MicroRNAs （miRNAs） are a class of naturally occurring small non-coding RNAs that target protein-coding mRNAs at the post-transcriptional level. Our previous studies suggest that mir-21 functions as an oncogene and h...MicroRNAs （miRNAs） are a class of naturally occurring small non-coding RNAs that target protein-coding mRNAs at the post-transcriptional level. Our previous studies suggest that mir-21 functions as an oncogene and has a role in tumorigenesis, in part through regulation of the tumor suppressor gene tropomyosin 1 （TPM1）. Given that TPM1 has been implicated in cell migration, in this study we further investigated the role of mir-21 in cell invasion and tumor metastasis. We found that suppression of mir-21 in metastatic breast cancer MDA-MB-231 cells significantly reduced invasion and lung metastasis. Consistent with this, ectopic expression of TPM1 remarkably reduced cell invasion. Furthermore, we identified two additional direct mir-21 targets, programmed cell death 4 （PDCD4） and maspin, both of which have been implicated in invasion and metastasis. Like TPM1, PDCD4 and maspin also reduced invasiveness of MDA-MB-231 cells. Finally, the expression of PDCD4 and maspin inversely correlated with mir-21 expression in human breast tumor specimens, indicating the potential regulation of PDCD4 and maspin by mir-21 in these tumors. Taken together, the results suggest that, as an oncogenic miRNA, mir-21 has a role not only in tumor growth but also in invasion and tumor metastasis by targeting multiple tumor/metastasis suppressor genes. Therefore, suppression of mir-21 may provide a novel approach for the treatment of advanced cancers.展开更多
Sulfide solid electrolytes(SEs)have attracted ever-increasing attention due to their superior roomtemperature ionic conductivity(~10^(-2) S cm^(-1)).Additionally,the integration of sulfide SEs and highvoltage cathodes...Sulfide solid electrolytes(SEs)have attracted ever-increasing attention due to their superior roomtemperature ionic conductivity(~10^(-2) S cm^(-1)).Additionally,the integration of sulfide SEs and highvoltage cathodes is promising to achieve higher energy density.However,the incompatible interfaces between sulfide SEs and high-voltage cathodes have been one of the key factors limiting their applications.Therefore,this review presents a critical summarization of the interfacial issues in all-solid-state lithium batteries based on sulfide SEs and high-voltage cathodes and proposes strategies to stabilize the electrolyte/cathode interfaces.Moreover,the future research direction of electrolyte/cathode interfaces and application prospects of powder technology in sulfide-based ASSLBs were also discussed.展开更多
The BRAF gene is an important signaling molecule in human cells that is involved in the regulation of cell growth,differentiation,and survival.When the BRAF gene mutates,it can lead to abnormal activation of the signa...The BRAF gene is an important signaling molecule in human cells that is involved in the regulation of cell growth,differentiation,and survival.When the BRAF gene mutates,it can lead to abnormal activation of the signaling pathway,which promotes cell proliferation,inhibits cell apoptosis,and ultimately contributes to the occurrence and development of cancer.BRAF mutations are widely present in various cancers,including malignant melanoma,thyroid cancer,colorectal cancer,non-small cell lung cancer,and hairy cell leukemia,among others.BRAF is an important target for the treatment of various solid tumors,and targeted combination therapies,represented by BRAF inhibitors,have become one of the main treatment modalities for a variety of BRAF-mutation-positive solid tumors.展开更多
Historical documents provide evidence for regional droughts preceding the political turmoil and fall of Beijing in 1644 CE,when more than 20 million people died in northern China during the late Ming famine period.How...Historical documents provide evidence for regional droughts preceding the political turmoil and fall of Beijing in 1644 CE,when more than 20 million people died in northern China during the late Ming famine period.However,the role climate and environmental changes may have played in this pivotal event in Chinese history remains unclear.Here,we provide tree-ring evidence of persistent megadroughts from1576 to 1593 CE and from 1628 to 1644 CE in northern China,which coincided with exceptionally cold summers just before the fall of Beijing.Our analysis reveals that these regional hydroclimatic extremes are part of a series of megadroughts along the Pacific Rim,which not only impacted the ecology and society of monsoonal northern China,but likely also exacerbated external geopolitical and economic pressures.This finding is corroborated by last millennium reanalysis data and numerical climate model simulations revealing internally driven Pacific sea surface temperature variations and the predominance of decadal scale La Ni?a-like conditions to be responsible for precipitation decreases over northern China,as well as extensive monsoon regions in the Americas.These teleconnection patterns provide a mechanistic explanation for reoccurring drought spells during the late Ming Dynasty and the environmental framework fostering the fall of Beijing in 1644 CE,and the subsequent demise of the Ming Dynasty.展开更多
Developing novel unfused building blocks with simple synthesis and low cost is essential to advance and enrich cost-effective poly-mer donors;however,it remains a challenge due to the lack of efficient molecular strat...Developing novel unfused building blocks with simple synthesis and low cost is essential to advance and enrich cost-effective poly-mer donors;however,it remains a challenge due to the lack of efficient molecular strategies.Herein,a class of low-cost and fully unfused polymer donors with precisely regulated backbone planarity via halogenation was designed and synthesized,namely PDTBTBz-2H,PDTBTBz-2F,and PDTBTBz-2Cl.These polymer donors possess a four-step synthesis route with over 80%yield from cheap raw chemicals comparable to existing low-cost polymer donors,such as PTQ10.Benefitting from the planar backbone via in-corporating the F…S non-covalent interactions,PDTBTBz-2F exhibits more robust J-type aggregation in solution and a long-ranged molecular stacking in film relative to PDTBTBz-2H and PDTBTBz-2Cl.Moreover,the systematical study of PDTBTBz-based organic so-lar cells(OSCs)reveals the close relationship between optimized molecular self-assembly and charge separation/transport regarding backbone halogenation when paired with the non-fullerene acceptor(Y6-BO-4F).As a result,the photovoltaic devices based on semicrystalline PDTBTBz-2F achieved a promising power conversion efficiency(PCE)of 12.37%.Our work highlighted the influence of backbone halogenation on the molecular self-assembly properties and a potential unfused backbone motif for further developing cost-effective OSCs.展开更多
针对低温条件下AAO工艺运行效率减慢,生物活性降低的问题,以商丘污水处理厂为例,基于污水处理工艺模拟软件-Sumo对该污水处理厂1月份的运行情况进行了动态模拟,并对该温度和进水条件下污水处理厂的运行加以优化。研究表明,通过灵敏度分...针对低温条件下AAO工艺运行效率减慢,生物活性降低的问题,以商丘污水处理厂为例,基于污水处理工艺模拟软件-Sumo对该污水处理厂1月份的运行情况进行了动态模拟,并对该温度和进水条件下污水处理厂的运行加以优化。研究表明,通过灵敏度分析和参数的修正,工艺模拟软件可较好的模拟低温条件下污水处理厂的运行情况。随着混合液回流比从50%提升至400%,污水处理厂的脱氮效果有所增强,除磷效果有所减弱,而COD的去除效率变化不大。好氧段的最佳DO浓度为1.95 g O_(2)/m^(3)。当DO浓度大于1.95 gO_(2)/m^(3)时,随着溶解氧的增加,TN的去除率有所下降,而NH_(3)-N、COD、TP的去除效果则基本不变。以混合液回流比为300%,DO浓度为1.95 g O_(2)/m^(3)作为优化后的污水处理厂运行条件,可知优化后出水TN有明显降低,出水TP并未出现明显下降,污水处理厂的运行效果得到进一步的优化。展开更多
文摘MicroRNAs （miRNAs） are a class of naturally occurring small non-coding RNAs that target protein-coding mRNAs at the post-transcriptional level. Our previous studies suggest that mir-21 functions as an oncogene and has a role in tumorigenesis, in part through regulation of the tumor suppressor gene tropomyosin 1 （TPM1）. Given that TPM1 has been implicated in cell migration, in this study we further investigated the role of mir-21 in cell invasion and tumor metastasis. We found that suppression of mir-21 in metastatic breast cancer MDA-MB-231 cells significantly reduced invasion and lung metastasis. Consistent with this, ectopic expression of TPM1 remarkably reduced cell invasion. Furthermore, we identified two additional direct mir-21 targets, programmed cell death 4 （PDCD4） and maspin, both of which have been implicated in invasion and metastasis. Like TPM1, PDCD4 and maspin also reduced invasiveness of MDA-MB-231 cells. Finally, the expression of PDCD4 and maspin inversely correlated with mir-21 expression in human breast tumor specimens, indicating the potential regulation of PDCD4 and maspin by mir-21 in these tumors. Taken together, the results suggest that, as an oncogenic miRNA, mir-21 has a role not only in tumor growth but also in invasion and tumor metastasis by targeting multiple tumor/metastasis suppressor genes. Therefore, suppression of mir-21 may provide a novel approach for the treatment of advanced cancers.
基金supported by the Beijing Natural Science Foundation(grant No.L223009)the National Natural Science Foundation of China(grant No.22075029)+1 种基金the National Key Research and Development Program of China(grant No.2021YFB2500300)the Key Research and Development(R&D)Projects of Shanxi Province(grant No.2021020660301013).
文摘Sulfide solid electrolytes(SEs)have attracted ever-increasing attention due to their superior roomtemperature ionic conductivity(~10^(-2) S cm^(-1)).Additionally,the integration of sulfide SEs and highvoltage cathodes is promising to achieve higher energy density.However,the incompatible interfaces between sulfide SEs and high-voltage cathodes have been one of the key factors limiting their applications.Therefore,this review presents a critical summarization of the interfacial issues in all-solid-state lithium batteries based on sulfide SEs and high-voltage cathodes and proposes strategies to stabilize the electrolyte/cathode interfaces.Moreover,the future research direction of electrolyte/cathode interfaces and application prospects of powder technology in sulfide-based ASSLBs were also discussed.
基金supported by the Natural Science Foundation of China(grant number 82002456)China Postdoctoral Science Foundation(grant number 2022M723207)+10 种基金the Medical Scientific Research Foundation of Zhejiang Province,China(grant number 2023KY666)Zhejiang Traditional Chinese Medicine Science Fund Project(grant number 2024ZL372)Qiantang Cross Fund Project(grant number 2023-16)National Natural Science Foundation of China of Zhejiang Cancer Hospital Cultivation Project(grant number PY2023006)the Medical Scientific Research Foundation of Zhejiang Province,China(grant number 2024KY812)the Natural Science Foundation of Zhejiang Province(grant number LQ24H160036)Beijing Health Technologies Promotion Program[grant number BHTPP2022041]Peking University Clinical Scientist Training Program and the Fundamental Research Funds for the Central Universities[grant number BMU2024PYJH010]Science Foundation of Peking University Cancer Hospital[grant number PY202333]the Beijing Natural Science Foundation[grant number 7232248]Beijing Hospitals Authority Youth Programme[grant number QML20231902].
文摘The BRAF gene is an important signaling molecule in human cells that is involved in the regulation of cell growth,differentiation,and survival.When the BRAF gene mutates,it can lead to abnormal activation of the signaling pathway,which promotes cell proliferation,inhibits cell apoptosis,and ultimately contributes to the occurrence and development of cancer.BRAF mutations are widely present in various cancers,including malignant melanoma,thyroid cancer,colorectal cancer,non-small cell lung cancer,and hairy cell leukemia,among others.BRAF is an important target for the treatment of various solid tumors,and targeted combination therapies,represented by BRAF inhibitors,have become one of the main treatment modalities for a variety of BRAF-mutation-positive solid tumors.
基金supported by the Basic Science Center for Tibetan Plateau Earth System(BSCTPES,41988101)the National Natural Science Foundation of China(32061123008)+3 种基金Ulf Büntgen and Jan Esper were supported by the ERC Advanced Grant Monostar(Ad G 882727)the Czech Science Foundation(23-08049S,HYDRO8)Fredrik Charpentier Ljungqvist was supported by the Swedish Research Council(Vetenskapsr?det,2018-01272)the Marianne and Marcus Wallenberg Foundation(MMW 20220114)。
文摘Historical documents provide evidence for regional droughts preceding the political turmoil and fall of Beijing in 1644 CE,when more than 20 million people died in northern China during the late Ming famine period.However,the role climate and environmental changes may have played in this pivotal event in Chinese history remains unclear.Here,we provide tree-ring evidence of persistent megadroughts from1576 to 1593 CE and from 1628 to 1644 CE in northern China,which coincided with exceptionally cold summers just before the fall of Beijing.Our analysis reveals that these regional hydroclimatic extremes are part of a series of megadroughts along the Pacific Rim,which not only impacted the ecology and society of monsoonal northern China,but likely also exacerbated external geopolitical and economic pressures.This finding is corroborated by last millennium reanalysis data and numerical climate model simulations revealing internally driven Pacific sea surface temperature variations and the predominance of decadal scale La Ni?a-like conditions to be responsible for precipitation decreases over northern China,as well as extensive monsoon regions in the Americas.These teleconnection patterns provide a mechanistic explanation for reoccurring drought spells during the late Ming Dynasty and the environmental framework fostering the fall of Beijing in 1644 CE,and the subsequent demise of the Ming Dynasty.
基金supported by the National Natural Science Foundation of China (52203241,21905225,22005121)the Science and Technology Program of Shaanxi Province (2022JM-229,2023-JC-QN-0448)+1 种基金Jiangsu Key Laboratory for Carbon-Based Functional Materials&Devices,Soochow University (KJS2208)H.Y.W.acknowledges the financial support from the National Research Foundation of Korea (2019R1A6A1A11044070,2020M3H4A3081814).
文摘Developing novel unfused building blocks with simple synthesis and low cost is essential to advance and enrich cost-effective poly-mer donors;however,it remains a challenge due to the lack of efficient molecular strategies.Herein,a class of low-cost and fully unfused polymer donors with precisely regulated backbone planarity via halogenation was designed and synthesized,namely PDTBTBz-2H,PDTBTBz-2F,and PDTBTBz-2Cl.These polymer donors possess a four-step synthesis route with over 80%yield from cheap raw chemicals comparable to existing low-cost polymer donors,such as PTQ10.Benefitting from the planar backbone via in-corporating the F…S non-covalent interactions,PDTBTBz-2F exhibits more robust J-type aggregation in solution and a long-ranged molecular stacking in film relative to PDTBTBz-2H and PDTBTBz-2Cl.Moreover,the systematical study of PDTBTBz-based organic so-lar cells(OSCs)reveals the close relationship between optimized molecular self-assembly and charge separation/transport regarding backbone halogenation when paired with the non-fullerene acceptor(Y6-BO-4F).As a result,the photovoltaic devices based on semicrystalline PDTBTBz-2F achieved a promising power conversion efficiency(PCE)of 12.37%.Our work highlighted the influence of backbone halogenation on the molecular self-assembly properties and a potential unfused backbone motif for further developing cost-effective OSCs.
文摘针对低温条件下AAO工艺运行效率减慢,生物活性降低的问题,以商丘污水处理厂为例,基于污水处理工艺模拟软件-Sumo对该污水处理厂1月份的运行情况进行了动态模拟,并对该温度和进水条件下污水处理厂的运行加以优化。研究表明,通过灵敏度分析和参数的修正,工艺模拟软件可较好的模拟低温条件下污水处理厂的运行情况。随着混合液回流比从50%提升至400%,污水处理厂的脱氮效果有所增强,除磷效果有所减弱,而COD的去除效率变化不大。好氧段的最佳DO浓度为1.95 g O_(2)/m^(3)。当DO浓度大于1.95 gO_(2)/m^(3)时,随着溶解氧的增加,TN的去除率有所下降,而NH_(3)-N、COD、TP的去除效果则基本不变。以混合液回流比为300%,DO浓度为1.95 g O_(2)/m^(3)作为优化后的污水处理厂运行条件,可知优化后出水TN有明显降低,出水TP并未出现明显下降,污水处理厂的运行效果得到进一步的优化。
