bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying Seepage‐Face Evaporation and Its Effects on Groundwater Flow and Solute Transport in Small‐Slope Tidal Flat
Authors: Luo Manhua , Wang Tianwei , Geng Xiaolong , Yu Shengchao , Li Hailong
Published: June 2024

Large‐scale seepage faces occur on tidal flats with gentle slope, which are widely distributed worldwide. Evaporation on these seepage faces, leading to salt retention and accumulation, may significantly impact the density‐dependent groundwater flow beneath the tidal flats. However, due to nonlinear complexities of the groundwater flow and solute transport on seepage faces, explicit boundary conditions and numerical models to quantify these processes are lacking. In this study, we present both mathematical and numerical models to quantify these processes. Compared to the results of our previous study, this paper shows that seepage‐face evaporation can (a) significantly increase the groundwater salinity in the upper intertidal zone, and form multiple groundwater circulation cells in the intertidal zone, (b) cause the disappearance of multiple seepage‐faces and reduce the spatial extent of seepage faces notably, (c) and intensify the groundwater and salt exchange as well as the seawater‐groundwater circulation through the intertidal zone.
Role of Impact Angle on Equatorial Electrojet (EEJ) Response to Interplanetary (IP) Shocks
Authors: Nilam B. , Tulasi Ram S. , Oliveira Denny M. , Dimri A. P.
Published: June 2024

Interplanetary (IP) shocks are one of the dominant solar wind structures that can significantly impact the Geospace when impinge on the Earth's magnetosphere. IP shocks severely distort the magnetosphere and induce dramatic changes in the magnetospheric currents, often leading to large disturbances in the geomagnetic field. Sudden enhancements in the solar wind dynamic pressure (PDyn) during IP shocks cause enhanced high‐latitude convection electric fields which penetrate promptly to equatorial latitudes. In response, the equatorial electrojet (EEJ) current exhibits sharp changes of magnitudes primarily controlled by the change in PDyn and the local time. In this paper, we further investigated the influence of shock impact angle on the EEJ response to a large number (306) of IP shocks that occurred during 2001–2021. The results consistently show that the EEJ exhibits a heightened response to the shocks that head‐on impact the magnetosphere (frontal shocks) than those with inclined impact (inclined shocks). The greater EEJ response during the frontal shocks could be due to a more intensified high‐latitude convection electric field resulting from the symmetric compression of the magnetosphere. Finally, an existing empirical relation involving PDyn and local time is improved by including the effects of impact angle, which can quantitatively better predict the EEJ response to IP shocks.
Tumor-resident microbiota contributes to colorectal cancer liver metastasis by lactylation and immune modulation
Authors: Gu Jian , Xu Xiaozhang , Li Xiangyu , Yue Lei , Zhu Xiaowen , Chen Qiuyang , Gao Ji , Takashi Maruyama , Zhao Wenhu , Zhao Bo , Zhang Yue , Lin Minjie , Zhou Jinren , Liang Yuan , Dai Shipeng , Pan Yufeng , Shao Qing , Li Yu , Wang Yiming , Xu Zibo , Qian Qufei , Huang Tianning , Qian Xiaofeng , Lu Ling
Published: June 2024

The role of tumor-resident microbiota in modulating tumor immunity remains unclear. Here, we discovered an abundance of intra-tumoral bacteria, such us E.coli, residing and resulting in Colorectal cancer liver metastasis (CRLM). E.coli enhanced lactate production, which mediated M2 macrophage polarization by suppressing nuclear factor-κB -gene binding (NF-κB) signaling through retinoic acid-inducible gene 1 (RIG-I) lactylation. Lactylation of RIG-I suppressed recruitment of NF-κB to the Nlrp3 promoter in macrophages, thereby reducing its transcription. This loss of Nlrp3 affected the immunosuppressive activities of regulatory T cells (Tregs) and the antitumor activities of and CD8+ T cells. Small-molecule compound screening identified a RIG-I lactylation inhibitor that suppressed M2 polarization and sensitized CRLM to 5-fluorouracil (5-FU). Our findings suggest that tumor-resident microbiota may be a potential target for preventing and treating CRLM.
Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets
Authors: Zhang Shaosen , Xiao Xinyi , Yi Yonglin , Wang Xinyu , Zhu Lingxuan , Shen Yanrong , Lin Dongxin , Wu Chen
Published: June 2024

Tumorigenesis is a multistep process, with oncogenic mutations in a normal cell conferring clonal advantage as the initial event. However, despite pervasive somatic mutations and clonal expansion in normal tissues, their transformation into cancer remains a rare event, indicating the presence of additional driver events for progression to an irreversible, highly heterogeneous, and invasive lesion. Recently, researchers are emphasizing the mechanisms of environmental tumor risk factors and epigenetic alterations that are profoundly influencing early clonal expansion and malignant evolution, independently of inducing mutations. Additionally, clonal evolution in tumorigenesis reflects a multifaceted interplay between cell-intrinsic identities and various cell-extrinsic factors that exert selective pressures to either restrain uncontrolled proliferation or allow specific clones to progress into tumors. However, the mechanisms by which driver events induce both intrinsic cellular competency and remodel environmental stress to facilitate malignant transformation are not fully understood. In this review, we summarize the genetic, epigenetic, and external driver events, and their effects on the co-evolution of the transformed cells and their ecosystem during tumor initiation and early malignant evolution. A deeper understanding of the earliest molecular events holds promise for translational applications, predicting individuals at high-risk of tumor and developing strategies to intercept malignant transformation.
Irritability in young people with copy number variants associated with neurodevelopmental disorders (ND-CNVs)
Authors: Hall Jessica H. , Chawner Samuel J. R. A. ,   IMAGINE-ID consortium, Housby Harriet , Lee Irene , Skuse David , Wolstencroft Jeanne , Mandy William , Dexanas Spiros , Baker Kate , Raymond Lucy , van den Bree Marianne , Chawner Samuel , Hall Jeremy , Holmans Peter , Hope-Bell Josh , Le Roux Danielle , Morrin Sally , Owen Michael , Sivakumar Shreeya , Wolstencroft Jeanne , Skuse David , Hall Jeremy , Holmans Peter , Owen Michael J. , van den Bree Marianne B. M.
Published: June 2024

A range of rare mutations involving micro-deletion or -duplication of genetic material (copy number variants (CNVs)) have been associated with high neurodevelopmental and psychiatric risk (ND-CNVs). Irritability is frequently observed in childhood neurodevelopmental conditions, yet its aetiology is largely unknown. Genetic variation may play a role, but there is a sparsity of studies investigating the presentation of irritability in young people with ND-CNVs. This study aimed to investigate whether there is a difference in irritability in young people with rare ND-CNVs compared to those without ND-CNVs, and to what extent irritability is associated with psychiatric diagnoses and cognitive ability (IQ). Irritability and broader psychopathology were assessed in 485 young people with ND-CNVs and 164 sibling controls, using the child and adolescent psychiatric assessment. Autism was assessed using the social communication questionnaire, and intelligence quotient (IQ) by the Wechsler abbreviated scale of intelligence. Fifty four percent of young people with ND-CNVs met the threshold for irritability; significantly more than controls (OR = 3.77, CI = 3.07–7.90, p = 5.31 × 10−11). When controlling for the presence of other psychiatric comorbidities, ND-CNV status was still associated with irritability. There was no evidence for a relationship between irritability and IQ. Irritability is an important aspect of the clinical picture in young people with ND-CNVs. This work shows that genetic variation is associated with irritability in young people with ND-CNVs, independent of psychiatric comorbidities or IQ impairment. Clinicians should be aware of this increased risk to inform management and interventions.
Real world predictors of response and 24-month survival in high-grade TP53-mutated myeloid neoplasms
Authors: Kaur Amandeep , Rojek Alexandra E. , Symes Emily , Nawas Mariam T. , Patel Anand A. , Patel Jay L. , Sojitra Payal , Aqil Barina , Sukhanova Madina , McNerney Megan E. , Wu Leo P. , Akmatbekov Aibek , Segal Jeremy , Tjota Melissa Y. , Gurbuxani Sandeep , Cheng Jason X. , Yeon Su-Yeon , Ravisankar Harini V. , Fitzpatrick Carrie , Lager Angela , Drazer Michael W. , Saygin Caner , Wanjari Pankhuri , Katsonis Panagiotis , Lichtarge Olivier , Churpek Jane E. , Ghosh Sharmila B. , Patel Ami B. , Menon Madhu P. , Arber Daniel A. , Wang Peng , Venkataraman Girish
Published: June 2024

Current therapies for high-gradeTP53-mutated myeloid neoplasms (≥10% blasts) do not offer a meaningful survival benefit except allogeneic stem cell transplantation in the minority who achieve a complete response to first line therapy (CR1). To identify reliable pre-therapy predictors of complete response to first-line therapy (CR1) and outcomes, we assembled a cohort of 242 individuals withTP53-mutated myeloid neoplasms and ≥10% blasts with well-annotated clinical, molecular and pathology data. Key outcomes examined were CR1 & 24-month survival (OS24). In this elderly cohort (median age 68.2 years) with 74.0% receiving frontline non-intensive regimens (hypomethylating agents +/- venetoclax), the overall cohort CR1 rate was 25.6% (50/195). We additionally identified several pre-therapy factors predictive of inferior CR1 including male gender (P = 0.026), ≥2 autosomal monosomies (P < 0.001), −17/17p (P = 0.011), multi-hitTP53allelic state (P < 0.001) andCUX1co-alterations (P = 0.010). In univariable analysis of the entire cohort, inferior OS24 was predicated by ≥2 monosomies (P = 0.004),TP53VAF > 25% (P = 0.002),TP53splice junction mutations (P = 0.007) and antecedent treated myeloid neoplasm (P = 0.001). In addition, mutations/deletions inCUX1,U2AF1,EZH2,TET2,CBL, orKRAS(‘EPI6’ signature) predicted inferior OS24 (HR = 2.0 [1.5–2.8];P < 0.0001). In a subgroup analysis of HMA +/-Ven treated individuals (N = 144),TP53VAF and monosomies did not impact OS24. A risk score for HMA +/-Ven treated individuals incorporating three pre-therapy predictors includingTP53splice junction mutations,EPI6and antecedent treated myeloid neoplasm stratified 3 prognostic distinct groups: intermediate, intermediate-poor, and poor with significantly different median (12.8, 6.0, 4.3 months) and 24-month (20.9%, 5.7%, 0.5%) survival (P < 0.0001). For the first time, in a seemingly monolithic high-risk cohort, our data identifies several baseline factors that predict response and 24-month survival.
AURKB/CDC37 complex promotes clear cell renal cell carcinoma progression via phosphorylating MYC and constituting an AURKB/E2F1-positive feedforward loop
Authors: Li Fang , Wang Xiaofei , Zhang Jinyuan , Jing Xintao , Zhou Jing , Jiang Qiuyu , Cao Li , Cai Shuang , Miao Jiyu , Tong Dongdong , Shyy John Y-J. , Huang Chen
Published: June 2024

As the second most common malignant tumor in the urinary system, renal cell carcinoma (RCC) is imperative to explore its early diagnostic markers and therapeutic targets. Numerous studies have shown that AURKB promotes tumor development by phosphorylating downstream substrates. However, the functional effects and regulatory mechanisms of AURKB on clear cell renal cell carcinoma (ccRCC) progression remain largely unknown. In the current study, we identified AURKB as a novel key gene in ccRCC progression based on bioinformatics analysis. Meanwhile, we observed that AURKB was highly expressed in ccRCC tissue and cell lines and knockdown AURKB in ccRCC cells inhibit cell proliferation and migration in vitro and in vivo. Identified CDC37 as a kinase molecular chaperone for AURKB, which phenocopy AURKB in ccRCC. AURKB/CDC37 complex mediate the stabilization of MYC protein by directly phosphorylating MYC at S67 and S373 to promote ccRCC development. At the same time, we demonstrated that the AURKB/CDC37 complex activates MYC to transcribe CCND1, enhances Rb phosphorylation, and promotes E2F1 release, which in turn activates AURKB transcription and forms a positive feedforward loop in ccRCC. Collectively, our study identified AURKB as a novel marker of ccRCC, revealed a new mechanism by which the AURKB/CDC37 complex promotes ccRCC by directly phosphorylating MYC to enhance its stability, and first proposed AURKB/E2F1-positive feedforward loop, highlighting AURKB may be a promising therapeutic target for ccRCC.
Synthesis and antibacterial action of 3’,6’-disubstituted spectinomycins
Authors: Dharuman Suresh , Phelps Gregory A. , Dunn Christine M. , Wilt Laura A. , Murphy Patricia A. , Lee Robin B. , Snoke Hannah E. , Selchow Petra , Haldimann Klara , Böttger Erik C. , Hobbie Sven N. , Sander Peter , Lee Richard E.
Published: June 2024

Spectinomycin is an aminocyclitol antibiotic with a unique ribosomal binding site. Prior synthetic modifications of spectinomycin have enhanced potency and antibacterial spectrum through addition at the 6’-position to produce trospectomycin and to the 3’-position to produce spectinamides and aminomethyl spectinomycins. This study focused on the design, synthesis, and evaluation of three 3’,6’-disubstituted spectinomycin analogs: trospectinamide, N-benzyl linked aminomethyl, and N-ethylene linked aminomethyl trospectomycins. Computational experiments predicted that these disubstituted analogs would be capable of binding within the SPC ribosomal binding site. The new analogs were synthesized from trospectomycin, adapting the previously established routes for the spectinamide and aminomethyl spectinomycin series. In a cell-free translation assay, the disubstituted analogs showed ribosomal inhibition similar to spectinomycin or trospectomycin. These disubstituted analogs demonstrated inhibitory MIC activity against various bacterial species with the 3’-modification dictating spectrum of activity, leading to improved activity against mycobacterium species. Notably, N-ethylene linked aminomethyl trospectomycins exhibited increased potency against Mycobacterium abscessus and trospectinamide displayed robust activity against M. tuberculosis, aligning with the selective efficacy of spectinamides. The study also found that trospectomycin is susceptible to efflux in M. tuberculosis and M. abscessus. These findings contribute to the understanding of the structure-activity relationship of spectinomycin analogs and can guide the design and synthesis of more effective spectinomycin compounds.
Electrochemical synthesis of peptide aldehydes via C‒N bond cleavage of cyclic amines
Authors: Fang Xinyue , Zeng Yong , Huang Yawen , Zhu Zile , Lin Shengsheng , Xu Wenyan , Zheng Chengwei , Hu Xinwei , Qiu Youai , Ruan Zhixiong
Published: June 2024

Peptide aldehydes are crucial biomolecules essential to various biological systems, driving a continuous demand for efficient synthesis methods. Herein, we develop a metal-free, facile, and biocompatible strategy for direct electrochemical synthesis of unnatural peptide aldehydes. This electro-oxidative approach enabled a step- and atom-economical ring-opening via C‒N bond cleavage, allowing for homoproline-specific peptide diversification and expansion of substrate scope to include amides, esters, and cyclic amines of various sizes. The remarkable efficacy of the electro-synthetic protocol set the stage for the efficient modification and assembly of linear and macrocyclic peptides using a concise synthetic sequence with racemization-free conditions. Moreover, the combination of experiments and density functional theory (DFT) calculations indicates that different N-acyl groups play a decisive role in the reaction activity.
Ecological trade-offs drive phenotypic and genetic differentiation of Arabidopsis thaliana in Europe
Authors: Bastias Cristina C. , Estarague Aurélien , Vile Denis , Gaignon Elza , Lee Cheng-Ruei , Exposito-Alonso Moises , Violle Cyrille , Vasseur François
Published: June 2024

Plant diversity is shaped by trade-offs between traits related to competitive ability, propagule dispersal, and stress resistance. However, we still lack a clear understanding of how these trade-offs influence species distribution and population dynamics. InArabidopsis thaliana, recent genetic analyses revealed a group of cosmopolitan genotypes that successfully recolonized Europe from its center after the last glaciation, excluding older (relict) lineages from the distribution except for their north and south margins. Here, we tested the hypothesis that cosmopolitans expanded due to higher colonization ability, while relicts persisted at the margins due to higher tolerance to competition and/or stress. We compared the phenotypic and genetic differentiation between 71 European genotypes originating from the center, and the south and north margins. We showed that a trade-off between plant fecundity and seed mass shapes the differentiation ofA. thalianain Europe, suggesting that the success of the cosmopolitan groups could be explained by their high dispersal ability. However, at both north and south margins, we found evidence of selection for alleles conferring low dispersal but highly competitive and stress-resistance abilities. This study sheds light on the role of ecological trade-offs as evolutionary drivers of the distribution and dynamics of plant populations.
Neural network variational Monte Carlo for positronic chemistry
Authors: Cassella Gino , Foulkes W. M. C. , Pfau David , Spencer James S.
Published: June 2024

Quantum chemical calculations of the ground-state properties of positron-molecule complexes are challenging. The main difficulty lies in employing an appropriate basis set for representing the coalescence between electrons and a positron. Here, we tackle this problem with the recently developed Fermionic neural network (FermiNet) wavefunction, which does not depend on a basis set. We find that FermiNet produces highly accurate, in some cases state-of-the-art, ground-state energies across a range of atoms and small molecules with a wide variety of qualitatively distinct positron binding characteristics. We calculate the binding energy of the challenging non-polar benzene molecule, finding good agreement with the experimental value, and obtain annihilation rates which compare favourably with those obtained with explicitly correlated Gaussian wavefunctions. Our results demonstrate a generic advantage of neural network wavefunction-based methods and broaden their applicability to systems beyond the standard molecular Hamiltonian.
Total and H-specific GDF-15 levels increase in caloric deprivation independently of leptin in humans
Authors: Chrysafi Pavlina , Valenzuela-Vallejo Laura , Stefanakis Konstantinos , Kelesidis Theodoros , Connelly Margery A. , Mantzoros Christos S.
Published: June 2024

Mitochondrial-secreted growth differentiation factor-15 (GDF-15) promotes weight loss in animals. Its effects in humans remain unclear, due to limited research and potential measurement interference from the H202D-variant. Our post-hoc analysis investigates total (irrespective of genetic variants) and H-specific GDF-15 (detected only in H202D-variant absence) in humans under acute and chronic energy deprivation, examining GDF-15 interaction with leptin (energy homeostasis regulator) and GDF-15 biologic activity modulation by the H202D-variant. Total and H-specific GDF-15 increased with acute starvation, and total GDF-15 increased with chronic energy deprivation, compared with healthy subjects and regardless of leptin repletion. Baseline GDF-15 positively correlated with triglyceride-rich particles and lipoproteins. During acute metabolic stress, GDF-15 associations with metabolites/lipids appeared to differ in subjects with the H202D-variant. Our findings suggest GDF-15 increases with energy deprivation in humans, questioning its proposed weight loss and suggesting its function as a mitokine, reflecting or mediating metabolic stress response.
Anisotropic thermal conductivity of antigorite along slab subduction impacts seismicity of intermediate-depth earthquakes
Authors: Chien Yu-Hsiang , Marzotto Enrico , Tsao Yi-Chi , Hsieh Wen-Pin
Published: June 2024

Double seismic zones (DSZs) are a feature of some subducting slabs, where intermediate-depth earthquakes (~70–300 km) align along two separate planes. The upper seismic plane is generally attributed to dehydration embrittlement, whereas mechanisms forming the lower seismic plane are still debated. Thermal conductivity of slab minerals is expected to control the temperature evolution of subducting slabs, and therefore their seismicity. However, effects of the potential anisotropic thermal conductivity of layered serpentine minerals with crystal preferred orientation on slab’s thermal evolution remain poorly understood. Here we measure the lattice thermal conductivity of antigorite, a hydrous serpentine mineral, along its crystallographic b- and c-axis at relevant high pressure-temperature conditions of subduction. We find that antigorite’s thermal conductivity along the c-axis is ~3–4 folds smaller than the b-axis. Our numerical models further reveal that when the low-thermal-conductivity c-axis is aligned normal to the slab dip, antigorite’s strongly anisotropic thermal conductivity enables heating at the top portion of the slab, facilitating dehydration embrittlement that causes the seismicity in the upper plane of DSZs. Potentially, the antigorite’s thermal insulating effect also hinders the dissipation of frictional heat inside shear zones, promoting thermal runaway along serpentinized faults that could trigger intermediate-depth earthquakes.
Cholesterol efflux from C1QB-expressing macrophages is associated with resistance to chimeric antigen receptor T cell therapy in primary refractory diffuse large B cell lymphoma
Authors: Yan Zi-Xun , Dong Yan , Qiao Niu , Zhang Yi-Lun , Wu Wen , Zhu Yue , Wang Li , Cheng Shu , Xu Peng-Peng , Zhou Zi-Song , Sheng Ling-Shuang , Zhao Wei-Li
Published: June 2024

Chimeric antigen receptor T (CAR-T) cell therapy has demonstrated promising efficacy in early trials for relapsed/refractory diffuse large B cell lymphoma (DLBCL). However, its efficacy in treating primary refractory DLBCL has not been comprehensively investigated, and the underlying resistance mechanisms remain unclear. Here, we report the outcomes of a phase I, open-label, single-arm clinical trial of relmacabtagene autoleucel (relma-cel), a CD19-targeted CAR-T cell product, with safety and efficacy as primary endpoints. Among the 12 enrolled patients, 8 experienced grade 4 hematologic toxicity of treatment-emergent adverse event. No grade ≥3 cytokine release syndrome or neurotoxicity occurred. Single-cell RNA sequencing revealed an increase proportion ofC1QB-expressing macrophages in patients with progressive disease before CAR-T cell therapy. Cholesterol efflux from M2 macrophages was found to inhibit CAR-T cells cytotoxicity by inducing an immunosuppressive state in CD8+T cells, leading to their exhaustion. Possible interactions between macrophages and CD8+T cells, mediating lipid metabolism (AFR1-FAS), immune checkpoint activation, and T cell exhaustion (LGALS9-HAVCR2, CD86-CTLA4, andNECTIN2-TIGIT) were enhanced during disease progression. These findings suggest that cholesterol efflux from macrophages may trigger CD8+T cell exhaustion, providing a rationale for metabolic reprogramming to counteract CAR-T treatment failure. Chinadrugtrials.org.cn identifier: CTR20200376.
Deciphering in-situ surface reconstruction in two-dimensional CdPS3 nanosheets for efficient biomass hydrogenation
Authors: Sendeku Marshet Getaye , Harrath Karim , Dajan Fekadu Tsegaye , Wu Binglan , Hussain Sabir , Gao Ning , Zhan Xueying , Yang Ying , Wang Zhenxing , Chen Chen , Liu Weiqiang , Wang Fengmei , Duan Haohong , Sun Xiaoming
Published: June 2024

Steering on the intrinsic active site of an electrode material is essential for efficient electrochemical biomass upgrading to valuable chemicals with high selectivity. Herein, we show that an in-situ surface reconstruction of a two-dimensional layered CdPS3 nanosheet electrocatalyst, triggered by electrolyte, facilitates efficient 5-hydroxymethylfurfural (HMF) hydrogenation to 2,5-bis(hydroxymethyl)furan (BHMF) under ambient condition. The in-situ Raman spectroscopy and comprehensive post-mortem catalyst characterizations evidence the construction of a surface-bounded CdS layer on CdPS3 to form CdPS3/CdS heterostructure. This electrocatalyst demonstrates promising catalytic activity, achieving a Faradaic efficiency for BHMF reaching 91.3 ± 2.3 % and a yield of 4.96 ± 0.16 mg/h at − 0.7 V versus reversible hydrogen electrode. Density functional theory calculations reveal that the in-situ generated CdPS3/CdS interface plays a pivotal role in optimizing the adsorption of HMF* and H* intermediate, thus facilitating the HMF hydrogenation process. Furthermore, the reconstructed CdPS3/CdS heterostructure cathode, when coupled with MnCo2O4.5 anode, enables simultaneous BHMF and formate synthesis from HMF and glycerol substrates with high efficiency.
Characterize direct protein interactions with enrichable, cleavable and latent bioreactive unnatural amino acids
Authors: Liu Dan-Dan , Ding Wenlong , Cheng Jin-Tao , Wei Qiushi , Lin Yinuo , Zhu Tian-Yi , Tian Jing , Sun Ke , Zhang Long , Lu Peilong , Yang Fan , Liu Chao , Tang Shibing , Yang Bing
Published: June 2024

Latent bioreactive unnatural amino acids (Uaas) have been widely used in the development of covalent drugs and identification of protein interactors, such as proteins, DNA, RNA and carbohydrates. However, it is challenging to perform high-throughput identification of Uaa cross-linking products due to the complexities of protein samples and the data analysis processes. Enrichable Uaas can effectively reduce the complexities of protein samples and simplify data analysis, but few cross-linked peptides were identified from mammalian cell samples with these Uaas. Here we develop an enrichable and multiple amino acids reactive Uaa, eFSY, and demonstrate that eFSY is MS cleavable when eFSY-Lys and eFSY-His are the cross-linking products. An identification software, AixUaa is developed to decipher eFSY mass cleavable data. We systematically identify direct interactomes of Thioredoxin 1 (Trx1) and Selenoprotein M (SELM) with eFSY and AixUaa.
Structural basis for an early stage of the photosystem II repair cycle in Chlamydomonas reinhardtii
Authors: Li Anjie , You Tingting , Pang Xiaojie , Wang Yidi , Tian Lijin , Li Xiaobo , Liu Zhenfeng
Published: June 2024

Photosystem II (PSII) catalyzes water oxidation and plastoquinone reduction by utilizing light energy. It is highly susceptible to photodamage under high-light conditions and the damaged PSII needs to be restored through a process known as the PSII repair cycle. The detailed molecular mechanism underlying the PSII repair process remains mostly elusive. Here, we report biochemical and structural features of a PSII-repair intermediate complex, likely arrested at an early stage of the PSII repair process in the green alga Chlamydomonas reinhardtii. The complex contains three protein factors associated with a damaged PSII core, namely Thylakoid Enriched Factor 14 (TEF14), Photosystem II Repair Factor 1 (PRF1), and Photosystem II Repair Factor 2 (PRF2). TEF14, PRF1 and PRF2 may facilitate the release of the manganese-stabilizing protein PsbO, disassembly of peripheral light-harvesting complexes from PSII and blockage of the QB site, respectively. Moreover, an α-tocopherol quinone molecule is located adjacent to the heme group of cytochrome b559, potentially fulfilling a photoprotective role by preventing the generation of reactive oxygen species.
Inhibiting perovskite decomposition by a creeper-inspired strategy enables efficient and stable perovskite solar cells
Authors: Du Shuxian , Huang Hao , Lan Zhineng , Cui Peng , Li Liang , Wang Min , Qu Shujie , Yan Luyao , Sun Changxu , Yang Yingying , Wang Xinxin , Li Meicheng
Published: June 2024

The commercialization of perovskite solar cells is badly limited by stability, an issue determined mainly by perovskite. Herein, inspired by a natural creeper that can cover the walls through suckers, we adopt polyhexamethyleneguanidine hydrochloride as a molecular creeper on perovskite to inhibit its decomposition starting from the annealing process. The molecule possesses a long-line molecular structure where the guanidinium groups can serve as suckers that strongly anchor cations through multiple hydrogen bonds. These features make the molecular creeper can cover perovskite grains and inhibit perovskite decomposition by suppressing cations’ escape. The resulting planar perovskite solar cells achieve an efficiency of 25.42% (certificated 25.36%). Moreover, the perovskite film and device exhibit enhanced stability even under harsh damp-heat conditions. The devices can maintain >96% of their initial efficiency after 1300 hours of operation under 1-sun illumination and 1000 hours of storage under 85% RH, respectively.
Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS
Authors: Chatterjee Madhurima , Özdemir Selcuk , Fritz Christian , Möbius Wiebke , Kleineidam Luca , Mandelkow Eckhard , Biernat Jacek , Doğdu Cem , Peters Oliver , Cosma Nicoleta Carmen , Wang Xiao , Schneider Luisa-Sophia , Priller Josef , Spruth Eike , Kühn Andrea A. , Krause Patricia , Klockgether Thomas , Vogt Ina R. , Kimmich Okka , Spottke Annika , Hoffmann Daniel C. , Fliessbach Klaus , Miklitz Carolin , McCormick Cornelia , Weydt Patrick , Falkenburger Björn , Brandt Moritz , Guenther René , Dinter Elisabeth , Wiltfang Jens , Hansen Niels , Bähr Mathias , Zerr Inga , Flöel Agnes , Nestor Peter J. , Düzel Emrah , Glanz Wenzel , Incesoy Enise , Bürger Katharina , Janowitz Daniel , Perneczky Robert , Rauchmann Boris S. , Hopfner Franziska , Wagemann Olivia , Levin Johannes , Teipel Stefan , Kilimann Ingo , Goerss Doreen , Prudlo Johannes , Gasser Thomas , Brockmann Kathrin , Mengel David , Zimmermann Milan , Synofzik Matthis , Wilke Carlo , Selma-González Judit , Turon-Sans Janina , Santos-Santos Miguel Angel , Alcolea Daniel , Rubio-Guerra Sara , Fortea Juan , Carbayo Álvaro , Lleó Alberto , Rojas-García Ricardo , Illán-Gala Ignacio , Wagner Michael , Frommann Ingo , Roeske Sandra , Bertram Lucas , Heneka Michael T. , Brosseron Frederic , Ramirez Alfredo , Schmid Matthias , Beschorner Rudi , Halle Annett , Herms Jochen , Neumann Manuela , Barthélemy Nicolas R. , Bateman Randall J. , Rizzu Patrizia , Heutink Peter , Dols-Icardo Oriol , Höglinger Günter , Hermann Andreas , Schneider Anja
Published: June 2024

Minimally invasive biomarkers are urgently needed to detect molecular pathology in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Here, we show that plasma extracellular vesicles (EVs) contain quantifiable amounts of TDP-43 and full-length tau, which allow the quantification of 3-repeat (3R) and 4-repeat (4R) tau isoforms. Plasma EV TDP-43 levels and EV 3R/4R tau ratios were determined in a cohort of 704 patients, including 37 genetically and 31 neuropathologically proven cases. Diagnostic groups comprised patients with TDP-43 proteinopathy ALS, 4R tauopathy progressive supranuclear palsy, behavior variant FTD (bvFTD) as a group with either tau or TDP-43 pathology, and healthy controls. EV tau ratios were low in progressive supranuclear palsy and high in bvFTD with tau pathology. EV TDP-43 levels were high in ALS and in bvFTD with TDP-43 pathology. Both markers discriminated between the diagnostic groups with area under the curve values >0.9, and between TDP-43 and tau pathology in bvFTD. Both markers strongly correlated with neurodegeneration, and clinical and neuropsychological markers of disease severity. Findings were replicated in an independent validation cohort of 292 patients including 34 genetically confirmed cases. Taken together, the combination of EV TDP-43 levels and EV 3R/4R tau ratios may aid the molecular diagnosis of FTD, FTD spectrum disorders and ALS, providing a potential biomarker to monitor disease progression and target engagement in clinical trials.
The cryoEM structure of the Hendra henipavirus nucleoprotein reveals insights into paramyxoviral nucleocapsid architectures
Authors: Passchier Tim C. , White Joshua B. R. , Maskell Daniel P. , Byrne Matthew J. , Ranson Neil A. , Edwards Thomas A. , Barr John N.
Published: June 2024

We report the first cryoEM structure of the Hendra henipavirus nucleoprotein in complex with RNA, at 3.5 Å resolution, derived from single particle analysis of a double homotetradecameric RNA-bound N protein ring assembly exhibiting D14 symmetry. The structure of the HeV N protein adopts the common bi-lobed paramyxoviral N protein fold; the N-terminal and C-terminal globular domains are bisected by an RNA binding cleft containing six RNA nucleotides and are flanked by the N-terminal and C-terminal arms, respectively. In common with other paramyxoviral nucleocapsids, the lateral interface between adjacent Ni and Ni+1 protomers involves electrostatic and hydrophobic interactions mediated primarily through the N-terminal arm and globular domains with minor contribution from the C-terminal arm. However, the HeV N multimeric assembly uniquely identifies an additional protomer-protomer contact between the Ni+1 N-terminus and Ni−1 C-terminal arm linker. The model presented here broadens the understanding of RNA-bound paramyxoviral nucleocapsid architectures and provides a platform for further insight into the molecular biology of HeV, as well as the development of antiviral interventions.
Association between blood groups and myocardial injury after non-cardiac surgery: a retrospective cohort study
Authors: Li Jinze , Li Wangyu , Li Longyun , Yang Shengze , Zhao Guoqing , Li Kai
Published: June 2024

Blood group is a potential genetic element in coronary artery disease. Nevertheless, the relationship between different ABO blood groups and myocardial injury after non-cardiac surgery (MINS) is poorly understood. This study verified whether ABO blood group is a potential MINS influencing factor. This retrospective cohort study included 1201 patients who underwent elective non-cardiac surgery and a mandatory troponin test on postoperative days 1 and 2 from 2019 to 2020 at a university-affiliated tertiary hospital. The primary outcome was associations between ABO blood groups and MINS, assessed using univariate and multivariate logistic-regression analyses. Path analysis was used to investigate direct and indirect effects between blood group and MINS. MINS incidence (102/1201, 8.5%) was higher in blood-type B patients than in non-B patients [blood-type B: 44/400 (11.0%) vs. non-B: 58/801 (7.2%); adjusted odds ratio = 1.57 (1.03–2.38); p = 0.036]. In the confounding factor model, preoperative hypertension and coronary artery disease medical history were associated with MINS risk [adjusted odds ratio: 2.00 (1.30–3.06), p = 0.002; 2.81 (1.71–4.61), p < 0.001, respectively]. Path analysis did not uncover any mediating role for hypertension, diabetes, or coronary artery disease between blood type and MINS. Therefore, blood-type B is associated with higher MINS risk; potential mediators of this association need to be investigated.
Biological direct-shortcut deep residual learning for sparse visual processing
Authors: Jahani Yekta Mohammad Mahdi
Published: June 2024

We show, based on the following three grounds, that the primary visual cortex (V1) is a biological direct-shortcut deep residual learning neural network (ResNet) for sparse visual processing: (1) We first highlight that Gabor-like sets of basis functions, which are similar to the receptive fields of simple cells in the primary visual cortex (V1), are excellent candidates for sparse representation of natural images; i.e., images from the natural world, affirming the brain to be optimized for this. (2) We then prove that the intra-layer synaptic weight matrices of this region can be reasonably first-order approximated by identity mappings, and are thus sparse themselves. (3) Finally, we point out that intra-layer weight matrices having identity mapping as their initial approximation, irrespective of this approximation being also a reasonable first-order one or not, resemble the building blocks of direct-shortcut digital ResNets, which completes the grounds. This biological ResNet interconnects the sparsity of the final representation of the image to that of its intra-layer weights. Further exploration of this ResNet, and understanding the joint effects of its architecture and learning rules, e.g. on its inductive bias, could lead to major advancements in the area of bio-inspired digital ResNets. One immediate line of research in this context, for instance, is to study the impact of forcing the direct-shortcuts to be good first-order approximations of each building block. For this, along with the $${{\ell}}_{1}$$

ℓ
1

-minimization posed on the basis function coefficients the ResNet finally provides at its output, another parallel one could e.g. also be posed on the weights of its residual layers.
Ti-based MOFs with acetic acid pendings as an efficient catalyst in the preparation of new spiropyrans with biological moieties
Authors: Torkashvand Zahra , Sepehrmansourie Hassan , Zolfigol Mohammad Ali , Gu Yanlong
Published: June 2024

The strategy of designing heterogeneous porous catalysts by a post-modification method is a smart strategy to increase the catalytic power of desired catalysts. Accordingly, in this report, metal-organic frameworks based on titanium with acetic acid pending were designed and synthesized via post-modification method. The structure of the target catalyst has been investigated using different techniques such as FT-IR, XRD, SEM, EDX, Mapping, and N2 adsorption/desorption (BET/the BJH) the correctness of its formation has been proven. The catalytic application of Ti-based MOFs functionalized with acetic acid was evaluated in the preparation of new spiropyrans, and the obtained results show that the catalytic performance is improved by this modification. The strategy of designing heterogeneous porous catalysts through post-modification methods presents a sophisticated approach to enhancing the catalytic efficacy of desired catalysts. In this context, our study focuses on the synthesis and characterization of metal-organic frameworks (MOFs) based on titanium, functionalized with acetic acid pendants, using a post-modification method. Various characterization techniques, including Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), mapping, and N2 adsorption/desorption (BET/BJH), were employed to investigate the structure and composition of the synthesized catalyst. These techniques collectively confirmed the successful formation and structural integrity of the target catalyst. The structure of the synthesized products was confirmed by melting point, 1H-NMR and 13C-NMR and FT-IR techniques. Examining the general process of catalyst synthesis and its catalytic application shows that the mentioned modification is very useful for catalytic purposes. The presented catalyst was used in synthesis of a wide range of biologically active spiropyrans with good yields. The simultaneous presence of several biologically active cores in the synthesized products will highlight the biological properties of these compounds. The present study offers a promising insight into the rational design, synthesis, and application of task-specific porous catalysts, particularly in the context of synthesizing biologically active candidate molecules.
Routine upper gastro-intestinal tract endoscopy before elective cholecystectomy for symptomatic gallstones-justified
Authors: Morrison Sherwyn , Mokoena Taole
Published: June 2024

Gallstones are common in Western countries and increasing in developing countries through adoption of western lifestyle. Gallstones may cause life-threatening complications, including acute cholecystitis, acute cholangitis, and acute pancreatitis. Cholecystectomy is the treatment of choice for symptomatic gallstones. Presentation of symptomatic gallstones may be indistinguishable from that of other upper gastro-intestinal tract (UGI) pathologies. Some surgeons routinely perform preoperative UGI endoscopy to diagnose and treat concomitant UGI pathology. A prospective cross-sectional observational study was undertaken at University of Pretoria teaching hospitals to evaluate this practice. Patients aged 18 years and older, with symptomatic gallstones but did not satisfy Tokyo guidelines for acute cholecystitis were recruited. UGI endoscopy was performed before cholecystectomy. There were 124 patients, 110 (88.7%) females and 14 (11.3%) males, mean age 44.0 (13.2) (range: 22–78) years. Most common symptoms were right upper quadrant (RUQ) pain (87%), epigastric pain (59.7%), nausea (58.1%) and vomiting (47.9%). Clinically, 80% had RUQ tenderness and 52.4% epigastric tenderness. UGI endoscopy found 35.4% pathology, 28.2% were active, and comprised acute gastritis (27.4%), peptic ulcers (4.8%), duodenitis (3.2%) and oesophagitis (2.4%). Twelve patients had more than one pathology. This warranted treatment before elective cholecystectomy and justifies the practice of routine preoperative UGI endoscopy.
Low-salinity water flooding by a novel hybrid of nano γ-Al2O3/SiO2 modified with a green surfactant for enhanced oil recovery
Authors: Khajeh Kulaki Azin , Hosseini-Nasab Seyed Mojtaba , Hormozi Faramarz
Published: June 2024

This paper introduces a hybrid enhanced oil recovery (HEOR) method that combines a low-salinity water flooding (LSWF) and nanoparticles (NPs) stabilized with a green surfactant. We experimentally investigated the use of combinations of silica (SiO2) and gamma alumina (γ-Al2O3) nanohybrids stabilized with Gum Arabic (GA) at different water salinities. Nanofluids (NFs) were prepared by dispersing γ-Al2O3and SiO2NPs (0.1 wt%) in deionized water (DW), synthetic seawater (SSW), 2, 5, and 10 times diluted samples of synthetic seawater (in short 2-DSSW, 5-DSSW and 10-DSSW, respectively). The challenge is that NPs become unstable in the presence of cations in saline water. Moreover, an attempt was made to introduce NFs with high stability for a long period of time as the optimal NFs. The effects of temperature on the behaviour of optimal NFs in the presence of different base fluids, distinct mass ratios of γ-Al2O3/SiO2and various concentrations of surfactant were analysed via interfacial tension (IFT) and viscosity measurements. The results of the viscosity measurement showed that with increasing temperature, the NPs dispersed in DW had lower viscosity than NPs dispersed in various salinities. However, the IFT measurement for NPs dispersed in different base-fluids revealed that with increasing temperature and presence of cations in saline water, IFT values decreases. Although, the minimum IFT for hybrid nanofluid (HNF) γ-Al2O3/SiO2modified with GA and dispersed in 10-DSSW was reported 0.99 mN/m. Finally, according to the micromodel flooding results, in oil-wet conditions, the highest oil recovery for combination γ-Al2O3/SiO2modified with GA and dispersed in 2-DSSW was reported 60.34%. It was concluded that NFs modified with GA could enhanced applicability of LSWF via delay in breakthrough time and improving sweep efficiency.
A platform technology for ultra-long acting intratumoral therapy
Authors: Henise Jeff , Hangasky John A. , Charych Deborah , Carreras Christopher W. , Ashley Gary W. , Santi Daniel V.
Published: June 2024

Intratumoral (IT) therapy is a powerful method of controlling tumor growth, but a major unsolved problem is the rapidity that injected drugs exit tumors, limiting on-target exposure and efficacy. We have developed a generic long acting IT delivery system in which a drug is covalently tethered to hydrogel microspheres (MS) by a cleavable linker; upon injection the conjugate forms a depot that slowly releases the drug and “bathes” the tumor for long periods. We established technology to measure tissue pharmacokinetics and studied MSs attached to SN-38, a topoisomerase 1 inhibitor. When MS ~ SN-38 was injected locally, tissues showed high levels of SN-38 with a long half-life of ~ 1 week. IT MS ~ SN-38 was ~ tenfold more efficacious as an anti-tumor agent than systemic SN-38. We also propose and provide an example that long-acting IT therapy might enable safe use of two drugs with overlapping toxicities. Here, long-acting IT MS ~ SN-38 is delivered with concurrent systemic PARP inhibitor. The tumor is exposed to both drugs whereas other tissues are exposed only to the systemic drug; synergistic anti-tumor activity supported the validity of this approach. We propose use of this approach to increase efficacy and reduce toxicities of combinations of immune checkpoint inhibitors such as αCTLA-4 and αPD-1.
Conservation status assessments of species-rich tropical taxa in the face of data availability limitations: insights from Sulawesi Begonia
Authors: Thomas Daniel C. , Ardi Wisnu H. , Chong Yu Hong , Thomas Philip , Hughes Mark
Published: June 2024

Species conservation assessments using the criteria outlined by the International Union for the Conservation of Nature Red List can be compromised by limited data availability. Species-rich tropical plant taxa with numerous microendemics are particularly problematic. This study focusses on the Begonia flora of the Indonesian island of Sulawesi, comprised of 65 herbaceous species mainly found in rainforest habitats. Sixty-two species are Sulawesi endemics, including 20 species restricted to limestone karst landscapes. Forty-eight species are represented by fewer than 10 herbarium collections. Here, we outline and discuss an approach that, despite these data limitations, allows meaningful conservation assessments by integrating analyses of occurrences, data primarily based on remote sensing approaches, including forest landscape integrity, forest cover loss, and land cover, and extent of suitable habitat estimation. The results indicate that most Sulawesi Begonia species are narrow endemics whose rainforest habitats have substantially deteriorated in the last two decades: 27 species are assessed as Critically Endangered, 24 as Endangered, six as Vulnerable, five as Least Concern, and three species are Data Deficient. Conservation action, including extension of the protected area network in Sulawesi with emphasis on areas of old-growth forest and limestone karst landscapes, and strengthening of ex-situ living collections, is recommended.