bluuebunny/crossref_metadata_2025 huggingface dataset:
Synergistic antitumor activity between HER2 antibody-drug conjugate and chemotherapy for treating advanced colorectal cancer
Authors: Liu Hongfu , Zhou Dongdong , Liu Dongqin , Xu Xi , Zhang Kai , Hu Ruxia , Xiong Peng , Wang Changxin , Zeng Xiangfu , Wang Liefeng , Zhang Shuyong
Published: March 2024

Colorectal cancer (CRC) is the third most common cancer associated with a poor prognosis. Effective targeted therapy alone or in combination for treating advanced CRC remains to be a major clinical challenge. Here, we propose the therapeutic efficacy and molecular mechanism underlying RC48, a FDA-approved anti-HER2 antibody conjugate via a cleavable linker to the microtubule inhibitor monomethyl auristatin E (MMAE), either alone or in combination with gemcitabine (GEM) in various models of HER2-positive advanced CRC. Our findings demonstrated that HER2 was widely expressed and located on the plasma membrane of CRC patient specimens, PDX xenograft tumors and cell lines. It confirmed that RC48 alone significantly targeted and eradicated HER2 positive CRC tumor in these models. Moreover, we screened a panel of FDA-approved first-line chemotherapy drugs in vitro. We found that GEM exhibited stronger antiproliferative activity compared to the other first-line anti-cancer agents. Furthermore, combination therapy of RC48 and GEM significantly showed synergetic antitumor activity in vitro and in vivo. To gain further mechanistic insights into the combination therapy, we performed RNA-seq analysis. The results revealed that combination treatment of RC48 and GEM regulated multiple signaling pathways, such as PI3K-AKT, MAPK, p53, Foxo, apoptosis, cell cycle and cell senescence, etc., to exert its antitumor activity in CRC cells. Collectively, these preclinical findings demonstrated that RC48 alone or combinational therapy exerted promising antitumor activity, and meriting the preclinical framework for combinational therapy of anti-HER2 drug conjugate drug and chemotherapy drugs for HER2-positive patients with advanced CRC.
Transmission and dynamics of mother-infant gut viruses during pregnancy and early life
Authors: Garmaeva Sanzhima , Sinha Trishla , Gulyaeva Anastasia , Kuzub Nataliia , Spreckels Johanne E. , Andreu-Sánchez Sergio , Gacesa Ranko , Vich Vila Arnau , Brushett Siobhan , Kruk Marloes ,   Lifelines NEXT cohort study, Dotinga Aafje , Gordijn Sanne , Jankipersadsing Soesma , de Jonge Ank , de Kroon Marlou L. A. , Koppelman Gerard H. , Peters Lilian L. , Prins Jelmer R. , Reijneveld Sijmen A. , Swertz Morris A. , Verkade Henkjan J. , Dekens Jackie , Sikkema Jan , Kuipers Folkert , Shkoporov Andrey N. , Hill Colin , Scherjon Sicco , Wijmenga Cisca , Fu Jingyuan , Kurilshikov Alexander , Zhernakova Alexandra
Published: March 2024

Early development of the gut ecosystem is crucial for lifelong health. While infant gut bacterial communities have been studied extensively, the infant gut virome remains under-explored. To study the development of the infant gut virome over time and the factors that shape it, we longitudinally assess the composition of gut viruses and their bacterial hosts in 30 women during and after pregnancy and in their 32 infants during their first year of life. Using shotgun metagenomic sequencing applied to dsDNA extracted from Virus-Like Particles (VLPs) and bacteria, we generate 205 VLP metaviromes and 322 total metagenomes. With this data, we show that while the maternal gut virome composition remains stable during late pregnancy and after birth, the infant gut virome is dynamic in the first year of life. Notably, infant gut viromes contain a higher abundance of active temperate phages compared to maternal gut viromes, which decreases over the first year of life. Moreover, we show that the feeding mode and place of delivery influence the gut virome composition of infants. Lastly, we provide evidence of co-transmission of viral and bacterial strains from mothers to infants, demonstrating that infants acquire some of their virome from their mother’s gut.
Crystallization of molecular layers produced under confinement onto a surface
Authors: Tong Jincheng , de Bruyn Nathan , Alieva Adriana , Legge Elizabeth. J. , Boyes Matthew , Song Xiuju , Walisinghe Alvin J. , Pollard Andrew J. , Anderson Michael W. , Vetter Thomas , Melle-Franco Manuel , Casiraghi Cinzia
Published: March 2024

It is well known that molecules confined very close to a surface arrange into molecular layers. Because solid-liquid interfaces are ubiquitous in the chemical, biological and physical sciences, it is crucial to develop methods to easily access molecular layers and exploit their distinct properties by producing molecular layered crystals. Here we report a method based on crystallization in ultra-thin puddles enabled by gas blowing, which allows to produce molecular layered crystals with thickness down to the monolayer onto a surface, making them directly accessible for characterization and further processing. By selecting four molecules with different types of polymorphs, we observed exclusive crystallization of polymorphs with Van der Waals interlayer interactions, which have not been observed with traditional confinement methods. In conclusion, the gas blowing approach unveils the opportunity to perform materials chemistry under confinement onto a surface, enabling the formation of distinct crystals with selected polymorphism.
Topological barrier to Cas12a activation by circular DNA nanostructures facilitates autocatalysis and transforms DNA/RNA sensing
Authors: Deng Fei , Li Yi , Yang Biyao , Sang Rui , Deng Wei , Kansara Maya , Lin Frank , Thavaneswaran Subotheni , Thomas David M. , Goldys Ewa M.
Published: March 2024

Control of CRISPR/Cas12a trans-cleavage is crucial for biosensor development. Here, we show that small circular DNA nanostructures which partially match guide RNA sequences only minimally activate Cas12a ribonucleoproteins. However, linearizing these structures restores activation. Building on this finding, an Autocatalytic Cas12a Circular DNA Amplification Reaction (AutoCAR) system is established which allows a single nucleic acid target to activate multiple ribonucleoproteins, and greatly increases the achievable reporter cleavage rates per target. A rate-equation-based model explains the observed near-exponential rate trends. Autocatalysis is also sustained with DNA nanostructures modified with fluorophore-quencher pairs achieving 1 aM level (<1 copy/μL) DNA detection (106 times improvement), without additional amplification, within 15 min, at room temperature. The detection range is tuneable, spanning 3 to 11 orders of magnitude. We demonstrate 1 aM level detection of SNP mutations in circulating tumor DNA from blood plasma, genomic DNA (H. Pylori) and RNA (SARS-CoV-2) without reverse transcription as well as colorimetric lateral flow tests of cancer mutations with ~100 aM sensitivity.
Neuronal miR-9 promotes HSV-1 epigenetic silencing and latency by repressing Oct-1 and Onecut family genes
Authors: Deng Yue , Lin Yuqi , Chen Siyu , Xiang Yuhang , Chen Hongjia , Qi Shuyuan , Oh Hyung Suk , Das Biswajit , Komazin-Meredith Gloria , Pesola Jean M. , Knipe David M. , Coen Donald M. , Pan Dongli
Published: March 2024

Herpes simplex virus 1 (HSV-1) latent infection entails repression of viral lytic genes in neurons. By functional screening using luciferase-expressing HSV-1, we identify ten neuron-specific microRNAs potentially repressing HSV-1 neuronal replication. Transfection of miR-9, the most active candidate from the screen, decreases HSV-1 replication and gene expression in Neuro-2a cells. Ectopic expression of miR-9 from lentivirus or recombinant HSV-1 suppresses HSV-1 replication in male primary mouse neurons in culture and mouse trigeminal ganglia in vivo, and reactivation from latency in the primary neurons. Target prediction and validation identify transcription factors Oct-1, a known co-activator of HSV transcription, and all three Onecut family members as miR-9 targets. Knockdown of ONECUT2 decreases HSV-1 yields in Neuro-2a cells. Overexpression of each ONECUT protein increases HSV-1 replication in Neuro-2a cells, human induced pluripotent stem cell-derived neurons, and primary mouse neurons, and accelerates reactivation from latency in the mouse neurons. Mutagenesis, ChIP-seq, RNA-seq, ChIP-qPCR and ATAC-seq results suggest that ONECUT2 can nonspecifically bind to viral genes via its CUT domain, globally stimulate viral gene transcription, reduce viral heterochromatin and enhance the accessibility of viral chromatin. Thus, neuronal miR-9 promotes viral epigenetic silencing and latency by targeting multiple host transcription factors important for lytic gene activation.
Mapping a 50-spin-qubit network through correlated sensing
Authors: van de Stolpe G. L. , Kwiatkowski D. P. , Bradley C. E. , Randall J. , Abobeih M. H. , Breitweiser S. A. , Bassett L. C. , Markham M. , Twitchen D. J. , Taminiau T. H.
Published: March 2024

Spins associated to optically accessible solid-state defects have emerged as a versatile platform for exploring quantum simulation, quantum sensing and quantum communication. Pioneering experiments have shown the sensing, imaging, and control of multiple nuclear spins surrounding a single electron spin defect. However, the accessible size of these spin networks has been constrained by the spectral resolution of current methods. Here, we map a network of 50 coupled spins through high-resolution correlated sensing schemes, using a single nitrogen-vacancy center in diamond. We develop concatenated double-resonance sequences that identify spin-chains through the network. These chains reveal the characteristic spin frequencies and their interconnections with high spectral resolution, and can be fused together to map out the network. Our results provide new opportunities for quantum simulations by increasing the number of available spin qubits. Additionally, our methods might find applications in nano-scale imaging of complex spin systems external to the host crystal.
A GREB1-steroid receptor feedforward mechanism governs differential GREB1 action in endometrial function and endometriosis
Authors: Chadchan Sangappa B. , Popli Pooja , Liao Zian , Andreas Eryk , Dias Michelle , Wang Tianyuan , Gunderson Stephanie J. , Jimenez Patricia T. , Lanza Denise G. , Lanz Rainer B. , Foulds Charles E. , Monsivais Diana , DeMayo Francesco J. , Yalamanchili Hari Krishna , Jungheim Emily S. , Heaney Jason D. , Lydon John P. , Moley Kelle H. , O’Malley Bert W. , Kommagani Ramakrishna
Published: March 2024

Cellular responses to the steroid hormones, estrogen (E2), and progesterone (P4) are governed by their cognate receptor’s transcriptional output. However, the feed-forward mechanisms that shape cell-type-specific transcriptional fulcrums for steroid receptors are unidentified. Herein, we found that a common feed-forward mechanism between GREB1 and steroid receptors regulates the differential effect of GREB1 on steroid hormones in a physiological or pathological context. In physiological (receptive) endometrium, GREB1 controls P4-responses in uterine stroma, affecting endometrial receptivity and decidualization, while not affecting E2-mediated epithelial proliferation. Of mechanism, progesterone-induced GREB1 physically interacts with the progesterone receptor, acting as a cofactor in a positive feedback mechanism to regulate P4-responsive genes. Conversely, in endometrial pathology (endometriosis), E2-induced GREB1 modulates E2-dependent gene expression to promote the growth of endometriotic lesions in mice. This differential action of GREB1 exerted by a common feed-forward mechanism with steroid receptors advances our understanding of mechanisms that underlie cell- and tissue-specific steroid hormone actions.
Static charge is an ionic molecular fragment
Authors: Fang Yan , Ao Chi Kit , Jiang Yan , Sun Yajuan , Chen Linfeng , Soh Siowling
Published: March 2024

What is static charge? Despite the long history of research, the identity of static charge and mechanism by which static is generated by contact electrification are still unknown. Investigations are challenging due to the complexity of surfaces. This study involves the molecular-scale analysis of contact electrification using highly well-defined surfaces functionalized with a self-assembled monolayer of alkylsilanes. Analyses show the elementary molecular steps of contact electrification: the exact location of heterolytic cleavage of covalent bonds (i.e., Si-C bond), exact charged species generated (i.e., alkyl carbocation), and transfer of molecular fragments. The strong correlation between charge generation and molecular fragments due to their signature odd-even effects further shows that contact electrification is based on cleavage of covalent bonds and transfer of ionic molecular fragments. Static charge is thus an alkyl carbocation; in general, it is an ionic molecular fragment. This mechanism based on cleavage of covalent bonds is applicable to general types of insulating materials, such as covalently bonded polymers. The odd-even effect of charging caused by the difference of only one atom explains the highly sensitive nature of contact electrification.
Long-term monitoring of ultratrace nucleic acids using tetrahedral nanostructure-based NgAgo on wearable microneedles
Authors: Yang Bin , Wang Haonan , Kong Jilie , Fang Xueen
Published: March 2024

Real-time and continuous monitoring of nucleic acid biomarkers with wearable devices holds potential for personal health management, especially in the context of pandemic surveillance or intensive care unit disease. However, achieving high sensitivity and long-term stability remains challenging. Here, we report a tetrahedral nanostructure-based Natronobacterium gregoryi Argonaute (NgAgo) for long-term stable monitoring of ultratrace unamplified nucleic acids (cell-free DNAs and RNAs) in vivo for sepsis on wearable device. This integrated wireless wearable consists of a flexible circuit board, a microneedle biosensor, and a stretchable epidermis patch with enrichment capability. We comprehensively investigate the recognition mechanism of nucleic acids by NgAgo/guide DNA and signal transformation within the Debye distance. In vivo experiments demonstrate the suitability for real-time monitoring of cell-free DNA and RNA with a sensitivity of 0.3 fM up to 14 days. These results provide a strategy for highly sensitive molecular recognition in vivo and for on-body detection of nucleic acid.
In-cell NMR suggests that DNA i-motif levels are strongly depleted in living human cells
Authors: Víšková Pavlína , Ištvánková Eva , Ryneš Jan , Džatko Šimon , Loja Tomáš , Živković Martina Lenarčič , Rigo Riccardo , El-Khoury Roberto , Serrano-Chacón Israel , Damha Masad J. , González Carlos , Mergny Jean-Louis , Foldynová-Trantírková Silvie , Trantírek Lukáš
Published: March 2024

I-Motifs (iM) are non-canonical DNA structures potentially forming in the accessible, single-stranded, cytosine-rich genomic regions with regulatory roles. Chromatin, protein interactions, and intracellular properties seem to govern iM formation at sites with i-motif formation propensity (iMFPS) in human cells, yet their specific contributions remain unclear. Using in-cell NMR with oligonucleotide iMFPS models, we monitor iM-associated structural equilibria in asynchronous and cell cycle-synchronized HeLa cells at 37 °C. Our findings show that iMFPS displaying pHT < 7 under reference in vitro conditions occur predominantly in unfolded states in cells, while those with pHT > 7 appear as a mix of folded and unfolded states depending on the cell cycle phase. Comparing these results with previous data obtained using an iM-specific antibody (iMab) reveals that cell cycle-dependent iM formation has a dual origin, and iM formation concerns only a tiny fraction (possibly 1%) of genomic sites with iM formation propensity. We propose a comprehensive model aligning observations from iMab and in-cell NMR and enabling the identification of iMFPS capable of adopting iM structures under physiological conditions in living human cells. Our results suggest that many iMFPS may have biological roles linked to their unfolded states.
Quantifying the photocurrent fluctuation in quantum materials by shot noise
Authors: Xiang Longjun , Jin Hao , Wang Jian
Published: March 2024

The DC photocurrent can detect the topology and geometry of quantum materials without inversion symmetry. Herein, we propose that the DC shot noise (DSN), as the fluctuation of photocurrent operator, can also be a diagnostic of quantum materials. Particularly, we develop the quantum theory for DSNs in gapped systems and identify the shift and injection DSNs by dividing the second-order photocurrent operator into off-diagonal and diagonal contributions, respectively. Remarkably, we find that the DSNs can not be forbidden by inversion symmetry, while the constraint from time-reversal symmetry depends on the polarization of light. Furthermore, we show that the DSNs also encode the geometrical information of Bloch electrons, such as the Berry curvature and the quantum metric. Finally, guided by symmetry, we apply our theory to evaluate the DSNs in monolayer GeS and bilayer MoS2 with and without inversion symmetry and find that the DSNs can be larger in centrosymmetric phase.
Cation desolvation-induced capacitance enhancement in reduced graphene oxide (rGO)
Authors: Ge Kangkang , Shao Hui , Raymundo-Piñero Encarnacion , Taberna Pierre-Louis , Simon Patrice
Published: March 2024

Understanding the local electrochemical processes is of key importance for efficient energy storage applications, including electrochemical double layer capacitors. In this work, we studied the charge storage mechanism of a model material - reduced graphene oxide (rGO) - in aqueous electrolyte using the combination of cavity micro-electrode, operando electrochemical quartz crystal microbalance (EQCM) and operando electrochemical dilatometry (ECD) tools. We evidence two regions with different charge storage mechanisms, depending on the cation-carbon interaction. Notably, under high cathodic polarization (region II), we report an important capacitance increase in Zn2+ containing electrolyte with minimum volume expansion, which is associated with Zn2+ desolvation resulting from strong electrostatic Zn2+-rGO interactions. These results highlight the significant role of ion-electrode interaction strength and cation desolvation in modulating the charging mechanisms, offering potential pathways for optimized capacitive energy storage. As a broader perspective, understanding confined electrochemical systems and the coupling between chemical, electrochemical and transport processes in confinement may open tremendous opportunities for energy, catalysis or water treatment applications in the future.
Structural insight into an Arl1–ArfGEF complex involved in Golgi recruitment of a GRIP-domain golgin
Authors: Duan H. Diessel , Jain Bhawik K. , Li Hua , Graham Todd R. , Li Huilin
Published: March 2024

Arl1 is an Arf-like (Arl) GTP-binding protein that interacts with the guanine nucleotide exchange factor Gea2 to recruit the golgin Imh1 to the Golgi. The Arl1–Gea2 complex also binds and activates the phosphatidylserine flippase Drs2 and these functions may be related, although the underlying molecular mechanism is unclear. Here we report high-resolution cryo-EM structures of the full-length Gea2 and the Arl1–Gea2 complex. Gea2 is a large protein with 1459 residues and is composed of six domains (DCB, HUS, SEC7, HDS1-3). We show that Gea2 assembles a stable dimer via an extensive interface involving hydrophobic and electrostatic interactions in the DCB and HUS region. Contrary to the previous report on a Gea2 homolog in which Arl1 binds to the dimerization surface of the DCB domain, implying a disrupted dimer upon Arl1 binding, we find that Arl1 binds to the outside surface of the Gea2 DCB domain, leaving the Gea2 dimer intact. The interaction between Arl1 and Gea2 involves the classic FWY aromatic residue triad as well as two Arl1-specific residues. We show that key mutations that disrupt the Arl1–Gea2 interaction abrogate Imh1 Golgi association. This work clarifies the Arl1–Gea2 interaction and improves our understanding of molecular events in the membrane trafficking.
Centrosome amplification and aneuploidy driven by the HIV-1-induced Vpr•VprBP•Plk4 complex in CD4+ T cells
Authors: Park Jung-Eun , Kim Tae-Sung , Zeng Yan , Mikolaj Melissa , Il Ahn Jong , Alam Muhammad S. , Monnie Christina M. , Shi Victoria , Zhou Ming , Chun Tae-Wook , Maldarelli Frank , Narayan Kedar , Ahn Jinwoo , Ashwell Jonathan D. , Strebel Klaus , Lee Kyung S.
Published: March 2024

HIV-1 infection elevates the risk of developing various cancers, including T-cell lymphoma. Whether HIV-1-encoded proteins directly contribute to oncogenesis remains unknown. We observe that approximately 1–5% of CD4+ T cells from the blood of people living with HIV-1 exhibit over-duplicated centrioles, suggesting that centrosome amplification underlies the development of HIV-1-associated cancers by driving aneuploidy. Through affinity purification, biochemical, and cellular analyses, we discover that Vpr, an accessory protein of HIV-1, hijacks the centriole duplication machinery and induces centrosome amplification and aneuploidy. Mechanistically, Vpr forms a cooperative ternary complex with an E3 ligase subunit, VprBP, and polo-like kinase 4 (Plk4). Unexpectedly, however, the complex enhances Plk4’s functionality by promoting its relocalization to the procentriole assembly and induces centrosome amplification. Loss of either Vpr’s C-terminal 17 residues or VprBP acidic region, the two elements required for binding to Plk4 cryptic polo-box, abrogates Vpr’s capacity to induce these events. Furthermore, HIV-1 WT, but not its Vpr mutant, induces multiple centrosomes and aneuploidy in human primary CD4+ T cells. We propose that the Vpr•VprBP•Plk4 complex serves as a molecular link that connects HIV-1 infection to oncogenesis and that inhibiting the Vpr C-terminal motif may reduce the occurrence of HIV-1-associated cancers.
Impact of preexisting proteinuria on the development of regorafenib-induced problematic proteinuria in real-world metastatic colorectal cancer treatment
Authors: Saito Yoshitaka , Takekuma Yoh , Komatsu Yoshito , Sugawara Mitsuru
Published: March 2024

Regorafenib is the first multikinase inhibitor for treating metastatic colorectal cancer (mCRC). Proteinuria is a frequently encountered adverse effect, regardless of prior administration of vascular endothelial growth factor inhibitors. Herein, we aimed to assess the impact of baseline preexisting proteinuria on regorafenib-induced problematic proteinuria during real-world mCRC therapy. Patients with mCRC receiving regorafenib (n = 100) were retrospectively assessed and divided into control and preexisting proteinuria (baseline grade of 1–2) groups. The primary endpoint was the development of grade ≥ 2 (grade ≥ 3 in case of baseline grade 2 patients) proteinuria. Propensity score-matching was performed to confirm the robustness of primary analyses. Defined proteinuria occurred in 30.7 and 57.9% of patients in the control and preexisting proteinuria groups, respectively, with significant differences in the all-patient population (P = 0.01). The preexisting proteinuria group exhibited significant defined proteinuria development within 7 days of regorafenib initiation, grade ≥ 3 symptoms, and treatment suspension owing to proteinuria. Similar results were obtained in the propensity score-matched population. According to multivariate logistic regression analysis, baseline proteinuria was a singular risk factor for defined proteinuria development (adjusted odds ratio; 3.76, 95% confidence interval; 1.45–9.75, P = 0.007). Collectively, our study revealed that patients with preexisting proteinuria develop regorafenib-induced proteinuria degradation.
Insights into subspecies classification and conservation priorities of Central Asian lynx populations revealed by morphometric and genetic analyses
Authors: Bizhanova Nazerke , Nanova Olga , Fadakar Davoud , Grachev Alexey , Hong Zijia , Mohd Sah Shahrul Anuar , Bizhanova Zhansaya , Sablin Mikhail , Grachev Yuriy
Published: March 2024

The Eurasian lynx(Lynx lynx) exhibits geographic variability and phylogenetic intraspecific relationships. Previous morphological studies have suggested the existence of multiple lynx subspecies, but recent genetic research has questioned this classification, particularly in Central Asia. In this study, we aimed to analyse the geographic and genetic variation in Central Asian lynx populations, particularly the Turkestan lynx and Altai lynx populations, using morphometric data and mtDNA sequences to contribute to their taxonomic classification. The comparative analysis of morphometric data revealed limited clinal variability between lynx samples from the Altai and Tien Shan regions. By examining mtDNA fragments (control region and cytochromeb) obtained from Kazakhstani lynx populations, two subspecies were identified:L. l. isabellinus(represented by a unique haplotype of the South clade, H46) andL. l. wrangeli(represented by haplotypes H36, H45, and H47 of the East clade).L. l. isabellinuswas recognized only in Tien Shan Mountain, while Altai lynx was likely identical toL. l. wrangeliand found in northern Kazakhstan, Altai Mountain, Saur and Tarbagatai Mountains, and Tien Shan Mountain. The morphological and mtDNA evidence presented in this study, although limited in sample size and number of genetic markers, renders the differentiation of the two subspecies challenging. Further sampling and compilation of whole-genome sequencing data are necessary to confirm whether the proposed subspecies warrant taxonomic standing.
Exploring strategies to optimise outcomes in hepatitis-associated aplastic anaemia patients following haematopoietic stem cell transplantation
Authors: Li Jia , Liu Yilin , Wang Jieru , Wang Yan , Pang Aiming , Yang Donglin , Chen Xin , Zhang Rongli , Wei Jialin , Ma Qiaoling , Zhai Weihua , He Yi , Jiang Erlie , Han Mingzhe , Feng Sizhou
Published: March 2024

This study aimed to assess haematopoietic stem cell transplantation (HSCT) safety and efficacy while exploring strategies for optimising outcomes in patients with hepatitis-associated aplastic anaemia (HAAA). We retrospectively reviewed 35 HAAA patients who underwent HSCT at a large Chinese blood disease hospital between 2008 and 2022. HAAA patients receiving HSCT typically presented with severe (28.6%) and very severe (65.7%) AA. Male patients predominated (68.6%), with a median onset age of 23 years (range, 9–44). Haploidentical donor-HSCT and matched sibling donor-HSCT were in comparable proportions. The 5-year overall survival (OS) rate was 74.0%, with cumulative incidences of grade II–IV acute and chronic graft-versus-host disease (GVHD) at 37.1% and 22.4%, respectively. A diagnosis-to-HSCT interval ≥ 75 days, acute GVHD, and post-HSCT liver events (e.g., hepatic GVHD and a three-fold increase in aminotransferase or bilirubin) significantly worsened 5-year OS. In the multivariate models, recipients with sex-matched grafts had better OS, and those with younger male donors had a lower incidence of II–IV aGVHD. Higher HLA matching degree (HLA > = 7/10) was an independent prognostic factor associated with better OS and GFFS. A diagnosis-to-HSCT interval ≥ 75 days was predictive of post-transplant liver events in HAAA patients. In conclusion, HSCT was a safe and effective treatment for HAAA. Early transplantation, careful donor selection and improving post-transplant liver events were crucial to optimise outcomes.
Research on the coupling mechanism and influencing factors of digital economy and green technology innovation in Chinese urban agglomerations
Authors: Zhong Xuesi , Duan Ziyi , Liu Chang , Chen Wei
Published: March 2024

This paper examines the coupling coordination degree between digital economy and green technology innovation in 19 urban agglomerations across China from 2011 to 2020. Through the analysis of the coupling coordination degree model, spatial autocorrelation, multi-distance spatial clustering analysis, kernel density analysis and grey correlation model, this study uncovers the mechanism of coupling between digital economy and green technology in Chinese urban agglomerations. Data analysis revealed a significant increase in the coupling coordination between the digital economy and green technology innovation within urban agglomerations. However, there are noticeable spatial imbalances in this trend. Additionally, the multi-distance spatial distance analysis highlights a shift from a random distribution to a clustered distribution of spatial characteristics. The polarization features vary among each urban agglomeration and exhibit a significant positive spatial correlation. Factors such as economic sustainability, creative talent, policy support, digital impetus, and technological support will affect the coupling mechanism of green technology innovation and the digital economy in China's urban agglomerations. Policy recommendations are proposed to foster the development of the digital economy, promote coordinated growth within and beyond urban clusters, and ultimately build a digital ecological civilization that is both green and intelligent.
Decoding the leaf apical meristem of Guarea glabra Vahl (Meliaceae): insight into the evolution of indeterminate pinnate leaves
Authors: Moriyama Yasutake , Koga Hiroyuki , Tsukaya Hirokazu
Published: March 2024

In seed plants, growth of shoots and roots is indeterminate, while leaves are typically determinate organs that cease to grow after a certain developmental stage. This is due to the characteristics of the leaf meristem, where cell proliferation activity is retained only for a limited period. However, several plants exhibit indeterminacy in their leaves, exemplified by the pinnate compound leaves of Guarea and Chisocheton genera in the Meliaceae family. In these plants, the leaf meristem at the tip of the leaf retains meristematic activity and produces leaflets over years, resulting in a single leaf that resembles a twig. The molecular mechanism underlying the indeterminate leaf meristem of these plants has not been examined. In this research, we used Guarea glabra as a model to investigate the development of indeterminate pinnate leaves. Transcriptome analyses revealed that the gene expression profile in leaf apex tissue differed from that in the shoot apex. However, a class 1 KNOTTED-LIKE HOMEOBOX (KNOX1) gene which is lost in Brassicaceae was highly expressed in both tissues. We established an in situ hybridisation system for this species using Technovit 9100 to analyse the spatial expression patterns of genes. We revealed that the leaf meristematic region of G. glabra expresses KNOX1, LEAFY and ANGUSTIFORIA3 simultaneously, suggesting the involvement of these genes in the indeterminacy of the leaf meristem.
Electrical facies of the Asmari Formation in the Mansouri oilfield, an application of multi-resolution graph-based and artificial neural network clustering methods
Authors: Eftekhari Seyedeh Hajar , Memariani Mahmoud , Maleki Zahra , Aleali Mohsen , Kianoush Pooria
Published: March 2024

Electrofacies analysis conducted the distribution effects throughout the reservoir despite the difficulty of characterizing stratigraphic relationships. Clustering methods quantitatively define the reservoir zone from non-reservoir considering electrofacies. Asmari Formation is the most significant reservoir of the Mansouri oilfield in SW Iran, generally composed of carbonate and sandstone layers. The stratigraphical study is determined by employing 250 core samples from one exploratory well in the studied field. Five zones with the best reservoir quality in zones 3 and 5 containing sandstone/shale are determined. Moreover, multi-resolution graph-based and artificial neural network clustering involving six logs are employed. Utilizing Geolog software, an optimal model with eight clusters with better rock separation is obtained. Eventually, five electrofacies with different lithological compositions and reservoir conditions are identified and based on lithofacies describing thin sections, sandstone, and shale in zones 3 and 5 show high reservoir quality. According to the depth related to these zones, most of the facies that exist in these depths include sandstone and dolomite facies, and this is affected by the two factors of the primary sedimentary texture and the effect of the diagenesis process on them. Results can compared to the clustering zone determination in other nearby sandstone reservoirs without cores.
The burden of atopic dermatitis in Portuguese patients: an observational study
Authors: Coelho Pedro S. , Apalhão Miguel , Victorino Guilherme , Cardoso Cristina , Camilo Joana , Silva João Maia
Published: March 2024

Atopic dermatitis (AD) is a common inflammatory skin condition that significantly affects patients' lives and imposes both economic and non-economic burdens. The precise societal and individual consequences of AD remain incompletely understood. This study aimed to characterize AD in Portuguese patients and assess its personal, familial, and societal implications, including health status and quality of life. The research, conducted from June 2019 to January 2020, involved 204 confirmed AD patients in Portugal, who completed a 70-question questionnaire. Results show that, on average, patients experienced a two-year delay in diagnosis, with two-thirds having allergic comorbidities. Late-onset AD (after age 20) was found to be correlated with worsening symptoms post-diagnosis. Globally, patients reported substantial effects on health, quality of life, and mental well-being. Effects include significant levels of anxiety, frustration and sleep disorders. Severe AD correlated with more suffering and reduced perceived health, indicating a link between disease severity and quality of life. Remarkably, despite questionable effectiveness, 92% of severe AD patients were prescribed antihistamines, while only 19% received biological treatments. In Portugal, delayed AD diagnosis hinders timely treatment, and despite its profound impact and high comorbidity rates, AD patients tend to remain undertreated. Recognizing the personal and societal repercussions is crucial for enhancing care, contributing to improving QoL, social functioning and global well-being.
Assessing hydrothermal changes in the upper Yellow River Basin amidst permafrost degradation
Authors: Song Lei , Wang Lei , Luo Dongliang , Chen Deliang , Zhou Jing
Published: March 2024

Since the 20th century, the temperature on the Qinghai–Tibetan Plateau (QTP) has increased at a rate of 2–3 times that of global warming. Consequently, the soil temperature and active layer thickness have also increased, which have directly caused severe degradation of the frozen ground on the QTP. Using a hydrological model driven by climate and vegetation forcing, the spatial and temporal changes in the hydrothermal characteristics of the Upper Yellow River Basin (UYRB) from 1960 to 2019 were modeled and the mechanism of the changes was analyzed. During the past six decades, the soil temperature in the UYRB exhibited an increasing trend. The degradation of permafrost in the UYRB was accompanied by thickening of the active layer, a reduction of the maximum depth of the seasonal frost penetration, and continuous extension of the basin thawing time. This degradation was also associated with the increase in the soil moisture content and decrease in the soil ice content, resulting in degradation of the permafrost area by one-tenth of the total area in the UYRB. The reduction of the permafrost area and the thickening of the active layer can profoundly impact hydrological processes and ecosystems. These findings play a critical role in designing efficient strategies to manage and protect frozen ground and serve as a valuable reference for understanding the consequences of frozen ground degradation globally.
Tertiary lymphoid structures predict survival and response to neoadjuvant therapy in locally advanced rectal cancer
Authors: Wang Qianyu , Zhong Wentao , Shen Xiaofei , Hao Zechen , Wan Meng , Yang Xiaopeng , An Ran , Zhu Hongyan , Cai Huiyun , Li Tao , Lv Yuan , Dong Xing , Chen Gang , Liu Aijun , Du Junfeng
Published: March 2024

Tertiary lymphoid structure (TLS) contributes to the anti-tumor immune response, and predicts the prognosis of colorectal cancer patients. However, the potential impact of TLS in shaping the immune status of rectal adenocarcinoma, and the intrinsic relationship between TLS and neoadjuvant therapies (neoTx) remain unclear. We performed hematoxylin-eosin staining, immunohistochemical and biomolecular analyses to investigate TLS and tumor-infiltrating lymphocytes (TILs) in 221 neoTx-treated and 242 treatment-naïve locally advanced rectal cancer (LARC) patients. High TLS density was significantly associated with the absence of vascular invasion, a lower neutrophil-to-lymphocyte ratio, increased TLS maturity, a longer recurrence-free survival (RFS) (hazard ratio [HR] 0.2985 95% confidence interval [CI] 0.1894–0.4706, p < 0.0001) and enhanced infiltration of adaptive immune cells. Biomolecular analysis showed that high TLS-score was strongly associated with more infiltration of immune cells and increased activation of immune-related pathways. TLS+ tumors in pre-treatment specimens were associated with a higher proportion of good respond (62.5% vs. 29.8%, p < 0.0002) and pathological complete remission (pCR) (40.0% vs. 11.1%, p < 0.0001), and significantly increased RFS (HR 0.3574 95%CI 0.1489–0.8578 p = 0.0213) compared with TLS- tumors in the neoTx cohort, which was confirmed in GSE119409 and GSE150082. Further studies showed that neoTx significantly reduced TLS density and maturity, and abolished the prognostic value of TLS. Our study illustrates that TLS may have a key role in mediating the T-cell-inflamed tumor microenvironment, which also provides a new direction for neoTx, especially neoadjuvant immunotherapy, in LRAC patients.
Biogeographic gradients of picoplankton diversity indicate increasing dominance of prokaryotes in warmer Arctic fjords
Authors: Hörstmann Cora , Hattermann Tore , Thomé Pauline C. , Buttigieg Pier Luigi , Morel Isidora , Waite Anya M. , John Uwe
Published: March 2024

Climate change is opening the Arctic Ocean to increasing human impact and ecosystem changes. Arctic fjords, the region’s most productive ecosystems, are sustained by a diverse microbial community at the base of the food web. Here we show that Arctic fjords become more prokaryotic in the picoplankton (0.2–3 µm) with increasing water temperatures. Across 21 fjords, we found that Arctic fjords had proportionally more trophically diverse (autotrophic, mixotrophic, and heterotrophic) picoeukaryotes, while subarctic and temperate fjords had relatively more diverse prokaryotic trophic groups. Modeled oceanographic connectivity between fjords suggested that transport alone would create a smooth gradient in beta diversity largely following the North Atlantic Current and East Greenland Current. Deviations from this suggested that picoeukaryotes had some strong regional patterns in beta diversity that reduced the effect of oceanographic connectivity, while prokaryotes were mainly stopped in their dispersal if strong temperature differences between sites were present. Fjords located in high Arctic regions also generally had very low prokaryotic alpha diversity. Ultimately, warming of Arctic fjords could induce a fundamental shift from more trophic diverse eukaryotic- to prokaryotic-dominated communities, with profound implications for Arctic ecosystem dynamics including their productivity patterns.
Salivary proteins potentially derived from horizontal gene transfer are critical for salivary sheath formation and other feeding processes
Authors: Huang Hai-Jian , Li Li-Li , Ye Zhuang-Xin , Lu Jia-Bao , Lou Yi-Han , Wei Zhong-Yan , Sun Zong-Tao , Chen Jian-Ping , Li Jun-Min , Zhang Chuan-Xi
Published: March 2024

Herbivorous insects employ an array of salivary proteins to aid feeding. However, the mechanisms behind the recruitment and evolution of these genes to mediate plant-insect interactions remain poorly understood. Here, we report a potential horizontal gene transfer (HGT) event from bacteria to an ancestral bug of Eutrichophora. The acquired genes subsequently underwent duplications and evolved through co-option. We annotated them as horizontal-transferred, Eutrichophora-specific salivary protein (HESPs) according to their origin and function. In Riptortus pedestris (Coreoidea), all nine HESPs are secreted into plants during feeding. The RpHESP4 to RpHESP8 are recently duplicated and found to be indispensable for salivary sheath formation. Silencing of RpHESP4-8 increases the difficulty of R. pedestris in probing the soybean, and the treated insects display a decreased survivability. Although silencing the other RpHESPs does not affect the salivary sheath formation, negative effects are also observed. In Pyrrhocoris apterus (Pyrrhocoroidea), five out of six PaHESPs are secretory salivary proteins, with PaHESP3 being critical for insect survival. The PaHESP5, while important for insects, no longer functions as a salivary protein. Our results provide insight into the potential origin of insect saliva and shed light on the evolution of salivary proteins.
Move the night way: how can physical activity facilitate adaptation to shift work?
Authors: Easton Dayna F. , Gupta Charlotte C. , Vincent Grace E. , Ferguson Sally A.
Published: March 2024

Shift work, involving night work, leads to impaired sleep, cognition, health and wellbeing, and an increased risk of occupational incidents. Current countermeasures include circadian adaptation to phase shift circadian biomarkers. However, evidence of real-world circadian adaptation is found primarily in occupations where light exposure is readily controlled. Despite this, non-photic adaptation to shift work remains under researched. Other markers of shift work adaptation exist (e.g., improvements in cognition and wellbeing outcomes) but are relatively unexplored. Timeframes for shift work adaptation involve changes which occur over a block of shifts, or over a shift working career. We propose an additional shift work adaptation timeframe exists which encompasses acute within shift changes in markers of adaptation. We also propose that physical activity might be an accessible and cost-effective countermeasure that could influence multiple markers of adaptation across three timeframes (Within Shift, Within Block, Within Work-span). Finally, practical considerations for shift workers, shift work industries and future research are identified.
Fiber optic computing using distributed feedback
Authors: Redding Brandon , Murray Joseph B. , Hart Joseph D. , Zhu Zheyuan , Pang Shuo S. , Sarma Raktim
Published: March 2024

The widespread adoption of machine learning and other matrix intensive computing algorithms has renewed interest in analog optical computing, which has the potential to perform large-scale matrix multiplications with superior energy scaling and lower latency than digital electronics. However, most optical techniques rely on spatial multiplexing, requiring a large number of modulators and detectors, and are typically restricted to performing a single kernel convolution operation per layer. Here, we introduce a fiber-optic computing architecture based on temporal multiplexing and distributed feedback that performs multiple convolutions on the input data in a single layer. Using Rayleigh backscattering in standard single mode fiber, we show that this technique can efficiently apply a series of random nonlinear projections to the input data, facilitating a variety of computing tasks. The approach enables efficient energy scaling with orders of magnitude lower power consumption than GPUs, while maintaining low latency and high data-throughput.
Verification of ultrafast spin transfer effects in iron-nickel alloys
Authors: Möller Christina , Probst Henrike , Jansen G. S. Matthijs , Schumacher Maren , Brede Mariana , Dewhurst John Kay , Reutzel Marcel , Steil Daniel , Sharma Sangeeta , Mathias Stefan
Published: March 2024

The optical intersite spin transfer (OISTR) effect was recently verified in Fe50Ni50 using extreme ultraviolet magneto-optical Kerr measurements. However, one of the main experimental signatures analyzed in this work, namely a magnetic moment increase at a specific energy in Ni, was subsequently found also in pure Ni, where no transfer from one element to another is possible. Hence, it is a much-discussed issue whether OISTR in FeNi alloys is real and whether it can be verified experimentally or not. Here, we present a comparative study of spin transfer in Fe50Ni50, Fe19Ni81 and pure Ni. We conclusively show that an increase in the magneto-optical signal is indeed insufficient to verify OISTR. However, we also show how an extended data analysis overcomes this problem and allows to unambiguously identify spin transfer effects. Concomitantly, our work solves the long-standing riddle about the origin of delayed demagnetization behavior of Ni in FeNi alloys.
Collective non-Hermitian skin effect: point-gap topology and the doublon-holon excitations in non-reciprocal many-body systems
Authors: Kim Beom Hyun , Han Jae-Ho , Park Moon Jip
Published: March 2024

Open quantum systems provide a plethora of exotic topological phases of matter that have no Hermitian counterpart. Non-Hermitian skin effect, macroscopic collapse of bulk states to the boundary, has been extensively studied in various experimental platforms. However, it remains an open question whether such topological phases persist in the presence of many-body interactions. Previous studies have shown that the Pauli exclusion principle suppresses the skin effect. In this study, we present a counterexample by demonstrating the presence of the skin effect in doublon-holon excitations. While the ground state of the spin-half Hatano-Nelson model shows no skin effect, the doublon-holon pairs, as its collective excitations, display the many-body skin effect even in strong coupling limit. We establish the robustness of this effect by revealing a bulk-boundary correspondence mediated by the point gap topology within the many-body energy spectrum. Our findings underscore the existence of non-Hermitian topological phases in collective excitations of many-body interacting systems.
Trees on smallholder farms and forest restoration are critical for Rwanda to achieve net zero emissions
Authors: Mugabowindekwe Maurice , Brandt Martin , Mukuralinda Athanase , Ciais Philippe , Reiner Florian , Kariryaa Ankit , Igel Christian , Chave Jérôme , Mertz Ole , Hiernaux Pierre , Tong Xiaoye , Rwanyiziri Gaspard , Gominski Dimitri , Li Sizhuo , Liu Siyu , Gasangwa Ivan , Hategekimana Yves , Ndoli Alain , Nduwamungu Jean , Saatchi Sassan , Fensholt Rasmus
Published: March 2024

Landscape restoration initiatives are mainly focusing on forest regeneration and agroforestry, especially in the Global South. However, due to a lack of monitoring tools, the carbon balance of restoration efforts remains poorly quantified. Here, we use satellite images from 2008 and 2019 to calculate carbon stocks for individual trees in Rwanda, a country which has been actively engaged in restoration activities over the past decade. We show that smallholder farmers on average planted about 3 trees per farm during 2008–2019, contributing about 50.4 million new trees at the national scale. The overall C sink of the new farmland trees was 0.13 Megagrams of Carbon per hectare per year, which is 6 times lower than gains observed from restoration of degraded forests (0.76 Megagrams of Carbon per hectare per year). If national greenhouse gas emissions remain at the level of 2019, agroforestry (~61% of national area coverage) and continued restoration of degraded natural forests (~0.5% of national area coverage) have the potential to offset about 80% of the national emissions before 2050. Our work monitors and quantifies progress and impact of landscape restoration projects and outlines a pathway to engage smallholder farmers with a limited number of on-farm trees into the expanding carbon market.