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
Stable isotope analysis of water(δD and δ^(18)O)is widely used to trace water cycle processes in aquatic ecosystems,based on the established assumption that biological activity does not cause isotopic fractionation ...Stable isotope analysis of water(δD and δ^(18)O)is widely used to trace water cycle processes in aquatic ecosystems,based on the established assumption that biological activity does not cause isotopic fractionation of water.Here,we found that phytoplankton photosynthesis elevated ambient water δ^(18)O and δD values,a conclusion supported by a large-scale survey across extensive spatiotemporal environmental gradients and further confirmed by a laboratory culture experiment.This biological effect depended on phytoplankton biomass and light utilization efficiency and could result in a deviation of at least 16.7% in the slope of the water δD-δ^(18)O regression line.We termed this phenomenon the“biological evaporation effect”.Given the potential universality of this effect across aquatic ecosystems,our findings challenge the conventional paradigm in isotope hydrology.展开更多
Driven by the increasing demand for high-energy-density batteries in electric vehicles and portable electronics,lithium metal batteries have made significant breakthroughs[1–3].While critical challenges associated wi...Driven by the increasing demand for high-energy-density batteries in electric vehicles and portable electronics,lithium metal batteries have made significant breakthroughs[1–3].While critical challenges associated with lithium metal anodes in liquid electrolytes(e.g.,dendrite growth,interface instability)have hindered commercialization[4–6],solid electrolyte systems have shown promise in mitigating these issues.Among these,solid polymer electrolytes(SPEs)have emerged as a viable solution for enabling stable quasisolid-state lithium metal batteries[7–9].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
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
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
Aqueous zinc-ion batteries (AZIBs) are fundamentally challenged by the instability of the electrode/electrolyte interface,predominantly due to irreversible zinc (Zn) deposition and hydrogen evolution.Particularly,the ...Aqueous zinc-ion batteries (AZIBs) are fundamentally challenged by the instability of the electrode/electrolyte interface,predominantly due to irreversible zinc (Zn) deposition and hydrogen evolution.Particularly,the intricate mechanisms behind the electrochemical discrepancies induced by interfacial Zn^(2+)-solvation and deposition behavior demand comprehensive investigation.Organic molecules endowed with special functional groups (such as hydroxyl,carboxyl,etc.) have the potential to significantly optimize the solvation structure of Zn^(2+)and regulate the interfacial electric double layer (EDL).By increasing nucleation overpotential and decreasing interfacial free energy,these functional groups facilitate a lower critical nucleation radius,thereby forming an asymptotic nucleation model to promote uniform Zn deposition.Herein,this study presents a pioneering approach by introducing trace amounts of n-butanol as solvation regulators to engineer the homogenized Zn (H-Zn) anode with a uniform and dense structure.The interfacial reaction and structure evolution are explored by in/ex-situ experimental techniques,indicating that the H-Zn anode exhibits dendrite-free growth,no by-products,and weak hydrogen evolution,in sharp contrast to the bare Zn.Consequently,the H-Zn anode achieves a remarkable Zn utilization rate of approximately 20% and simultaneously sustains a prolonged cycle life exceeding 500 h.Moreover,the H-Zn//NH_(4)V_(4)O^(10)(NVO) full battery showcases exceptional cycle stability,retaining 95.04%capacity retention after 400 cycles at a large current density of 5 A g^(-1).This study enlightens solvation-regulated additives to develop Zn anode with superior utilization efficiency and extended operational lifespan.展开更多
In this paper,we study the Bowen entropy of stable sets in positive entropy G-system of amenable group actions.The lower bound of the Bowen entropy of these sets are estimated.
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.
基金financially supported by the National Natural Science Foundation of China(Grant Nos.42293264&42293262)the Postdoctoral Fellowship Program of CPSF(Grant No.GZC20241196).
文摘Stable isotope analysis of water(δD and δ^(18)O)is widely used to trace water cycle processes in aquatic ecosystems,based on the established assumption that biological activity does not cause isotopic fractionation of water.Here,we found that phytoplankton photosynthesis elevated ambient water δ^(18)O and δD values,a conclusion supported by a large-scale survey across extensive spatiotemporal environmental gradients and further confirmed by a laboratory culture experiment.This biological effect depended on phytoplankton biomass and light utilization efficiency and could result in a deviation of at least 16.7% in the slope of the water δD-δ^(18)O regression line.We termed this phenomenon the“biological evaporation effect”.Given the potential universality of this effect across aquatic ecosystems,our findings challenge the conventional paradigm in isotope hydrology.
基金supported by the National Natural Science Foundation of China(22279028,21975063,22421001)the Natural Science Foundation of Hebei Province(B2021205019)the 333 Project of Hebei Province(C20231106)。
文摘Driven by the increasing demand for high-energy-density batteries in electric vehicles and portable electronics,lithium metal batteries have made significant breakthroughs[1–3].While critical challenges associated with lithium metal anodes in liquid electrolytes(e.g.,dendrite growth,interface instability)have hindered commercialization[4–6],solid electrolyte systems have shown promise in mitigating these issues.Among these,solid polymer electrolytes(SPEs)have emerged as a viable solution for enabling stable quasisolid-state lithium metal batteries[7–9].
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.
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.
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National Natural Science Foundation of China (52301273, 52072411)Science and Technology Innovation Program of Hunan Province (2024RC3222)+3 种基金Key project of scientific research project of Hunan Provincial Department of Education (22A0479)China Postdoctoral Science Foundation (2024M753668)Central South University Innovation-Driven Research Programme (2023CXQD038)Hunan Provincial Postgraduate Research Innovation Programme(CX20240970)。
文摘Aqueous zinc-ion batteries (AZIBs) are fundamentally challenged by the instability of the electrode/electrolyte interface,predominantly due to irreversible zinc (Zn) deposition and hydrogen evolution.Particularly,the intricate mechanisms behind the electrochemical discrepancies induced by interfacial Zn^(2+)-solvation and deposition behavior demand comprehensive investigation.Organic molecules endowed with special functional groups (such as hydroxyl,carboxyl,etc.) have the potential to significantly optimize the solvation structure of Zn^(2+)and regulate the interfacial electric double layer (EDL).By increasing nucleation overpotential and decreasing interfacial free energy,these functional groups facilitate a lower critical nucleation radius,thereby forming an asymptotic nucleation model to promote uniform Zn deposition.Herein,this study presents a pioneering approach by introducing trace amounts of n-butanol as solvation regulators to engineer the homogenized Zn (H-Zn) anode with a uniform and dense structure.The interfacial reaction and structure evolution are explored by in/ex-situ experimental techniques,indicating that the H-Zn anode exhibits dendrite-free growth,no by-products,and weak hydrogen evolution,in sharp contrast to the bare Zn.Consequently,the H-Zn anode achieves a remarkable Zn utilization rate of approximately 20% and simultaneously sustains a prolonged cycle life exceeding 500 h.Moreover,the H-Zn//NH_(4)V_(4)O^(10)(NVO) full battery showcases exceptional cycle stability,retaining 95.04%capacity retention after 400 cycles at a large current density of 5 A g^(-1).This study enlightens solvation-regulated additives to develop Zn anode with superior utilization efficiency and extended operational lifespan.
基金Supported by NSFC(No.11861010),also supported by NSFC(No.12171175),also supported by NSFC(No.12261006)NSF of Guangxi Province(No.2018GXNSFFA281008)Project of Guangxi First Class Disciplines of Statistics(No.GJKY-2022-01)。
文摘In this paper,we study the Bowen entropy of stable sets in positive entropy G-system of amenable group actions.The lower bound of the Bowen entropy of these sets are estimated.
