21 results on '"Chen, Chen"'
Search Results
2. Trident cold atmospheric plasma blocks three cancer survival pathways to overcome therapy resistance
- Author
-
Guo, Bo, Pomicter, Anthony D., Li, Francis, Bhatt, Sudhir, Chen, Chen, Li, Wen, Qi, Miao, Huang, Chen, Deininger, Michael W., Kong, Michael G., and Chen, Hai-Lan
- Published
- 2021
3. Computational prediction of the effect of amino acid changes on the binding affinity between SARS-CoV-2 spike RBD and human ACE2
- Author
-
Chen, Chen, Boorla, Veda Sheersh, Banerjee, Deepro, Chowdhury, Ratul, Cavener, Victoria S., Nissly, Ruth H., Gontu, Abhinay, Boyle, Nina R., Vandegrift, Kurt, Nair, Meera Surendran, Kuchipudi, Suresh V., and Maranas, Costas D.
- Published
- 2021
4. Landscape of innate lymphoid cells in human head and neck cancer reveals divergent NK cell states in the tumor microenvironment
- Author
-
Moreno-Nieves, Uriel Y., Tay, Joshua K., Saumyaa, Saumyaa, Horowitz, Nina B., Shin, June Ho, Mohammad, Imran A., Luca, Bogdan, Mundy, David C., Gulati, Gunsagar S., Bedi, Nikita, Chang, Serena, Chen, Chen, Kaplan, Michael J., Rosenthal, Eben L., Holsinger, F. Christopher, Divi, Vasu, Baik, Fred M., Sirjani, Davud B., Gentles, Andrew J., Newman, Aaron M., Freud, Aharon G., and Sunwoo, John B.
- Published
- 2021
5. Enhanced charge-carrier dynamics and efficient solar-to-urea conversion on Si-based photocathodes.
- Author
-
Xiaoran Zhang, Yanhong Lyu, Chen Chen, Jianyun Zheng, San Ping Jiang, and Shuangyin Wang
- Subjects
PHOTOCATHODES ,UREA ,ELECTROCATALYSIS ,CARBON dioxide ,BIODIESEL fuel manufacturing ,CATALYSTS ,PHOTOVOLTAIC power systems - Abstract
Photoelectrochemical (PEC) coupling of CO2 and nitrate can provide a useful and green source of urea, but the process is affected by the photocathodes with poor charge-carrier dynamics and low conversion efficiency. Here, a NiFe diatomic catalysts/TiO2 layer/nanostructured n+p-Si photocathode is rationally designed, achieving a good charge-separation efficiency of 78.8% and charge-injection efficiency of 56.9% in the process of PEC urea synthesis. Compared with the electrocatalytic urea synthesis by using the same catalysts, the Si-based photocathode shows a similar urea yield rate (81.1 mg·h-1·cm-2) with a higher faradic efficiency (24.2%, almost twice than the electrocatalysis) at a lower applied potential under 1 sun illumination, meaning that a lower energy-consumption method acquires more aimed productions. Integrating the PEC measurements and characterization results, the synergistic effect of hierarchical structure is the dominating factor for enhancing the charge-carrier separation, transfer, and injection by the matched band structure and favorable electron-migration channels. This work provides a direct and efficient route of solar-to-urea conversion. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
6. Association of cumulative loneliness with all-cause mortality among middle-aged and older adults in the United States, 1996 to 2019.
- Author
-
Xuexin Yu, Tsai-Chin Cho, Westrick, Ashly C., Chen Chen, Langa, Kenneth M., and Kobayashi, Lindsay C.
- Subjects
MIDDLE-aged persons ,OLDER people ,MORTALITY ,LONELINESS ,PROPORTIONAL hazards models - Abstract
Loneliness is a growing public health concern worldwide. We characterized the association between cumulative loneliness and subsequent all-cause mortality, using data from 9,032 participants aged 50+ in the population-based US Health and Retirement Study (HRS) from 1996 to 2019. Loneliness status (yes; no) was measured biennially from 1996 to 2004, and we categorized the experience of cumulative loneliness over the 8-y period as never, one time point, two time points, and ≥three time points. A multivariable-adjusted age-stratified Cox proportional hazards regression model was fitted to examine the association between cumulative loneliness from 1996 to 2004 and all-cause mortality from 2004 to 2019. Excess deaths due to each category of cumulative loneliness were calculated. Compared to those who never reported loneliness from 1996 to 2004, participants experiencing loneliness at one time point, two time points, and ≥three time points respectively had 1.05 (95% CI: 0.96 to 1.15), 1.06 (95% CI: 0.95 to 1.19), and 1.16 (95% CI: 1.02 to 1.33) times higher hazards of mortality from 2004 to 2019 (P trend = 0.01). These results correspond to 106 (95% CI: 68 to 144), 202 (95% CI: 146 to 259), and 288 (95% CI: 233 to 343) excess deaths per 10,000 person-years, for those experiencing loneliness at each of one, two, or ≥three time points from 1996 to 2004. Cumulative loneliness in mid-to-later life may thus be a mortality risk factor with a notable impact on excess mortality. Loneliness may be an important target for interventions to improve life expectancy in the United States. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
7. Surfaceome analysis of extracellular vesicles from senescent cells uncovers uptake repressor DPP4.
- Author
-
Qiong Meng, Chen Chen, Na Yang, Gololobova, Olesia, Changyou Shi, Dunn, Christopher A., Rossi, Martina, Martindale, Jennifer L., Basisty, Nathan, Jun Ding, Delannoy, Michael, Basu, Srikanta, Mazan-Mamczarz, Krystyna, Chang Hoon Shin, Jen-Hao Yang, Johnson, Peter F., Witwer, Kenneth W., Biragyn, Arya, Sen, Payel, and Abdelmohsen, Kotb
- Subjects
- *
EXTRACELLULAR vesicles , *HELA cells , *IONIZING radiation , *CANCER cells , *CERVICAL cancer - Abstract
Senescent cells are beneficial for repairing acute tissue damage, but they are harmful when they accumulate in tissues, as occurs with advancing age. Senescence-associated extracellular vesicles (S-EVs) can mediate cell-to-cell communication and export intracellular content to the microenvironment of aging tissues. Here, we studied the uptake of EVs from senescent cells (S-EVs) and proliferating cells (P-EVs) and found that P-EVs were readily taken up by proliferating cells (fibroblasts and cervical cancer cells) while S-EVs were not. We thus investigated the surface proteome (surfaceome) of P-EVs relative to S-EVs derived from cells that had reached senescence via replicative exhaustion, exposure to ionizing radiation, or treatment with etoposide. We found that relative to P-EVs, S-EVs from all senescence models were enriched in proteins DPP4, ANXA1, ANXA6, S10AB, AT1A1, and EPHB2. Among them, DPP4 was found to selectively prevent uptake by proliferating cells, as ectopic overexpression of DPP4 in HeLa cells rendered DPP4-expressing EVs that were no longer taken up by other proliferating cells. We propose that DPP4 on the surface of S-EVs makes these EVs refractory to internalization by proliferating cells, advancing our knowledge of the impact of senescent cells in aging-associated processes. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
8. CRISPR editing of CCR5 and HIV-1 facilitates viral elimination in antiretroviral drug-suppressed virus-infected humanized mice.
- Author
-
Dash, Prasanta K., Chen Chen, Kaminski, Rafal, Hang Su, Mancuso, Pietro, Sillman, Brady, Chen Zhang, Shuren Liao, Sravanam, Sruthi, Hong Liu, Waight, Emiko, Lili Guo, Mathews, Saumi, Sariyer, Rahsan, Mosley, R. Lee, Poluektova, Larisa Y., Caocci, Maurizio, Amini, Shohreh, Gorantla, Santhi, and Burdo, Tricia H.
- Subjects
- *
CHEMOKINE receptors , *HIV , *CRISPRS , *GENOME editing , *NUCLEIC acids , *FIREPROOFING agents - Abstract
Treatment of HIV-1ADA-infected CD34+ NSG-humanized mice with long-acting ester prodrugs of cabotegravir, lamivudine, and abacavir in combination with native rilpivirine was followed by dual CRISPR-Cas9 C-C chemokine receptor type five (CCR5) and HIV-1 proviral DNA gene editing. This led to sequential viral suppression, restoration of absolute human CD4+ T cell numbers, then elimination of replication-competent virus in 58% of infected mice. Dual CRISPR therapies enabled the excision of integrated proviral DNA in infected human cells contained within live infected animals. Highly sensitive nucleic acid nested and droplet digital PCR, RNAscope, and viral outgrowth assays affirmed viral elimination. HIV-1 was not detected in the blood, spleen, lung, kidney, liver, gut, bone marrow, and brain of virus-free animals. Progeny virus from adoptively transferred and CRISPR-treated virus-free mice was neither detected nor recovered. Residual HIV-1 DNA fragments were easily seen in untreated and viral-rebounded animals. No evidence of off-target toxicities was recorded in any of the treated animals. Importantly, the dual CRISPR therapy demonstrated statistically significant improvements in HIV-1 cure percentages compared to single treatments. Taken together, these observations underscore a pivotal role of combinatorial CRISPR gene editing in achieving the elimination of HIV-1 infection. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
9. Understanding the coevolution of mask wearing and epidemics
- Author
-
Zirou Qiu, Baltazar Espinoza, Vitor V. Vasconcelos, Chen Chen, Sara M. Constantino, Stefani A. Crabtree, Luojun Yang, Anil Vullikanti, Jiangzhuo Chen, Jörgen Weibull, Kaushik Basu, Avinash Dixit, Simon A. Levin, Madhav V. Marathe, and Computational Science Lab (IVI, FNWI)
- Subjects
Multidisciplinary ,Masks ,Humans ,Epidemics - Abstract
Nonpharmaceutical interventions (NPIs) such as mask wearing can be effective in mitigating the spread of infectious diseases. Therefore, understanding the behavioral dynamics of NPIs is critical for characterizing the dynamics of disease spread. Nevertheless, standard infection models tend to focus only on disease states, overlooking the dynamics of “beneficial contagions,” e.g., compliance with NPIs. In this work, we investigate the concurrent spread of disease and mask-wearing behavior over multiplex networks. Our proposed framework captures both the competing and complementary relationships between the dueling contagion processes. Further, the model accounts for various behavioral mechanisms that influence mask wearing, such as peer pressure and fear of infection. Our results reveal that under the coupled disease–behavior dynamics, the attack rate of a disease—as a function of transition probability—exhibits a critical transition. Specifically, as the transmission probability exceeds a critical threshold, the attack rate decreases abruptly due to sustained mask-wearing responses. We empirically explore the causes of the critical transition and demonstrate the robustness of the observed phenomena. Our results highlight that without proper enforcement of NPIs, reductions in the disease transmission probability via other interventions may not be sufficient to reduce the final epidemic size.
- Published
- 2022
10. Myeloid-derived MIF drives RIPK1-mediated cerebromicrovascular endothelial cell death to exacerbate ischemic brain injury.
- Author
-
Yan Li, Chengyu Zou, Chen Chen, Sixuan Li, Ziyu Zhu, Qiuyue Fan, Rui Pang, Fengshi Li, Zengai Chen, Zhenghong Wang, Weifeng Yu, Junying Yuan, and Peiying Li
- Subjects
CELL death ,MACROPHAGE migration inhibitory factor ,BRAIN injuries ,ENDOTHELIAL cells ,MONONUCLEAR leukocytes - Abstract
Macrophage migration inhibitory factor (MIF) is a multifaced protein that plays important roles in multiple inflammatory conditions. However, the role of MIF in endothelial cell (EC) death under inflammatory condition remains largely unknown. Here we show that MIF actively promotes receptor-interacting protein kinase 1 (RIPK1)-mediated cell death under oxygen-glucose deprivation condition. MIF expression is induced by surgical trauma in peripheral myeloid cells both in perioperative humans and mice. We demonstrate that MIF-loaded myeloid cells induced by peripheral surgery adhere to the brain ECs after distal middle cerebral artery occlusion (dMCAO) and exacerbate the blood–brain barrier (BBB) disruption. Genetic depletion of myeloid-derived MIF in perioperative ischemic stroke (PIS) mice with MCAO following a surgical insult leads to significant reduction in ECs apoptosis and necroptosis and the associated BBB disruption. The adoptive transfer of peripheral blood mononuclear cells (PBMC) from surgical MIF
ΔLyz2 mice to wild-type (WT) MCAO mice also shows reduced ECs apoptosis and necroptosis compared to the transfer of PBMC from surgical MIFf l/f l mice to MCAO recipients. The genetic inhibition of RIPK1 also attenuates BBB disruption and ECs death compared to that of WT mice in PIS. The administration of MIF inhibitor (ISO1) and RIPK1 inhibitor (Nec-1s) can both reduce the brain EC death and neurological deficits following PIS. We conclude that myeloid-derived MIF promotes ECs apoptosis and necroptosis through RIPK1 kinase-dependent pathway. The above findings may provide insights into the mechanism as how peripheral inflammation promotes the pathology in central nervous system. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF
11. Impact of lowering fine particulate matter from major emission sources on mortality in Canada: A nationwide causal analysis.
- Author
-
Hong Chen, Quick, Matthew, Kaufman, Jay S., Chen Chen, Kwong, Jeffrey C., van Donkelaar, Aaron, Jun Meng, Martin, Randall V., JinHee Kim, Lavigne, Eric, Li Bai, Yi Li, Tjepkema, Michael, Benmarhnia, Tarik, and Burnett, Richard T.
- Subjects
PARTICULATE matter ,ATMOSPHERIC chemistry ,ATMOSPHERIC transport ,OLDER people ,CHEMICAL models - Abstract
Emissions of fine particulate matter (PM
2.5 ) from human activities have been linked to substantial disease burdens, but evidence regarding how reducing PM2.5 at its sources would improve public health is sparse. We followed a population-based cohort of 2.7 million adults across Canada from 2007 through 2016. For each participant, we estimated annual mean concentrations of PM2.5 and the fractional contributions to PM2.5 from the five leading anthropogenic sources at their residential address using satellite observations in combination with a global atmospheric chemistry transport model. For each source, we estimated the causal effects of six hypothetical interventions on 10-y nonaccidental mortality risk using the parametric g-formula, a structural causal model. We conducted stratified analyses by age, sex, and income. This cohort would have experienced tangible health gains had contributions to PM2.5 from any of the five sources been reduced. Compared with no intervention, a 10% annual reduction in PM2.5 contributions from transportation and power generation, Canada's largest and fifth-largest anthropogenic sources, would have prevented approximately 175 (95%CI: 123-226) and 90 (95%CI: 63-117) deaths per million by 2016, respectively. A more intensive 50% reduction per year in PM2.5 contributions from the two sources would have averted 360 and 185 deaths per million, respectively, by 2016. The potential health benefits were greater among men, older adults, and low-income earners. In Canada, where PM2.5 levels are among the lowest worldwide, reducing PM2.5 contributions from anthropogenic sources by as little as 10% annually would yield meaningful health gains. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
12. Trident cold atmospheric plasma blocks three cancer survival pathways to overcome therapy resistance.
- Author
-
Bo Guo, Pomicter, Anthony D., Li, Francis, Bhatt, Sudhir, Chen Chen, Wen Li, Miao Qi, Chen Huang, Deininger, Michael W., Kong, Michael G., and Hai-Lan Chen
- Subjects
LOW temperature plasmas ,STEM cell donors ,CURCUMIN ,HEMATOPOIETIC stem cell transplantation ,CHRONIC myeloid leukemia ,HEMATOPOIETIC stem cells ,GLOW discharges - Abstract
Therapy resistance is responsible for most cancer-related death and is mediated by the unique ability of cancer cells to leverage metabolic conditions, signaling molecules, redox status, and other pathways for their survival. Interestingly, many cancer survival pathways are susceptible to disturbances in cellular reactive oxygen species (ROS) and may therefore be disrupted by exogenous ROS. Here, we explore whether trident cold atmospheric plasma (Tri-CAP), a gas discharge with exceptionally low-level ROS, could inhibit multiple cancer survival pathways together in a murine cell line model of therapy-resistant chronic myeloid leukemia (CML). We show that Tri-CAP simultaneously disrupts three cancer survival pathways of redox deregulation, glycolysis, and proliferative AKT/mTOR/HIF-1α signaling in this cancer model. Significantly, Tri-CAP blockade induces a very high rate of apoptotic death in CML cell lines and in primary CD34
+ hematopoietic stem and progenitor cells from CML patients, both harboring the therapy-resistant T315I mutation. In contrast, nonmalignant controls are minimally affected by Tri-CAP, suggesting it selectively targets resistant cancer cells. We further demonstrate that Tri-CAP elicits similar lethality in human melanoma, breast cancer, and CML cells with disparate, resistant mechanisms and that it both reduces tumor formation in two mouse models and improves survival of tumor-bearing mice. For use in patients, administration of Tri-CAP may be extracorporeal for hematopoietic stem cell transplantation therapy, transdermal, or through its activated solution for infusion therapy. Collectively, our results suggest that Tri-CAP represents a potent strategy for disrupting cancer survival pathways and overcoming therapy resistance in a variety of malignancies. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
13. Enhanced charge-carrier dynamics and efficient solar-to-urea conversion on Si-based photocathodes.
- Author
-
Zhang X, Lyu Y, Chen C, Zheng J, Jiang SP, and Wang S
- Abstract
Photoelectrochemical (PEC) coupling of CO
2 and nitrate can provide a useful and green source of urea, but the process is affected by the photocathodes with poor charge-carrier dynamics and low conversion efficiency. Here, a NiFe diatomic catalysts/TiO2 layer/nanostructured n+ p-Si photocathode is rationally designed, achieving a good charge-separation efficiency of 78.8% and charge-injection efficiency of 56.9% in the process of PEC urea synthesis. Compared with the electrocatalytic urea synthesis by using the same catalysts, the Si-based photocathode shows a similar urea yield rate (81.1 mg·h-1 ·cm-2 ) with a higher faradic efficiency (24.2%, almost twice than the electrocatalysis) at a lower applied potential under 1 sun illumination, meaning that a lower energy-consumption method acquires more aimed productions. Integrating the PEC measurements and characterization results, the synergistic effect of hierarchical structure is the dominating factor for enhancing the charge-carrier separation, transfer, and injection by the matched band structure and favorable electron-migration channels. This work provides a direct and efficient route of solar-to-urea conversion., Competing Interests: Competing interests statement:The authors declare no competing interest.- Published
- 2024
- Full Text
- View/download PDF
14. Association of cumulative loneliness with all-cause mortality among middle-aged and older adults in the United States, 1996 to 2019.
- Author
-
Yu X, Cho TC, Westrick AC, Chen C, Langa KM, and Kobayashi LC
- Subjects
- Middle Aged, Humans, United States epidemiology, Aged, Risk Factors, Loneliness
- Abstract
Loneliness is a growing public health concern worldwide. We characterized the association between cumulative loneliness and subsequent all-cause mortality, using data from 9,032 participants aged 50+ in the population-based US Health and Retirement Study (HRS) from 1996 to 2019. Loneliness status (yes; no) was measured biennially from 1996 to 2004, and we categorized the experience of cumulative loneliness over the 8-y period as never, one time point, two time points, and ≥three time points. A multivariable-adjusted age-stratified Cox proportional hazards regression model was fitted to examine the association between cumulative loneliness from 1996 to 2004 and all-cause mortality from 2004 to 2019. Excess deaths due to each category of cumulative loneliness were calculated. Compared to those who never reported loneliness from 1996 to 2004, participants experiencing loneliness at one time point, two time points, and ≥three time points respectively had 1.05 (95% CI: 0.96 to 1.15), 1.06 (95% CI: 0.95 to 1.19), and 1.16 (95% CI: 1.02 to 1.33) times higher hazards of mortality from 2004 to 2019 ( P trend = 0.01). These results correspond to 106 (95% CI: 68 to 144), 202 (95% CI: 146 to 259), and 288 (95% CI: 233 to 343) excess deaths per 10,000 person-years, for those experiencing loneliness at each of one, two, or ≥three time points from 1996 to 2004. Cumulative loneliness in mid-to-later life may thus be a mortality risk factor with a notable impact on excess mortality. Loneliness may be an important target for interventions to improve life expectancy in the United States., Competing Interests: Competing interests statement:The authors declare no competing interest.
- Published
- 2023
- Full Text
- View/download PDF
15. Surfaceome analysis of extracellular vesicles from senescent cells uncovers uptake repressor DPP4.
- Author
-
Meng Q, Chen C, Yang N, Gololobova O, Shi C, Dunn CA, Rossi M, Martindale JL, Basisty N, Ding J, Delannoy M, Basu S, Mazan-Mamczarz K, Shin CH, Yang JH, Johnson PF, Witwer KW, Biragyn A, Sen P, Abdelmohsen K, De S, and Gorospe M
- Subjects
- Humans, Dipeptidyl Peptidase 4 genetics, Dipeptidyl Peptidase 4 metabolism, HeLa Cells, Aging, Cellular Senescence, Extracellular Vesicles metabolism
- Abstract
Senescent cells are beneficial for repairing acute tissue damage, but they are harmful when they accumulate in tissues, as occurs with advancing age. Senescence-associated extracellular vesicles (S-EVs) can mediate cell-to-cell communication and export intracellular content to the microenvironment of aging tissues. Here, we studied the uptake of EVs from senescent cells (S-EVs) and proliferating cells (P-EVs) and found that P-EVs were readily taken up by proliferating cells (fibroblasts and cervical cancer cells) while S-EVs were not. We thus investigated the surface proteome (surfaceome) of P-EVs relative to S-EVs derived from cells that had reached senescence via replicative exhaustion, exposure to ionizing radiation, or treatment with etoposide. We found that relative to P-EVs, S-EVs from all senescence models were enriched in proteins DPP4, ANXA1, ANXA6, S10AB, AT1A1, and EPHB2. Among them, DPP4 was found to selectively prevent uptake by proliferating cells, as ectopic overexpression of DPP4 in HeLa cells rendered DPP4-expressing EVs that were no longer taken up by other proliferating cells. We propose that DPP4 on the surface of S-EVs makes these EVs refractory to internalization by proliferating cells, advancing our knowledge of the impact of senescent cells in aging-associated processes.
- Published
- 2023
- Full Text
- View/download PDF
16. Myeloid-derived MIF drives RIPK1-mediated cerebromicrovascular endothelial cell death to exacerbate ischemic brain injury.
- Author
-
Li Y, Zou C, Chen C, Li S, Zhu Z, Fan Q, Pang R, Li F, Chen Z, Wang Z, Yu W, Yuan J, and Li P
- Subjects
- Animals, Humans, Mice, Apoptosis, Cell Death, Endothelial Cells metabolism, Intramolecular Oxidoreductases genetics, Intramolecular Oxidoreductases metabolism, Leukocytes, Mononuclear metabolism, Brain Injuries, Macrophage Migration-Inhibitory Factors genetics, Macrophage Migration-Inhibitory Factors metabolism, Receptor-Interacting Protein Serine-Threonine Kinases metabolism
- Abstract
Macrophage migration inhibitory factor (MIF) is a multifaced protein that plays important roles in multiple inflammatory conditions. However, the role of MIF in endothelial cell (EC) death under inflammatory condition remains largely unknown. Here we show that MIF actively promotes receptor-interacting protein kinase 1 (RIPK1)-mediated cell death under oxygen-glucose deprivation condition. MIF expression is induced by surgical trauma in peripheral myeloid cells both in perioperative humans and mice. We demonstrate that MIF-loaded myeloid cells induced by peripheral surgery adhere to the brain ECs after distal middle cerebral artery occlusion (dMCAO) and exacerbate the blood-brain barrier (BBB) disruption. Genetic depletion of myeloid-derived MIF in perioperative ischemic stroke (PIS) mice with MCAO following a surgical insult leads to significant reduction in ECs apoptosis and necroptosis and the associated BBB disruption. The adoptive transfer of peripheral blood mononuclear cells (PBMC) from surgical MIF
ΔLyz2 mice to wild-type (WT) MCAO mice also shows reduced ECs apoptosis and necroptosis compared to the transfer of PBMC from surgical MIFf l/f l mice to MCAO recipients. The genetic inhibition of RIPK1 also attenuates BBB disruption and ECs death compared to that of WT mice in PIS. The administration of MIF inhibitor (ISO-1) and RIPK1 inhibitor (Nec-1s) can both reduce the brain EC death and neurological deficits following PIS. We conclude that myeloid-derived MIF promotes ECs apoptosis and necroptosis through RIPK1 kinase-dependent pathway. The above findings may provide insights into the mechanism as how peripheral inflammation promotes the pathology in central nervous system.- Published
- 2023
- Full Text
- View/download PDF
17. Impact of lowering fine particulate matter from major emission sources on mortality in Canada: A nationwide causal analysis.
- Author
-
Chen H, Quick M, Kaufman JS, Chen C, Kwong JC, van Donkelaar A, Meng J, Martin RV, Kim J, Lavigne E, Bai L, Li Y, Tjepkema M, Benmarhnia T, and Burnett RT
- Subjects
- Male, Humans, Aged, Causality, Canada epidemiology, Transportation, Particulate Matter, Income
- Abstract
Emissions of fine particulate matter (PM
2.5 ) from human activities have been linked to substantial disease burdens, but evidence regarding how reducing PM2.5 at its sources would improve public health is sparse. We followed a population-based cohort of 2.7 million adults across Canada from 2007 through 2016. For each participant, we estimated annual mean concentrations of PM2.5 and the fractional contributions to PM2.5 from the five leading anthropogenic sources at their residential address using satellite observations in combination with a global atmospheric chemistry transport model. For each source, we estimated the causal effects of six hypothetical interventions on 10-y nonaccidental mortality risk using the parametric g-formula, a structural causal model. We conducted stratified analyses by age, sex, and income. This cohort would have experienced tangible health gains had contributions to PM2.5 from any of the five sources been reduced. Compared with no intervention, a 10% annual reduction in PM2.5 contributions from transportation and power generation, Canada's largest and fifth-largest anthropogenic sources, would have prevented approximately 175 (95%CI: 123-226) and 90 (95%CI: 63-117) deaths per million by 2016, respectively. A more intensive 50% reduction per year in PM2.5 contributions from the two sources would have averted 360 and 185 deaths per million, respectively, by 2016. The potential health benefits were greater among men, older adults, and low-income earners. In Canada, where PM2.5 levels are among the lowest worldwide, reducing PM2.5 contributions from anthropogenic sources by as little as 10% annually would yield meaningful health gains.- Published
- 2022
- Full Text
- View/download PDF
18. Voltage-gated sodium channel scn8a is required for innervation and regeneration of amputated adult zebrafish fins.
- Author
-
Osorio-Méndez D, Miller A, Begeman IJ, Kurth A, Hagle R, Rolph D, Dickson AL, Chen CH, Halloran M, Poss KD, and Kang J
- Subjects
- Animals, Mutation, Animal Fins innervation, Animal Fins physiology, NAV1.6 Voltage-Gated Sodium Channel genetics, NAV1.6 Voltage-Gated Sodium Channel physiology, Regeneration genetics, Regeneration physiology, Zebrafish genetics, Zebrafish physiology, Zebrafish Proteins genetics, Zebrafish Proteins physiology
- Abstract
Teleost fishes and urodele amphibians can regenerate amputated appendages, whereas this ability is restricted to digit tips in adult mammals. One key component of appendage regeneration is reinnervation of the wound area. However, how innervation is regulated in injured appendages of adult vertebrates has seen limited research attention. From a forward genetics screen for temperature-sensitive defects in zebrafish fin regeneration, we identified a mutation that disrupted regeneration while also inducing paralysis at the restrictive temperature. Genetic mapping and complementation tests identify a mutation in the major neuronal voltage-gated sodium channel (VGSC) gene scn8ab . Conditional disruption of scn8ab impairs early regenerative events, including blastema formation, but does not affect morphogenesis of established regenerates. Whereas scn8ab mutations reduced neural activity as expected, they also disrupted axon regrowth and patterning in fin regenerates, resulting in hypoinnervation. Our findings indicate that the activity of VGSCs plays a proregenerative role by promoting innervation of appendage stumps.
- Published
- 2022
- Full Text
- View/download PDF
19. Understanding the coevolution of mask wearing and epidemics: A network perspective.
- Author
-
Qiu Z, Espinoza B, Vasconcelos VV, Chen C, Constantino SM, Crabtree SA, Yang L, Vullikanti A, Chen J, Weibull J, Basu K, Dixit A, Levin SA, and Marathe MV
- Subjects
- Humans, Epidemics prevention & control, Masks
- Abstract
Nonpharmaceutical interventions (NPIs) such as mask wearing can be effective in mitigating the spread of infectious diseases. Therefore, understanding the behavioral dynamics of NPIs is critical for characterizing the dynamics of disease spread. Nevertheless, standard infection models tend to focus only on disease states, overlooking the dynamics of "beneficial contagions," e.g., compliance with NPIs. In this work, we investigate the concurrent spread of disease and mask-wearing behavior over multiplex networks. Our proposed framework captures both the competing and complementary relationships between the dueling contagion processes. Further, the model accounts for various behavioral mechanisms that influence mask wearing, such as peer pressure and fear of infection. Our results reveal that under the coupled disease-behavior dynamics, the attack rate of a disease-as a function of transition probability-exhibits a critical transition. Specifically, as the transmission probability exceeds a critical threshold, the attack rate decreases abruptly due to sustained mask-wearing responses. We empirically explore the causes of the critical transition and demonstrate the robustness of the observed phenomena. Our results highlight that without proper enforcement of NPIs, reductions in the disease transmission probability via other interventions may not be sufficient to reduce the final epidemic size.
- Published
- 2022
- Full Text
- View/download PDF
20. Inhibition of EZH2 transactivation function sensitizes solid tumors to genotoxic stress.
- Author
-
Liao Y, Chen CH, Xiao T, de la Peña Avalos B, Dray EV, Cai C, Gao S, Shah N, Zhang Z, Feit A, Xue P, Liu Z, Yang M, Lee JH, Xu H, Li W, Mei S, Pierre RS, Shu S, Fei T, Duarte M, Zhao J, Bradner JE, Polyak K, Kantoff PW, Long H, Balk SP, Liu XS, Brown M, and Xu K
- Subjects
- CRISPR-Cas Systems, Cell Line, Tumor, DNA Repair genetics, DNA Repair physiology, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, Gene Knockout Techniques, Hepatocyte Nuclear Factor 3-alpha genetics, Hepatocyte Nuclear Factor 3-alpha metabolism, Humans, Male, Prostatic Neoplasms, Castration-Resistant genetics, Prostatic Neoplasms, Castration-Resistant metabolism, DNA Damage genetics, DNA Damage physiology, Enhancer of Zeste Homolog 2 Protein genetics, Enhancer of Zeste Homolog 2 Protein metabolism, Transcriptional Activation
- Abstract
Drugs that block the activity of the methyltransferase EZH2 are in clinical development for the treatment of non-Hodgkin lymphomas harboring EZH2 gain-of-function mutations that enhance its polycomb repressive function. We have previously reported that EZH2 can act as a transcriptional activator in castration-resistant prostate cancer (CRPC). Now we show that EZH2 inhibitors can also block the transactivation activity of EZH2 and inhibit the growth of CRPC cells. Gene expression and epigenomics profiling of cells treated with EZH2 inhibitors demonstrated that in addition to derepressing gene expression, these compounds also robustly down-regulate a set of DNA damage repair (DDR) genes, especially those involved in the base excision repair (BER) pathway. Methylation of the pioneer factor FOXA1 by EZH2 contributes to the activation of these genes, and interaction with the transcriptional coactivator P300 via the transactivation domain on EZH2 directly turns on the transcription. In addition, CRISPR-Cas9-mediated knockout screens in the presence of EZH2 inhibitors identified these BER genes as the determinants that underlie the growth-inhibitory effect of EZH2 inhibitors. Interrogation of public data from diverse types of solid tumors expressing wild-type EZH2 demonstrated that expression of DDR genes is significantly correlated with EZH2 dependency and cellular sensitivity to EZH2 inhibitors. Consistent with these findings, treatment of CRPC cells with EZH2 inhibitors dramatically enhances their sensitivity to genotoxic stress. These studies reveal a previously unappreciated mechanism of action of EZH2 inhibitors and provide a mechanistic basis for potential combination cancer therapies., Competing Interests: Competing interest statement: N.S. receives research grant funding from AstraZeneca. J.E.B. is an executive and shareholder of Novartis AG and has been a founder and shareholder of SHAPE (acquired by Medivir), Acetylon (acquired by Celgene), Tensha (acquired by Roche), Syros, Regency, and C4 Therapeutics. P.W.K. serves on the scientific advisory board (SAB) of BIND Biosciences, BN Immunotherapeutics, GE Healthcare, Janssen, New England Research Institutes, OncoCellMDX, Progenity, Sanofi, and Thermo Fisher. He shares investment interests in Context Therapeutics, Druggability Technologies Holdings Ltd. (DRGT), Placon, Seer Biosciences, and Tarveda Therapeutics. He also serves on the Data and Safety Monitoring Board (DSMB) of Genetch and Merck. X.S.L. is a cofounder, board member, SAB, and consultant of GV20 Oncotherapy and its subsidiaries. M.B. is a consultant to and receives sponsored research support from Novartis and is a consultant to MPM Capital and serves on the SAB of Kronos Bio, H3 Biomedicine, and GV20 Oncotherapy., (Copyright © 2022 the Author(s). Published by PNAS.)
- Published
- 2022
- Full Text
- View/download PDF
21. Opinion: Allow Golden Rice to save lives.
- Author
-
Wu F, Wesseler J, Zilberman D, Russell RM, Chen C, and Dubock AC
- Subjects
- Gene Expression Regulation, Plant, Humans, Poverty, Vitamin A genetics, Vitamin A Deficiency prevention & control, Food, Genetically Modified, Oryza genetics, Oryza metabolism, Plants, Genetically Modified, Vitamin A metabolism, Vitamin A Deficiency diet therapy
- Published
- 2021
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.