang Ning , Li Kailong , Xiong Chunyang , Liu Yuying
Published: November 2024

Increasing evidence highlights the importance of immune mechanoregulation in establishing and sustaining tumor-specific cytotoxicity required for desirable immunotherapeutic outcomes. However, the molecular connections between mechanobiological inputs and outputs and the designated immune activities remain largely unclear. Here, we show that partial inhibition of non-muscle myosin II (NM II) augmented the traction force exerted by T cells and potentiated T cell cytotoxicity against tumors. By using T cells from mice and patients with cancer, we found that NM II is required for the activity of NKX3-2 in maintaining the expression of ADGRB3, which shapes the filamentous actin (F-actin) organization and ultimately attributes to the reduced traction force of T cells in the tumor microenvironment. In animal models, suppressing the NM II–NKX3-2–ADGRB3 pathway in T cells effectively suppressed tumor growth and improved the efficacy of the checkpoint-specific immunotherapy. Overall, this work provides insights into the biomechanical regulation of T cell cytotoxicity that can be exploited to optimize clinical immunotherapies.
High mitochondrial DNA levels accelerate lung adenocarcinoma progression
Authors: Mennuni Mara , Wilkie Stephen E. , Michon Pauline , Alsina David , Filograna Roberta , Lindberg Markus , Sanin David E. , Rosenberger Florian , Schaaf Alina , Larsson Erik , Pearce Erika L. , Larsson Nils-Göran
Published: November 2024

Lung adenocarcinoma is a common aggressive cancer and a leading cause of mortality worldwide. Here, we report an important in vivo role for mitochondrial DNA (mtDNA) copy number during lung adenocarcinoma progression in the mouse. We found that lung tumors induced by KRAS
G12D
expression have increased mtDNA levels and enhanced mitochondrial respiration. To experimentally assess a possible causative role in tumor progression, we induced lung cancer in transgenic mice with a general increase in mtDNA copy number and found that they developed a larger tumor burden, whereas mtDNA depletion in tumor cells reduced tumor growth. Immune cell populations in the lung and cytokine levels in plasma were not affected by increased mtDNA levels. Analyses of large cancer databases indicate that mtDNA copy number is also important in human lung cancer. Our study thus reports experimental evidence for a tumor-intrinsic causative role for mtDNA in lung cancer progression, which could be exploited for development of future cancer therapies.
Membrane potential stimulates ADP import and ATP export by the mitochondrial ADP/ATP carrier due to its positively charged binding site
Authors: Mavridou Vasiliki , King Martin S. , Bazzone Andre , Springett Roger , Kunji Edmund R. S.
Published: November 2024

The mitochondrial adenosine 5′-diphosphate (ADP)/adenosine 5′-triphosphate (ATP) carrier imports ADP into the mitochondrion and exports ATP to the cell. Here, we demonstrate that 3.3 positive charges are translocated with the negatively charged substrate in each transport step. They can be assigned to three positively charged residues of the central substrate-binding site and two asparagine/arginine pairs. In this way, the membrane potential stimulates not only the ATP
4−
export step, as a net −0.7 charge is transported, but also the ADP
3−
import step, as a net +0.3 charge is transported with the electric field. These positive charge movements also inhibit the import of ATP and export of ADP in the presence of a membrane potential, allowing these nucleotides to be maintained at high concentrations in the cytosol and mitochondrial matrix to drive the hydrolysis and synthesis of ATP, respectively. Thus, this is the mechanism by which the membrane potential drives adenine nucleotide exchange with high directional fluxes to fuel the cellular processes.
Real-space investigation of polarons in hematite Fe
2
O
3
Authors: Redondo Jesus , Reticcioli Michele , Gabriel Vit , Wrana Dominik , Ellinger Florian , Riva Michele , Franceschi Giada , Rheinfrank Erik , Sokolović Igor , Jakub Zdenek , Kraushofer Florian , Alexander Aji , Belas Eduard , Patera Laerte L. , Repp Jascha , Schmid Michael , Diebold Ulrike , Parkinson Gareth S. , Franchini Cesare , Kocan Pavel , Setvin Martin
Published: November 2024

In polarizable materials, electronic charge carriers interact with the surrounding ions, leading to quasiparticle behavior. The resulting polarons play a central role in many materials properties including electrical transport, interaction with light, surface reactivity, and magnetoresistance, and polarons are typically investigated indirectly through these macroscopic characteristics. Here, noncontact atomic force microscopy (nc-AFM) is used to directly image polarons in Fe
2
O
3
at the single quasiparticle limit. A combination of Kelvin probe force microscopy (KPFM) and kinetic Monte Carlo (KMC) simulations shows that the mobility of electron polarons can be markedly increased by Ti doping. Density functional theory (DFT) calculations indicate that a transition from polaronic to metastable free-carrier states can play a key role in migration of electron polarons. In contrast, hole polarons are significantly less mobile, and their hopping is hampered further by trapping centers.
Polymer semiconductor films and bacteria hybrid artificial bio-leaves
Authors: Wen Na , Jiang Qianqing , Liu Dianyi
Published: November 2024

Bio-artificial photosynthetic systems can reduce CO
2
into multicarbon compounds by simulating natural photosynthesis. Here, inspired by organic photovoltaic structures, we demonstrate a bio-artificial photosynthetic system based on the hybridization of polymer semiconductor films and bacteria. The study suggests that the polymer-based semiconductor film can efficiently drive the non-photosynthetic bacteria to convert CO
2
to acetate. By systematically characterizing the charge transport behavior of the bio-artificial photosynthetic system, the bulk-heterojunction structure and charge transport layers are proven to enhance the system performance markedly. The scalable floating artificial bio-leaf system can produce acetate to gram scale in a week. Notably, the semiconductor film is easy to recycle and maintains stable performance, showing good sustainable production capability of the system. A quasi–solid-state artificial bio-leaf is successfully prepared using agar to simulate the morphology and function of natural leaves. Last, the acetate production converted from CO
2
was used to grow yeast for food production, thus achieving a complete simulation of natural photosynthesis.
20.4% Power conversion efficiency from albedo-collecting organic solar cells under 0.2 albedo
Authors: Ren Hao , Chen Jing-De , Zhang Ye-Fan , Zhang Jia-Liang , Chen Wei-Shuo , Li Yan-Qing , Tang Jian-Xin
Published: November 2024

Highly efficient bifacial organic solar cells (OSCs) have not been reported due to limited thickness of the active layer in conventional configurations, not allowing for efficient harvesting of front sunlight and albedo light. Here, bifacial OSCs are reported with efficiency higher than the monofacial counterparts. The incorporation of pyramid-based asymmetrical optical transmission (AOT) array to a transparent silver electrode suppresses the escaping of front sunlight without sacrificing the harvesting of albedo light. Parasitic absorption induced by the excitation of surface plasmons in an AOT electrode is further reduced by doping organic emitter in electron transport layer and capping high dielectric constant film to silver. The rear electrode achieves a front transmittance of 7% and a rear transmission of 86%. At a conventional albedo of 0.2, the synergistic effect of AOT and minimized optical loss endow the bifacial OSCs with power conversion efficiency of 20.4%. This work paves the way for the utilization of albedo light in OSCs.
Mouse α-synuclein fibrils are structurally and functionally distinct from human fibrils associated with Lewy body diseases
Authors: Sokratian Arpine , Zhou Ye , Tatli Meltem , Burbidge Kevin J. , Xu Enquan , Viverette Elizabeth , Donzelli Sonia , Duda Addison M. , Yuan Yuan , Li Huizhong , Strader Samuel , Patel Nirali , Shiell Lauren , Malankhanova Tuyana , Chen Olivia , Mazzulli Joseph R. , Perera Lalith , Stahlberg Henning , Borgnia Mario , Bartesaghi Alberto , Lashuel Hilal A. , West Andrew B.
Published: November 2024

The intricate process of α-synuclein aggregation and fibrillization holds pivotal roles in Parkinson’s disease (PD) and multiple system atrophy (MSA). While mouse α-synuclein can fibrillize in vitro, whether these fibrils commonly used in research to induce this process or form can reproduce structures in the human brain remains unknown. Here, we report the first atomic structure of mouse α-synuclein fibrils, which was solved in parallel by two independent teams. The structure shows striking similarity to MSA-amplified and PD-associated E46K fibrils. However, mouse α-synuclein fibrils display altered packing arrangements, reduced hydrophobicity, and heightened fragmentation sensitivity and evoke only weak immunological responses. Furthermore, mouse α-synuclein fibrils exhibit exacerbated pathological spread in neurons and humanized α-synuclein mice. These findings provide critical insights into the structural underpinnings of α-synuclein pathogenicity and emphasize a need to reassess the role of mouse α-synuclein fibrils in the development of related diagnostic probes and therapeutic interventions.
Stem cell–homing biomimetic hydrogel promotes the repair of osteoporotic bone defects through osteogenic and angiogenic coupling
Authors: Wei Fei-Long , Zhai Yuan , Wang Tian-Fu , Zhao Jing-Wei , Wang Chao-Li , Tang Zhen , Shen Kuo , Wu Hao , Zheng Rui , Du Ming-Rui , Heng Wei , Li Xiao-Xiang , Yan Xiao-Dong , Gao Quan-You , Guo Zheng , Qian Ji-Xian , Zhou Cheng-Pei
Published: November 2024

Osteoporotic bone defects refer to the disruption of bone structural integrity in patients with osteoporosis and pose a substantial challenge to orthopedic surgeons. In this study, we developed a biomimetic hydrogel to improve the osteogenic microenvironment and promote stem cell homing. This hydrogel served as a container for S-nitrosoglutathione and Ca
2+
, promoting the release of bioactive nitric oxide (NO) from bone marrow mesenchymal stem cells (BMSCs) and human vascular endothelial cells and activating the NO/cyclic guanosine monophosphate signaling pathway. These changes promote osteogenic and angiogenic couplings. The hydrogel simultaneously recruited BMSCs by conjugating the stem cell homing peptide SKPPGTSS. Using a rat distal femoral defect model, it was demonstrated that this hydrogel can effectively increase the formation of bone tissue and new blood vessels and has immune-regulating functions. We envision that this hydrogel may be a minimally invasive yet highly effective strategy for expediting the healing of osteoporotic bone defects.
TAM-ing the beast with IL-34 blockade
Authors: Gyorgypal Aron , Anthony Robert M.
Published: November 2024

TP53
mutation triggers IL-34 secretion by cancer stem cells, reprogramming macrophages to suppress T cells and promote tumor immune escape.
CAR-ving away OX40L with engineered T
regs
Authors: Maltzman Jonathan S.
Published: November 2024

OX40L–CAR-T
regs
show promise for treating autoimmunity and transplantation rejection.
Targeted discovery of polyketides with antioxidant activity through integrated omics and cocultivation strategies
Authors: Wang Cancan , Wang Chenjie , Liu Yanjun , Yue Yujie , Lu Xingyue , Wang Hong , Ying Youmin , Chen Jianwei
Published: November 2024

Fungi generate a diverse array of bioactive compounds with significant pharmaceutical applications. However, the chemical diversity of natural products in fungi remains largely unexplored. Here, we present a paradigm for specifically discovering diverse and bioactive compounds from fungi by integrating genome mining with building block molecular network and coculture analysis. Through pangenome and sequence similarity network analysis, we identified a rare type I polyketide enzyme from
Penicillium
sp. ZJUT-34. Subsequent building block molecular network and coculture strategy led to the identification and isolation of a pair of novel polyketides, (±)-peniphenone E [(±)−
1
], three known polyketides (
2–4
), and three precursor compounds (
5–7
) from a combined culture of
Penicillium
sp. ZJUT-34 and
Penicillium
sp. ZJUT23. Their structures were established through extensive spectroscopic analysis, including NMR and HRESIMS. Chiral HPLC separation of compound
1
yielded a pair of enantiomers (+)−
1
and (−)−
1
, with their absolute configurations determined using calculated ECD methods. Compound (±)−
1
is notable for its unprecedented structure, featuring a unique 2-methyl-hexenyl-3-one moiety fused with a polyketide clavatol core. We proposed a hypothetical biosynthetic pathway for (±)−
1
. Furthermore, compounds
2
,
5
, and
6
exhibited strong antioxidant activity, whereas (−)−
1
, (+)−
1
,
3
, and four exhibited moderate antioxidant activity compared to the positive control, ascorbic acid. Our research demonstrates a pioneering strategy for uncovering novel polyketides by merging genome mining, metabolomics, and cocultivation methods. This approach addresses the challenge of discovering natural compounds produced by rare biosynthetic enzymes that are often silent under conventional conditions due to gene regulation.

IMPORTANCE

Polyketides, particularly those with complex structures, are crucial in drug development and synthesis. This study introduces a novel approach to discover new polyketides by integrating genomics, metabolomics, and cocultivation strategies. By combining genome mining, building block molecular networks, and coculturing techniques, we identified and isolated a unique polyketide, (±)-peniphenone E, along with three known polyketides and three precursor compounds from
Penicillium
sp. ZJUT-34 and
Penicillium
sp. ZJUT23. This approach highlights the potential of using combined strategies to explore fungal chemical diversity and discover novel bioactive compounds. The successful identification of (±)-peniphenone E, with its distinctive structure, demonstrates the effectiveness of this integrated method in enhancing natural product discovery and underscores the value of innovative approaches in natural product research.
How does a soft collision orogen uplift and collapse? Insight from the eastern Central Asian Orogenic Belt
Authors: Wang Honghui , Ma Xinghua , Hawkesworth Chris J. , Seltmann Reimar , Lai Yong , Guo Chunli , Zhu Di-Cheng , Wilde Simon A.
Published: November 2024

The mechanism of uplift and collapse is critical for understanding orogenic evolution within the Wilson cycle. The Central Asian Orogenic Belt (CAOB) represents one of the largest Phanerozoic accretionary orogens on Earth, experiencing terminal soft collision following the closure of the Paleo-Asian Ocean. However, the timing and mechanism of crustal thickening and thinning in the eastern CAOB remain unclear. Here, we present geochronological, mineralogical, geochemical, and Sr-Nd-Hf isotopic data of the newly identified Late Triassic bimodal dike associations in the easternmost CAOB. The ca. 236–230 Ma mafic dikes can be divided into two groups based on petrographic and geochemical characteristics. Major element modeling using the MELTS software indicates that they evolved via independent differentiation paths. Trace element and isotope simulations reveal that the ca. 236–230 Ma mafic dikes originated from the 4%–10% partial melting of spinel- to garnet-lherzolite lithospheric mantle sources over a range of depths, with varying inputs of asthenospheric mantle materials. Coeval ca. 233 Ma felsic dikes exhibit adakitic geochemical characteristics and strong imprints of crust-mantle interaction, suggesting derivation from melting of a heated juvenile mafic lower crust as a result of the upwelling of asthenospheric mantle. The formation of bimodal dike associations records the transition from lithospheric mantle thinning to delamination. Integrating a large dataset and employing multiple geochemical proxies, our results reveal that the crust of the easternmost CAOB reached a thickness of 54 ± 3 km at ca. 280–255 Ma, likely resulting from magmatic underplating due to rollback of the subducting Paleo-Asian Oceanic slab. This region underwent a further slight increase in crustal thickness to 61 ± 2 km at ca. 254–237 Ma in response to limited tectonic shortening associated with soft collision orogeny before it thinned to 45 ± 13 km at ca. 236–210 Ma due to lithospheric delamination during post-collisional extension. Our findings reveal that the uplift of the eastern CAOB was primarily driven by magmatic underplating, with minimal contribution from tectonic shortening. Lithospheric delamination emerged as an important factor leading to the eventual collapse of the eastern CAOB. Compared to typical hard collisional orogens (e.g., the Himalaya-Tibet orogen), the CAOB experienced significantly weaker tectonic shortening followed by similar lithospheric delamination during post-collisional extension. This study highlights the importance of integrating geochemical and isotopic data in quantifying the complex evolutionary histories of ancient collisional orogenic belts.
Supplemental Material: Exploring the impact of deglaciation on fault slip in the Sangre de Cristo Mountains, Colorado, USA
Authors: Hurtado Cecilia , Gallen Sean
Published: November 2024

Extended methods, supplemental figures, and supporting citations.  
Supplemental Material: A chlorine isotope transect across Sudbury Basin (Canada) impact deposits reveals systematic isotope fractionation
Authors: Barrett T.J. , al. et
Published: November 2024

Information pertaining to the samples and methodology.  
Supplemental Material: A dendritic growth mechanism for producing oscillatory zoning in igneous zircon
Authors: Gillespie Jack , al. et
Published: November 2024

 The supplemental text describes the analytical methods applied and the geological background of the samples studied in this work. Figures S1–S3 contain additional SEM images, EPMA compositional maps, and plots of EPMA spot analyses of zircon grains from the Torres del Paine sample described in the text. Table S1 shows EPMA spot analyses of zircon depicted in Figs. 1D–1E and in Fig. 3.  
Supplemental Material: Formation of a granite-related Sn-Pb-Zn-(Ag) deposit from three discrete mineralization events around a common magmatic-hydrothermal center over a span of ~45 million years at Changpu, eastern Guangdong, South China
Authors: Yan Qing-He , al. et
Published: November 2024

Figures S1–S4 and Tables S1–S7.
Gravitational Field of a Self-Gravitating Continuous Medium and Dark Matter
Authors: Zhuravlev V. M.
Published: November 2024

A method to describe the hidden mass effect or dark matter has been proposed on the basis of a new general solution of the Poisson equation for the gravitational field strength in a continuous self-gravitating medium. This solution is a consequence of the theory of space and matter alternative to the general relativity. Conditions have been derived to distinguish between the cases where the obtained solution describes the classical Newtonian gravitational field and the cases where this solution leads to the hidden mass effect. The representation obtained for the gravitational field strength has been analyzed within the model of the dynamic equilibrium of disk galaxies and the possibility of describing the observed properties of the hidden mass effect within this approach has been discussed.
Generalized Bloch Theorem and Band-Structure Topology
Authors: Kudasov Yu. B.
Published: November 2024

Dispersion relations in a metal with a commensurate helical magnetic order are considered in the framework of one- and two-dimensional tight-binding models. The generalized Bloch theorem for translations combined with spin rotations, together with the Born–Karman periodic boundary conditions, leads to the appearance of multisheet dispersion curves (surfaces). It is demonstrated that the resulting band structure is topologically nontrivial, which can lead to a spin textured Fermi surface and cause transport anomalies.
Measurement of the Cross Section for the Neutron-Induced Fission of 237Np Nuclei in the Energy Range of 0.3–500 MeV
Authors: Vorobyev A. S. , Gagarski A. M. , Shcherbakov O. A. , Vaishnene L. A. , Tyagelskaya A. M. , Olkhovich N. M. , Barabanov A. L.
Published: November 2024

The cross section for the neutron-induced fission of 237Np nuclei in the neutron energy range of 0.3–500 MeV has been measured using the time-of-flight spectrometer of the GNEIS neutron complex at the Petersburg Nuclear Physics Institute, National Research Center Kurchatov Institute. The 237Np(n, f) fission cross section has been measured with respect to the 235U(n, f) fission cross section and fission fragments have been detected by low-pressure position-sensitive multiwire proportional counters. The data obtained have been compared to the previous experimental results and to estimates from various evaluated data libraries.
Super Long-Lived Neutral Excitations of the 1/3 Laughlin Liquid
Authors: Larionov A. V. , Zhuravlev A. S. , Kulik L. V. , Zagitova A. A. , Kukushkin I. V.
Published: November 2024

The long-term relaxation dynamics of neutral excitations with spin 1 in the Laughlin liquid at an electron filling factor of 1/3 has been studied. It has been found that there are two types of excitations with the same energies, the relaxation times of which to the ground state differ by at least two orders of magnitude. Assumptions are made about the nature of these excitations.
Association between measures of kidney function and preserved ratio impaired spirometry in diabetes: NHANES 2007–2012
Authors: Patel Ikramulhaq , Gong Hong-Jian , Xu Hui , Chai Yin-He , Qiao Yu-Shun , Zhang Jin-Yan , Zhang Meng-Ting , Stehouwer Coen D A , Zhou Jianbo
Published: November 2024

Objectives

This study aimed to examine the relationship between measures of kidney function and impaired lung function in individuals with diabetes and to assess all-cause mortality risk associated with having chronic kidney disease (CKD) and or impaired lung function.

Design

Cross-sectional and retrospective cohort study.

Setting

The National Health and Nutrition Examination Survey 2007–2012.

Participants

A total of 10 809 participants aged over 20 years were included in this study: 9503 with normal spirometry, 951 with preserved ratio impaired spirometry (PRISm) and 355 with variable obstruction (VO).

Exposure and outcome measures

Kidney function measures, including estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR), were considered exposure variables. PRISm and VO were outcome variables. PRISm was defined as a forced expiratory volume in 1 s (FEV1)<80% predicted and an FEV1/forced vital capacity (FVC) ratio≥0.7, while VO was defined as an FEV1/FVC ratio <0.7 prebronchodilator and ≥0.7 postbronchodilator. In the cross-sectional analysis, multivariate logistic regression models were used to assess the relationship between kidney function measures and spirometry findings. In the retrospective cohort analysis, Cox proportional hazards models were employed to evaluate the impact of having PRISm or VO, combined with CKD, on all-cause mortality.

Results

An increase in UACR was significantly associated with higher odds of PRISm (OR (95% CI)=1.10 (1.01, 1.21), p=0.03). Additionally, eGFR <60 was associated with the odds of variable obstructive lung function (OR (95% CI)=1.72 (1.07, 2.74), p=0.03) compared with eGFR >60. After adjustments, an increase in UACR was associated with higher odds of PRISm in individuals with diabetes (OR (95% CI)=1.21 (1.08, 1.36), p=0.002), and UACR ≥300 mg/g significantly increased odds of having PRISm in idividuals with diabetes (OR (95% CI)=2.34 (1.23, 4.47), p=0.01). During a mean follow-up of 12.3 years, 10 500 deaths occurred. In the diabetic group, compared with normal spirometry without CKD, those with both PRISm and CKD had a significantly increased risk of all-cause mortality (HR (95% CI)=3.46 (1.94, 6.16), p<0.0001).

Conclusion

An elevated UACR and albuminuria were linked to a higher risk of PRISm. Our study emphasises that kidney and lung function are correlated. Further research is necessary to confirm our findings.
Prevalence of falls in the last weeks of life and relationship between falls, independence and quality of dying in Japan: a large prospective cohort study
Authors: Otani Hiroyuki , Shimoinaba Junichi , Kashiwagi Hideyuki , Morita Tatsuya , Maeda Isseki , Yokomichi Naosuke , Hamano Jun , Yamaguchi Takashi , Mori Masanori
Published: November 2024

Objective

This study aims to determine the frequency of falls and their serious complications in palliative care units (PCUs), as well as explore the complex interplay between falls, independence and quality of dying.

Design

A prospective cohort study.

Setting and participants

The dying process of patients with advanced cancer in 23 PCUs in Japan.

Outcome measures

Palliative care specialist physicians recorded whether patients experienced falls, serious complications from falls, activities that led to falls, independence (workability in the last days and use of indwelling urinary catheter) and Good Death Scale as an indicator of quality of dying.

Results

Of the 1633 patients evaluated, 150 patients (9.2%; 95% CI 7.8% to 11%) experienced falls within 30 days prior to death. The patients who fell were mostly men, had Eastern Cooperative Oncology Group performance status 3 on admission, a longer estimated prognosis on admission and delirium during hospitalisation. Serious falls causing fractures or intracranial haemorrhages were rare in five patients (0.3%; 95% CI 0.038% to 0.57%). The most common reason for falls was the need to use the toilet (64.7%). The Good Death Scale and indwelling urinary catheter use were not significantly associated with falls (p=0.34; p=0.34).

Conclusion

Falls occur in approximately 10% of patients in PCUs, but serious complications are rare. The relationship between falls, independence and quality of dying is complex, that is, a fall may not be necessarily bad, if it is the result of respect for the patient’s independence. Healthcare providers need to consider fall prevention while supporting patients’ desire to move on their own to maintain independence.
Effectiveness and clinical relevance of kinesio taping in musculoskeletal disorders: a protocol for an overview of systematic reviews and evidence mapping
Authors: Mo Qingcong , Xu Siqi , Hu Fangfei , Zheng Xiaoyan
Published: November 2024

Introduction

Kinesio taping (KT) has been extensively applied in the management of musculoskeletal disorders (MSDs). Although plentiful systematic reviews (SRs) have evaluated its efficacy, there are no convincing conclusions due to dispersed and inconclusive results, and its clinical relevance remains unclear. Hence, there is a need to summarise all the SRs for comprehensive and consistent evidence. This overview aims to appraise the overall effectiveness of KT in MSDs and provide evidence maps to visualise the findings.

Method and analysis

Electronic databases (Cochrane Database of Systematic Reviews, MEDLINE, Embase, Epistemonikos, PEDro, Scopus and ISI Web of Science) and reference lists will be searched from inception to September 2024 for the SRs of randomised controlled trials (RCTs). The SRs involving comparisons of the effectiveness between single or adjunctive KT and other interventions for patients with MSDs will be included. The primary and additional outcomes to be considered will be the core outcome set, and the patient-reported outcome measure and patient-important outcome, respectively. Two reviewers will independently screen and select studies, extract the data and evaluate the reporting and methodological quality of eligible SRs as well as the risk of bias of included RCTs. For the SRs without meta-analysis, we will collate the number of RCTs that showed any differences in outcomes. For the SRs with meta-analysis, we will provide the original summary of evidence (eg, pooled effects and heterogeneity) for outcomes with an evaluation of missing results and clinical relevance. The certainty of each outcome will be measured, and user-friendly maps of findings will be presented graphically.

Ethics and dissemination

Formal ethical approval for this study is not required since the data will be only collected from published literature in public databases. The results will be disseminated in the peer-reviewed academic journal, and relevant datasets will be preserved in the online repository.

PROSPERO registration number

CRD42024517528.