bluuebunny/crossref_metadata_2025 huggingface dataset:
Are Workers Effective Lawmakers?
Authors: Lollis Jacob M.
Published: May 2024

Are workers effective lawmakers? Throughout American history, some politicians and elites have argued that white-collar Americans are more qualified than working-class Americans to govern. To date, however, we know relatively little about the legislative effectiveness of working-class lawmakers. I develop a theory of class-based electoral selection that links class-based discrimination in elections to legislators’ performance in office. I argue that working-class candidates face class-based biases in elections that make it more difficult to emerge and successfully win elective office. As a result, I expect the working-class candidates who do become lawmakers to be equally or more effective than their white-collar colleagues. To test these expectations, I create a data set merging the occupational background of more than 14,000 individual state legislators with their state legislative effectiveness score (SLES). The resulting data set includes more than 50,000 state legislator-term specific observations. Consistent with my expectations, I find that working-class lawmakers do not underperform white-collar lawmakers. Further, I provide evidence that, across various models and specifications, the gap between working-class and white-collar legislators’ effectiveness is negligible.
Advantage in Aging Cognition Associated with the CREBRF variant rs373863828 Among Samoans
Authors: Levy Becca R. , Viali Satupa’itea , Naseri Take , Reupena Muagututia Sefuiva , Faasalele-Savusa Kima , Filipo Vaimoana , Kershaw Erin E. , Huang Yuan , Slade Martin D.
Published: May 2024

Abstract: We examined whether the A allele of CREBRF rs373863828, which is common in Samoans but rare in non-Pacific Islanders, predicts better cognition. Samoan interviewers interviewed participants who were 60 years and older, lived in the Independent State of Samoa, and had four Samoan grandparents. The AA genotype significantly predicted older Samoans’ better subjective and objective cognition; it also contributed 5.9 times more than APOE to subjective cognition and 12.3 times more than APOE to objective cognition, in effect-size analyses. Since CREBRF operates in the universal CREB system, the findings could inform general aging-cognition resilience.
Highlighting the Old in the “New Normal”
Authors: Schulte Anna , Baldwin Matthew , Lammers Joris
Published: May 2024

Abstract: During the COVID-19 pandemic, a wide ideological gap frustrated an effective response to the health crisis. Whereas most liberals supported protective measures, many conservatives opposed them. Five studies ( Ntotal = 3,090) demonstrate that American and German conservatives’ opposition to COVID-19 measures arose partially from nostalgic emotions. We show that framing COVID-19 measures as a return to the past reduces conservatives’ opposition to face masks and vaccinations. An internal meta-analysis shows that although the overall effect of temporal framing is significant, it is small. This research identifies conservatives’ focus on the past as a theoretically relevant antecedent to their opposition to COVID-19 measures and introduces temporal framing as a small but practically feasible strategy to reduce such opposition.
High‐Resolution Mantle Transition Zone Imaging Using Multi‐Dimensional Reconstruction of SS Precursors
Authors: Innocent Oboué Yapo Abolé Serge , Chen Yunfeng , Wang Jingchuan , Jiang Xiuxuan , Dokht Ramin M. H. , Gu Yu Jeffrey , Koroni Maria , Chen Yangkang
Published: May 2024

The SS precursors have been extensively utilized in mapping the mantle transition zone (MTZ). However, their applications are often challenged by weak phases that arise from small impedance contrasts of the mantle discontinuities, noise contamination, and localized thermal/compositional heterogeneities. We develop a new data processing workflow for more reliable MTZ imaging by adopting the recently proposed robust damped rank‐reduction (RDRR) method from exploration seismology. This method exploits the signal coherency in the four‐dimensional data and allows simultaneously attenuating noise and interpolating missing traces. We utilize synthetic data sets generated with realistic earth structures and MTZ topography to evaluate the capability of the proposed workflow. Our test results show that the RDRR method can well capture the topographic variation of mantle discontinuities, improving the SNR of the SS precursor data by an order of magnitude. The application to SS precursors from the western Pacific successfully removes contaminating noises, mitigates imaging artifacts of small‐scale anomalies, and improves the lateral coherency of the MTZ structure, revealing a clear first‐order structural transition. Compared with earlier global and regional models, our model reveals more structural details including a localized thin MTZ near the Changbai volcano in East Asia. This observation, in conjunction with the reported low‐velocity structure in the MTZ in earlier tomographic studies, may support the presence of deep mantle up‐welling through a slab gap. In summary, our work enables resolving MTZ structures with high fidelity and highlights the importance of advanced array methods in improving SS precursor imaging.
Metabolic profiling of galectin-1 and galectin-3: a cross-sectional, multi-omics, association study
Authors: Fryk Emanuel , Rodrigues Silva Vagner Ramon , Strindberg Lena , Strand Robin , Ahlström Håkan , Michaëlsson Karl , Kullberg Joel , Lind Lars , Jansson Per-Anders
Published: May 2024

Objectives

Experimental studies indicate a role for galectin-1 and galectin-3 in metabolic disease, but clinical evidence from larger populations is limited.

Methods

We measured circulating levels of galectin-1 and galectin-3 in the Prospective investigation of Obesity, Energy and Metabolism (POEM) study, participants (n = 502, all aged 50 years) and characterized the individual association profiles with metabolic markers, including clinical measures, metabolomics, adipose tissue distribution (Imiomics) and proteomics.

Results

Galectin-1 and galectin-3 were associated with fatty acids, lipoproteins and triglycerides including lipid measurements in the metabolomics analysis adjusted for body mass index (BMI). Galectin-1 was associated with several measurements of adiposity, insulin secretion and insulin sensitivity, while galectin-3 was associated with triglyceride-glucose index (TyG) and fasting insulin levels. Both galectins were associated with inflammatory pathways and fatty acid binding protein (FABP)4 and -5-regulated triglyceride metabolic pathways. Galectin-1 was also associated with several proteins related to adipose tissue differentiation.

Conclusions

The association profiles for galectin-1 and galectin-3 indicate overlapping metabolic effects in humans, while the distinctly different associations seen with fat mass, fat distribution, and adipose tissue differentiation markers may suggest a functional role of galectin-1 in obesity.
Development of pharmacological immunoregulatory anti-cancer therapeutics: current mechanistic studies and clinical opportunities
Authors: Yin Nanhao , Li Xintong , Zhang Xuanwei , Xue Shaolong , Cao Yu , Niedermann Gabriele , Lu You , Xue Jianxin
Published: May 2024

Immunotherapy represented by anti-PD-(L)1 and anti-CTLA-4 inhibitors has revolutionized cancer treatment, but challenges related to resistance and toxicity still remain. Due to the advancement of immuno-oncology, an increasing number of novel immunoregulatory targets and mechanisms are being revealed, with relevant therapies promising to improve clinical immunotherapy in the foreseeable future. Therefore, comprehending the larger picture is important. In this review, we analyze and summarize the current landscape of preclinical and translational mechanistic research, drug development, and clinical trials that brought about next-generation pharmacological immunoregulatory anti-cancer agents and drug candidates beyond classical immune checkpoint inhibitors. Along with further clarification of cancer immunobiology and advances in antibody engineering, agents targeting additional inhibitory immune checkpoints, including LAG-3, TIM-3, TIGIT, CD47, and B7 family members are becoming an important part of cancer immunotherapy research and discovery, as are structurally and functionally optimized novel anti-PD-(L)1 and anti-CTLA-4 agents and agonists of co-stimulatory molecules of T cells. Exemplified by bispecific T cell engagers, newly emerging bi-specific and multi-specific antibodies targeting immunoregulatory molecules can provide considerable clinical benefits. Next-generation agents also include immune epigenetic drugs and cytokine-based therapeutics. Cell therapies, cancer vaccines, and oncolytic viruses are not covered in this review. This comprehensive review might aid in further development and the fastest possible clinical adoption of effective immuno-oncology modalities for the benefit of patients.
TRIM65 promotes renal cell carcinoma through ubiquitination and degradation of BTG3
Authors: Zhang Qi , Li Yong , Zhu Qing , Xie Tao , Xiao Yue , Zhang Feng , Li Na , Deng Keyu , Xin Hongbo , Huang Xuan
Published: May 2024

As a typical E3 ligase, TRIM65 (tripartite motif containing 65) is involved in the regulation of antiviral innate immunity and the pathogenesis of certain tumors. However, the role of TRIM65 in renal cell carcinoma (RCC) and the underlying mechanism has not been determined yet. In this study, we identified TRIM65 as a novel oncogene in RCC, which enhanced the tumor cell proliferation and anchorage-independent growth abilities both in vitro and in vivo. Moreover, we found that TRIM65-regulated RCC proliferation mainly via direct interaction with BTG3 (BTG anti-proliferation factor 3), which in turn induced the K48-linked ubiquitination and subsequent degradation through K41 amino acid. Furthermore, TRIM65 relieved G2/M phase cell cycle arrest via degradation of BTG3 and regulated downstream factors. Further studies revealed that TRIM65 acts through TRIM65-BTG3-CyclinD1 axis and clinical sample IHC chip data indicated a negative correction between TRIM65 and BTG3. Taken together, our findings demonstrated that TRIM65 promotes RCC cell proliferation via regulation of the cell cycle through degradation of BTG3, suggesting that TRIM65 may be a promising target for RCC therapy.
IL-33/NF-κB/ST2L/Rab37 positive-feedback loop promotes M2 macrophage to limit chemotherapeutic efficacy in lung cancer
Authors: Yang You-En , Hu Meng-Hsuan , Zeng Yen-Chen , Tseng Yau-Lin , Chen Ying-Yuan , Su Wu-Chou , Chang Chih-Peng , Wang Yi-Ching
Published: May 2024

IL-33 is a danger signal that binds to its receptor ST2L to promote tumor progression. This study identifies the IL-33/ST2L positive-feedback loop and the trafficking of ST2L membrane presentation in macrophages that contribute to lung tumor progression. Mechanistically, IL-33 induces ST2L upregulation by activating NF-κB, which binds to the promoter region of the ST2L gene. Moreover, Rab37, a small GTPase involved in membrane trafficking, mediates ST2L trafficking to the plasma membrane of M2 macrophages. This IL-33/NF-κB/ST2L/Rab37 axis promotes positive-feedback loops that enhance ST2L expression and membrane trafficking in M2 macrophages. Notably, neutralizing antibodies against IL-33 or ST2L block NF-κB activity, suppress M2 macrophage polarization, and synergistically inhibit tumor growth when combined with cisplatin treatment in vitro/vivo. Clinically, Rab37+/ST2L+/CD206+ tumor-infiltrating M2 macrophages correlate with advanced-stage lung cancer patients with poor response to chemotherapy. These findings unveil a positive-feedback mechanism and provide a basis for IL-33/ST2L-targeting therapy for cancer.
Eliminating elevated p53 signaling fails to rescue skeletal muscle defects or extend survival in lamin A/C-deficient mice
Authors: Kirby Tyler J. , Zahr Hind C. , Fong Ern Hwei Hannah , Lammerding Jan
Published: May 2024

Lamins A and C, encoded by the LMNA gene, are nuclear intermediate filaments that provide structural support to the nucleus and contribute to chromatin organization and transcriptional regulation. LMNA mutations cause muscular dystrophies, dilated cardiomyopathy, and other diseases. The mechanisms by which many LMNA mutations result in muscle-specific diseases have remained elusive, presenting a major hurdle in the development of effective treatments. Previous studies using striated muscle laminopathy mouse models found that cytoskeletal forces acting on mechanically fragile Lmna-mutant nuclei led to transient nuclear envelope rupture, extensive DNA damage, and activation of DNA damage response (DDR) pathways in skeletal muscle cells in vitro and in vivo. Furthermore, hearts of Lmna mutant mice have elevated activation of the tumor suppressor protein p53, a central regulator of DDR signaling. We hypothesized that elevated p53 activation could present a pathogenic mechanism in striated muscle laminopathies, and that eliminating p53 activation could improve muscle function and survival in laminopathy mouse models. Supporting a pathogenic function of p53 activation in muscle, stabilization of p53 was sufficient to reduce contractility and viability in wild-type muscle cells in vitro. Using three laminopathy models, we found that increased p53 activity in Lmna-mutant muscle cells primarily resulted from mechanically induced damage to the myonuclei, and not from altered transcriptional regulation due to loss of lamin A/C expression. However, global deletion of p53 in a severe muscle laminopathy model did not reduce the disease phenotype or increase survival, indicating that additional drivers of disease must contribute to the disease pathogenesis.
Androgen deprivation induces neuroendocrine phenotypes in prostate cancer cells through CREB1/EZH2-mediated downregulation of REST
Authors: Zheng Dayong , Zhang Yan , Yang Sukjin , Su Ning , Bakhoum Michael , Zhang Guoliang , Naderinezhad Samira , Mao Zhengmei , Wang Zheng , Zhou Ting , Li Wenliang
Published: May 2024

Although effective initially, prolonged androgen deprivation therapy (ADT) promotes neuroendocrine differentiation (NED) and prostate cancer (PCa) progression. It is incompletely understood how ADT transcriptionally induces NE genes in PCa cells. CREB1 and REST are known to positively and negatively regulate neuronal gene expression in the brain, respectively. No direct link between these two master neuronal regulators has been elucidated in the NED of PCa. We show that REST mRNA is downregulated in NEPC cell and mouse models, as well as in patient samples. Phenotypically, REST overexpression increases ADT sensitivity, represses NE genes, inhibits colony formation in culture, and xenograft tumor growth of PCa cells. As expected, ADT downregulates REST in PCa cells in culture and in mouse xenografts. Interestingly, CREB1 signaling represses REST expression. In studying the largely unclear mechanism underlying transcriptional repression of REST by ADT, we found that REST is a direct target of EZH2 epigenetic repression. Finally, genetic rescue experiments demonstrated that ADT induces NED through EZH2’s repression of REST, which is enhanced by ADT-activated CREB1 signaling. In summary, our study has revealed a key pathway underlying NE gene upregulation by ADT, as well as established novel relationships between CREB1 and REST, and between EZH2 and REST, which may also have implications in other cancer types and in neurobiology.
TIMP-1 is an activator of MHC-I expression in myeloid dendritic cells with implications for tumor immunogenicity
Authors: Langguth Miriam , Maranou Eleftheria , Koskela Saara A. , Elenius Oskar , Kallionpää Roosa E. , Birkman Eva-Maria , Pulkkinen Otto I. , Sundvall Maria , Salmi Marko , Figueiredo Carlos R.
Published: May 2024

Immune checkpoint therapies (ICT) for advanced solid tumors mark a new milestone in cancer therapy. Yet their efficacy is often limited by poor immunogenicity, attributed to inadequate priming and generation of antitumor T cells by dendritic cells (DCs). Identifying biomarkers to enhance DC functions in such tumors is thus crucial. Tissue Inhibitor of Metalloproteinases-1 (TIMP-1), recognized for its influence on immune cells, has an underexplored relationship with DCs. Our research reveals a correlation between high TIMP1 levels in metastatic melanoma and increased CD8 + T cell infiltration and survival. Network studies indicate a functional connection with HLA genes. Spatial transcriptomic analysis of a national melanoma cohort revealed that TIMP1 expression in immune compartments associates with an HLA-A/MHC-I peptide loading signature in lymph nodes. Primary human and bone-marrow-derived DCs secrete TIMP-1, which notably increases MHC-I expression in classical type 1 dendritic cells (cDC1), especially under melanoma antigen exposure. TIMP-1 affects the immunoproteasome/TAP complex, as seen by upregulated PSMB8 and TAP-1 levels of myeloid DCs. This study uncovers the role of TIMP-1 in DC-mediated immunogenicity with insights into CD8 + T cell activation, providing a foundation for mechanistic exploration and highlighting its potential as a new target for combinatorial immunotherapy to enhance ICT effectiveness.
Trends and outcomes of hospitalized patients with priapism in Germany: results from the GRAND study
Authors: Pyrgidis Nikolaos , Schulz Gerald B. , Chaloupka Michael , Volz Yannic , Pfitzinger Paulo L. , Berg Elena , Weinhold Philipp , Jokisch Friedrich , Stief Christian G. , Becker Armin J. , Marcon Julian
Published: May 2024

We aimed to provide evidence on the trends and in-hospital outcomes of patients with low- and high-flow priapism through the largest study in the field. We used the GeRmAn Nationwide inpatient Data (GRAND), provided by the Research Data Center of the Federal Bureau of Statistics (2008-2021), and performed multiple patient-level analyses. We included 6,588 men with low-flow and 729 with high-flow priapism. Among patients with low-flow priapism, 156 (2.4%) suffered from sickle cell disease, and 1,477 (22.4%) patients required shunt surgery. Of them, only 37 (2.5%) received a concomitant penile prosthesis implantation (30 inflatable and 7 semi-rigid prosthesis). In Germany, the total number of patients with low-flow priapism requiring hospital stay has steadily increased, while the number of patients with high-flow priapism requiring hospital stay has decreased in the last years. Among patients with high-flow priapism, 136 (18.7%) required selective artery embolization. In men with low-flow priapism, sickle cell disease was associated with high rates of exchange transfusion (OR: 21, 95% CI: 14–31, p < 0.001). The length of hospital stay (p = 0.06) and the intensive care unit admissions (p = 0.9) did not differ between patients with low-flow priapism due to sickle cell disease versus other causes of low-flow priapism. Accordingly, in men with high-flow priapism, embolization was not associated with worse outcomes in terms of length of hospital stay (p > 0.9), transfusion (p = 0.8), and intensive care unit admission (p = 0.5). Low-flow priapism is an absolute emergency that requires shunt surgery in more than one-fifth of all patients requiring hospital stay. On the contrary, high-flow priapism is still managed, in most cases, conservatively.
Far-East Asian Toxoplasma isolates share ancestry with North and South/Central American recombinant lineages
Authors: Ihara Fumiaki , Kyan Hisako , Takashima Yasuhiro , Ono Fumiko , Hayashi Kei , Matsuo Tomohide , Igarashi Makoto , Nishikawa Yoshifumi , Hikosaka Kenji , Sakamoto Hirokazu , Nakamura Shota , Motooka Daisuke , Yamauchi Kiyoshi , Ichikawa-Seki Madoka , Fukumoto Shinya , Sasaki Motoki , Ikadai Hiromi , Kusakisako Kodai , Ohari Yuma , Yoshida Ayako , Sasai Miwa , Grigg Michael E. , Yamamoto Masahiro
Published: May 2024

Toxoplasma gondii is a global protozoan pathogen. Clonal lineages predominate in Europe, North America, Africa, and China, whereas highly recombinant parasites are endemic in South/Central America. Far East Asian T. gondii isolates are not included in current global population genetic structure analyses at WGS resolution. Here we report a genome-wide population study that compared eight Japanese and two Chinese isolates against representative worldwide T. gondii genomes using POPSICLE, a novel population structure analyzing software. Also included were 7 genomes resurrected from non-viable isolates by target enrichment sequencing. Visualization of the genome structure by POPSICLE shows a mixture of Chinese haplogroup (HG) 13 haploblocks introgressed within the genomes of Japanese HG2 and North American HG12. Furthermore, two ancestral lineages were identified in the Japanese strains; one lineage shares a common ancestor with HG11 found in both Japanese strains and North American HG12. The other ancestral lineage, found in T. gondii isolates from a small island in Japan, is admixed with genetically diversified South/Central American strains. Taken together, this study suggests multiple ancestral links between Far East Asian and American T. gondii strains and provides insight into the transmission history of this cosmopolitan organism.
Localized and global representation of prior value, sensory evidence, and choice in male mouse cerebral cortex
Authors: Ishizu Kotaro , Nishimoto Shosuke , Ueoka Yutaro , Funamizu Akihiro
Published: May 2024

Adaptive behavior requires integrating prior knowledge of action outcomes and sensory evidence for making decisions while maintaining prior knowledge for future actions. As outcome- and sensory-based decisions are often tested separately, it is unclear how these processes are integrated in the brain. In a tone frequency discrimination task with two sound durations and asymmetric reward blocks, we found that neurons in the medial prefrontal cortex of male mice represented the additive combination of prior reward expectations and choices. The sensory inputs and choices were selectively decoded from the auditory cortex irrespective of reward priors and the secondary motor cortex, respectively, suggesting localized computations of task variables are required within single trials. In contrast, all the recorded regions represented prior values that needed to be maintained across trials. We propose localized and global computations of task variables in different time scales in the cerebral cortex.
Dual-mode harvest solar energy for photothermal Cu2-xSe biomineralization and seawater desalination by biotic-abiotic hybrid
Authors: Gong Sheng-Lan , Tian YangChao , Sheng Guo-Ping , Tian Li-Jiao
Published: May 2024

Biotic-abiotic hybrid photocatalytic system is an innovative strategy to capture solar energy. Diversifying solar energy conversion products and balancing photoelectron generation and transduction are critical to unravel the potential of hybrid photocatalysis. Here, we harvest solar energy in a dual mode for Cu2-xSe nanoparticles biomineralization and seawater desalination by integrating the merits of Shewanella oneidensis MR-1 and biogenic nanoparticles. Photoelectrons generated by extracellular Se0 nanoparticles power Cu2-xSe synthesis through two pathways that either cross the outer membrane to activate periplasmic Cu(II) reduction or are directly delivered into the extracellular space for Cu(I) evolution. Meanwhile, photoelectrons drive periplasmic Cu(II) reduction by reversing MtrABC complexes in S. oneidensis. Moreover, the unique photothermal feature of the as-prepared Cu2-xSe nanoparticles, the natural hydrophilicity, and the linking properties of bacterium offer a convenient way to tailor photothermal membranes for solar water production. This study provides a paradigm for balancing the source and sink of photoelectrons and diversifying solar energy conversion products in biotic-abiotic hybrid platforms.
DNA methylation-based high-resolution mapping of long-distance chromosomal interactions in nucleosome-depleted regions
Authors: Li Yi , Lee James , Bai Lu
Published: May 2024

3C-based methods have significantly advanced our understanding of 3D genome organization. However, it remains a formidable task to precisely capture long-range chromosomal interactions between individual loci, such as those between promoters and distal enhancers. Here, we present Methyltransferase Targeting-based chromosome Architecture Capture (MTAC), a method that maps the contacts between a target site (viewpoint) and the rest of the genome in budding yeast with high resolution and sensitivity. MTAC detects hundreds of intra- and inter-chromosomal interactions within nucleosome-depleted regions (NDRs) that cannot be captured by 4C, Hi-C, or Micro-C. By applying MTAC to various viewpoints, we find that (1) most long-distance chromosomal interactions detected by MTAC reflect tethering by the nuclear pore complexes (NPCs), (2) genes co-regulated by methionine assemble into inter-chromosomal clusters near NPCs upon activation, (3) mediated by condensin, the mating locus forms a highly specific interaction with the recombination enhancer (RE) in a mating-type specific manner, and (4) correlation of MTAC signals among NDRs reveal spatial mixing and segregation of the genome. Overall, these results demonstrate MTAC as a powerful tool to resolve fine-scale long-distance chromosomal interactions and provide insights into the 3D genome organization.
Controlled oxygen delivery to power tissue regeneration
Authors: Zoneff Elizabeth , Wang Yi , Jackson Colin , Smith Oliver , Duchi Serena , Onofrillo Carmine , Farrugia Brooke , Moulton Simon E. , Williams Richard , Parish Clare , Nisbet David R. , Caballero-Aguilar Lilith M.
Published: May 2024

Oxygen plays a crucial role in human embryogenesis, homeostasis, and tissue regeneration. Emerging engineered regenerative solutions call for novel oxygen delivery systems. To become a reality, these systems must consider physiological processes, oxygen release mechanisms and the target application. In this review, we explore the biological relevance of oxygen at both a cellular and tissue level, and the importance of its controlled delivery via engineered biomaterials and devices. Recent advances and upcoming trends in the field are also discussed with a focus on tissue-engineered constructs that could meet metabolic demands to facilitate regeneration.
Environmental conditions associated with initial northern expansion of anatomically modern humans
Authors: Saltré Frédérik , Chadœuf Joël , Higham Thomas , Ochocki Monty , Block Sebastián , Bunney Ellyse , Llamas Bastien , Bradshaw Corey J. A.
Published: May 2024

The ability of our ancestors to switch food sources and to migrate to more favourable environments enabled the rapid global expansion of anatomically modern humans beyond Africa as early as 120,000 years ago. Whether this versatility was largely the result of environmentally determined processes or was instead dominated by cultural drivers, social structures, and interactions among different groups, is unclear. We develop a statistical approach that combines both archaeological and genetic data to infer the more-likely initial expansion routes in northern Eurasia and the Americas. We then quantify the main differences in past environmental conditions between the more-likely routes and other potential (less-likely) routes of expansion. We establish that, even though cultural drivers remain plausible at finer scales, the emergent migration corridors were predominantly constrained by a combination of regional environmental conditions, including the presence of a forest-grassland ecotone, changes in temperature and precipitation, and proximity to rivers.
Diastereoselective dearomatization of indoles via photocatalytic hydroboration on hydramine-functionalized carbon nitride
Authors: Zhang Qiao , Xu Wengang , Liu Qiong , Xia Congjian , Shao Qi , Ma Lishuang , Wu Mingbo
Published: May 2024

A protocol for trans-hydroboration of indole derivatives using heterogeneous photocatalysis with NHC-borane has been developed, addressing a persistent challenge in organic synthesis. The protocol, leveraging high crystalline vacancy-engineered polymeric carbon nitride as a catalyst, enables diastereoselective synthesis, expanding substrate scope and complementing existing methods. The approach emphasizes eco-friendliness, cost-effectiveness, and scalability, making it suitable for industrial applications, particularly in renewable energy contexts. The catalyst’s superior performance, attributed to its rich carbon-vacancies and well-ordered structure, surpasses more expensive homogeneous alternatives, enhancing viability for large-scale use. This innovation holds promise for synthesizing bioactive compounds and materials relevant to medicinal chemistry and beyond.
Central-Pacific El Niño-Southern Oscillation less predictable under greenhouse warming
Authors: Chen Hui , Jin Yishuai , Liu Zhengyu , Sun Daoxun , Chen Xianyao , McPhaden Michael J. , Capotondi Antonietta , Lin Xiaopei
Published: May 2024

El Niño-Southern Oscillation (ENSO) is the dominant mode of interannual climate variability in the tropical Pacific, whose nature nevertheless may change significantly in a warming climate. Here, we show that the predictability of ENSO may decrease in the future. Across the models in the Coupled Model Intercomparison Project Phase 6 (CMIP6), we find a robust decrease of the persistence and predictability for the Central Pacific (CP) ENSO under global warming, notably in passing through the boreal spring. The strength of spring predictability barrier will be increased by 25% in the future. The reduced predictability of CP ENSO is caused by the faster warming over surface ocean in tropical Pacific and, in turn, the enhanced thermodynamical damping rate on CP ENSO in response to global warming. In contrast, the predictability of Eastern Pacific ENSO will not change. Our results suggest that future greenhouse warming will make the prediction of CP ENSO more challenging, with far-reaching implications on future climate predictions.
Rediscovery of mononuclear phagocyte system blockade for nanoparticle drug delivery
Authors: Zelepukin Ivan V. , Shevchenko Konstantin G. , Deyev Sergey M.
Published: May 2024

Rapid uptake of nanoparticles by mononuclear phagocyte system (MPS) significantly hampers their therapeutic efficacy. Temporal MPS blockade is one of the few ways to overcome this barrier – the approach rediscovered many times under different names but never extensively used in clinic. Using meta-analysis of the published data we prove the efficacy of this technique for enhancing particle circulation in blood and their delivery to tumours, describe a century of its evolution and potential combined mechanism behind it. Finally, we discuss future directions of the research focusing on the features essential for successful clinical translation of the method.
A programmable topological photonic chip
Authors: Dai Tianxiang , Ma Anqi , Mao Jun , Ao Yutian , Jia Xinyu , Zheng Yun , Zhai Chonghao , Yang Yan , Li Zhihua , Tang Bo , Luo Jun , Zhang Baile , Hu Xiaoyong , Gong Qihuang , Wang Jianwei
Published: May 2024

Controlling topological phases of light allows the observation of abundant topological phenomena and the development of robust photonic devices. The prospect of more sophisticated control with topological photonic devices for practical implementations requires high-level programmability. Here we demonstrate a fully programmable topological photonic chip with large-scale integration of silicon photonic nanocircuits and microresonators. Photonic artificial atoms and their interactions in our compound system can be individually addressed and controlled, allowing the arbitrary adjustment of structural parameters and geometrical configurations for the observation of dynamic topological phase transitions and diverse photonic topological insulators. Individual programming of artificial atoms on the generic chip enables the comprehensive statistical characterization of topological robustness against relatively weak disorders, and counterintuitive topological Anderson phase transitions induced by strong disorders. This generic topological photonic chip can be rapidly reprogrammed to implement multifunctionalities, providing a flexible and versatile platform for applications across fundamental science and topological technologies.
Electric recycling of Portland cement at scale
Authors: Dunant Cyrille F. , Joseph Shiju , Prajapati Rohit , Allwood Julian M.
Published: May 2024

Cement production causes 7.5% of global anthropogenic CO2 emissions, arising from limestone decarbonation and fossil-fuel combustion1–3. Current decarbonation strategies include substituting Portland clinker with supplementary materials, but these mainly arise in emitting processes, developing alternative binders but none yet promises scale, or adopting carbon capture and storage that still releases some emissions4–8. However, used cement is potentially an abundant, decarbonated feedstock. Here we show that recovered cement paste can be reclinkered if used as a partial substitute for the lime–dolomite flux used in steel recycling nowadays. The resulting slag can meet existing specifications for Portland clinker and can be blended effectively with calcined clay and limestone. The process is sensitive to the silica content of the recovered cement paste, and silica and alumina that may come from the scrap, but this can be adjusted easily. We show that the proposed process may be economically competitive, and if powered by emissions-free electricity, can lead to zero emissions cement while also reducing the emissions of steel recycling by reducing lime flux requirements. The global supply of scrap steel for recycling may treble by 2050, and it is likely that more slag can be made per unit of steel recycled. With material efficiency in construction9,10, future global cement requirements could be met by this route.
Metals strengthen with increasing temperature at extreme strain rates
Authors: Dowding Ian , Schuh Christopher A.
Published: May 2024

The strength of materials depends on the rate at which they are tested, as defects, for example dislocations, that move in response to applied strains have intrinsic kinetic limitations1–4. As the deformation strain rate increases, more strengthening mechanisms become active and increase the strength4–7. However, the regime in which this transition happens has been difficult to access with traditional micromechanical strength measurements. Here, with microballistic impact testing at strain rates greater than 106 s−1, and without shock conflation, we show that the strength of copper increases by about 30% for a 157 °C increase in temperature, an effect also observed in pure titanium and gold. This effect is counterintuitive, as almost all materials soften when heated under normal conditions. This anomalous thermal strengthening across several pure metals is the result of a change in the controlling deformation mechanism from thermally activated strengthening to ballistic transport of dislocations, which experience drag through phonon interactions1,8–10. These results point to a pathway to better model and predict materials properties under various extreme strain rate conditions, from high-speed manufacturing operations11 to hypersonic transport12.
A whole-slide foundation model for digital pathology from real-world data
Authors: Xu Hanwen , Usuyama Naoto , Bagga Jaspreet , Zhang Sheng , Rao Rajesh , Naumann Tristan , Wong Cliff , Gero Zelalem , González Javier , Gu Yu , Xu Yanbo , Wei Mu , Wang Wenhui , Ma Shuming , Wei Furu , Yang Jianwei , Li Chunyuan , Gao Jianfeng , Rosemon Jaylen , Bower Tucker , Lee Soohee , Weerasinghe Roshanthi , Wright Bill J. , Robicsek Ari , Piening Brian , Bifulco Carlo , Wang Sheng , Poon Hoifung
Published: May 2024

Digital pathology poses unique computational challenges, as a standard gigapixel slide may comprise tens of thousands of image tiles1–3. Prior models have often resorted to subsampling a small portion of tiles for each slide, thus missing the important slide-level context4. Here we present Prov-GigaPath, a whole-slide pathology foundation model pretrained on 1.3 billion 256 × 256 pathology image tiles in 171,189 whole slides from Providence, a large US health network comprising 28 cancer centres. The slides originated from more than 30,000 patients covering 31 major tissue types. To pretrain Prov-GigaPath, we propose GigaPath, a novel vision transformer architecture for pretraining gigapixel pathology slides. To scale GigaPath for slide-level learning with tens of thousands of image tiles, GigaPath adapts the newly developed LongNet5 method to digital pathology. To evaluate Prov-GigaPath, we construct a digital pathology benchmark comprising 9 cancer subtyping tasks and 17 pathomics tasks, using both Providence and TCGA data6. With large-scale pretraining and ultra-large-context modelling, Prov-GigaPath attains state-of-the-art performance on 25 out of 26 tasks, with significant improvement over the second-best method on 18 tasks. We further demonstrate the potential of Prov-GigaPath on vision–language pretraining for pathology7,8 by incorporating the pathology reports. In sum, Prov-GigaPath is an open-weight foundation model that achieves state-of-the-art performance on various digital pathology tasks, demonstrating the importance of real-world data and whole-slide modelling.
Geolocated fish spawning habitats
Authors: Oremus Kimberly L. , Rising James , Ramesh Nandini , Ostroski Audrey J.
Published: May 2024

Fish spawning locations are a crucial input into fisheries management and conservation plans, and many stocks are especially sensitive to the environmental conditions within these localized zones. Globally collated data on spawning locations across many species has been unavailable, hindering global stock assessments and analyses of sustainable development and global environmental change. To address this, we created a geocoded fish spawning dataset using qualitative spawning information from FishBase and Science and Conservation of Fish Aggregations (SCRFA). We cleaned and geocoded the spawning locations of 1,045 marine fish species into 2,931 regions. Each spawning region is defined by one or more polygons, and most spawning regions are associated with spawning months. The resulting dataset covers oceans globally. This dataset will be useful to scientists studying marine fish population dynamics and their interactions with the physical environment on regional to large scales.
The first chromosomal-level genome assembly and annotation of white suckerfish Remora albescens
Authors: Zhou Chaowei , Liu Qi , Qu Yinquan , Qiao Ying , Gao Tianxiang , Wang Danyang
Published: May 2024

Remora albescens, also known as white suckerfish, recognized for its distinctive suction-cup attachment behavior and medicinal significance. In this study, we produced a high-quality chromosome-level genome assembly of R. albescens through the integration of 23.87 Gb PacBio long reads, 64.54 Gb T7 short reads, and 88.63 Gb Hi-C data. Initially, we constructed a contig-level genome assembly totaling 605.30 Mb with a contig N50 of 23.12 Mb. Subsequently, employing Hi-C technology, approximately 99.68% (603.38 Mb) of the contig-level genome was successfully assigned to 23 pseudo-chromosomes. Through the integration of homologous-based predictions, ab initio predictions, and RNA-sequencing methods, we successfully identified a comprehensive set of 22,445 protein-coding genes. Notably, 96.36% (21,629 genes) of these were effectively annotated with functional information. The genome assembly achieved an estimated completeness of 98.1% according to BUSCO analysis. This work promotes the applicability of the R. albescens genome, laying a solid foundation for future investigations into genomics, biology, and medicinal importance within this species.
Metricizing policy texts: Comprehensive dataset on China’s Agri-policy intensity spanning 1982–2023
Authors: Wu Yehui , Wang Canyu , Ji Rongbiao , Li Yadong , Yang Junkui , Wang Yixuan , Li Rujia , Wu Mengyao , Chen Jiaojiao , Yang Jianping
Published: May 2024

Due to the lack of direct assessment metrics, existing studies on the intensity of agricultural policies often utilize indicators such as Gross Domestic Product (GDP) of agriculture or the quantity of agricultural policies as measures. Optimizing methods for analyzing the intensity of agricultural policies will significantly impact parameter selection in agricultural policy research and the evaluation of policy effectiveness. In this study, we constructed a Chinese Agricultural Policy Corpus using agricultural policies released by various governmental agencies at the national level in China from 1982 to April 2023. We quantified the values of agricultural domain terms in the corpus and evaluated the intensity of each agricultural policy document. The validation results of this study indicate a strong correlation between the intensity of agricultural policies and agricultural GDP. The trend in agricultural GDP changes lags behind policy intensity by 2.5 years (at a 95% confidence level), thus validating the rationality of our constructed corpus, agricultural policy scoring dataset, and methodology.
A bi-directional segmentation method for prostate ultrasound images under semantic constraints
Authors: Li Zexiang , Du Wei , Shi Yongtao , Li Wei , Gao Chao
Published: May 2024

Due to the lack of sufficient labeled data for the prostate and the extensive and complex semantic information in ultrasound images, accurately and quickly segmenting the prostate in transrectal ultrasound (TRUS) images remains a challenging task. In this context, this paper proposes a solution for TRUS image segmentation using an end-to-end bidirectional semantic constraint method, namely the BiSeC model. The experimental results show that compared with classic or popular deep learning methods, this method has better segmentation performance, with the Dice Similarity Coefficient (DSC) of 96.74% and the Intersection over Union (IoU) of 93.71%. Our model achieves a good balance between actual boundaries and noise areas, reducing costs while ensuring the accuracy and speed of segmentation.
Investigation into the application of remimazolamin conjunction with low-dose propofolfor pediatricfiberoptic bronchoscopy
Authors: Chen Wenjing , Bao Wenjuan , Shi Jing , Shi Lei , Cui Jianli
Published: May 2024

This study delves into the effectiveness of combining remimazolam with low-dose propofol in pediatric fiberoptic bronchoscopy. Ninety children scheduled for fiberoptic bronchoscopy in our hospital were enrolled as research participants. Based on the intraoperative anesthetic drug regimen, the children were divided into three groups: group R (remimazolam 0.2–0.4 mg/kg), group P (propofol 1–3 mg/kg), and group RP (remimazolam0.2 mg/kg, propofol 0.5 mg/kg). Immediately post-anesthesia, group P exhibited lower blood pressure and heart rate (HR) compared to both group R and group RP (P < 0.05). As bronchoscope approached the glottis and epiglottis, group P continued to display lower blood pressure and HR compared to group R and group RP (P < 0.05). During lavage, group P maintained lower blood pressure and HR compared to both the R and RP groups (P < 0.05). Immediately post-anesthesia, group P demonstrated lower SpO2 compared to the R and RP groups (P < 0.05).During lavage, group P maintained lower SpO2 than group R and group RP (P < 0.05). In comparison with group R and group PR, group P showed shortened induction and recovery times (P < 0.05). The one-time entry success rate into the microscope was higher in group R than in group P, with the RP group showing an intermediate decreased (P < 0.05). Moreover, the cough score in R group was higher than in the P and RP groups (P < 0.05). Furthermore, the satisfaction rates of the RP group exceeded those of the R and P groups (P < 0.05). Remimazolam combined with low-dose propofol effectively balances the strengths and weaknesses of remimazolam and propofol, ensuring more stable hemodynamics, a lower incidence of adverse reactions, and optimal surgical conditions in pediatric fiberoptic bronchoscopy.
Comprehensive data mining reveals RTK/RAS signaling pathway as a promoter of prostate cancer lineage plasticity through transcription factors and CNV
Authors: Wei Guanyun , Zhang Xu , Liu Siyuan , Hou Wanxin , Dai Zao
Published: May 2024

Prostate cancer lineage plasticity is a key driver in the transition to neuroendocrine prostate cancer (NEPC), and the RTK/RAS signaling pathway is a well-established cancer pathway. Nevertheless, the comprehensive link between the RTK/RAS signaling pathway and lineage plasticity has received limited investigation. In particular, the intricate regulatory network governing the interplay between RTK/RAS and lineage plasticity remains largely unexplored. The multi-omics data were clustered with the coefficient of argument and neighbor joining algorithm. Subsequently, the clustered results were analyzed utilizing the GSEA, gene sets related to stemness, multi-lineage state datasets, and canonical cancer pathway gene sets. Finally, a comprehensive exploration of the data based on the ssGSEA, WGCNA, GSEA, VIPER, prostate cancer scRNA-seq data, and the GPSAdb database was conducted. Among the six modules in the clustering results, there are 300 overlapping genes, including 3 previously unreported prostate cancer genes that were validated to be upregulated in prostate cancer through RT-qPCR. Function Module 6 shows a positive correlation with prostate cancer cell stemness, multi-lineage states, and the RTK/RAS signaling pathway. Additionally, the 19 leading-edge genes of the RTK/RAS signaling pathway promote prostate cancer lineage plasticity through a complex network of transcriptional regulation and copy number variations. In the transcriptional regulation network, TP63 and FOXO1 act as suppressors of prostate cancer lineage plasticity, whereas RORC exerts a promoting effect. This study provides a comprehensive perspective on the role of the RTK/RAS pathway in prostate cancer lineage plasticity and offers new clues for the treatment of NEPC.
Optimal and scalable entanglement distribution over crossbar quantum networks
Authors: Ciobanu Bogdan-Călin , Verzotti Luca Perju , Popescu Pantelimon George
Published: May 2024

Crossbar networks are a cornerstone of network architectures, capable of operating both as standalone interconnections or as integral switching components in complex, multi-stage systems. The main advantages of crossbar networks are their non-blocking operation and unparalleled minimal latency. With the advent of large scale quantum networks, crossbars might be an important asset towards the Quantum Internet. This study proposes a solution for the problem of distributing entanglement within crossbar quantum networks. Entangled particles are a consumable resource in quantum networks, and are being used by most quantum protocols. By ensuring that nodes within quantum networks are being supplied with entanglement, the reliability and efficiency of the network is maintained. By providing an efficient, scalable framework that can be used to achieve optimal entanglement distribution within crossbar quantum networks, this study offers a theoretical achievement which can be also used for enhancing quantum network performance. An algorithm for selecting an optimal entanglement distribution configuration is proposed and fully tested on realistic possible configurations.