bluuebunny/crossref_metadata_2025 huggingface dataset:
Neoadjuvant–adjuvant pertuzumab in HER2-positive early breast cancer: final analysis of the randomized phase III PEONY trial
Authors: Huang Liang , Pang Da , Yang Hongjian , Li Wei , Wang Shusen , Cui Shude , Liao Ning , Wang Yongsheng , Wang Chuan , Chang Yuan-Ching , Wang Hwei-Chung , Kang Seok Yun , Seo Jae Hong , Shen Kunwei , Laohawiriyakamol Suphawat , Jiang Zefei , Wang Haiyan , Lamour François , Song Grace , Curran Michelle , Duan Chunzhe , Lysbet de Haas Sanne , Restuccia Eleonora , Shao Zhimin
Published: March 2024

The randomized, multicenter, double-blind, placebo-controlled, phase III PEONY trial (NCT02586025) demonstrated significantly improved total pathologic complete response (primary endpoint) with dual HER2 blockade in HER2-positive early/locally advanced breast cancer, as previously reported. Here, we present the final, long-term efficacy (secondary endpoints: event-free survival, disease-free survival, overall survival) and safety analysis (62.9 months’ median follow-up). Patients (female; n = 329; randomized 2:1) received neoadjuvant pertuzumab/placebo with trastuzumab and docetaxel, followed by adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide, then pertuzumab/placebo with trastuzumab until disease recurrence or unacceptable toxicity, for up to 1 year. Five-year event-free survival estimates are 84.8% with pertuzumab and 73.7% with placebo (hazard ratio 0.53; 95% confidence interval 0.32–0.89); 5-year disease-free survival rates are 86.0% and 75.0%, respectively (hazard ratio 0.52; 95% confidence interval 0.30–0.88). Safety data are consistent with the known pertuzumab safety profile and generally comparable between arms, except for diarrhea. Limitations include the lack of ado-trastuzumab emtansine as an option for patients with residual disease and the descriptive nature of the secondary, long-term efficacy endpoints. PEONY confirms the positive benefit:risk ratio of neoadjuvant/adjuvant pertuzumab, trastuzumab, and docetaxel treatment in this patient population.
Inhalation of ACE2-expressing lung exosomes provides prophylactic protection against SARS-CoV-2
Authors: Wang Zhenzhen , Hu Shiqi , Popowski Kristen D. , Liu Shuo , Zhu Dashuai , Mei Xuan , Li Junlang , Hu Yilan , Dinh Phuong-Uyen C. , Wang Xiaojie , Cheng Ke
Published: March 2024

Continued emergence of SARS-CoV-2 variants of concern that are capable of escaping vaccine-induced immunity highlights the urgency of developing new COVID-19 therapeutics. An essential mechanism for SARS-CoV-2 infection begins with the viral spike protein binding to the human ACE2. Consequently, inhibiting this interaction becomes a highly promising therapeutic strategy against COVID-19. Herein, we demonstrate that ACE2-expressing human lung spheroid cells (LSC)-derived exosomes (LSC-Exo) could function as a prophylactic agent to bind and neutralize SARS-CoV-2, protecting the host against SARS-CoV-2 infection. Inhalation of LSC-Exo facilitates its deposition and biodistribution throughout the whole lung in a female mouse model. We show that LSC-Exo blocks the interaction of SARS-CoV-2 with host cells in vitro and in vivo by neutralizing the virus. LSC-Exo treatment protects hamsters from SARS-CoV-2-induced disease and reduced viral loads. Furthermore, LSC-Exo intercepts the entry of multiple SARS-CoV-2 variant pseudoviruses in female mice and shows comparable or equal potency against the wild-type strain, demonstrating that LSC-Exo may act as a broad-spectrum protectant against existing and emerging virus variants.
Marine heatwaves disrupt ecosystem structure and function via altered food webs and energy flux
Authors: Gomes Dylan G. E. , Ruzicka James J. , Crozier Lisa G. , Huff David D. , Brodeur Richard D. , Stewart Joshua D.
Published: March 2024

The prevalence and intensity of marine heatwaves is increasing globally, disrupting local environmental conditions. The individual and population-level impacts of prolonged heatwaves on marine species have recently been demonstrated, yet whole-ecosystem consequences remain unexplored. We leveraged time series abundance data of 361 taxa, grouped into 86 functional groups, from six long-term surveys, diet information from a new diet database, and previous modeling efforts, to build two food web networks using an extension of the popular Ecopath ecosystem modeling framework, Ecotran. We compare ecosystem models parameterized before and after the onset of recent marine heatwaves to evaluate the cascading effects on ecosystem structure and function in the Northeast Pacific Ocean. While the ecosystem-level contribution (prey) and demand (predators) of most functional groups changed following the heatwaves, gelatinous taxa experienced the largest transformations, underscored by the arrival of northward-expanding pyrosomes. We show altered trophic relationships and energy flux have potentially profound consequences for ecosystem structure and function, and raise concerns for populations of threatened and harvested species.
Selective hydrodeoxygenation of α, β-unsaturated carbonyl compounds to alkenes
Authors: Wang Tianjiao , Xin Yu , Chen Bingfeng , Zhang Bin , Luan Sen , Dong Minghua , Wu Yuxuan , Cheng Xiaomeng , Liu Ye , Liu Huizhen , Han Buxing
Published: March 2024

Achieving selective hydrodeoxygenation of α, β-unsaturated carbonyl groups to alkenes poses a substantial challenge due to the presence of multiple functional groups. In this study, we develop a ZnNC-X catalyst (X represents the calcination temperature) that incorporates both Lewis acidic-basic sites and Zn-Nx sites to address this challenge. Among the catalyst variants, ZnNC-900 catalyst exhibits impressive selectivity for alkenes in the hydrodeoxygenation of α, β-unsaturated carbonyl compounds, achieving up to 94.8% selectivity. Through comprehensive mechanism investigations and catalyst characterization, we identify the Lewis acidic-basic sites as responsible for the selective hydrogenation of C=O bonds, while the Zn-Nx sites facilitate the subsequent selective hydrodeoxygenation step. Furthermore, ZnNC-900 catalyst displays broad applicability across a diverse range of unsaturated carbonyl compounds. These findings not only offer valuable insights into the design of effective catalysts for controlling alkene selectivity but also extend the scope of sustainable transformations in synthetic chemistry.
Structure-based prediction and characterization of photo-crosslinking in native protein–RNA complexes
Authors: Feng Huijuan , Lu Xiang-Jun , Maji Suvrajit , Liu Linxi , Ustianenko Dmytro , Rudnick Noam D. , Zhang Chaolin
Published: March 2024

UV-crosslinking of protein and RNA in direct contacts has been widely used to study protein-RNA complexes while our understanding of the photo-crosslinking mechanisms remains poor. This knowledge gap is due to the challenge of precisely mapping the crosslink sites in protein and RNA simultaneously in their native sequence and structural contexts. Here we systematically analyze protein-RNA interactions and photo-crosslinking by bridging crosslinked nucleotides and amino acids mapped using different assays with protein-RNA complex structures. We developed a computational method PxR3D-map which reliably predicts crosslink sites using structural information characterizing protein-RNA interaction interfaces. Analysis of the informative features revealed that photo-crosslinking is facilitated by base stacking with not only aromatic residues, but also dipeptide bonds that involve glycine, and distinct mechanisms are utilized by different RNA-binding domains. Our work suggests protein-RNA photo-crosslinking is highly selective in the cellular environment, which can guide data interpretation and further technology development for UV-crosslinking-based assays.
GWAS reveals determinants of mobilization rate and dynamics of an active endogenous retrovirus of cattle
Authors: Tang Lijing , Swedlund Benjamin , Dupont Sébastien , Harland Chad , Costa Monteiro Moreira Gabriel , Durkin Keith , Artesi Maria , Mullaart Eric , Sartelet Arnaud , Karim Latifa , Coppieters Wouter , Georges Michel , Charlier Carole
Published: March 2024

Five to ten percent of mammalian genomes is occupied by multiple clades of endogenous retroviruses (ERVs), that may count thousands of members. New ERV clades arise by retroviral infection of the germline followed by expansion by reinfection and/or retrotransposition. ERV mobilization is a source of deleterious variation, driving the emergence of ERV silencing mechanisms, leaving “DNA fossils”. Here we show that the ERVK[2-1-LTR] clade is still active in the bovine and a source of disease-causing alleles. We develop a method to measure the rate of ERVK[2-1-LTR] mobilization, finding an average of 1 per ~150 sperm cells, with >10-fold difference between animals. We perform a genome-wide association study and identify eight loci affecting ERVK[2-1-LTR] mobilization. We provide evidence that polymorphic ERVK[2-1-LTR] elements in four of these loci cause the association. We generate a catalogue of full length ERVK[2-1-LTR] elements, and show that it comprises 15% of C-type autonomous elements, and 85% of D-type non-autonomous elements lacking functional genes. We show that >25% of the variance of mobilization rate is determined by the number of C-type elements, yet that de novo insertions are dominated by D-type elements. We propose that D-type elements act as parasite-of-parasite gene drives that may contribute to the observed demise of ERV elements.
TERRA-LSD1 phase separation promotes R-loop formation for telomere maintenance in ALT cancer cells
Authors: Xu Meng , Senanayaka Dulmi , Zhao Rongwei , Chigumira Tafadzwa , Tripathi Astha , Tones Jason , Lackner Rachel M. , Wondisford Anne R. , Moneysmith Laurel N. , Hirschi Alexander , Craig Sara , Alishiri Sahar , O’Sullivan Roderick J. , Chenoweth David M. , Reiter Nicholas J. , Zhang Huaiying
Published: March 2024

The telomere repeat-containing RNA (TERRA) forms R-loops to promote homology-directed DNA synthesis in the alternative lengthening of telomere (ALT) pathway. Here we report that TERRA contributes to ALT via interacting with the lysine-specific demethylase 1A (LSD1 or KDM1A). We show that LSD1 localizes to ALT telomeres in a TERRA dependent manner and LSD1 function in ALT is largely independent of its demethylase activity. Instead, LSD1 promotes TERRA recruitment to ALT telomeres via RNA binding. In addition, LSD1 and TERRA undergo phase separation, driven by interactions between the RNA binding properties of LSD1 and the G-quadruplex structure of TERRA. Importantly, the formation of TERRA-LSD1 condensates enriches the R-loop stimulating protein Rad51AP1 and increases TERRA-containing R-loops at telomeres. Our findings suggest that LSD1-TERRA phase separation enhances the function of R-loop regulatory molecules for ALT telomere maintenance, providing a mechanism for how the biophysical properties of histone modification enzyme-RNA interactions impact chromatin function.
Room-temperature strong coupling in a single-photon emitter-metasurface system
Authors: Do T. Thu Ha , Nonahal Milad , Li Chi , Valuckas Vytautas , Tan Hark Hoe , Kuznetsov Arseniy I. , Nguyen Hai Son , Aharonovich Igor , Ha Son Tung
Published: March 2024

Solid state single-photon sources with high brightness and long coherence time are promising qubit candidates for modern quantum technology. To prevent decoherence processes and preserve the integrity of the qubits, decoupling the emitters from their surrounding environment is essential. To this end, interfacing single photon emitters (SPEs) with high-finesse cavities is required, especially in the strong coupling regime, when the interaction between emitters can be mediated by cavity fields. However, achieving strong coupling at elevated temperatures is challenging due to competing incoherent processes. Here, we address this long-standing problem by using a quantum system, which comprises a class of SPEs in hexagonal boron nitride and a dielectric cavity based on bound states in the continuum (BIC). We experimentally demonstrate, at room temperature, strong coupling of the system with a large Rabi splitting of ~4 meV thanks to the combination of the narrow linewidth and large oscillator strength of the emitters and the efficient photon trapping of the BIC cavity. Our findings unveil opportunities to advance the fundamental understanding of quantum dynamical system in strong coupling regime and to realise scalable quantum devices capable of operating at room temperature.
Structural characterization of the oligomerization of full-length Hantaan virus polymerase into symmetric dimers and hexamers
Authors: Durieux Trouilleton Quentin , Housset Dominique , Tarillon Paco , Arragain Benoît , Malet Hélène
Published: March 2024

Hantaan virus is a dangerous human pathogen whose segmented negative-stranded RNA genome is replicated and transcribed by a virally-encoded multi-functional polymerase. Here we describe the complete cryo-electron microscopy structure of Hantaan virus polymerase in several oligomeric forms. Apo polymerase protomers can adopt two drastically different conformations, which assemble into two distinct symmetric homodimers, that can themselves gather to form hexamers. Polymerase dimerization induces the stabilization of most polymerase domains, including the C-terminal domain that contributes the most to dimer’s interface, along with a lariat region that participates to the polymerase steadying. Binding to viral RNA induces significant conformational changes resulting in symmetric oligomer disruption and polymerase activation, suggesting the possible involvement of apo multimers as protecting systems that would stabilize the otherwise flexible C-terminal domains. Overall, these results provide insights into the multimerization capability of Hantavirus polymerase and may help to define antiviral compounds to counteract these life-threatening viruses.
An isotropic zero thermal expansion alloy with super-high toughness
Authors: Yu Chengyi , Lin Kun , Zhang Qinghua , Zhu Huihui , An Ke , Chen Yan , Yu Dunji , Li Tianyi , Fu Xiaoqian , Yu Qian , You Li , Kuang Xiaojun , Cao Yili , Li Qiang , Deng Jinxia , Xing Xianran
Published: March 2024

Zero thermal expansion (ZTE) alloys with high mechanical response are crucial for their practical usage. Yet, unifying the ZTE behavior and mechanical response in one material is a grand obstacle, especially in multicomponent ZTE alloys. Herein, we report a near isotropic zero thermal expansion (αl = 1.10 × 10−6 K−1, 260–310 K) in the natural heterogeneous LaFe54Co3.5Si3.35 alloy, which exhibits a super-high toughness of 277.8 ± 14.7 J cm−3. Chemical partition, in the dual-phase structure, assumes the role of not only modulating thermal expansion through magnetic interaction but also enhancing mechanical properties via interface bonding. The comprehensive analysis reveals that the hierarchically synergistic enhancement among lattice, phase interface, and heterogeneous structure is significant for strong toughness. Our findings pave the way to tailor thermal expansion and obtain prominent mechanical properties in multicomponent alloys, which is essential to ultra-stable functional materials.
Dendritic cell-targeted therapy expands CD8 T cell responses to bona-fide neoantigens in lung tumors
Authors: López Lucía , Morosi Luciano Gastón , La Terza Federica , Bourdely Pierre , Rospo Giuseppe , Amadio Roberto , Piperno Giulia Maria , Russo Valentina , Volponi Camilla , Vodret Simone , Joshi Sonal , Giannese Francesca , Lazarevic Dejan , Germano Giovanni , Stoitzner Patrizia , Bardelli Alberto , Dalod Marc , Pace Luigia , Caronni Nicoletta , Guermonprez Pierre , Benvenuti Federica
Published: March 2024

Cross-presentation by type 1 DCs (cDC1) is critical to induce and sustain antitumoral CD8 T cell responses to model antigens, in various tumor settings. However, the impact of cross-presenting cDC1 and the potential of DC-based therapies in tumors carrying varied levels of bona-fide neoantigens (neoAgs) remain unclear. Here we develop a hypermutated model of non-small cell lung cancer in female mice, encoding genuine MHC-I neoepitopes to study neoAgs-specific CD8 T cell responses in spontaneous settings and upon Flt3L + αCD40 (DC-therapy). We find that cDC1 are required to generate broad CD8 responses against a range of diverse neoAgs. DC-therapy promotes immunogenicity of weaker neoAgs and strongly inhibits the growth of high tumor-mutational burden (TMB) tumors. In contrast, low TMB tumors respond poorly to DC-therapy, generating mild CD8 T cell responses that are not sufficient to block progression. scRNA transcriptional analysis, immune profiling and functional assays unveil the changes induced by DC-therapy in lung tissues, which comprise accumulation of cDC1 with increased immunostimulatory properties and less exhausted effector CD8 T cells. We conclude that boosting cDC1 activity is critical to broaden the diversity of anti-tumoral CD8 T cell responses and to leverage neoAgs content for therapeutic advantage.
MINSTED tracking of single biomolecules
Authors: Scheiderer Lukas , von der Emde Henrik , Hesselink Mira , Weber Michael , Hell Stefan W.
Published: March 2024

Here we show that MINSTED localization, a method whereby the position of a fluorophore is identified with precisely controlled beams of a STED microscope, tracks fluorophores and hence labeled biomolecules with nanometer/millisecond spatiotemporal precision. By updating the position for each detected photon, MINSTED recognizes fluorophore steps of 16 nm within <250 μs using about 13 photons. The power of MINSTED tracking is demonstrated by resolving the stepping of the motor protein kinesin-1 walking on microtubules and switching protofilaments.
Super-resolution deep neural network (SRDNN) based multi-image steganography for highly secured lossless image transmission
Authors: Priya S. , Abirami S. P. , Arunkumar B. , Mishachandar B.
Published: March 2024

Information exchange and communication through the Internet are one of the most crucial aspects of today’s information technology world. The security of information transmitted online has grown to be a critical concern, particularly in the transfer of medical data. To overcome this, the data must be delivered securely without being altered or lost. This can be possibly done by combining the principles of cryptography and steganography. In the recent past, steganography is used with simpler methods like the least significant bit manipulation technique, in order to encode a lower-resolution image into a higher-resolution image. Here, we attempt to use deep neural networks to combine many two-dimensional colour images of the same resolution into a single cover image with the same resolution. In this technique, many secret images are concealed inside a single cover image using deep neural networks. The embedded cover image is then encrypted using a 3D chaotic map for diffusion and elliptic curve cryptography (ECC) for confusion to increase security.Supporting the fact that neural networks experience losses, the proposed system recovers up to 93% of the hidden image concealed in the original image. As the secret image features are identified and combined along with the cover image, the time complexity involved in the security process is minimized by 78% compared to securing the original data.
Voltage-controlled two-dimensional Fresnel diffraction pattern in quantum dot molecules
Authors: Mehrabzadeh Hamed , Khoshdel Hamid , Mahmoudi Mohammad , Amini Sabegh Zahra , Rasouli Saifollah
Published: March 2024

This study explores the influence of inter-dot tunneling effects within a quantum dot molecule on the Fresnel diffraction phenomenon. Our findings indicate that the Fresnel diffraction of the output probe Gaussian field can be manipulated by adjusting the inter-dot tunneling parameter’s strength and the characteristics of the coupling field. The inter-dot tunneling effect establishes a closed-loop system, setting conditions for the interference of the applied fields. We specifically examine a Laguerre–Gaussian (LG) coupling field, investigating how its properties-such as strength, value, and sign of the orbital angular momentum (OAM)-impact the Fresnel diffraction of the output probe field. Increasing the inter-dot tunneling parameter and the coupling LG field’s strength allows for control over the spatial distribution of the Fresnel diffraction pattern. Notably, the inter-dot tunneling parameter can disturb the symmetry of the diffraction patterns. Additionally, considering a negative OAM for the coupling LG field transforms the diffraction pattern into its inverse shape. This suggests that, in the presence of the inter-dot tunneling effect, the Fresnel diffraction pattern is contingent on the direction of rotation of the helical phase front of the coupling LG field. Our results offer insights into quantum control of Fresnel diffraction patterns and the identification of OAM in LG beams, presenting potential applications in quantum technologies.
Analyzing the effects of physical activity levels on aggressive behavior in college students using a chain-mediated model
Authors: Yu Haohan , Ma Qiaochu , Sun Yao , Jiang Shan , Hu Songhan , Wang Xin
Published: March 2024

This study aims to examine the mediating role of self-efficacy (SE) and self-control (SC) in the relationship between physical activity (PA) and aggressive behaviors (AB) among college students. It provides a basis for the prevention and control of AB among college students. This study employed a survey research methodology, including the PA Level Scale, the General Self-efficacy Scale, the Self-control Scale, and the Chinese Aggressive Behaviors Scale on 950 college students. The chain mediating effect test and Bootstrap analysis were applied. The results were as follows: (1) There was a main effect of PA on SE, SC, and AB as well as all sub-indicators (physical aggression, verbal aggression, anger, hostility, self-directed aggression), i.e., PA had a direct effect on the control of all three; (2) PA level was significantly negatively correlated with AB and significantly positively correlated with SE and SC. That is, the higher the level of PA, the better the SE and SC, and the lower the probability of AB; (3) The three pathways had mediating effects: PA → SE → AB, PA → SC → AB, PA → SE → SC → AB, with effect sizes of 8.78%, 28.63%, and 19.08%, respectively. It is concluded that regular PA is a potent method for decreasing aggressive behavior and psychological issues in university students while additionally promoting self-efficacy and self-control. Increasing the intensity of PA may enhance the effectiveness of these chain benefits.
The analysis on groundwater storage variations from GRACE/GRACE-FO in recent 20 years driven by influencing factors and prediction in Shandong Province, China
Authors: Li Wanqiu , Bao Lifeng , Yao Guobiao , Wang Fengwei , Guo Qiuying , Zhu Jie , Zhu Jinjie , Wang Zhiwei , Bi Jingxue , Zhu Chengcheng , Zhong Yulong , Lu Shanbo
Published: March 2024

Monitoring and predicting the regional groundwater storage (GWS) fluctuation is an essential support for effectively managing water resources. Therefore, taking Shandong Province as an example, the data from Gravity Recovery and Climate Experiment (GRACE) and GRACE Follow-On (GRACE-FO) is used to invert GWS fluctuation from January 2003 to December 2022 together with Watergap Global Hydrological Model (WGHM), in-situ groundwater volume and level data. The spatio-temporal characteristics are decomposed using Independent Components Analysis (ICA), and the impact factors, such as precipitation and human activities, which are also analyzed. To predict the short-time changes of GWS, the Support Vector Machines (SVM) is adopted together with three commonly used methods Long Short-Term Memory (LSTM), Singular Spectrum Analysis (SSA), Auto-Regressive Moving Average Model (ARMA), as the comparison. The results show that: (1) The loss intensity of western GWS is significantly greater than those in coastal areas. From 2003 to 2006, GWS increased sharply; during 2007 to 2014, there exists a loss rate − 5.80 ± 2.28 mm/a of GWS; the linear trend of GWS change is − 5.39 ± 3.65 mm/a from 2015 to 2022, may be mainly due to the effect of South-to-North Water Diversion Project. The correlation coefficient between GRACE and WGHM is 0.67, which is consistent with in-situ groundwater volume and level. (2) The GWS has higher positive correlation with monthly Global Precipitation Climatology Project (GPCP) considering time delay after moving average, which has the similar energy spectrum depending on Continuous Wavelet Transform (CWT) method. In addition, the influencing facotrs on annual GWS fluctuation are analyzed, the correlation coefficient between GWS and in-situ data including the consumption of groundwater mining, farmland irrigation is 0.80, 0.71, respectively. (3) For the GWS prediction, SVM method is adopted to analyze, three training samples with 180, 204 and 228 months are established with the goodness-of-fit all higher than 0.97. The correlation coefficients are 0.56, 0.75, 0.68; RMSE is 5.26, 4.42, 5.65 mm; NSE is 0.28, 0.43, 0.36, respectively. The performance of SVM model is better than the other methods for the short-term prediction.
Machine learning developed a CD8+ exhausted T cells signature for predicting prognosis, immune infiltration and drug sensitivity in ovarian cancer
Authors: Chen Rujun , Zheng Yicai , Fei Chen , Ye Jun , Fei He
Published: March 2024

CD8+exhausted T cells (CD8+Tex) played a vital role in the progression and therapeutic response of cancer. However, few studies have fully clarified the characters of CD8+Texrelated genes in ovarian cancer (OC). The CD8+Texrelated prognostic signature (TRPS) was constructed with integrative machine learning procedure including 10 methods using TCGA, GSE14764, GSE26193, GSE26712, GSE63885 and GSE140082 dataset. Several immunotherapy benefits indicators, including Tumor Immune Dysfunction and Exclusion (TIDE) score, immunophenoscore (IPS), TMB score and tumor escape score, were used to explore performance of TRPS in predicting immunotherapy benefits of OC. The TRPS constructed by Enet (alpha = 0.3) method acted as an independent risk factor for OC and showed stable and powerful performance in predicting clinical outcome of patients. The C-index of the TRPS was higher than that of tumor grade, clinical stage, and many developed signatures. Low TRPS score indicated a higher level of CD8+T cell, B cell, macrophage M1, and NK cells, representing a relative immunoactivated ecosystem in OC. OC patients with low risk score had a higher PD1&CTLA4 immunophenoscore, higher TMB score, lower TIDE score and lower tumor escape score, suggesting a better immunotherapy response. Moreover, higher TRPS score indicated a higher score of cancer-related hallmarks, including angiogenesis, EMT, hypoxia, glycolysis, and notch signaling. Vitro experiment showed that ARL6IP5 was downregulated in OC tissues and inhibited tumor cell proliferation. The current study constructed a novel TRPS for OC, which could serve as an indicator for predicting the prognosis, immune infiltration and immunotherapy benefits for OC patients.
Research on dynamic characteristics of cutter breaking frozen soil and optimal drum rotation speed of the new shaft tunneling machine
Authors: Chen Xin-ming , Yang Zhi , Jiao Hua-zhe , Zhang Jiang-ling , Wang Jie , Sun Jin-yu
Published: March 2024

To improve the efficiency of frozen soil excavation, the new shaft tunneling machine was developed. The new shaft tunneling machine exerts pressure on the frozen soil through the cutter under the joint action of its own gravity, the drum rotational force and the inertia force, and the frozen soil is damaged. By unique way of breaking frozen soil to improve the efficiency of frozen soil excavation, the drum rotation speed is one of the factors affecting the performance of frozen soil excavation. This article applies SolidWorks software to establish the model of cutter breaking frozen soil, takes advantage of Hyper Mesh finite element software coupled with LS-DYNA solver to acquire the regular pattern of change in the force change, frozen soil stress–strain and specific energy of cutter crushing frozen soil, etc., which analyzes the destruction of frozen soil when the drum of the new shaft tunneling machine is rotating at the speed of 25–40 rpm. Combine with field test to investigate the mechanism of cutter breaking frozen soil under the optimal drum rotation speed. The investigation results demonstrate that: when frozen soil's self-bearing capacity is lower than the force of cutter, it breaks up and detaches from the soil body, and frozen soil undergoes tensile, compressive and shear damages. For this research, it is instructive for practical engineering.
Cardiac biopsies reveal differences in transcriptomics between left and right ventricle in patients with or without diagnostic signs of heart failure
Authors: Frisk Christoffer , Das Sarbashis , Eriksson Maria J. , Walentinsson Anna , Corbascio Matthias , Hage Camilla , Kumar Chanchal , Ekström Mattias , Maret Eva , Persson Hans , Linde Cecilia , Persson Bengt
Published: March 2024

New or mild heart failure (HF) is mainly caused by left ventricular dysfunction. We hypothesised that gene expression differ between the left (LV) and right ventricle (RV) and secondly by type of LV dysfunction. We compared gene expression through myocardial biopsies from LV and RV of patients undergoing elective coronary bypass surgery (CABG). Patients were categorised based on LV ejection fraction (EF), diastolic function and NT-proBNP into pEF (preserved; LVEF ≥ 45%), rEF (reduced; LVEF < 45%) or normal LV function. Principal component analysis of gene expression displayed two clusters corresponding to LV and RV. Up-regulated genes in LV included natriuretic peptides NPPA and NPPB, transcription factors/coactivators STAT4 and VGLL2, ion channel related HCN2 and LRRC38 associated with cardiac muscle contraction, cytoskeleton, and cellular component movement. Patients with pEF phenotype versus normal differed in gene expression predominantly in LV, supporting that diastolic dysfunction and structural changes reflect early LV disease in pEF. DKK2 was overexpressed in LV of HFpEF phenotype, potentially leading to lower expression levels of β-catenin, α-SMA (smooth muscle actin), and enhanced apoptosis, and could be a possible factor in the development of HFpEF. CXCL14 was down-regulated in both pEF and rEF, and may play a role to promote development of HF.
Ordered weighted evaluation method of lifting operation safety risks considering coupling effect
Authors: Yan Kesheng , Jin Lianghai , Yu Xiaoyun
Published: March 2024

In order to accurately evaluate the safety risk degree of lifting operations and improve the safety control level of lifting operations, firstly, Work Breakdown Structure (WBS) is used to decompose the construction process of lifting operations, Risk Breakdown Structure (RBS) is used to decompose the safety risk, 16 safety risk factors of lifting operations are identified, and the risk evaluation system is constructed. Then, the safety risk assessment model of lifting operations is constructed by integrating risk coupling theory, joint ordered weighting operators, and an interaction matrix to identify key risk factors and safety risk levels. Finally, taking the lifting operation construction project of Yangfanggou Hydropower Station as an example, the evaluation index system and method are applied. The results show that the high-risk safety risks of the lifting operation construction of the project are: 'Low safety awareness causes workers to operate illegally X23', 'Operation error caused by illegal command X33', 'Workers' risky work caused by low safety awareness X34', 'Edge, high and climbing operation protection is not in place X36', and 'Improper binding of components caused by workers' illegal operation X25'. The construction of the lifting operation poses a significant risk level, and the evaluation results are consistent with the actual situation. The rationality of the evaluation system and model constructed in this paper can provide a reference for the safety management and control of the construction site of the lifting operation and the safety of the lifting operation.
Investigation of physio-mechanical, antioxidant and antimicrobial properties of starch–zinc oxide nanoparticles active films reinforced with Ferula gummosa Boiss essential oil
Authors: Sarhadi Hamid , Shahdadi Fatemeh , Salehi Sardoei Ali , Hatami Mehrnaz , Ghorbanpour Mansour
Published: March 2024

The production of surface compounds coated with active substances has gained significant attention in recent years. This study investigated the physical, mechanical, antioxidant, and antimicrobial properties of a composite made of starch and zinc oxide nanoparticles (ZnO NPs) containing various concentrations of Ferula gummosa essential oil (0.5%, 1%, and 1.5%). The addition of ZnO NPs improved the thickness, mechanical and microbial properties, and reduced the water vapor permeability of the starch active film. The addition of F. gummosa essential oil to the starch nanocomposite decreased the water vapor permeability from 6.25 to 5.63 g mm−2 d−1 kPa−1, but this decrease was significant only at the concentration of 1.5% of essential oils (p < 0.05). Adding 1.5% of F. gummosa essential oil to starch nanocomposite led to a decrease in Tensile Strength value, while an increase in Elongation at Break values was observed. The results of the antimicrobial activity of the nanocomposite revealed that the pure starch film did not show any lack of growth zone. The addition of ZnO NPs to the starch matrix resulted in antimicrobial activity on both studied bacteria (Staphylococcus aureus and Escherichia coli). The highest antimicrobial activity was observed in the starch/ZnO NPs film containing 1.5% essential oil with an inhibition zone of 340 mm2 on S. aureus. Antioxidant activity increased significantly with increasing concentration of F. gummosa essential oil (P < 0.05). The film containing 1.5% essential oil had the highest (50.5%) antioxidant activity. Coating also improved the chemical characteristics of fish fillet. In conclusion, the starch nanocomposite containing ZnO NPs and F. gummosa essential oil has the potential to be used in the aquatic packaging industry.
Dynamic identification of important nodes in complex networks based on the KPDN–INCC method
Authors: Zhang Jieyong , Zhao Liang , Sun Peng , Liang Wei
Published: March 2024

This article focuses on the cascading failure problem and node importance evaluation method in complex networks. To address the issue of identifying important nodes in dynamic networks, the method used in static networks is introduced and the necessity of re-evaluating node status during node removal is proposed. Studies have found that the methods for identifying dynamic and static network nodes are two different directions, and most literature only uses dynamic methods to verify static methods. Therefore, it is necessary to find suitable node evaluation methods for dynamic networks. Based on this, this article proposes a method that integrates local and global correlation properties. In terms of global features, we introduce an improved k-shell method with fusion degree to improve the resolution of node ranking. In terms of local features, we introduce Solton factor and structure hole factor improved by INCC (improved network constraint coefficient), which effectively improves the algorithm’s ability to identify the relationship between adjacent nodes. Through comparison with existing methods, it is found that the KPDN–INCC method proposed in this paper complements the KPDN method and can accurately identify important nodes, thereby helping to quickly disintegrate the network. Finally, the effectiveness of the proposed method in identifying important nodes in a small-world network with a random parameter less than 0.4 was verified through artificial network experiments.
In-plane oxygen diffusion measurements in polymer films using time-resolved imaging of programmable luminescent tags
Authors: Kantelberg Richard , Achenbach Tim , Kirch Anton , Reineke Sebastian
Published: March 2024

Oxygen diffusion properties in thin polymer films are key parameters in industrial applications from food packaging, over medical encapsulation to organic semiconductor devices and have been continuously investigated in recent decades. The established methods have in common that they require complex pressure-sensitive setups or vacuum technology and usually do not come without surface effects. In contrast, this work provides a low-cost, precise and reliable method to determine the oxygen diffusion coefficient D in bulk polymer films based on tracking the phosphorescent pattern of a programmable luminescent tag over time. Our method exploits two-dimensional image analysis of oxygen-quenched organic room-temperature phosphors in a host polymer with high spatial accuracy. It avoids interface effects and accounts for the photoconsumption of oxygen. As a role model, the diffusion coefficients of polystyrene glasses with molecular weights between 13k and 350k g/mol are determined to be in the range of (0.8–1.5) × 10–7 cm2/s, which is in good agreement with previously reported values. We finally demonstrate the reduction of the oxygen diffusion coefficient in polystyrene by one quarter upon annealing above its glass transition temperature.
Biosynthesis of palladium, platinum, and their bimetallic nanoparticles using rosemary and ginseng herbal plants: evaluation of anticancer activity
Authors: Alinaghi Moloud , Mokarram Pooneh , Ahmadi Mazaher , Bozorg-ghalati Farzaneh
Published: March 2024

In this research, palladium (II) and platinum (II), as well as their bimetallic nanoparticles were synthesized using medicinal plants in an eco-friendly manner. Rosemary and Ginseng extracts were chosen due to their promising anticancer potential. The synthesized nanoparticles underwent characterization through FT-IR spectroscopy, DLS, XRD, EDX, SEM, and TEM techniques. Once the expected structures were confirmed, the performance of these nanoparticles, which exhibited an optimal size, was evaluated as potential anticancer agents through in vitro method on colon cancer cell lines (Ls180, SW480). MTT assay studies showed that the synthesized nanoparticles induced cell death. Moreover, real-time PCR was employed to investigate autophagy markers and the effect of nanoparticles on the apoptosis process, demonstrating a significant effect of the synthesized compounds in this regard.
High Arctic “hotspots” for sperm whales (Physeter macrocephalus) off western and northern Svalbard, Norway, revealed by multi-year Passive Acoustic Monitoring (PAM)
Authors: Pöyhönen Viivi , Thomisch Karolin , Kovacs Kit M. , Lydersen Christian , Ahonen Heidi
Published: March 2024

Despite the well-documented, broad global distribution of sperm whales (Physeter macrocephalus), their distributional patterns remain poorly known in Arctic regions, where year-round monitoring is challenging. Adult male sperm whales are known to migrate seasonally between nutrient-rich high latitude waters and low latitude breeding grounds. However, knowledge is limited regarding fine-scale distribution and seasonal presence at high latitudes. To investigate the acoustic occurrence of this vocally active species in the High Arctic of the Northeast Atlantic, this study combined automated and manual click detection methods to analyze passive acoustic data collected at eight locations around the Svalbard Archipelago, Norway, between 2012 and 2021. The results revealed the presence of sperm whales at six recording sites and demonstrated sperm whale “hotspots” in ice-free areas in eastern Fram Strait along the shelf break and close to the west coast of Spitsbergen from May–January, with some variation between years and locations. Although acoustic presence decreased with increasing latitude, even the northern-most location (81° N) recorded sperm whale vocal activity between August and January. This study provides a baseline for sperm whale acoustic presence in the High Arctic, which will be essential in the context of detecting future changes and also for predicting future distribution patterns in the rapidly changing Arctic marine environment.
Integrating X-ray phase-contrast imaging and histology for comparative evaluation of breast tissue malignancies in virtual histology analysis
Authors: Donato Sandro , Arana Peña Lucia Mariel , Arfelli Fulvia , Brombal Luca , Colmo Luisella , Longo Renata , Martellani Fulvia , Tromba Giuliana , Zanconati Fabrizio , Bonazza Deborah
Published: March 2024

Detecting breast tissue alterations is essential for cancer diagnosis. However, inherent bidimensionality limits histological procedures’ effectiveness in identifying these changes. Our study applies a 3D virtual histology method based on X-ray phase-contrast microtomography (PhC $$\mu$$
μ
CT), performed at a synchrotron facility, to investigate breast tissue samples including different types of lesions, namely intraductal papilloma, micropapillary intracystic carcinoma, and invasive lobular carcinoma. One-to-one comparisons of X-ray and histological images explore the clinical potential of 3D X-ray virtual histology. Results show that PhC $$\mu$$
μ
CT technique provides high spatial resolution and soft tissue sensitivity, while being non-destructive, not requiring a dedicated sample processing and being compatible with conventional histology. PhC $$\mu$$
μ
CT can enhance the visualization of morphological characteristics such as stromal tissue, fibrovascular core, terminal duct lobular unit, stromal/epithelium interface, basement membrane, and adipocytes. Despite not reaching the (sub) cellular level, the three-dimensionality of PhC $$\mu$$
μ
CT images allows to depict in-depth alterations of the breast tissues, potentially revealing pathologically relevant details missed by a single histological section. Compared to serial sectioning, PhC $$\mu$$
μ
CT allows the virtual investigation of the sample volume along any orientation, possibly guiding the pathologist in the choice of the most suitable cutting plane. Overall, PhC $$\mu$$
μ
CT virtual histology holds great promise as a tool adding to conventional histology for improving efficiency, accessibility, and diagnostic accuracy of pathological evaluation.
Clinical characteristics of Guillain–Barré syndrome in patients with primary Sjögren’s syndrome
Authors: Cao Xiaoyu , Guo Juan , Yang Yaran , Yu Zhibo , Pan Hua , Zhou Wei
Published: March 2024

To investigate the clinical characteristics of Guillain–Barré syndrome (GBS) in patients with primary Sjögren’s syndrome (SS). Records of patients with positive anti-SSA antibodies hospitalized in the Beijing Tiantan Hospital between December 2011 and May 2020 were retrieved. Patients who fulfilled the criteria for diagnosis of GBS and primary SS were included, and their clinical data were analyzed. Among the 785 patients with positive anti-SSA, 52 patients were identified in this study. They were 27 males and 25 females with median age of 59 years old. Besides anti-SSA antibodies, multiple autoantibodies were detected in these patients including antinuclear antibody, anti-Ro52, anti-mitochondrial M2, anti-thyroid peroxidase and anti-thyroglobulin autoantibodies. Preceding infection was reported in 42 patients. Hyporeflexia/areflexia and limbs weakness were the most common manifestation and 35 patients presented cranial nerve injuries. GBS disability score of 3, 4 and 5 was scaled in 28 (53.8%), 15 (28.8%) and 3 (5.8%) patients respectively. Forty-six patients received intravenous immunoglobulin (IVIG) monotherapy, 5 patients were treated by IVIG plus glucocorticoids, and 51 patients improved during hospitalization. The frequency of male gender among the patients with both GBS and primary SS suggests an independent onset of GBS and the co-existence of these autoimmune diseases in patients with multiple autoantibodies. Majority of patients with GBS and primary SS experience benign disease course.
Label-free functional analysis of root-associated microbes with dynamic quantitative oblique back-illumination microscopy
Authors: Serafini Caroline E. , Green Madison , Diering Abigail , Cicerone Marcus T. , Cheung Lily S. , Kostka Joel E. , Robles Francisco E.
Published: March 2024

The increasing global demand for food, coupled with concerns about the environmental impact of synthetic fertilizers, underscores the urgency of developing sustainable agricultural practices. Nitrogen-fixing bacteria, known as diazotrophs, offer a potential solution by converting atmospheric nitrogen into bioavailable forms, reducing the reliance on synthetic fertilizers. However, a deeper understanding of their interactions with plants and other microbes is needed. In this study, we introduce a recently developed label-free 3D quantitative phase imaging technology called dynamic quantitative oblique back-illumination microscopy (DqOBM) to assess the functional dynamic activity of diazotrophs in vitro and in situ. Our experiments involved three different diazotrophs (Sinorhizobium meliloti, Azotobacter vinelandii, and Rahnella aquatilis) cultured on media with amendments of carbon and nitrogen sources. Over 5 days, we observed increased dynamics in nutrient-amended media. These results suggest that the observed bacterial dynamics correlate with their metabolic activity. Furthermore, we applied qOBM to visualize microbial dynamics within the root cap and elongation zone of Arabidopsis thaliana primary roots. This allowed us to identify distinct areas of microbial infiltration in plant roots without the need for fluorescent markers. Our findings demonstrate that DqOBM can effectively characterize microbial dynamics and provide insights into plant-microbe interactions in situ, offering a valuable tool for advancing our understanding of sustainable agriculture.
Optimization of the seat position for a personal vehicle equipped with a crankset: pilot study
Authors: Bereś Łukasz , Pyrzanowska Justyna , Mirowska-Guzel Dagmara , Obszański Marcin , Pyrzanowski Paweł
Published: March 2024

The aim of the study was to optimize the seat for a personal vehicle equipped with a crankset mechanism, meant for everyday use. The inclination of the seat backrest was selected on the basis of theoretical considerations. Then dynamic tests were carried out on a group of young, healthy men in order to verify the ergonomic aspects of the seat position in relation to the crankset and determine the efficiency of the human-mechanism system with a load of 50 W. The data obtained from the dynamic tests were subject to statistical analysis. Research has shown that higher seat positions result in statistically higher efficiencies. In addition, a holistic analysis of the personal vehicle design problem shows that the upper position of the seat is also the best. The results of the research can be used to optimize personal vehicles using human force as a drive.