The complement system plays a fundamental role in immunity, and its dysregulation is implicated in numerous human diseases. Activation of complement occurs through three main pathways: classical, lectin, and alternative; which converge at the central component, component of complement 3 (C3). The classical and lectin pathways use the C4b2a convertase to cleave C3 and initiate complement activation, while the alternative pathway uses the C3bBb convertase, which is further stabilized by properdin. The molecular mechanisms governing C3 recognition by these convertase complexes remain incompletely understood. Here, we present the 3.1-angstrom cryo–electron microscopy structure of the C4b2a-C3 Michaelis complex, alongside 2.9- and 3.1-angstrom structures of the C4b2 zymogen in loading and activation states, elucidating the structural basis for C3 engagement by C4b2a and conformational changes during the classical and lectin pathway convertase maturation. Furthermore, a 2.6-angstrom structure of C3bBb-properdin in complex with C3 uncovers unique substrate-binding features of C3bBb and properdin’s stabilizing role in the alternative pathway. These results offer comprehensive mechanistic insights into complement activation.
{"title":"Complement C3 recognition by C3 convertases","authors":"Changhao Jia, Xiaoke Yang, Ming-hui Zhao, Ying Tan, Junyu Xiao","doi":"10.1126/sciadv.adz5404","DOIUrl":"https://doi.org/10.1126/sciadv.adz5404","url":null,"abstract":"The complement system plays a fundamental role in immunity, and its dysregulation is implicated in numerous human diseases. Activation of complement occurs through three main pathways: classical, lectin, and alternative; which converge at the central component, component of complement 3 (C3). The classical and lectin pathways use the C4b2a convertase to cleave C3 and initiate complement activation, while the alternative pathway uses the C3bBb convertase, which is further stabilized by properdin. The molecular mechanisms governing C3 recognition by these convertase complexes remain incompletely understood. Here, we present the 3.1-angstrom cryo–electron microscopy structure of the C4b2a-C3 Michaelis complex, alongside 2.9- and 3.1-angstrom structures of the C4b2 zymogen in loading and activation states, elucidating the structural basis for C3 engagement by C4b2a and conformational changes during the classical and lectin pathway convertase maturation. Furthermore, a 2.6-angstrom structure of C3bBb-properdin in complex with C3 uncovers unique substrate-binding features of C3bBb and properdin’s stabilizing role in the alternative pathway. These results offer comprehensive mechanistic insights into complement activation.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"40 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146222926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yang Zhang, Huan Liang, Yajing Liu, Dong Li, Shuai Dong, Jing Wang, Weiwei Li, Ce-Wen Nan
Relaxor ferroelectric materials are promising for next-generation capacitors due to their high energy storage capacity. Polymorphic phase engineering, where different ferroelectric phases coexist, has been widely demonstrated as an effective approach to further boost capacitive energy storage performance of relaxor ferroelectrics, but the reasons for these improvements and how they compare to single-phase systems remain unclear. Here, taking dendrite-like PbZr 1- x Ti x O 3 /MgO nanocomposites with defected as a model system, we systematically examine properties and capacitive energy storage performance for rhombohedral-dominant, rhombohedral/tetragonal-mixed, and tetragonal-dominant phases through phase-field simulations. We find that the rhombohedral/tetragonal mixtures deliver the best results in most cases, mainly due to their low switching barriers and substantial local inhomogeneity. These results offer a detailed view of improved energy storage in relaxor ferroelectrics and provide theoretical guidance for designing high-performance capacitors.
弛豫铁电材料具有较高的储能能力，有望成为下一代电容器。不同铁电相共存的多晶相工程已被广泛证明是进一步提高弛豫铁电体电容储能性能的有效方法，但这些改进的原因以及它们与单相系统的比较尚不清楚。本文以枝晶状PbZr 1- x Ti x O 3 /MgO纳米复合材料为模型体系，通过相场模拟系统地考察了菱形为主相、菱形/四边形混合相和四边形为主相的性能和电容储能性能。我们发现，在大多数情况下，菱形/四边形混合物提供了最好的结果，这主要是由于它们的低开关势垒和大量的局部不均匀性。这些结果提供了改进弛豫铁电体能量存储的详细视图，并为设计高性能电容器提供了理论指导。
{"title":"Boosting capacitive energy storage in relaxor ferroelectrics through polymorphic phase engineering","authors":"Yang Zhang, Huan Liang, Yajing Liu, Dong Li, Shuai Dong, Jing Wang, Weiwei Li, Ce-Wen Nan","doi":"10.1126/sciadv.aeb7173","DOIUrl":"https://doi.org/10.1126/sciadv.aeb7173","url":null,"abstract":"Relaxor ferroelectric materials are promising for next-generation capacitors due to their high energy storage capacity. Polymorphic phase engineering, where different ferroelectric phases coexist, has been widely demonstrated as an effective approach to further boost capacitive energy storage performance of relaxor ferroelectrics, but the reasons for these improvements and how they compare to single-phase systems remain unclear. Here, taking dendrite-like PbZr <jats:sub> 1- <jats:italic toggle=\"yes\">x</jats:italic> </jats:sub> Ti <jats:italic toggle=\"yes\"> <jats:sub>x</jats:sub> </jats:italic> O <jats:sub>3</jats:sub> /MgO nanocomposites with defected as a model system, we systematically examine properties and capacitive energy storage performance for rhombohedral-dominant, rhombohedral/tetragonal-mixed, and tetragonal-dominant phases through phase-field simulations. We find that the rhombohedral/tetragonal mixtures deliver the best results in most cases, mainly due to their low switching barriers and substantial local inhomogeneity. These results offer a detailed view of improved energy storage in relaxor ferroelectrics and provide theoretical guidance for designing high-performance capacitors.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"6 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146222944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Conventional semiconductor device engineering regards intrinsic device nonidealities as reliability concerns to be minimized or eliminated. Here, we demonstrate the strategic repurposing of these nonidealities as functional resources for advanced stochastic analog computing. We leverage two underutilized phenomena—deep-level channel trap-induced generation-recombination (G-R) noise and impact ionization–induced negative differential resistance (NDR) in body current—which have received limited attention compared to the extensively studied 1/ f noise and monotonic drain current behavior in logic-centric transistors. By exploiting G-R noise with controllable temporal correlation and NDR with an unprecedented peak-to-valley ratio (2.78 × 10 4 ) within fully depleted silicon-on-insulator transistors fabricated in industry silicon complementary metal-oxide semiconductor (CMOS) process, we achieve multifunctional analog computation at the single-device level. Our transistor seamlessly performs stochastic encryption, deterministic signal readout, and analog inversion simply through reconfiguration of applied bias conditions, thereby eliminating the need for peripheral random-number generators, dedicated analog inverters, or amplifiers. This approach not only reveals the previously unrecognized computational potential embedded in mature CMOS technologies but also presents a scalable and energy-efficient alternative to architecture based on exotic materials, laying the foundation for next-generation analog computing systems.
{"title":"Repurposing Si CMOS nonidealities for stochastic and analog image processing","authors":"Been Kwak, Ryun-Han Koo, Changhyeon Han, Yunho Shin, Joonhyeok Choi, Dongbin Kim, Jongwoo Lee, Jiseong Im, Youngchan Cho, Jong-Ho Lee, Wonjun Shin, Daewoong Kwon","doi":"10.1126/sciadv.aea2328","DOIUrl":"https://doi.org/10.1126/sciadv.aea2328","url":null,"abstract":"Conventional semiconductor device engineering regards intrinsic device nonidealities as reliability concerns to be minimized or eliminated. Here, we demonstrate the strategic repurposing of these nonidealities as functional resources for advanced stochastic analog computing. We leverage two underutilized phenomena—deep-level channel trap-induced generation-recombination (G-R) noise and impact ionization–induced negative differential resistance (NDR) in body current—which have received limited attention compared to the extensively studied 1/ <jats:italic toggle=\"yes\">f</jats:italic> noise and monotonic drain current behavior in logic-centric transistors. By exploiting G-R noise with controllable temporal correlation and NDR with an unprecedented peak-to-valley ratio (2.78 × 10 <jats:sup>4</jats:sup> ) within fully depleted silicon-on-insulator transistors fabricated in industry silicon complementary metal-oxide semiconductor (CMOS) process, we achieve multifunctional analog computation at the single-device level. Our transistor seamlessly performs stochastic encryption, deterministic signal readout, and analog inversion simply through reconfiguration of applied bias conditions, thereby eliminating the need for peripheral random-number generators, dedicated analog inverters, or amplifiers. This approach not only reveals the previously unrecognized computational potential embedded in mature CMOS technologies but also presents a scalable and energy-efficient alternative to architecture based on exotic materials, laying the foundation for next-generation analog computing systems.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146222953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katherine A. Legg, Giovanni Gonzalez-Gutierrez, Katherine A. Edmonds, Philip G. Shushkov, David P. Giedroc
Many bacteria harbor an ATP-binding cassette (ABC) transporter named EgtU specific for the human dietary antioxidant and 2-thioimidazole–containing low–molecular weight thiol ergothioneine (ET). How the solute binding domain, EgtUC, discriminates among ET and other similar molecules is unknown. Here, we use a “chimeric” mutagenesis strategy and two distantly related EgtUCs from Streptococcus pneumoniae and Helicobacter pylori to show that a suite of EgtUC alkyl CH•••S hydrogen bonds to the ET thione S atom are central determinants of molecular recognition. Small perturbations in CH•••S distance and angle give rise to sharply attenuated transport-competent ET-bound “closed” state lifetimes and increased motional disorder in the binding pocket, not around the S atom itself, but distally in weakening NH•••O hydrogen bonds. This work highlights the impact of alkyl CH•••S H bonding in a biological protein-ligand complex in water.
{"title":"CH•••S hydrogen bonds drive molecular recognition of ergothioneine by the microbial transporter","authors":"Katherine A. Legg, Giovanni Gonzalez-Gutierrez, Katherine A. Edmonds, Philip G. Shushkov, David P. Giedroc","doi":"10.1126/sciadv.aeb0426","DOIUrl":"https://doi.org/10.1126/sciadv.aeb0426","url":null,"abstract":"Many bacteria harbor an ATP-binding cassette (ABC) transporter named EgtU specific for the human dietary antioxidant and 2-thioimidazole–containing low–molecular weight thiol ergothioneine (ET). How the solute binding domain, EgtUC, discriminates among ET and other similar molecules is unknown. Here, we use a “chimeric” mutagenesis strategy and two distantly related EgtUCs from <jats:italic toggle=\"yes\">Streptococcus pneumoniae and Helicobacter pylori</jats:italic> to show that a suite of EgtUC alkyl CH•••S hydrogen bonds to the ET thione S atom are central determinants of molecular recognition. Small perturbations in CH•••S distance and angle give rise to sharply attenuated transport-competent ET-bound “closed” state lifetimes and increased motional disorder in the binding pocket, not around the S atom itself, but distally in weakening NH•••O hydrogen bonds. This work highlights the impact of alkyl CH•••S H bonding in a biological protein-ligand complex in water.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"75 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146222955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
With increasing understanding of cadmium (Cd) exposure levels and toxicity mechanisms, the adequacy of current Cd limit standards for protecting public health requires comprehensive evaluation. Here, we found that 39.04% of rice Cd content surpassed the fifth percentile of benchmark dose lower limit (BMDL5; 17.100 micrograms per day) threshold for dietary Cd associated with chronic kidney disease in Jiangsu Province. Moreover, more than 90% of rice Cd levels posed potential health hazards, with some samples presenting lifetime carcinogenic risks. Blood and urinary Cd levels demonstrated age-dependent increases, with 48.40 and 20.61% of participants exceeding BMDL5 levels for blood Cd (0.640 micrograms per liter) and urinary Cd (0.120 micrograms per liter), respectively. The derived reference values for dietary Cd were 0.149 and 0.018 micrograms per kilogram of body weight per day for adults and children, respectively. The lowest concentrations of Cd in rice consumed by adults and children were also observed, which indicated that current Cd limit standards appear insufficient to protect public health, indicating a need for more stringent safety thresholds.
{"title":"Assessing the health risks of rice cadmium content standards in China","authors":"Haiyan Chu, Huilin Zhang, Dahua Ren, Xuanying Jiang, Yang Yu, Jialei Zhu, Kexin Li, Haiping Liu, Linfan Xu, Xiaoting Li, Zhen Ding","doi":"","DOIUrl":"","url":null,"abstract":"<div >With increasing understanding of cadmium (Cd) exposure levels and toxicity mechanisms, the adequacy of current Cd limit standards for protecting public health requires comprehensive evaluation. Here, we found that 39.04% of rice Cd content surpassed the fifth percentile of benchmark dose lower limit (BMDL<sub>5</sub>; 17.100 micrograms per day) threshold for dietary Cd associated with chronic kidney disease in Jiangsu Province. Moreover, more than 90% of rice Cd levels posed potential health hazards, with some samples presenting lifetime carcinogenic risks. Blood and urinary Cd levels demonstrated age-dependent increases, with 48.40 and 20.61% of participants exceeding BMDL<sub>5</sub> levels for blood Cd (0.640 micrograms per liter) and urinary Cd (0.120 micrograms per liter), respectively. The derived reference values for dietary Cd were 0.149 and 0.018 micrograms per kilogram of body weight per day for adults and children, respectively. The lowest concentrations of Cd in rice consumed by adults and children were also observed, which indicated that current Cd limit standards appear insufficient to protect public health, indicating a need for more stringent safety thresholds.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 8","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The ability of multitasking (MT) learning in neuro-inspired artificial intelligence (AI) systems offers promise for energy-efficient deployment in robotics, health care, and autonomous vehicles. Here, an MT learning framework is established using a dual-output electroluminescent synaptic device array based on a mixed-dimensional stacked configuration with Cs1−xFAxPbBr3 (0.00 ≤ x ≤ 0.15) quantum dots. The device concurrently processes postsynaptic current (PSC) and postsynaptic electroluminescence (PSEL) signals, demonstrating stable and adjustable long-term plasticity with ~1000 individual states, along with spike rate-dependent plasticity and paired-pulse facilitation. By synthesizing the update behavior of both PSC and PSEL pathways, the MT framework simultaneously executes classification-regression and classification-image reconstruction tasks. This approach achieves computational speed improvements of up to 47.09 and 29.17% while reducing energy consumption by up to 8.2- and 32.4-fold compared to a combined single-tasking framework and graphics processing unit–based hardware accelerators, respectively. This innovative method emphasizes the potential of dual-output electroluminescent artificial synapse for MT learning applications.
{"title":"Electroluminescent perovskite QD–based neural networks for energy-efficient and accelerate multitasking learning","authors":"Young Ran Park, Gunuk Wang","doi":"","DOIUrl":"","url":null,"abstract":"<div >The ability of multitasking (MT) learning in neuro-inspired artificial intelligence (AI) systems offers promise for energy-efficient deployment in robotics, health care, and autonomous vehicles. Here, an MT learning framework is established using a dual-output electroluminescent synaptic device array based on a mixed-dimensional stacked configuration with Cs<sub>1−<i>x</i></sub>FA<i><sub>x</sub></i>PbBr<sub>3</sub> (0.00 ≤ <i>x</i> ≤ 0.15) quantum dots. The device concurrently processes postsynaptic current (PSC) and postsynaptic electroluminescence (PSEL) signals, demonstrating stable and adjustable long-term plasticity with ~1000 individual states, along with spike rate-dependent plasticity and paired-pulse facilitation. By synthesizing the update behavior of both PSC and PSEL pathways, the MT framework simultaneously executes classification-regression and classification-image reconstruction tasks. This approach achieves computational speed improvements of up to 47.09 and 29.17% while reducing energy consumption by up to 8.2- and 32.4-fold compared to a combined single-tasking framework and graphics processing unit–based hardware accelerators, respectively. This innovative method emphasizes the potential of dual-output electroluminescent artificial synapse for MT learning applications.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 8","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christopher Douville, Jeeun Parksong, Marco Dal Molin, Sarah Graham, Patricia T. Greipp, Ryan Knudson, Samuel Curtis, Yuxuan Wang, Lisa Dobbyn, Maria Popoli, Janine Ptak, Natalie Silliman, Katharine Romans, Christine A. Iacobuzio-Donahue, Alvin P. Makoohon-Moore, Anne Marie Lennon, Michael Goggins, Ralph H. Hruban, Ashley Kiemen, Chetan Bettegowda, Kenneth W. Kinzler, Nickolas Papadopoulos, Laura D. Wood, Bert Vogelstein
We searched for oncogenes activated by copy number increases using whole-genome sequencing data of 535 pancreatic ductal adenocarcinomas (PDACs). We found that gains of 1q were the second most common gain, occurring in 213 (39.8%) of PDACs. Single-cell analysis via fluorescence in situ hybridization on 33 cancers confirmed these results. A portion of 1q, rather than the entire 1q arm, was gained in 75 (14.0%) PDACs, allowing us to pinpoint two ~3-megabase regions of 1q that were nearly always gained. These two regions contained NCSTN and PSEN2, genes that code two subunits of the γ-secretase complex. Evaluation of 267 precancerous lesions revealed that extra copies of NCSTN and PSEN2 were common (49%) in noninvasive neoplasms (high-grade pancreatic intraepithelial neoplasms), which are at relatively high risk for progression to PDACs, but uncommon (6%) in low-grade pancreatic intraepithelial neoplasia lesions, which have low malignant potential. We hypothesize that γ-secretase genes are genetically activated oncogenes in the early phases of pancreatic neoplasia.
{"title":"Evidence that extra copies of chromosome 1q play a role in the early phases of pancreatic neoplasia","authors":"Christopher Douville, Jeeun Parksong, Marco Dal Molin, Sarah Graham, Patricia T. Greipp, Ryan Knudson, Samuel Curtis, Yuxuan Wang, Lisa Dobbyn, Maria Popoli, Janine Ptak, Natalie Silliman, Katharine Romans, Christine A. Iacobuzio-Donahue, Alvin P. Makoohon-Moore, Anne Marie Lennon, Michael Goggins, Ralph H. Hruban, Ashley Kiemen, Chetan Bettegowda, Kenneth W. Kinzler, Nickolas Papadopoulos, Laura D. Wood, Bert Vogelstein","doi":"","DOIUrl":"","url":null,"abstract":"<div >We searched for oncogenes activated by copy number increases using whole-genome sequencing data of 535 pancreatic ductal adenocarcinomas (PDACs). We found that gains of 1q were the second most common gain, occurring in 213 (39.8%) of PDACs. Single-cell analysis via fluorescence in situ hybridization on 33 cancers confirmed these results. A portion of 1q, rather than the entire 1q arm, was gained in 75 (14.0%) PDACs, allowing us to pinpoint two ~3-megabase regions of 1q that were nearly always gained. These two regions contained <i>NCSTN</i> and <i>PSEN2</i>, genes that code two subunits of the γ-secretase complex. Evaluation of 267 precancerous lesions revealed that extra copies of <i>NCSTN</i> and <i>PSEN2</i> were common (49%) in noninvasive neoplasms (high-grade pancreatic intraepithelial neoplasms), which are at relatively high risk for progression to PDACs, but uncommon (6%) in low-grade pancreatic intraepithelial neoplasia lesions, which have low malignant potential. We hypothesize that γ-secretase genes are genetically activated oncogenes in the early phases of pancreatic neoplasia.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 8","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lei Yu, Shixiong Zhang, Liang Liu, Di Li, Yongli Cai, Chenxin Wu, Lei Hua, Haiyang Li, Dehui Deng, Ping Chen, Zhenfeng Xi, Jianping Guo, Junnian Wei
Directly converting dinitrogen (N2) into valuable nitrogen-containing compounds remains an enduring challenge in chemical synthesis. Here, we report the direct cyanation of aromatic substrates using N2 and methane (CH4) at atmospheric pressure facilitated by a custom-built, air-free dielectric barrier discharge (DBD) plasma system. A broad range of aromatic compounds, including benzene, were successfully transformed into their corresponding aromatic nitriles. Both experimental and computational evidence suggested that the reaction proceeds primarily via the in situ generation of •CN radicals from N2 and CH4 within the plasma zone. Subsequent radical addition to aromatic rings allowed the one-pot formation of aryl nitriles. This approach represents a major advancement in dinitrogen-based organic methodologies, providing an efficient alternative to conventional cyanation methods that heavily rely on lengthy synthetic routes and hazardous cyanide reagents.
{"title":"Direct cyanation of aromatic rings using dinitrogen and methane promoted by nonthermal plasma","authors":"Lei Yu, Shixiong Zhang, Liang Liu, Di Li, Yongli Cai, Chenxin Wu, Lei Hua, Haiyang Li, Dehui Deng, Ping Chen, Zhenfeng Xi, Jianping Guo, Junnian Wei","doi":"","DOIUrl":"","url":null,"abstract":"<div >Directly converting dinitrogen (N<sub>2</sub>) into valuable nitrogen-containing compounds remains an enduring challenge in chemical synthesis. Here, we report the direct cyanation of aromatic substrates using N<sub>2</sub> and methane (CH<sub>4</sub>) at atmospheric pressure facilitated by a custom-built, air-free dielectric barrier discharge (DBD) plasma system. A broad range of aromatic compounds, including benzene, were successfully transformed into their corresponding aromatic nitriles. Both experimental and computational evidence suggested that the reaction proceeds primarily via the in situ generation of •CN radicals from N<sub>2</sub> and CH<sub>4</sub> within the plasma zone. Subsequent radical addition to aromatic rings allowed the one-pot formation of aryl nitriles. This approach represents a major advancement in dinitrogen-based organic methodologies, providing an efficient alternative to conventional cyanation methods that heavily rely on lengthy synthetic routes and hazardous cyanide reagents.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 8","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Accurate reconstruction of paleo-ocean depths is essential for understanding the interplay between tectonic evolution and global climate change, yet existing methods face substantial limitations. Here, we assess the potential of glycerol dialkyl glycerol tetraethers (GDGTs)—archaeal lipid biomarkers—as a quantitative proxy for paleobathymetry. Analyzing a global dataset of marine surface sediments, we find that GDGT distributions exhibit systematic shifts with water depth. Using random forest machine learning models trained on combined isoGDGT and OH-GDGT profiles, we achieve high predictive performance ( R2 = 0.85, RMSE = 646 m). Applying this approach to a 6-million-year sedimentary record from the northwest Australian Shelf reproduces key features captured by foraminifera-based reconstructions and reveals tectonically driven bathymetric evolution, including potential influences on the development of the Leeuwin Current. These results demonstrate the GDGT-based machine learning models offer a robust and effective framework for reconstructing paleo-ocean depths and probing the links between oceanography and tectonics.
{"title":"Machine learning-based paleobathymetric reconstructions using archaeal lipid biomarkers","authors":"Jiaming Zhou, Dujuan Kang, Shijie Chen, Liang Dong","doi":"10.1126/sciadv.adz3284","DOIUrl":"https://doi.org/10.1126/sciadv.adz3284","url":null,"abstract":"Accurate reconstruction of paleo-ocean depths is essential for understanding the interplay between tectonic evolution and global climate change, yet existing methods face substantial limitations. Here, we assess the potential of glycerol dialkyl glycerol tetraethers (GDGTs)—archaeal lipid biomarkers—as a quantitative proxy for paleobathymetry. Analyzing a global dataset of marine surface sediments, we find that GDGT distributions exhibit systematic shifts with water depth. Using random forest machine learning models trained on combined isoGDGT and OH-GDGT profiles, we achieve high predictive performance ( <jats:italic toggle=\"yes\">R</jats:italic> <jats:sup>2</jats:sup> = 0.85, RMSE = 646 m). Applying this approach to a 6-million-year sedimentary record from the northwest Australian Shelf reproduces key features captured by foraminifera-based reconstructions and reveals tectonically driven bathymetric evolution, including potential influences on the development of the Leeuwin Current. These results demonstrate the GDGT-based machine learning models offer a robust and effective framework for reconstructing paleo-ocean depths and probing the links between oceanography and tectonics.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"36 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146222925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Erfei Chen, Qiqi Yang, Haoyang Dai, Yixin Chen, Yihui Zhang, Qianglong Wang, Rongrong Hou, Ming Chen, Jie Wang, Qianwen Xie, Wenju Sun, Yong-Qiang Ning, Ligang Fan, Jian Yan
Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, yet the functional impact of noncoding variants on enhancer activity remains largely unexplored. In this study, we adapted and applied two high-throughput techniques, SNP-STARR-seq and Methyl-STARR-seq, to systematically evaluate the influence of 30,790 noncoding SNPs and more than 134,000 CpG sites on enhancer activity in primary and metastatic CRC cells. We identified 922 SNPs and 487 CpG-containing elements modulating enhancer activity in primary cells and found 3136 SNPs and 3008 methylation-sensitive elements with metastasis-specific regulatory effects. Multi-omics integration linked these variants to target genes, and CRISPR editing validated their roles in driving tumorigenic and metastatic phenotypes. Furthermore, we identified two CRC-specific hypermethylated loci, cg08640619 and cg25982657, as exceptional tissue-based early detection biomarkers (AUC > 0.96). Mechanistically, hypermethylation at cg08640619 disrupts RUNX2 binding, leading to inhibition of KIRREL1 and ETV3 . Our study provides a comprehensive platform for understanding how genetic and epigenetic variants disrupt transcriptional programs in CRC, offering insights into disease susceptibility and identifying potential diagnostic and therapeutic targets.
{"title":"Systematic analysis of functional genetic and epigenetic variants in colorectal cancer","authors":"Erfei Chen, Qiqi Yang, Haoyang Dai, Yixin Chen, Yihui Zhang, Qianglong Wang, Rongrong Hou, Ming Chen, Jie Wang, Qianwen Xie, Wenju Sun, Yong-Qiang Ning, Ligang Fan, Jian Yan","doi":"10.1126/sciadv.aeb2473","DOIUrl":"https://doi.org/10.1126/sciadv.aeb2473","url":null,"abstract":"Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, yet the functional impact of noncoding variants on enhancer activity remains largely unexplored. In this study, we adapted and applied two high-throughput techniques, SNP-STARR-seq and Methyl-STARR-seq, to systematically evaluate the influence of 30,790 noncoding SNPs and more than 134,000 CpG sites on enhancer activity in primary and metastatic CRC cells. We identified 922 SNPs and 487 CpG-containing elements modulating enhancer activity in primary cells and found 3136 SNPs and 3008 methylation-sensitive elements with metastasis-specific regulatory effects. Multi-omics integration linked these variants to target genes, and CRISPR editing validated their roles in driving tumorigenic and metastatic phenotypes. Furthermore, we identified two CRC-specific hypermethylated loci, cg08640619 and cg25982657, as exceptional tissue-based early detection biomarkers (AUC > 0.96). Mechanistically, hypermethylation at cg08640619 disrupts RUNX2 binding, leading to inhibition of <jats:italic toggle=\"yes\">KIRREL1</jats:italic> and <jats:italic toggle=\"yes\">ETV3</jats:italic> . Our study provides a comprehensive platform for understanding how genetic and epigenetic variants disrupt transcriptional programs in CRC, offering insights into disease susceptibility and identifying potential diagnostic and therapeutic targets.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"75 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146222943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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