The acute effect of acupuncture on Alzheimer＇s disease,i.e.,on brain activation during treatment,has been reported.However,the effect of long-term acupuncture on brain activation in Alzheimer＇s disease is unclear.Th...The acute effect of acupuncture on Alzheimer＇s disease,i.e.,on brain activation during treatment,has been reported.However,the effect of long-term acupuncture on brain activation in Alzheimer＇s disease is unclear.Therefore,in this study,we performed long-term needling at Zusanli（ST36）or a sham point（1.5 mm lateral to ST36）in a rat Alzheimer＇s disease model,for 30 minutes,once per day,for 30 days.The rats underwent 18F-fluorodeoxyglucose positron emission tomography scanning.Positron emission tomography images were processed with SPM2.The brain areas activated after needling at ST36 included the left hippocampus,the left orbital cortex,the left infralimbic cortex,the left olfactory cortex,the left cerebellum and the left pons.In the sham-point group,the activated regions were similar to those in the ST36 group.However,the ST36 group showed greater activation in the cerebellum and pons than the sham-point group.These findings suggest that long-term acupuncture treatment has targeted regulatory effects on multiple brain regions in rats with Alzheimer＇s disease.展开更多
Dear Editor,Rosacea is characterized by persistent or transient erythema,papules,pustules,telangiectasia,and/or phymatous lesions[1].Although multiple treatments are available for rosacea,the advent of biological agen...Dear Editor,Rosacea is characterized by persistent or transient erythema,papules,pustules,telangiectasia,and/or phymatous lesions[1].Although multiple treatments are available for rosacea,the advent of biological agents and small-molecule agents has significantly advanced our ability to target the disease more effectively[2].In the current review,we summarize the outcomes of targeted therapies in rosacea,mainly focusing on interleukin(IL)-17 inhibitors and Janus kinase(JAK)inhibitors.展开更多
Persistence of drug-resistant breast cancer stem cells(brCSCs)after a chemotherapeutic regime correlates with disease recurrence and elevated mortality.Therefore,deciphering mechanisms that dictate their drug-resistan...Persistence of drug-resistant breast cancer stem cells(brCSCs)after a chemotherapeutic regime correlates with disease recurrence and elevated mortality.Therefore,deciphering mechanisms that dictate their drug-resistant phenotype is imperative for designing targeted and more effective therapeutic strategies.The transcription factor SOX2 has been recognized as a protagonist in brCSC maintenance,and previous studies have confirmed that inhibition of SOX2 purportedly eliminated these brCSCs.However,pharmacological targeting of transcription factors like SOX2 is challenging due to their structural incongruities and intrinsic disorders in their binding interfaces.Therefore,transcriptional co-activators may serve as a feasible alternative for effectively targeting the brCSCs.Incidentally,transcriptional co-activators YAP/TAZ were found to be upregulated in CD44^(+)/CD24^(-)/ALDH^(+)cells isolated from patient breast tumors and CSC-enriched mammospheres.Interestingly,it was observed that YAP/TAZ exhibited direct physical interaction with SOX2 and silencing YAP/TAZ attenuated SOX2 expression in mammospheres,leading to significantly reduced sphere forming efficiency and cell viability.YAP/TAZ additionally manipulated redox homeostasis and regulated mitochondrial dynamics by restraining the expression of the mitochondrial fission marker,DRP1.Furthermore,YAP/TAZ inhibition induced DRP1 expression and impaired OXPHOS,consequently inducing apoptosis in mammospheres.In order to enhance clinical relevance of the study,an FDA-approved drug verteporfin(VP),was used for pharmacological inhibition of YAP/TAZ.Surprisingly,VP administration was found to reduce tumor-initiating capacity of the mammospheres,concomitant with disrupted mitochondrial homeostasis and significantly reduced brCSC population.Therefore,VP holds immense potential for repurposing and decisively eliminating the chemoresistant brCSCs,offering a potent strategy for managing tumor recurrence effectively.展开更多
Poor prognosis is associated with oral squamous cell carcinoma(OSCC),an aggressive form of malignant tumor.1 Developing effective targeted therapies against OSCC is anticipated to have significant clinical implication...Poor prognosis is associated with oral squamous cell carcinoma(OSCC),an aggressive form of malignant tumor.1 Developing effective targeted therapies against OSCC is anticipated to have significant clinical implications.Fisetin(3,30,40,7-tetrahydroxyflavone),a natural flavonoid,the most common phytochemical found in a variety of fruits and vegetables,may bring several therapeutic potential benefits to people.2 Investigating the pharmacological impact of natural flavonoid fisetin on the management of OSCC was the aim of the current investigation.By focusing on the tumor-associated antigen MUC1(mucin 1),fisetin prevents OSCC cells from transforming malignant.This study aims to provide new diagnostic indicators and therapeutic targets for the diagnosis and treatment of OSCC by exploring the role and mechanism of fisetin in OSCC.展开更多
This study proposes a low-energy pulse current(LEPC)rapid solution treatment method,which can dis-solve more primaryγ'phase in a shorter time and effectively suppress abnormal grain growth,thereby successfully ac...This study proposes a low-energy pulse current(LEPC)rapid solution treatment method,which can dis-solve more primaryγ'phase in a shorter time and effectively suppress abnormal grain growth,thereby successfully achieving microstructure optimization and property enhancement.The microstructure anal-ysis showed that,compared with the 62.5%dissolution rate of the standard traditional solution treat-ment(1100℃/4 h),LEPC achieved an 88.9%dissolution of the primaryγ'phase in just 5 min at the same temperature.Furthermore,due to the rapidity of the LEPC treatment and its“targeted dissolution effect”on theγ'phase,excessivegrain growthwas effectivelysuppressed,resultingingrain sizecom-parable to those obtained with traditional solution treatment.Mechanical property testing indicated that the alloy treated with LEPC had a hardness of 531 HV at room temperature,while the yield strength,Ultimate strength,and maximum strain reached 994 MPa,1030 MPa,and 5.1%at the service tempera-ture(750℃).Compared to the standard traditional solution treatment,these properties were improved by 10.4%,11.1%,10.4%,and 17.5%,respectively.Finally,theoretical calculations revealed that the non-thermal effect of LEPC reduced the dissolution-free energy by approximately 49.4 kJ/mol and increased the diffusion coefficient by about 76 times,which was the fundamental reason for the accelerated disso-lution of the primaryγ’phase.展开更多
With the advancement of combat equipment technology and combat concepts,new requirements have been put forward for air defense operations during a group target attack.To achieve high-efficiency and lowloss defensive o...With the advancement of combat equipment technology and combat concepts,new requirements have been put forward for air defense operations during a group target attack.To achieve high-efficiency and lowloss defensive operations,a reasonable air defense weapon assignment strategy is a key step.In this paper,a multi-objective and multi-constraints weapon target assignment(WTA)model is established that aims to minimize the defensive resource loss,minimize total weapon consumption,and minimize the target residual effectiveness.An optimization framework of air defense weapon mission scheduling based on the multiobjective artificial bee colony(MOABC)algorithm is proposed.The solution for point-to-point saturated attack targets at different operational scales is achieved by encoding the nectar with real numbers.Simulations are performed for an imagined air defense scenario,where air defense weapons are saturated.The non-dominated solution sets are obtained by the MOABC algorithm to meet the operational demand.In the case where there are more weapons than targets,more diverse assignment schemes can be selected.According to the inverse generation distance(IGD)index,the convergence and diversity for the solutions of the non-dominated sorting genetic algorithm III(NSGA-III)algorithm and the MOABC algorithm are compared and analyzed.The results prove that the MOABC algorithm has better convergence and the solutions are more evenly distributed among the solution space.展开更多
Greenhouse gas emissions are increas- ing every year and their effect on the environment is becoming increasingly serious. In 2009, the concen- tration of carbon dioxide in the earth＇s atmosphere reached 387 μL/L, t...Greenhouse gas emissions are increas- ing every year and their effect on the environment is becoming increasingly serious. In 2009, the concen- tration of carbon dioxide in the earth＇s atmosphere reached 387 μL/L, the highest level in recorded histo- ry. This paper summarizes the global carbon emission situation, sources of greenhouse gases, and the con-tribution of agriculture to the accumutauon ot green- house gases. Several scientific measures are proposed to reduce greenhouse gas emissions resulting from ru- minant production such as improving animal perform- ance, regulating the rumen environment, and reduc- ing the amount of greenhouse gases emitted from live- stock manure.展开更多
The biggest challenge in using CRISPR technologies,which limits their widespread application in medicine,is off-target effects.These effects could,in principle,be minimized by ensuring that CRISPR is activated primari...The biggest challenge in using CRISPR technologies,which limits their widespread application in medicine,is off-target effects.These effects could,in principle,be minimized by ensuring that CRISPR is activated primarily in the targeted cells,thereby reducing the likelihood of unintended genetic modifications in non-target tissues.Therefore,the development of a light activatable CRISPR approach to dynamically control gene activation in both space and time would be highly beneficial.A drawback is that the overwhelming majority of recently introduced light activatable CRISPR systems require UV or blue light exposure,severely limiting the penetration depth of light in tissue at which CRISPR can be activated,and,in the case of UV light,raising safety concerns.A small number of systems that activate CRISPR using longer wavelengths are hindered by either slow light activation or issues related to toxicity and biocompatibility of the proposed techniques in humans.To address this,we developed a split-Cas9/dCas9 system in which activation is achieved through a near-infrared photocleavable dimerization complex.This photoactivation method can be safely used in humans in vivo,easily adapted to different split-Cas9/dCas9 systems,and enables rapid,spatially precise light activation across various cell types.展开更多
In this work,a facile and sensitive colorimetric detection method was firstly reported for RNase A activity detection based on target regulated protection effect of chimeric DNA probe on the salt-induced aggregation o...In this work,a facile and sensitive colorimetric detection method was firstly reported for RNase A activity detection based on target regulated protection effect of chimeric DNA probe on the salt-induced aggregation of plasmonic gold nanoparticles.Compared with previous works of RNase A activity detection,this colorimetric assay integrated the advantages of sensitive,low cost,facile operation,rapid response and low biological toxicity.展开更多
Objective: To explore the antitumor and potential off-target effects of systemically delivered cholesterol-conjugatedlet-7a mimics(Chol-let-7a) and control mimics(Chol-miRCtrl) on hepatocellular carcinomain vivo.Metho...Objective: To explore the antitumor and potential off-target effects of systemically delivered cholesterol-conjugatedlet-7a mimics(Chol-let-7a) and control mimics(Chol-miRCtrl) on hepatocellular carcinomain vivo.Methods: The antitumor effects of two intravenous dosing regimens ofChol-let-7a on heptocellular carcinoma growth were compared using an orthotopic xenograft mouse model. Off-targets were analyzed with histopathological and ultrapathological features of heparenal tissue and cells in theChol-let-7a-, Chol-miRCtrl-, and saline-treated (blank) xenograft mice and normal control mice. Then,let-7a abundance in orthotopic tumors, corresponding paracancerous hepatic tissue, and normal liver tissue from healthy nude mice was examined by reverse transcription-polymerase chain reaction. The distribution ofChol-let-7a andChol-miRCtrl in vivo was examined by whole-animal imaging and frozen-sections observation. The experiments were approved by the Institutional Research Board of Peking Union Medical College Hospital.Results: Continuous treatment withChol-let-7a resulted in tumors that were 35.86% and 40.02% the size of those in theChol-miRCtrl and blank xenograft group (P < 0.01 andP < 0.01, respectively), while intermittent dosing withChol-let-7a resulted in tumors that were 65.42% and 56.66% the size of those in theChol-miRCtrl and the blank control group, respectively (P < 0.05 andP < 0.05). In addition, some histopathological and ultrapathological features were only observed after treatment with the two cholesterol-conjugated molecules, however mild with intermittent dosingChol-let-7a treatment, such as diffuse sinusoidal dilation and edema, primarily around the centrolobular vein in heptic tissues;mild hypercellularity with dilated capillary lumens in the renal tissue;and some organelle abnormalities found in heptic and renal cells. Furthermore, whole-animal imaging showed thatChol-let-7a andChol-miRCtrl were predominantly distributed in the liver, kidney, and bladder regions after injection, and that the concentration ofChol-let-7a andChol-miRCtrl in the kidney and the bladder decreased much slowly in the xenograft animals, especially in theChol-miRCtrl group. Finally, RT-PCR analysis showed thatlet-7a levels were significantly increased in Chol-let-7a-treated xenografts compared withChol-miRCtrl group (P=0.003) and blank xenograft group (P=0.001);however, the level was only equivalent to 50.6% and 40.7% of that in paracancerous hepatic tissue and hepatic tissue in normal mice, respectively.Conclusions: Chol-let-7a, administered either continuously or intermittently, showed effective antitumor efficacy.Chol-let-7a had some off-target effects, such as mild acute hepatitis-like inflammation and non-specific drug-induced kidney injury. The intermittent dosing regimen resulted in less damage than the continuous regimen, while maintaining relatively satisfactory antitumor efficacy, which could be useful for the investigation and possible clinical use of miRNA treatment regimens in the future.展开更多
Impact and torsion pendulums are applied in impulse coupling experiments of high-energy laser irradiation of space debris. It is difficult to achieve a multi-pulse experiment and thus hard to analyze the multi-pulse i...Impact and torsion pendulums are applied in impulse coupling experiments of high-energy laser irradiation of space debris. It is difficult to achieve a multi-pulse experiment and thus hard to analyze the multi-pulse impulse coupling effect. Here, we designed a new recoil impulse experimental measurement system of non-contact, multidegrees of freedom, and multi-pulse irradiation. The system used a low-pressure and low-temperature vacuum chamber to simulate the space environment, the pinning effect of magnetic levitation to achieve aluminum target suspension, and high-speed cameras to record the displacement over time to calculate the impulse of the target.Then the impulse coupling experiment of multi-pulse laser irradiation on the aluminum target was performed.The result shows that the multi-pulse impulse coupling effect is not the linear accumulation of coupling results by every single-pulse and multi-pulse coefficient that decreases with the increase of the number of pulses, and eventually stabilizes as the decrease gets smaller.展开更多
Cancer immunotherapy has appeared as a prospective therapeutic modality.Therapeutic antibodies induced in an in vitro expression system act as"targeting missiles"against tumor-associated binding sites,and su...Cancer immunotherapy has appeared as a prospective therapeutic modality.Therapeutic antibodies induced in an in vitro expression system act as"targeting missiles"against tumor-associated binding sites,and subsequently,immune system attack on tumors is restored or boosted.These antibody regimens are engineered towards enhanced Fc efficacy,humanization,and fragmentation to specifically recognize and bind to effective tumor-associated targets.The challenge lies in obtaining efficient therapeutic regimens with low response rates,acquisition of resistance,and immune-related undesirable effects of artificially designed therapeutic antibodies,which is crucial for enhancing clinical efficacy.This review provides an in-depth introduction to antibodies that perform direct/indirect roles in cancer treatment by binding to immune checkpoints,costimulatory receptors,and extracellular membrane receptors.It also discusses how antibodies kill tumors and modulate microenvironment of tumor through these targets.The classification of expression systems for antibody production is summarized to guide appropriate selection based on different specificities.Understanding antibody sources,ongoing evaluation of engineered antibodies,and tumor-associated antigen research pave the way for designing appropriate antibody-based immunotherapy regimens.展开更多
基金supported by the National Basic Research Program of China(973 Program),No.2006CB504505,2012CB518504the National Natural Science Foundation of China,No.90709027+1 种基金the Student's Platform for Innovation and Entrepreneurship Training Program of Southern Medical University of China,No.201512121165the Doctoral Foundation of Guangdong Medical University of China,No.2XB13058
文摘The acute effect of acupuncture on Alzheimer＇s disease,i.e.,on brain activation during treatment,has been reported.However,the effect of long-term acupuncture on brain activation in Alzheimer＇s disease is unclear.Therefore,in this study,we performed long-term needling at Zusanli（ST36）or a sham point（1.5 mm lateral to ST36）in a rat Alzheimer＇s disease model,for 30 minutes,once per day,for 30 days.The rats underwent 18F-fluorodeoxyglucose positron emission tomography scanning.Positron emission tomography images were processed with SPM2.The brain areas activated after needling at ST36 included the left hippocampus,the left orbital cortex,the left infralimbic cortex,the left olfactory cortex,the left cerebellum and the left pons.In the sham-point group,the activated regions were similar to those in the ST36 group.However,the ST36 group showed greater activation in the cerebellum and pons than the sham-point group.These findings suggest that long-term acupuncture treatment has targeted regulatory effects on multiple brain regions in rats with Alzheimer＇s disease.
文摘Dear Editor,Rosacea is characterized by persistent or transient erythema,papules,pustules,telangiectasia,and/or phymatous lesions[1].Although multiple treatments are available for rosacea,the advent of biological agents and small-molecule agents has significantly advanced our ability to target the disease more effectively[2].In the current review,we summarize the outcomes of targeted therapies in rosacea,mainly focusing on interleukin(IL)-17 inhibitors and Janus kinase(JAK)inhibitors.
基金supported by Department of Science and Technology and Biotechnology,GoWB,India(Sanction No.:140(Sanc.)-BT/P/Budget/RD-75/2017 dated 16.11.2018)to U.CDST-FIST,GoI for providing infrastructure support to Department of Zoology,University of Calcutta+2 种基金CSIR,GoI,for funding their fellowship(File No.09/028(1066)/2018-EMRI and 09/028(1138)/2019-EMR-I,respectively)supported by a grant from the Natural Sciences and Engineering Research Council of Canadasupported by a Queen Elizabeth Ⅱ Diamond Jubilee Scholarship and an FRQ-NT scholarship.
文摘Persistence of drug-resistant breast cancer stem cells(brCSCs)after a chemotherapeutic regime correlates with disease recurrence and elevated mortality.Therefore,deciphering mechanisms that dictate their drug-resistant phenotype is imperative for designing targeted and more effective therapeutic strategies.The transcription factor SOX2 has been recognized as a protagonist in brCSC maintenance,and previous studies have confirmed that inhibition of SOX2 purportedly eliminated these brCSCs.However,pharmacological targeting of transcription factors like SOX2 is challenging due to their structural incongruities and intrinsic disorders in their binding interfaces.Therefore,transcriptional co-activators may serve as a feasible alternative for effectively targeting the brCSCs.Incidentally,transcriptional co-activators YAP/TAZ were found to be upregulated in CD44^(+)/CD24^(-)/ALDH^(+)cells isolated from patient breast tumors and CSC-enriched mammospheres.Interestingly,it was observed that YAP/TAZ exhibited direct physical interaction with SOX2 and silencing YAP/TAZ attenuated SOX2 expression in mammospheres,leading to significantly reduced sphere forming efficiency and cell viability.YAP/TAZ additionally manipulated redox homeostasis and regulated mitochondrial dynamics by restraining the expression of the mitochondrial fission marker,DRP1.Furthermore,YAP/TAZ inhibition induced DRP1 expression and impaired OXPHOS,consequently inducing apoptosis in mammospheres.In order to enhance clinical relevance of the study,an FDA-approved drug verteporfin(VP),was used for pharmacological inhibition of YAP/TAZ.Surprisingly,VP administration was found to reduce tumor-initiating capacity of the mammospheres,concomitant with disrupted mitochondrial homeostasis and significantly reduced brCSC population.Therefore,VP holds immense potential for repurposing and decisively eliminating the chemoresistant brCSCs,offering a potent strategy for managing tumor recurrence effectively.
基金supported by the National Natural Science Foundation of China(No.81902701 to Y.L.,82103649 to H.Z.)the Natural Science Foundation of Liaoning Province,China(No.20180530037 to Y.L.,2022-MS-183 to W.D.).
文摘Poor prognosis is associated with oral squamous cell carcinoma(OSCC),an aggressive form of malignant tumor.1 Developing effective targeted therapies against OSCC is anticipated to have significant clinical implications.Fisetin(3,30,40,7-tetrahydroxyflavone),a natural flavonoid,the most common phytochemical found in a variety of fruits and vegetables,may bring several therapeutic potential benefits to people.2 Investigating the pharmacological impact of natural flavonoid fisetin on the management of OSCC was the aim of the current investigation.By focusing on the tumor-associated antigen MUC1(mucin 1),fisetin prevents OSCC cells from transforming malignant.This study aims to provide new diagnostic indicators and therapeutic targets for the diagnosis and treatment of OSCC by exploring the role and mechanism of fisetin in OSCC.
基金financially supported by the National Key R&D Program of China(Nos.2020YFA0714901 and 2020YFA0714904).
文摘This study proposes a low-energy pulse current(LEPC)rapid solution treatment method,which can dis-solve more primaryγ'phase in a shorter time and effectively suppress abnormal grain growth,thereby successfully achieving microstructure optimization and property enhancement.The microstructure anal-ysis showed that,compared with the 62.5%dissolution rate of the standard traditional solution treat-ment(1100℃/4 h),LEPC achieved an 88.9%dissolution of the primaryγ'phase in just 5 min at the same temperature.Furthermore,due to the rapidity of the LEPC treatment and its“targeted dissolution effect”on theγ'phase,excessivegrain growthwas effectivelysuppressed,resultingingrain sizecom-parable to those obtained with traditional solution treatment.Mechanical property testing indicated that the alloy treated with LEPC had a hardness of 531 HV at room temperature,while the yield strength,Ultimate strength,and maximum strain reached 994 MPa,1030 MPa,and 5.1%at the service tempera-ture(750℃).Compared to the standard traditional solution treatment,these properties were improved by 10.4%,11.1%,10.4%,and 17.5%,respectively.Finally,theoretical calculations revealed that the non-thermal effect of LEPC reduced the dissolution-free energy by approximately 49.4 kJ/mol and increased the diffusion coefficient by about 76 times,which was the fundamental reason for the accelerated disso-lution of the primaryγ’phase.
基金supported by the National Natural Science Foundation of China(71771216).
文摘With the advancement of combat equipment technology and combat concepts,new requirements have been put forward for air defense operations during a group target attack.To achieve high-efficiency and lowloss defensive operations,a reasonable air defense weapon assignment strategy is a key step.In this paper,a multi-objective and multi-constraints weapon target assignment(WTA)model is established that aims to minimize the defensive resource loss,minimize total weapon consumption,and minimize the target residual effectiveness.An optimization framework of air defense weapon mission scheduling based on the multiobjective artificial bee colony(MOABC)algorithm is proposed.The solution for point-to-point saturated attack targets at different operational scales is achieved by encoding the nectar with real numbers.Simulations are performed for an imagined air defense scenario,where air defense weapons are saturated.The non-dominated solution sets are obtained by the MOABC algorithm to meet the operational demand.In the case where there are more weapons than targets,more diverse assignment schemes can be selected.According to the inverse generation distance(IGD)index,the convergence and diversity for the solutions of the non-dominated sorting genetic algorithm III(NSGA-III)algorithm and the MOABC algorithm are compared and analyzed.The results prove that the MOABC algorithm has better convergence and the solutions are more evenly distributed among the solution space.
文摘Greenhouse gas emissions are increas- ing every year and their effect on the environment is becoming increasingly serious. In 2009, the concen- tration of carbon dioxide in the earth＇s atmosphere reached 387 μL/L, the highest level in recorded histo- ry. This paper summarizes the global carbon emission situation, sources of greenhouse gases, and the con-tribution of agriculture to the accumutauon ot green- house gases. Several scientific measures are proposed to reduce greenhouse gas emissions resulting from ru- minant production such as improving animal perform- ance, regulating the rumen environment, and reduc- ing the amount of greenhouse gases emitted from live- stock manure.
基金supported by US National Science Foundation grants EFRI 1830878,CBET 1948722,CBET 2220273,and CBET 2325317US National Institutes of Health grants R01 EB025173,R01 CA228029,R01 CA293050,R01 GM143749,and R21 AG085089.
文摘The biggest challenge in using CRISPR technologies,which limits their widespread application in medicine,is off-target effects.These effects could,in principle,be minimized by ensuring that CRISPR is activated primarily in the targeted cells,thereby reducing the likelihood of unintended genetic modifications in non-target tissues.Therefore,the development of a light activatable CRISPR approach to dynamically control gene activation in both space and time would be highly beneficial.A drawback is that the overwhelming majority of recently introduced light activatable CRISPR systems require UV or blue light exposure,severely limiting the penetration depth of light in tissue at which CRISPR can be activated,and,in the case of UV light,raising safety concerns.A small number of systems that activate CRISPR using longer wavelengths are hindered by either slow light activation or issues related to toxicity and biocompatibility of the proposed techniques in humans.To address this,we developed a split-Cas9/dCas9 system in which activation is achieved through a near-infrared photocleavable dimerization complex.This photoactivation method can be safely used in humans in vivo,easily adapted to different split-Cas9/dCas9 systems,and enables rapid,spatially precise light activation across various cell types.
基金supported by the National Natural Science Foundation of China(21625502、21974070)。
文摘In this work,a facile and sensitive colorimetric detection method was firstly reported for RNase A activity detection based on target regulated protection effect of chimeric DNA probe on the salt-induced aggregation of plasmonic gold nanoparticles.Compared with previous works of RNase A activity detection,this colorimetric assay integrated the advantages of sensitive,low cost,facile operation,rapid response and low biological toxicity.
基金supported partly by the National Human and Health Scientific Data Sharing Platform,Clinical Center of China(No.2004DKA20240-2014)National Program funded by the Ministry of Science and Technology of China(No.2015KJRK1L01).
文摘Objective: To explore the antitumor and potential off-target effects of systemically delivered cholesterol-conjugatedlet-7a mimics(Chol-let-7a) and control mimics(Chol-miRCtrl) on hepatocellular carcinomain vivo.Methods: The antitumor effects of two intravenous dosing regimens ofChol-let-7a on heptocellular carcinoma growth were compared using an orthotopic xenograft mouse model. Off-targets were analyzed with histopathological and ultrapathological features of heparenal tissue and cells in theChol-let-7a-, Chol-miRCtrl-, and saline-treated (blank) xenograft mice and normal control mice. Then,let-7a abundance in orthotopic tumors, corresponding paracancerous hepatic tissue, and normal liver tissue from healthy nude mice was examined by reverse transcription-polymerase chain reaction. The distribution ofChol-let-7a andChol-miRCtrl in vivo was examined by whole-animal imaging and frozen-sections observation. The experiments were approved by the Institutional Research Board of Peking Union Medical College Hospital.Results: Continuous treatment withChol-let-7a resulted in tumors that were 35.86% and 40.02% the size of those in theChol-miRCtrl and blank xenograft group (P < 0.01 andP < 0.01, respectively), while intermittent dosing withChol-let-7a resulted in tumors that were 65.42% and 56.66% the size of those in theChol-miRCtrl and the blank control group, respectively (P < 0.05 andP < 0.05). In addition, some histopathological and ultrapathological features were only observed after treatment with the two cholesterol-conjugated molecules, however mild with intermittent dosingChol-let-7a treatment, such as diffuse sinusoidal dilation and edema, primarily around the centrolobular vein in heptic tissues;mild hypercellularity with dilated capillary lumens in the renal tissue;and some organelle abnormalities found in heptic and renal cells. Furthermore, whole-animal imaging showed thatChol-let-7a andChol-miRCtrl were predominantly distributed in the liver, kidney, and bladder regions after injection, and that the concentration ofChol-let-7a andChol-miRCtrl in the kidney and the bladder decreased much slowly in the xenograft animals, especially in theChol-miRCtrl group. Finally, RT-PCR analysis showed thatlet-7a levels were significantly increased in Chol-let-7a-treated xenografts compared withChol-miRCtrl group (P=0.003) and blank xenograft group (P=0.001);however, the level was only equivalent to 50.6% and 40.7% of that in paracancerous hepatic tissue and hepatic tissue in normal mice, respectively.Conclusions: Chol-let-7a, administered either continuously or intermittently, showed effective antitumor efficacy.Chol-let-7a had some off-target effects, such as mild acute hepatitis-like inflammation and non-specific drug-induced kidney injury. The intermittent dosing regimen resulted in less damage than the continuous regimen, while maintaining relatively satisfactory antitumor efficacy, which could be useful for the investigation and possible clinical use of miRNA treatment regimens in the future.
文摘Impact and torsion pendulums are applied in impulse coupling experiments of high-energy laser irradiation of space debris. It is difficult to achieve a multi-pulse experiment and thus hard to analyze the multi-pulse impulse coupling effect. Here, we designed a new recoil impulse experimental measurement system of non-contact, multidegrees of freedom, and multi-pulse irradiation. The system used a low-pressure and low-temperature vacuum chamber to simulate the space environment, the pinning effect of magnetic levitation to achieve aluminum target suspension, and high-speed cameras to record the displacement over time to calculate the impulse of the target.Then the impulse coupling experiment of multi-pulse laser irradiation on the aluminum target was performed.The result shows that the multi-pulse impulse coupling effect is not the linear accumulation of coupling results by every single-pulse and multi-pulse coefficient that decreases with the increase of the number of pulses, and eventually stabilizes as the decrease gets smaller.
基金This work was supported by National Natural Science Foundation of China(22204015)Shenyang Young and Middle-aged Scientific and Technological Innovation Talents Project(RC220478)the Fundamental Research Funds for the Central Universities(N2405010).
文摘Cancer immunotherapy has appeared as a prospective therapeutic modality.Therapeutic antibodies induced in an in vitro expression system act as"targeting missiles"against tumor-associated binding sites,and subsequently,immune system attack on tumors is restored or boosted.These antibody regimens are engineered towards enhanced Fc efficacy,humanization,and fragmentation to specifically recognize and bind to effective tumor-associated targets.The challenge lies in obtaining efficient therapeutic regimens with low response rates,acquisition of resistance,and immune-related undesirable effects of artificially designed therapeutic antibodies,which is crucial for enhancing clinical efficacy.This review provides an in-depth introduction to antibodies that perform direct/indirect roles in cancer treatment by binding to immune checkpoints,costimulatory receptors,and extracellular membrane receptors.It also discusses how antibodies kill tumors and modulate microenvironment of tumor through these targets.The classification of expression systems for antibody production is summarized to guide appropriate selection based on different specificities.Understanding antibody sources,ongoing evaluation of engineered antibodies,and tumor-associated antigen research pave the way for designing appropriate antibody-based immunotherapy regimens.
