Osteosarcoma is a very serious primary bone cancer with a high death rate and a dismal prognosis.Since there is no permanent therapy for this condition,it is necessary to develop a cure.Therefore,this investigation wa...Osteosarcoma is a very serious primary bone cancer with a high death rate and a dismal prognosis.Since there is no permanent therapy for this condition,it is necessary to develop a cure.Therefore,this investigation was carried out to assess the impacts and biological functions of hydroxysafflor yellow A(HYSA)in osteosarcoma cell lines(MG63).In this investigational study,MG63 cells were utilized.Microarray experiments,quantitative polymerase chain reaction(qPCR),immunofluorescent staining,extracellular acidification rate(ECAR),oxygen consumption rate(OCR),glucose consumption,lactate production,and ATP levels,proliferation assay,5-Ethynyl-2′-deoxyuridine(EDU)staining,and Western blot were performed.In MG63 cells,HYSA lowered cell proliferation and metastasis rates,suppressed EDU cell number,and enhanced caspase-3/9 activity levels.HYSA reduced the Warburg effect and induced ferroptosis(FPT)in MG63 cells.Inhibiting ferroptosis diminished HYSA’s anti-cancer activities in MG63 cells.The stimulation of the HIF-1α/SLC7A11 pathway decreased HYSA’s anti-cancer activities in MG63 cells.HIF-1αis one target spot for HYSA in a model of osteosarcoma cancer(OC).HYSA altered HIF-1α’s thermophoretic activity;following binding with HYSA,HIF-1α’s melting point increased from~55°C to~60°C.HYSA significantly enhanced the thermal stability of exogenous WT HIF-1αwhile not affecting Mut HIF-1α,suggesting that ARG-311,GLY-312,GLN-347,and GLN-387 may be involved in the interaction between HIF-1αand HYSA.Conclusively,our study revealed that HYSA induced FPT and reduced the Warburg effect of OC through mitochondrial damage by HIF-1α/HK2/SLC7A11 pathway.HYSA is a possible therapeutic option for OC or other cancers.展开更多
The utilization of processing capabilities within the detector holds significant promise in addressing energy consumption and latency challenges. Especially in the context of dynamic motion recognition tasks, where su...The utilization of processing capabilities within the detector holds significant promise in addressing energy consumption and latency challenges. Especially in the context of dynamic motion recognition tasks, where substantial data transfers are necessitated by the generation of extensive information and the need for frame-by-frame analysis. Herein, we present a novel approach for dynamic motion recognition, leveraging a spatial-temporal in-sensor computing system rooted in multiframe integration by employing photodetector. Our approach introduced a retinomorphic MoS_(2) photodetector device for motion detection and analysis. The device enables the generation of informative final states, nonlinearly embedding both past and present frames. Subsequent multiply-accumulate (MAC) calculations are efficiently performed as the classifier. When evaluating our devices for target detection and direction classification, we achieved an impressive recognition accuracy of 93.5%. By eliminating the need for frame-by-frame analysis, our system not only achieves high precision but also facilitates energy-efficient in-sensor computing.展开更多
物联网(Internet of Things,IOT)是由大量连接的对象或设备组成的一种新型互联网络。物联网中的物理对象或传感设备能够收集周围环境产生的敏感数据,然后通过不安全的公开信道进行数据信息的交换和共享。因此,必须创建安全的媒介来保护...物联网(Internet of Things,IOT)是由大量连接的对象或设备组成的一种新型互联网络。物联网中的物理对象或传感设备能够收集周围环境产生的敏感数据,然后通过不安全的公开信道进行数据信息的交换和共享。因此,必须创建安全的媒介来保护数据的机密性和完整性,防止遭受敌手的攻击。在这方面,认证密钥协商(Authenticated Key Agreement,AKA)协议能够实现网络通信实体之间的相互认证,并生成一个共享的对称会话密钥,用于加密未来传送的数据。首先,回顾了一些面向物联网应用场景提出的AKA协议,这些AKA协议使用椭圆曲线密码学或切比雪夫混沌映射密码机制作为构建模块进行设计。随后,列举了这些AKA协议容易遭受的攻击和缺乏的安全属性。最后,针对设计安全高效的AKA协议提出了几条有用的建议,这些建议有助于AKA协议设计者实现其所声称的安全功能属性。展开更多
The introduction of immune-checkpoint blockade in the cancer therapy led to a paradigm change of the management of late stage cancers. There are already multiple FDA approved checkpoint inhibitors and many other agent...The introduction of immune-checkpoint blockade in the cancer therapy led to a paradigm change of the management of late stage cancers. There are already multiple FDA approved checkpoint inhibitors and many other agents are undergoing phase 2 and early phase 3 clinical trials. The therapeutic indication of immune checkpoint inhibitors expanded in the last years, but still remains unclear who can benefit. Micro RNAs are small RNAs with no coding potential. By complementary pairing to the 3' untranslated region of messenger RNA, microRNAs exert posttranscriptional control of protein expression. A network of microRNAs directly and indirectly controls the expression of checkpoint receptors and several microRNAs can target multiple checkpoint molecules,mimicking the therapeutic effect of a combined immune checkpoint blockade. In this review, we will describe the microRNAs that control the expression of immune checkpoints and we will present four specific issues of the immune checkpoint therapy in cancer:(1) imprecise therapeutic indication,(2) difficult response evaluation,(3) numerous immunologic adverse-events, and(4)the absence of response to immune therapy. Finally, we propose microRNAs as possible solutions for these pitfalls. We consider that in the near future microRNAs could become important therapeutic partners of the immune checkpoint therapy.展开更多
文摘Osteosarcoma is a very serious primary bone cancer with a high death rate and a dismal prognosis.Since there is no permanent therapy for this condition,it is necessary to develop a cure.Therefore,this investigation was carried out to assess the impacts and biological functions of hydroxysafflor yellow A(HYSA)in osteosarcoma cell lines(MG63).In this investigational study,MG63 cells were utilized.Microarray experiments,quantitative polymerase chain reaction(qPCR),immunofluorescent staining,extracellular acidification rate(ECAR),oxygen consumption rate(OCR),glucose consumption,lactate production,and ATP levels,proliferation assay,5-Ethynyl-2′-deoxyuridine(EDU)staining,and Western blot were performed.In MG63 cells,HYSA lowered cell proliferation and metastasis rates,suppressed EDU cell number,and enhanced caspase-3/9 activity levels.HYSA reduced the Warburg effect and induced ferroptosis(FPT)in MG63 cells.Inhibiting ferroptosis diminished HYSA’s anti-cancer activities in MG63 cells.The stimulation of the HIF-1α/SLC7A11 pathway decreased HYSA’s anti-cancer activities in MG63 cells.HIF-1αis one target spot for HYSA in a model of osteosarcoma cancer(OC).HYSA altered HIF-1α’s thermophoretic activity;following binding with HYSA,HIF-1α’s melting point increased from~55°C to~60°C.HYSA significantly enhanced the thermal stability of exogenous WT HIF-1αwhile not affecting Mut HIF-1α,suggesting that ARG-311,GLY-312,GLN-347,and GLN-387 may be involved in the interaction between HIF-1αand HYSA.Conclusively,our study revealed that HYSA induced FPT and reduced the Warburg effect of OC through mitochondrial damage by HIF-1α/HK2/SLC7A11 pathway.HYSA is a possible therapeutic option for OC or other cancers.
基金supported by the National Natural Science Foundation of China (52322210, 52172144, 22375069, 21825103, and U21A2069)National Key R&D Program of China (2021YFA1200501)+2 种基金Shenzhen Science and Technology Program (JCYJ20220818102215033, JCYJ20200109105422876)the Innovation Project of Optics Valley Laboratory (OVL2023PY007)Science and Technology Commission of Shanghai Municipality (21YF1454700)。
文摘The utilization of processing capabilities within the detector holds significant promise in addressing energy consumption and latency challenges. Especially in the context of dynamic motion recognition tasks, where substantial data transfers are necessitated by the generation of extensive information and the need for frame-by-frame analysis. Herein, we present a novel approach for dynamic motion recognition, leveraging a spatial-temporal in-sensor computing system rooted in multiframe integration by employing photodetector. Our approach introduced a retinomorphic MoS_(2) photodetector device for motion detection and analysis. The device enables the generation of informative final states, nonlinearly embedding both past and present frames. Subsequent multiply-accumulate (MAC) calculations are efficiently performed as the classifier. When evaluating our devices for target detection and direction classification, we achieved an impressive recognition accuracy of 93.5%. By eliminating the need for frame-by-frame analysis, our system not only achieves high precision but also facilitates energy-efficient in-sensor computing.
文摘物联网(Internet of Things,IOT)是由大量连接的对象或设备组成的一种新型互联网络。物联网中的物理对象或传感设备能够收集周围环境产生的敏感数据,然后通过不安全的公开信道进行数据信息的交换和共享。因此,必须创建安全的媒介来保护数据的机密性和完整性,防止遭受敌手的攻击。在这方面,认证密钥协商(Authenticated Key Agreement,AKA)协议能够实现网络通信实体之间的相互认证,并生成一个共享的对称会话密钥,用于加密未来传送的数据。首先,回顾了一些面向物联网应用场景提出的AKA协议,这些AKA协议使用椭圆曲线密码学或切比雪夫混沌映射密码机制作为构建模块进行设计。随后,列举了这些AKA协议容易遭受的攻击和缺乏的安全属性。最后,针对设计安全高效的AKA协议提出了几条有用的建议,这些建议有助于AKA协议设计者实现其所声称的安全功能属性。
基金supported by National Institutes of Health (NIH/NCATS) grant UH3TR00943-01 through the NIH Common Fund, Office of Strategic Coordination(OSC)the NIH/NCI grant 1 R01 CA182905-01+6 种基金a U54 grant-UPR/MDACC Partnership for Excellence in Cancer Research 2016 Pilot Projecta Team DOD (Grant No.CA160445P1) granta Ladies Leukemia League granta CLL Moonshot Flagship projecta SINF 2017 grantthe Estate of C.G.Johnson,Jr.supported by a POC grant, entitled "Clinical and economical impact of personalized targeted anti-microRNA therapies in reconverting lung cancer chemoresistance"-CANTEMIR, Competitively Operational Program, 2014-2020, Grant No.35/01.09.2016,My SMIS 103375
文摘The introduction of immune-checkpoint blockade in the cancer therapy led to a paradigm change of the management of late stage cancers. There are already multiple FDA approved checkpoint inhibitors and many other agents are undergoing phase 2 and early phase 3 clinical trials. The therapeutic indication of immune checkpoint inhibitors expanded in the last years, but still remains unclear who can benefit. Micro RNAs are small RNAs with no coding potential. By complementary pairing to the 3' untranslated region of messenger RNA, microRNAs exert posttranscriptional control of protein expression. A network of microRNAs directly and indirectly controls the expression of checkpoint receptors and several microRNAs can target multiple checkpoint molecules,mimicking the therapeutic effect of a combined immune checkpoint blockade. In this review, we will describe the microRNAs that control the expression of immune checkpoints and we will present four specific issues of the immune checkpoint therapy in cancer:(1) imprecise therapeutic indication,(2) difficult response evaluation,(3) numerous immunologic adverse-events, and(4)the absence of response to immune therapy. Finally, we propose microRNAs as possible solutions for these pitfalls. We consider that in the near future microRNAs could become important therapeutic partners of the immune checkpoint therapy.
