BACKGROUND Colorectal cancer is one of the malignant tumors with a high incidence and mortality rate globally,and the occurrence of liver metastasis significantly affects patient survival prognosis.In recent years,the...BACKGROUND Colorectal cancer is one of the malignant tumors with a high incidence and mortality rate globally,and the occurrence of liver metastasis significantly affects patient survival prognosis.In recent years,the application of immune checkpoint inhibitors(ICIs)in cancer treatment has made important progress,especially showing good therapeutic effects in patients with high microsatellite instability or mismatch repair deficiency.However,for the majority of patients with microsatellite stable(MSS)or proficient mismatch repair(pMMR)colorectal cancer,the efficacy of ICIs is limited,prompting researchers to explore combination therapy strategies to improve efficacy.Targeted drugs such as tyrosine kinase inhibitors(TKIs)and radiotherapy are believed to work synergistically with ICIs by modifying the tumor microenvironment and enhancing antigen presentation.AIM To investigate the efficacy and safety of the combination therapy of radiotherapy,ICIs,and TKIs in patients with MSS or pMMR colorectal cancer liver metastasis(CCLM),in order to provide new clinical treatment references.METHODS A retrospective analysis was conducted on the clinical data of 43 MSS or pMMR CCLM patients treated at our hospital from September 2021 to July 2024.Based on the treatment interventions received,the patients were divided into a control group(n=21,receiving ICIs and TKIs combination therapy)and an observation group(n=22,receiving radiotherapy,ICIs,and TKIs triple therapy).The therapeutic effects,serum tumor markers(carcinoembryonic antigen and RESULTS The disease control rate in the observation group(63.64%)was significantly higher than that of the control group(23.81%)(P<0.05)).Both groups showed a decrease in carcinoembryonic antigen and carbohydrate antigen 199 levels post-treatment,with the observation group demonstrating a more significant change(P<0.05).The median progression-free survival and median overall survival in the control group were 5.1 months and 7.6 months,respectively,while the observation group had a median progression-free survival and overall survival of 4.3 months and 6.9 months,respectively.The control group had longer survival times than the observation group,but the differences were not statistically significant(P>0.05).The incidence of adverse reactions,including nausea and vomiting,gastrointestinal reactions,skin reactions,bone marrow suppression,liver and kidney function impairment,neurotoxicity,leukopenia,neutropenia,and thrombocytopenia,showed no significant differences between the two groups(P>0.05).CONCLUSION Compared to the ICIs and TKIs combination therapy,the radiotherapy,ICIs,and TKIs triple therapy can further improve the disease control rate and serum tumor marker levels in MSS or pMMR CCLM patients without increasing the risk of related adverse reactions,making it a treatment regimen worthy of further validation.展开更多
With the rapid development of generative artificial intelligence(GenAI),the task of story visualization,which transforms natural language narratives into coherent and consistent image sequences,has attracted growing r...With the rapid development of generative artificial intelligence(GenAI),the task of story visualization,which transforms natural language narratives into coherent and consistent image sequences,has attracted growing research attention.However,existing methods still face limitations in balancing multi-frame character consistency and generation efficiency,which restricts their feasibility for large-scale practical applications.To address this issue,this study proposes a modular cloud-based distributed system built on Stable Diffusion.By separating the character generation and story generation processes,and integratingmulti-feature control techniques,a cachingmechanism,and an asynchronous task queue architecture,the system enhances generation efficiency and scalability.The experimental design includes both automated and human evaluations of character consistency,performance testing,and multinode simulation.The results show that the proposed system outperforms the baseline model StoryGen in both CLIP-I and human evaluation metrics.In terms of performance,under the experimental environment of this study,dual-node deployment reduces average waiting time by approximately 19%,while the four-node simulation further reduces it by up to 65%.Overall,this study demonstrates the advantages of cloud-distributed GenAI in maintaining character consistency and reducing generation latency,highlighting its potential value inmulti-user collaborative story visualization applications.展开更多
Li_(7)La_(3)Zr_(2)O_(12)-based electrolytes have got great promise for solid-state lithium(Li)metal batteries because of their high elastic modulus and wide electrochemical stability window.However,the insufficient co...Li_(7)La_(3)Zr_(2)O_(12)-based electrolytes have got great promise for solid-state lithium(Li)metal batteries because of their high elastic modulus and wide electrochemical stability window.However,the insufficient contact and heterogeneous Li deposition severely hinder their practical applications.Here,a flexible ternary polymethacrylate(PMA)matrix is designed to incorporate with Ta-doped Li_(7)La_(3)Zr_(2)O_(12)(LLZTO-PMA).The PMA matrix ensures excellent interfacial contact,while the synergistic effects of its polar carbonyl groups and its interaction with LLZTO creating fast interfacial Li^(+)pathways yield a high ionic conductivity of 0.266 mS cm^(-1)at 20℃.Moreover,the interaction between LLZTO and PMA matrix further guides the formation of a hybrid LiF/Li_(3)N-rich solid electrolyte interphase,which allows a fast Li^(+)interfacial kinetic due to its lowered Li^(+)diffusion barrier.Consequently,the LLZTO-PMA electrolyte contributes an ultra-stable Li anode interphase,attaining a lifespan exceeding 10,000 h in symmetric cells and retaining over 96%capacity after 600 cycles in full battery,demonstrating a breakthrough for high-performance solid-state batteries.展开更多
The zigzag nitrogen chain,similar to the Ch-N structure,has long been considered as a potential high-energy-density structure.However,all the previously predicted zigzag N-chain structures,similar to Ch-N,exhibited im...The zigzag nitrogen chain,similar to the Ch-N structure,has long been considered as a potential high-energy-density structure.However,all the previously predicted zigzag N-chain structures,similar to Ch-N,exhibited imaginary frequencies in their phonon spectra at 0 GPa.Here,we conducted a systematic investigation of P-N compounds using first-principles calculations,uncovering a series of structurally similar stable phases,C2/m-PN_(x)(x=6,8,10,12,and 14),in which N forms zigzag N chains similar to those in Ch-N.In P-N compounds,the longest zigzag N-chain,which can theoretically remain stable under ambient pressure,is the N-chain composed of 14 N atoms in C2/m-PN14.If the N-chain continues to grow,imaginary interchain vibrational frequencies arise in the system.Notably,N chains with an even number of atoms were more likely to be energetically favorable.The five C2/m-PN_(x) phases and one metastable phase(R-PN_(6))exhibited remarkable stability and excellent detonability at ambient pressure,indicating that they are promising candidates for high-energy-density materials.In addition,R-PN_(6) was the first structure to stabilize the N_(6) ring through covalent bonding,with the covalent network contributing to its high hardness(47.59 GPa).展开更多
BACKGROUND Endometrial cancer(EC)is one of the most common cancers of the female reproductive tract,and the incidence is increasing rapidly.Immunotherapy using programmed cell death-1(PD-1)inhibitors is an emerging re...BACKGROUND Endometrial cancer(EC)is one of the most common cancers of the female reproductive tract,and the incidence is increasing rapidly.Immunotherapy using programmed cell death-1(PD-1)inhibitors is an emerging research topic and treatment strategy for refractory gynecological malignancies.However,clinical management of EC with checkpoint inhibitors requires improvement.Herein,we discuss a case of refractory proficient mismatch repair(pMMR)/miscrosatellitestable(MSS)EC treated with a combination of PD-1 and angiogenesis inhibitors and offer a review of the pathophysiology and clinical outcomes based on previous studies.CASE SUMMARY A 62-year-old woman diagnosed with invasive or metastatic EC in 2015 was treated with six courses of chemotherapy and refused further radiotherapy.Four years later,she developed chest pain,and lung biopsy indicated thyroid transcription factor-1(-),Napsin A(-),estrogen receptor(+),progesterone receptor(+),anaplastic lymphoma kinase(D5F3)(-),and receptor tyrosine kinase(D4D6)(-)metastatic EC.Genetic testing results showed low tumor mutation burden,pMMR,PD ligand 1(-),MSS,and HLA-class 1 heterogeneous disease.The patient was started on toripalimab combined with nab-paclitaxel for seven cycles(every 3 wk),but this regimen was terminated because of an intolerable chemotherapy adverse event.The disease progressed in 2020,and the patient’s treatment was switched from nab-paclitaxel to anlotinib,while immunotherapy using toripalimab was continued.The patient achieved a major partial response with well-tolerated toxicities,and treatment is ongoing.CONCLUSION Molecular testing is advised for clinical classifications of EC owing to its high heterogeneity.In this case,the patient had pMMR/MSS EC and achieved a positive outcome with combination PD-1 inhibitor treatment.These results warrant further clinical exploration.展开更多
The properties of electrolytes are critical for fast-charging and stable-cycling applications in lithium metal batteries(LMBs).However,the slow kinetics of Li^(+)transport and desolvation in commercial carbonate elect...The properties of electrolytes are critical for fast-charging and stable-cycling applications in lithium metal batteries(LMBs).However,the slow kinetics of Li^(+)transport and desolvation in commercial carbonate electrolytes,cou pled with the formation of unstable solid electrolyte interphases(SEI),exacerbate the degradation of LMB performance at high current densities.Herein,we propose a versatile electrolyte design strategy that incorporates cyclohexyl methyl ether(CME)as a co-solvent to reshape the Li^(+)solvation environment by the steric-hindrance effect of bulky molecules and their competitive coordination with other solvent molecules.Simulation calculations and spectral analysis demonstrate that the addition of CME molecules reduces the involvement of other solvent molecules in the Li solvation sheath and promotes the formation of Li^(+)-PF_(6)^(-)coordination,thereby accelerating Li^(+)transport kinetics.Additionally,this electrolyte composition improves Li^(+)desolvation kinetics and fosters the formation of inorganic-rich SEI,ensuring cycle stability under fast charging.Consequently,the Li‖LiNi_(0.8)Co_(0.1)Mn_(0.1)O_(2)battery with the modified electrolyte retains 82% of its initial capacity after 463 cycles at 1 C.Even under the extreme fast-charging condition of 5 C,the battery can maintain 80% capacity retention after 173 cycles.This work provides a promising approach for the development of highperformance LMBs by modulating solvation environment of electrolytes.展开更多
Biomarker and stable carbon isotope analyses are presented for the Garau Formation of the Cretaceous Age,an important source rock in western Iran,to reveal its potential as an oilprone source rock.The C_(28)/C_(29)ste...Biomarker and stable carbon isotope analyses are presented for the Garau Formation of the Cretaceous Age,an important source rock in western Iran,to reveal its potential as an oilprone source rock.The C_(28)/C_(29)sterane ratio value range(0.72 to 0.83)of bitumen samples from the formation suggests that they were likely formed during phytoplankton blooms.Sterane,hopane,and isoprenoid/n-alkane ratios indicate that the formation's organic matter predominantly consists of algae,and bacteria,accompanied by some reworked material derived from higher plants.Due to the predominance of anoxic conditions and the actions of sulfate-reducing bacteria,the bitumen present is enriched with sulfur compounds.The percentages of saturates,aromatics,and nitrogen-sulfuroxygen(NSO)fractions in the bitumen samples classify them as naphthenic oils.Isotope analysis reveals that biodegradation and water-washing have reduced the concentrations of some volatile saturates and low molecular weight aromatics in the bitumen samples.These actions have resulted in distinctiveδ^(13)C values for the formation's kerogen and bitumen fractions.The formation's organic matter has been subjected to high-temperature thermal regimes and has entered the oil-generation window at the sampled localities,with vitrinite reflectance(%R_(C))varying between 0.7%and 0.75%.展开更多
Despite the promising progress in conductive hydrogels made with pure conducting polymer,great challenges remain in the interface adhesion and robustness in longterm monitoring.To address these challenges,Prof.Seung H...Despite the promising progress in conductive hydrogels made with pure conducting polymer,great challenges remain in the interface adhesion and robustness in longterm monitoring.To address these challenges,Prof.Seung Hwan Ko and Taek-Soo Kim’s team introduced a laserinduced phase separation and adhesion method for fabricating conductive hydrogels consisting of pure poly(3,4-ethylenedioxythiophene):polystyrene sulfonate on polymer substrates.The laser-induced phase separation and adhesion treated conducting polymers can be selectively transformed into conductive hydrogels that exhibit wet conductivities of 101.4 S cm^(−1) with a spatial resolution down to 5μm.Moreover,they maintain impedance and charge-storage capacity even after 1 h of sonication.The micropatterned electrode arrays demonstrate their potential in long-term in vivo signal recordings,highlighting their promising role in the field of bioelectronics.展开更多
文摘BACKGROUND Colorectal cancer is one of the malignant tumors with a high incidence and mortality rate globally,and the occurrence of liver metastasis significantly affects patient survival prognosis.In recent years,the application of immune checkpoint inhibitors(ICIs)in cancer treatment has made important progress,especially showing good therapeutic effects in patients with high microsatellite instability or mismatch repair deficiency.However,for the majority of patients with microsatellite stable(MSS)or proficient mismatch repair(pMMR)colorectal cancer,the efficacy of ICIs is limited,prompting researchers to explore combination therapy strategies to improve efficacy.Targeted drugs such as tyrosine kinase inhibitors(TKIs)and radiotherapy are believed to work synergistically with ICIs by modifying the tumor microenvironment and enhancing antigen presentation.AIM To investigate the efficacy and safety of the combination therapy of radiotherapy,ICIs,and TKIs in patients with MSS or pMMR colorectal cancer liver metastasis(CCLM),in order to provide new clinical treatment references.METHODS A retrospective analysis was conducted on the clinical data of 43 MSS or pMMR CCLM patients treated at our hospital from September 2021 to July 2024.Based on the treatment interventions received,the patients were divided into a control group(n=21,receiving ICIs and TKIs combination therapy)and an observation group(n=22,receiving radiotherapy,ICIs,and TKIs triple therapy).The therapeutic effects,serum tumor markers(carcinoembryonic antigen and RESULTS The disease control rate in the observation group(63.64%)was significantly higher than that of the control group(23.81%)(P<0.05)).Both groups showed a decrease in carcinoembryonic antigen and carbohydrate antigen 199 levels post-treatment,with the observation group demonstrating a more significant change(P<0.05).The median progression-free survival and median overall survival in the control group were 5.1 months and 7.6 months,respectively,while the observation group had a median progression-free survival and overall survival of 4.3 months and 6.9 months,respectively.The control group had longer survival times than the observation group,but the differences were not statistically significant(P>0.05).The incidence of adverse reactions,including nausea and vomiting,gastrointestinal reactions,skin reactions,bone marrow suppression,liver and kidney function impairment,neurotoxicity,leukopenia,neutropenia,and thrombocytopenia,showed no significant differences between the two groups(P>0.05).CONCLUSION Compared to the ICIs and TKIs combination therapy,the radiotherapy,ICIs,and TKIs triple therapy can further improve the disease control rate and serum tumor marker levels in MSS or pMMR CCLM patients without increasing the risk of related adverse reactions,making it a treatment regimen worthy of further validation.
文摘With the rapid development of generative artificial intelligence(GenAI),the task of story visualization,which transforms natural language narratives into coherent and consistent image sequences,has attracted growing research attention.However,existing methods still face limitations in balancing multi-frame character consistency and generation efficiency,which restricts their feasibility for large-scale practical applications.To address this issue,this study proposes a modular cloud-based distributed system built on Stable Diffusion.By separating the character generation and story generation processes,and integratingmulti-feature control techniques,a cachingmechanism,and an asynchronous task queue architecture,the system enhances generation efficiency and scalability.The experimental design includes both automated and human evaluations of character consistency,performance testing,and multinode simulation.The results show that the proposed system outperforms the baseline model StoryGen in both CLIP-I and human evaluation metrics.In terms of performance,under the experimental environment of this study,dual-node deployment reduces average waiting time by approximately 19%,while the four-node simulation further reduces it by up to 65%.Overall,this study demonstrates the advantages of cloud-distributed GenAI in maintaining character consistency and reducing generation latency,highlighting its potential value inmulti-user collaborative story visualization applications.
基金supported by the National Natural Science Foundation of China(No.22305106)the Postdoctoral Fellowship Program of CPSF(GZC20230682)Beijing Key Laboratory of High-Entropy Energy materials and Devices,Beijing Institute of Nanoenergy and Nanosystems(No.GS 2025ZD005)。
文摘Li_(7)La_(3)Zr_(2)O_(12)-based electrolytes have got great promise for solid-state lithium(Li)metal batteries because of their high elastic modulus and wide electrochemical stability window.However,the insufficient contact and heterogeneous Li deposition severely hinder their practical applications.Here,a flexible ternary polymethacrylate(PMA)matrix is designed to incorporate with Ta-doped Li_(7)La_(3)Zr_(2)O_(12)(LLZTO-PMA).The PMA matrix ensures excellent interfacial contact,while the synergistic effects of its polar carbonyl groups and its interaction with LLZTO creating fast interfacial Li^(+)pathways yield a high ionic conductivity of 0.266 mS cm^(-1)at 20℃.Moreover,the interaction between LLZTO and PMA matrix further guides the formation of a hybrid LiF/Li_(3)N-rich solid electrolyte interphase,which allows a fast Li^(+)interfacial kinetic due to its lowered Li^(+)diffusion barrier.Consequently,the LLZTO-PMA electrolyte contributes an ultra-stable Li anode interphase,attaining a lifespan exceeding 10,000 h in symmetric cells and retaining over 96%capacity after 600 cycles in full battery,demonstrating a breakthrough for high-performance solid-state batteries.
基金supported by the Anhui Provincial Natural Science Foundation (Grant No.2508085J006)CASHIPS Director's Fund (Grant No.YZJJ202207-CX)。
文摘The zigzag nitrogen chain,similar to the Ch-N structure,has long been considered as a potential high-energy-density structure.However,all the previously predicted zigzag N-chain structures,similar to Ch-N,exhibited imaginary frequencies in their phonon spectra at 0 GPa.Here,we conducted a systematic investigation of P-N compounds using first-principles calculations,uncovering a series of structurally similar stable phases,C2/m-PN_(x)(x=6,8,10,12,and 14),in which N forms zigzag N chains similar to those in Ch-N.In P-N compounds,the longest zigzag N-chain,which can theoretically remain stable under ambient pressure,is the N-chain composed of 14 N atoms in C2/m-PN14.If the N-chain continues to grow,imaginary interchain vibrational frequencies arise in the system.Notably,N chains with an even number of atoms were more likely to be energetically favorable.The five C2/m-PN_(x) phases and one metastable phase(R-PN_(6))exhibited remarkable stability and excellent detonability at ambient pressure,indicating that they are promising candidates for high-energy-density materials.In addition,R-PN_(6) was the first structure to stabilize the N_(6) ring through covalent bonding,with the covalent network contributing to its high hardness(47.59 GPa).
基金Supported by the Hangzhou Health and Family Planning and Science and Technology Program,No.OO20190347。
文摘BACKGROUND Endometrial cancer(EC)is one of the most common cancers of the female reproductive tract,and the incidence is increasing rapidly.Immunotherapy using programmed cell death-1(PD-1)inhibitors is an emerging research topic and treatment strategy for refractory gynecological malignancies.However,clinical management of EC with checkpoint inhibitors requires improvement.Herein,we discuss a case of refractory proficient mismatch repair(pMMR)/miscrosatellitestable(MSS)EC treated with a combination of PD-1 and angiogenesis inhibitors and offer a review of the pathophysiology and clinical outcomes based on previous studies.CASE SUMMARY A 62-year-old woman diagnosed with invasive or metastatic EC in 2015 was treated with six courses of chemotherapy and refused further radiotherapy.Four years later,she developed chest pain,and lung biopsy indicated thyroid transcription factor-1(-),Napsin A(-),estrogen receptor(+),progesterone receptor(+),anaplastic lymphoma kinase(D5F3)(-),and receptor tyrosine kinase(D4D6)(-)metastatic EC.Genetic testing results showed low tumor mutation burden,pMMR,PD ligand 1(-),MSS,and HLA-class 1 heterogeneous disease.The patient was started on toripalimab combined with nab-paclitaxel for seven cycles(every 3 wk),but this regimen was terminated because of an intolerable chemotherapy adverse event.The disease progressed in 2020,and the patient’s treatment was switched from nab-paclitaxel to anlotinib,while immunotherapy using toripalimab was continued.The patient achieved a major partial response with well-tolerated toxicities,and treatment is ongoing.CONCLUSION Molecular testing is advised for clinical classifications of EC owing to its high heterogeneity.In this case,the patient had pMMR/MSS EC and achieved a positive outcome with combination PD-1 inhibitor treatment.These results warrant further clinical exploration.
基金supported by the Lithium Resources and Lithium Materials Key Laboratory of Sichuan Province(LRMKF202405)the National Natural Science Foundation of China(52402226)+3 种基金the Natural Science Foundation of Sichuan Province(2024NSFSC1016)the Scientific Research Startup Foundation of Chengdu University of Technology(10912-KYQD2023-10240)the opening funding from Key Laboratory of Engineering Dielectrics and Its Application(Harbin University of Science and Technology)(KFM202507,Ministry of Education)the funding provided by the Alexander von Humboldt Foundation。
文摘The properties of electrolytes are critical for fast-charging and stable-cycling applications in lithium metal batteries(LMBs).However,the slow kinetics of Li^(+)transport and desolvation in commercial carbonate electrolytes,cou pled with the formation of unstable solid electrolyte interphases(SEI),exacerbate the degradation of LMB performance at high current densities.Herein,we propose a versatile electrolyte design strategy that incorporates cyclohexyl methyl ether(CME)as a co-solvent to reshape the Li^(+)solvation environment by the steric-hindrance effect of bulky molecules and their competitive coordination with other solvent molecules.Simulation calculations and spectral analysis demonstrate that the addition of CME molecules reduces the involvement of other solvent molecules in the Li solvation sheath and promotes the formation of Li^(+)-PF_(6)^(-)coordination,thereby accelerating Li^(+)transport kinetics.Additionally,this electrolyte composition improves Li^(+)desolvation kinetics and fosters the formation of inorganic-rich SEI,ensuring cycle stability under fast charging.Consequently,the Li‖LiNi_(0.8)Co_(0.1)Mn_(0.1)O_(2)battery with the modified electrolyte retains 82% of its initial capacity after 463 cycles at 1 C.Even under the extreme fast-charging condition of 5 C,the battery can maintain 80% capacity retention after 173 cycles.This work provides a promising approach for the development of highperformance LMBs by modulating solvation environment of electrolytes.
文摘Biomarker and stable carbon isotope analyses are presented for the Garau Formation of the Cretaceous Age,an important source rock in western Iran,to reveal its potential as an oilprone source rock.The C_(28)/C_(29)sterane ratio value range(0.72 to 0.83)of bitumen samples from the formation suggests that they were likely formed during phytoplankton blooms.Sterane,hopane,and isoprenoid/n-alkane ratios indicate that the formation's organic matter predominantly consists of algae,and bacteria,accompanied by some reworked material derived from higher plants.Due to the predominance of anoxic conditions and the actions of sulfate-reducing bacteria,the bitumen present is enriched with sulfur compounds.The percentages of saturates,aromatics,and nitrogen-sulfuroxygen(NSO)fractions in the bitumen samples classify them as naphthenic oils.Isotope analysis reveals that biodegradation and water-washing have reduced the concentrations of some volatile saturates and low molecular weight aromatics in the bitumen samples.These actions have resulted in distinctiveδ^(13)C values for the formation's kerogen and bitumen fractions.The formation's organic matter has been subjected to high-temperature thermal regimes and has entered the oil-generation window at the sampled localities,with vitrinite reflectance(%R_(C))varying between 0.7%and 0.75%.
基金supported by the National Natural Science Foundation of China(52475610)Zhejiang Provincial Natural Science Foundation of China(LDQ24E050001).
文摘Despite the promising progress in conductive hydrogels made with pure conducting polymer,great challenges remain in the interface adhesion and robustness in longterm monitoring.To address these challenges,Prof.Seung Hwan Ko and Taek-Soo Kim’s team introduced a laserinduced phase separation and adhesion method for fabricating conductive hydrogels consisting of pure poly(3,4-ethylenedioxythiophene):polystyrene sulfonate on polymer substrates.The laser-induced phase separation and adhesion treated conducting polymers can be selectively transformed into conductive hydrogels that exhibit wet conductivities of 101.4 S cm^(−1) with a spatial resolution down to 5μm.Moreover,they maintain impedance and charge-storage capacity even after 1 h of sonication.The micropatterned electrode arrays demonstrate their potential in long-term in vivo signal recordings,highlighting their promising role in the field of bioelectronics.
