Publications by authors named "Zhou Lyu"

18 Publications

  • Page 1 of 1

Sustainable and Inexpensive Polydimethylsiloxane Sponges for Daytime Radiative Cooling.

Adv Sci (Weinh) 2021 12 20;8(23):e2102502. Epub 2021 Oct 20.

Department of Electrical Engineering, The State University of New York at Buffalo, Buffalo, NY, 14260, USA.

Radiative cooling is an emerging cooling technology that can passively release heat to the environment. To obtain a subambient cooling effect during the daytime, chemically engineered structural materials are widely explored to simultaneously reject sunlight and preserve strong thermal emission. However, many previously reported fabrication processes involve hazardous chemicals, which can hinder a material's ability to be mass produced. In order to eliminate the hazardous chemicals used in the fabrication of previous works, this article reports a white polydimethylsiloxane (PDMS) sponge fabricated by a sustainable process using microsugar templates. By substituting the chemicals for sugar, the manufacturing procedure produces zero toxic waste and can also be endlessly recycled via methods widely used in the sugar industry. The obtained porous PDMS exhibits strong visible scattering and thermal emission, resulting in an efficient temperature reduction of 4.6 °C and cooling power of 43 W m under direct solar irradiation. In addition, due to the air-filled voids within the PDMS sponge, its thermal conductivity remains low at 0.06 W (m K) . This unique combination of radiative cooling and thermal insulation properties can efficiently suppress the heat exchange with the solar-heated rooftop or the environment, representing a promising future for new energy-efficient building envelope material.
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http://dx.doi.org/10.1002/advs.202102502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8655219PMC
December 2021

Microfiber from textile dyeing and printing wastewater of a typical industrial park in China: Occurrence, removal and release.

Sci Total Environ 2020 Oct 19;739:140329. Epub 2020 Jun 19.

School of Environment, Tsinghua University, Beijing 100084, PR China.

Microfibers (MFs) are fibrous micro particles of longitude <5 mm, including natural fibers and fibrous microplastics. Microplastic pollution has become a world issue. As the major section of fiber production and processing, textile industry is an important potential source of microfibers, while receiving limited attention. To better understand the source and fate of textile microfibers, in this study, a typical textile industrial park in China is selected as the studying site. Microfibers in textile wastewater from typical textile mills and centralized wastewater treatments plants (WWTPs) of the park, and microfibers in nearby surface water were identified and characterized. The main results showed that the microfiber concentration in textile printing and dyeing wastewater could reach as high as 54,100 MFs/L. Although the removal efficiencies of microfibers by existing wastewater treatment processes can be over 85%, the average microfiber concentration in the effluents from the centralized WWTPs of the industrial park still reached 537.5 MFs/L, releasing 430 billion microfiber items per day. Microfiber release from textile wastewater is considerably higher than that from municipal sewage treatment plants, making it a significant contributor to microfibers in natural water bodies. Small-sized and colored microfibers increased in proportion in the treated effluents. Given the complex textile wastewater constituents, the potential negative environmental impacts of textile microfibers may be intensified by the enhanced adsorption and transfer of textile pollutants through these microfibers.
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http://dx.doi.org/10.1016/j.scitotenv.2020.140329DOI Listing
October 2020

Matrix-transmitted paratensile signaling enables myofibroblast-fibroblast cross talk in fibrosis expansion.

Proc Natl Acad Sci U S A 2020 05 1;117(20):10832-10838. Epub 2020 May 1.

Department of Biomedical Engineering, School of Medicine, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China;

While the concept of intercellular mechanical communication has been revealed, the mechanistic insights have been poorly evidenced in the context of myofibroblast-fibroblast interaction during fibrosis expansion. Here we report and systematically investigate the mechanical force-mediated myofibroblast-fibroblast cross talk via the fibrous matrix, which we termed paratensile signaling. Paratensile signaling enables instantaneous and long-range mechanotransduction via collagen fibers (less than 1 s over 70 μm) to activate a single fibroblast, which is intracellularly mediated by DDR2 and integrin signaling pathways in a calcium-dependent manner through the mechanosensitive Piezo1 ion channel. By correlating in vitro fibroblast foci growth models with mathematical modeling, we demonstrate that the single-cell-level spatiotemporal feature of paratensile signaling can be applied to elucidate the tissue-level fibrosis expansion and that blocking paratensile signaling can effectively attenuate the fibroblast to myofibroblast transition at the border of fibrotic and normal tissue. Our comprehensive investigation of paratensile signaling in fibrosis expansion broadens the understanding of cellular dynamics during fibrogenesis and inspires antifibrotic intervention strategies targeting paratensile signaling.
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http://dx.doi.org/10.1073/pnas.1910650117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245086PMC
May 2020

mTORC1-Sch9 regulates hydrogen sulfide production through the transsulfuration pathway.

Aging (Albany NY) 2019 10 3;11(19):8418-8432. Epub 2019 Oct 3.

Key Laboratory of Bio-Resources and Eco-Environment of Ministry of Education, College of Life Science, Sichuan University, Chengdu 610064, Sichuan, China.

Endogenous hydrogen sulfide mediates anti-aging benefits of dietary restriction (DR). However, it is unclear how HS production is regulated by pathways related to DR. Due to the importance of mTORC1 pathway in DR, we investigated the effects of Sch9, a yeast homolog of mammalian S6K1 and a major substrate of mTORC1 on HS production in yeast . We found that inhibition of the mTORC1-Sch9 pathway by deletion, rapamycin or myriocin treatment resulted in a dramatic decrease in HS production. Although deficiency of did not alter the intracellular level of methionine, the intracellular level of cysteine increased in cells. The expression of and , two transsulfuration pathway genes encoding cystathionine gamma-lyase (CGL) and cystathionine beta-synthase (CBS), were also decreased under mTORC1-Sch9 inhibition. Overexpression of or in cells or WT cells treated with rapamycin rescued the deficiency of HS production. Finally, we also observed a reduction in HS production and lowering of both mRNA and protein levels of CGL and CBS in cultured human cells treated with rapamycin to reduce mTORC1 pathway activity. Thus, our findings reveal a probably conserved mechanism in which HS production by the transsulfuration pathway is regulated by mTORC1-Sch9 signaling.
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http://dx.doi.org/10.18632/aging.102327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814617PMC
October 2019

Cold Vapor Generation beyond the Input Solar Energy Limit.

Adv Sci (Weinh) 2018 Aug 3;5(8):1800222. Epub 2018 May 3.

Department of Electrical Engineering The State University of New York at Buffalo Buffalo NY 14260 USA.

100% efficiency is the ultimate goal for all energy harvesting and conversion applications. However, no energy conversion process is reported to reach this ideal limit before. Here, an example with near perfect energy conversion efficiency in the process of solar vapor generation below room temperature is reported. Remarkably, when the operational temperature of the system is below that of the surroundings (i.e., under low density solar illumination), the total vapor generation rate is higher than the upper limit that can be produced by the input solar energy because of extra energy taken from the warmer environment. Experimental results are provided to validate this intriguing strategy under 1 sun illumination. The best measured rate is ≈2.20 kg m h under 1 sun illumination, well beyond its corresponding upper limit of 1.68 kg m h and is even faster than the one reported by other systems under 2 sun illumination.
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http://dx.doi.org/10.1002/advs.201800222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096986PMC
August 2018

Optimization of preparing a high yield and high cationic degree starch graft copolymer as environmentally friendly flocculant: Through response surface methodology.

Int J Biol Macromol 2018 Oct 1;118(Pt B):1431-1437. Epub 2018 Jul 1.

School of Environment, Tsinghua University, Beijing 100084, PR China.

To pursuit effective and environmentally friendly flocculant, a bio-copolymer was prepared by starch grafting with acrylamide (AM) and dimethyl diallyl ammonium chloride (DMDAAC) through an initiator system KMnO/HIO. The initiation and grafting reaction were optimized by the Response Surface Methodology. In the initiation reaction, the optimum condition was KMnO at 0.28 mmol, HIO at 0.25 mmol, and the temperature at 67.64 °C, when the highest copolymer yield of 13.43 g was obtained from 4 g raw starch. In the grafting reaction, the optimum condition was the temperature at 68.71 °C, (AM + DMDAAC)/starch anhydroglucose units molar ratio at 2 and the AM / (AM + DMDAAC) molar ratio at 0.34, when the copolymer had the maximum cationic degree of 1.54 meq/g. The optimized preparing method had a high grafting efficiency of 97.12 ± 0.14% and high raw material utilization. The flocculation ability of the optimized graft copolymer was also tested. The result showed the graft starch was effective to remove reactive dyes and disperse dyes from wastewater. The dye removal efficiency of the graft starch was nearly 10% higher than polyacrylamide. Therefore, through the optimization of initiation and grafting reaction, the graft starch was a promising environmentally friendly flocculant.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.06.155DOI Listing
October 2018

Assessing historical and projected carbon balance of Alaska: A synthesis of results and policy/management implications.

Ecol Appl 2018 09 30;28(6):1396-1412. Epub 2018 Jul 30.

U.S. Geological Survey, Reston, Virginia, 12201, USA.

We summarize the results of a recent interagency assessment of land carbon dynamics in Alaska, in which carbon dynamics were estimated for all major terrestrial and aquatic ecosystems for the historical period (1950-2009) and a projection period (2010-2099). Between 1950 and 2009, upland and wetland (i.e., terrestrial) ecosystems of the state gained 0.4 Tg C/yr (0.1% of net primary production, NPP), resulting in a cumulative greenhouse gas radiative forcing of 1.68 × 10  W/m . The change in carbon storage is spatially variable with the region of the Northwest Boreal Landscape Conservation Cooperative (LCC) losing carbon because of fire disturbance. The combined carbon transport via various pathways through inland aquatic ecosystems of Alaska was estimated to be 41.3 Tg C/yr (17% of terrestrial NPP). During the projection period (2010-2099), carbon storage of terrestrial ecosystems of Alaska was projected to increase (22.5-70.0 Tg C/yr), primarily because of NPP increases of 10-30% associated with responses to rising atmospheric CO , increased nitrogen cycling, and longer growing seasons. Although carbon emissions to the atmosphere from wildfire and wetland CH were projected to increase for all of the climate projections, the increases in NPP more than compensated for those losses at the statewide level. Carbon dynamics of terrestrial ecosystems continue to warm the climate for four of the six future projections and cool the climate for only one of the projections. The attribution analyses we conducted indicated that the response of NPP in terrestrial ecosystems to rising atmospheric CO (~5% per 100 ppmv CO ) saturates as CO increases (between approximately +150 and +450 ppmv among projections). This response, along with the expectation that permafrost thaw would be much greater and release large quantities of permafrost carbon after 2100, suggests that projected carbon gains in terrestrial ecosystems of Alaska may not be sustained. From a national perspective, inclusion of all of Alaska in greenhouse gas inventory reports would ensure better accounting of the overall greenhouse gas balance of the nation and provide a foundation for considering mitigation activities in areas that are accessible enough to support substantive deployment.
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http://dx.doi.org/10.1002/eap.1768DOI Listing
September 2018

The role of environmental driving factors in historical and projected carbon dynamics of wetland ecosystems in Alaska.

Ecol Appl 2018 09 25;28(6):1377-1395. Epub 2018 Jun 25.

U.S. Geological Survey, Reston, Virginia, 12201, USA.

Wetlands are critical terrestrial ecosystems in Alaska, covering ~177,000 km , an area greater than all the wetlands in the remainder of the United States. To assess the relative influence of changing climate, atmospheric carbon dioxide (CO ) concentration, and fire regime on carbon balance in wetland ecosystems of Alaska, a modeling framework that incorporates a fire disturbance model and two biogeochemical models was used. Spatially explicit simulations were conducted at 1-km resolution for the historical period (1950-2009) and future projection period (2010-2099). Simulations estimated that wetland ecosystems of Alaska lost 175 Tg carbon (C) in the historical period. Ecosystem C storage in 2009 was 5,556 Tg, with 89% of the C stored in soils. The estimated loss of C as CO and biogenic methane (CH ) emissions resulted in wetlands of Alaska increasing the greenhouse gas forcing of climate warming. Simulations for the projection period were conducted for six climate change scenarios constructed from two climate models forced under three CO emission scenarios. Ecosystem C storage averaged among climate scenarios increased 3.94 Tg C/yr by 2099, with variability among the simulations ranging from 2.02 to 4.42 Tg C/yr. These increases were driven primarily by increases in net primary production (NPP) that were greater than losses from increased decomposition and fire. The NPP increase was driven by CO fertilization (~5% per 100 parts per million by volume increase) and by increases in air temperature (~1% per °C increase). Increases in air temperature were estimated to be the primary cause for a projected 47.7% mean increase in biogenic CH emissions among the simulations (~15% per °C increase). Ecosystem CO sequestration offset the increase in CH emissions during the 21st century to decrease the greenhouse gas forcing of climate warming. However, beyond 2100, we expect that this forcing will ultimately increase as wetland ecosystems transition from being a sink to a source of atmospheric CO because of (1) decreasing sensitivity of NPP to increasing atmospheric CO , (2) increasing availability of soil C for decomposition as permafrost thaws, and (3) continued positive sensitivity of biogenic CH emissions to increases in soil temperature.
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http://dx.doi.org/10.1002/eap.1755DOI Listing
September 2018

High throughput scaffold-based 3D micro-tumor array for efficient drug screening and chemosensitivity testing.

Biomaterials 2019 04 16;198:167-179. Epub 2018 May 16.

Department of Biomedical Engineering, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing, 100084, PR China. Electronic address:

Oncology drug development is greatly hampered by inefficient drug screening using 2D culture. Herein, we present ready-to-use micro-scaffolds in 384-well format to generate uniform 3D micro-tumor array (3D-MTA, CV < 0.15) that predicts in vivo drug responses more accurately than 2D monolayer. 3D-MTA generated from both cell lines and primary cells achieved high screen quality (Z' > 0.5), and were compatible with standard high throughput and high content instruments. Doxorubicin identified by 3D-MTA and 2D successfully inhibited tumor growth in mice bearing lung cancer cell line (H226) xenografts, but not gemcitabine and vinorelbine, which were selected solely by 2D. Resistance towards targeted therapy was modeled on 3D-MTA, which elicited SK-BR-3 to express higher proliferation-related genes in response to gefitinb, as compared to 2D. Screening of 56 MAPK inhibitors identified pisamertib to synergistically improve cytotoxicity effect in combination with gefitinib. Primary tumor cells derived from patient-derived xenografts further attested concordance of drug response in 3D-MTA with in vivo response. 3D-MTA was further extended to realize chemosensitivity testing using patient-derived cells. Overall, 3D-MTA demonstrated strong potential to accelerate drug discovery and improve cancer treatment by providing efficient drug screening.
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http://dx.doi.org/10.1016/j.biomaterials.2018.05.020DOI Listing
April 2019

Mechanotransduction-modulated fibrotic microniches reveal the contribution of angiogenesis in liver fibrosis.

Nat Mater 2017 12 13;16(12):1252-1261. Epub 2017 Nov 13.

Department of Biomedical Engineering, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing 100084, China.

The role of pathological angiogenesis on liver fibrogenesis is still unknown. Here, we developed fibrotic microniches (FμNs) that recapitulate the interaction of liver sinusoid endothelial cells (LSECs) and hepatic stellate cells (HSCs). We investigated how the mechanical properties of their substrates affect the formation of capillary-like structures and how they relate to the progression of angiogenesis during liver fibrosis. Differences in cell response in the FμNs were synonymous of the early and late stages of liver fibrosis. The stiffness of the early-stage FμNs was significantly elevated due to condensation of collagen fibrils induced by angiogenesis, and led to activation of HSCs by LSECs. We utilized these FμNs to understand the response to anti-angiogenic drugs, and it was evident that these drugs were effective only for early-stage liver fibrosis in vitro and in an in vivo mouse model of liver fibrosis. Late-stage liver fibrosis was not reversed following treatment with anti-angiogenic drugs but rather with inhibitors of collagen condensation. Our work reveals stage-specific angiogenesis-induced liver fibrogenesis via a previously unrevealed mechanotransduction mechanism which may offer precise intervention strategies targeting stage-specific disease progression.
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http://dx.doi.org/10.1038/nmat5024DOI Listing
December 2017

3D Microtissues for Injectable Regenerative Therapy and High-throughput Drug Screening.

J Vis Exp 2017 10 4(128). Epub 2017 Oct 4.

Department of Biomedical Engineering, School of Medicine, Tsinghua University; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases;

To upgrade traditional 2D cell culture to 3D cell culture, we have integrated microfabrication with cryogelation technology to produce macroporous microscale cryogels (microcryogels), which can be loaded with a variety of cell types to form 3D microtissues. Herein, we present the protocol to fabricate versatile 3D microtissues and their applications in regenerative therapy and drug screening. Size and shape-controllable microcryogels can be fabricated on an array chip, which can be harvested off-chip as individual cell-loaded carriers for injectable regenerative therapy or be further assembled on-chip into 3D microtissue arrays for high-throughput drug screening. Due to the high elastic nature of these microscale cryogels, the 3D microtissues exhibit great injectability for minimally invasive cell therapy by protecting cells from mechanical shear force during injection. This ensures enhanced cell survival and therapeutic effect in the mouse limb ischemia model. Meanwhile, assembly of 3D microtissue arrays in a standard 384-multi-well format facilitates the use of common laboratory facilities and equipment, enabling high-throughput drug screening on this versatile 3D cell culture platform.
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http://dx.doi.org/10.3791/55982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5752368PMC
October 2017

The role of driving factors in historical and projected carbon dynamics of upland ecosystems in Alaska.

Ecol Appl 2018 01 27;28(1):5-27. Epub 2017 Dec 27.

U.S. Geological Survey, Reston, Virginia, 12201, USA.

It is important to understand how upland ecosystems of Alaska, which are estimated to occupy 84% of the state (i.e., 1,237,774 km ), are influencing and will influence state-wide carbon (C) dynamics in the face of ongoing climate change. We coupled fire disturbance and biogeochemical models to assess the relative effects of changing atmospheric carbon dioxide (CO ), climate, logging and fire regimes on the historical and future C balance of upland ecosystems for the four main Landscape Conservation Cooperatives (LCCs) of Alaska. At the end of the historical period (1950-2009) of our analysis, we estimate that upland ecosystems of Alaska store ~50 Pg C (with ~90% of the C in soils), and gained 3.26 Tg C/yr. Three of the LCCs had gains in total ecosystem C storage, while the Northwest Boreal LCC lost C (-6.01 Tg C/yr) because of increases in fire activity. Carbon exports from logging affected only the North Pacific LCC and represented less than 1% of the state's net primary production (NPP). The analysis for the future time period (2010-2099) consisted of six simulations driven by climate outputs from two climate models for three emission scenarios. Across the climate scenarios, total ecosystem C storage increased between 19.5 and 66.3 Tg C/yr, which represents 3.4% to 11.7% increase in Alaska upland's storage. We conducted additional simulations to attribute these responses to environmental changes. This analysis showed that atmospheric CO fertilization was the main driver of ecosystem C balance. By comparing future simulations with constant and with increasing atmospheric CO , we estimated that the sensitivity of NPP was 4.8% per 100 ppmv, but NPP becomes less sensitive to CO increase throughout the 21st century. Overall, our analyses suggest that the decreasing CO sensitivity of NPP and the increasing sensitivity of heterotrophic respiration to air temperature, in addition to the increase in C loss from wildfires weakens the C sink from upland ecosystems of Alaska and will ultimately lead to a source of CO to the atmosphere beyond 2100. Therefore, we conclude that the increasing regional C sink we estimate for the 21st century will most likely be transitional.
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http://dx.doi.org/10.1002/eap.1641DOI Listing
January 2018

Biomechanically primed liver microtumor array as a high-throughput mechanopharmacological screening platform for stroma-reprogrammed combinatorial therapy.

Biomaterials 2017 04 27;124:12-24. Epub 2017 Jan 27.

Department of Biomedical Engineering, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing, 100084, China. Electronic address:

Recent breakthrough in stroma-reprogrammed combinatorial therapy (SRCT) for pancreatic tumor opens a new route for improving conventional chemotherapeutic efficacy, which utilizes VDR ligand to reprogram activated stromal cells in stiffened microenvironment, leading to reduced 'barrier effects' and increased tissue-infiltration of the chemotherapy drug. As a novel therapeutic strategy and mechanism of action, the progress of SRCT relies on tailored in vitro drug assessment platforms to further optimize its efficacy and extend to applications in other tumor types. Here, a high-throughput mechanopharmacological drug screening platform for SRCT was established based on biomechanically primed hepatic stromal stellate cells to recapitulate state-specific liver microtumors with barrier effects. Fifteen generic chemotherapy drugs co-administered with VDR ligand were screened to obtain optimal SRCT formulations (e.g. carboplatin + calcipotriol), which efficacy was successfully verified in xenograft tumor models. Overall, this platform provides a powerful tool for discovery and optimization of tissue-specific SRCT and realizes 'mechanopharmacology' to translate insights of stromal mechanobiology to pharmaceutical applications.
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http://dx.doi.org/10.1016/j.biomaterials.2017.01.030DOI Listing
April 2017

Developmental Times of Chrysomya megacephala (Fabricius) (Diptera: Calliphoridae) at Constant Temperatures and Applications in Forensic Entomology.

J Forensic Sci 2016 Sep 1;61(5):1278-84. Epub 2016 Sep 1.

Department of Forensic Medicine, School of Basic Medical Sciences, Chongqing Medical University, Yixueyuan Road No. 1, Yuzhong District, Chongqing, 400016, China.

The characteristic life stages of infesting blowflies (Calliphoridae) such as Chrysomya megacephala (Fabricius) are powerful evidence for estimating the death time of a corpse, but an established reference of developmental times for local blowfly species is required. We determined the developmental rates of C. megacephala from southwest China at seven constant temperatures (16-34°C). Isomegalen and isomorphen diagrams were constructed based on the larval length and time for each developmental event (first ecdysis, second ecdysis, wandering, pupariation, and eclosion), at each temperature. A thermal summation model was constructed by estimating the developmental threshold temperature D0 and the thermal summation constant K. The thermal summation model indicated that, for complete development from egg hatching to eclosion, D0 = 9.07 ± 0.54°C and K = 3991.07 ± 187.26 h °C. This reference can increase the accuracy of estimations of postmortem intervals in China by predicting the growth of C. megacephala.
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http://dx.doi.org/10.1111/1556-4029.13159DOI Listing
September 2016

A checklist of beetles (Insecta, Coleoptera) on pig carcasses in the suburban area of southwestern China: A preliminary study and its forensic relevance.

J Forensic Leg Med 2016 Jul 9;41:42-8. Epub 2016 Apr 9.

Department of Forensic Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China.

Examining the succession pattern of carrion insects on vertebrate carcasses is widely accepted as an effective method to estimate the postmortem interval (PMI) of decayed bodies. Investigation of the community of sarcosaprophagous insects, especially flies and beetles, is the foundation of the succession pattern study. This study aimed to investigate the sarcosaprophagous beetles succession on animal carcasses in the suburban area of southwestern China and to establish a basic catalog for forensic application. The present study was conducted in 2013 in a mountain in Chongqing municipality with modified Schoenly traps. Carcasses of miniature pig were used to simulate human bodies. For most carcasses, five decomposition stages were observed. A total of 2108 adult coleopterans belonging to at least 61 species and 18 families were collected in the study, and most of the specimens occurred at the advanced decay stage. Omosita colon (Linnaeus, 1758), Necrodes nigricornis (Harold, 1875), Necrobia ruficollis (Fabricius, 1775) and Neosilusa ceylonica (Kraatz, 1857) were the dominant species.
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http://dx.doi.org/10.1016/j.jflm.2016.04.009DOI Listing
July 2016

Bi-content micro-collagen chip provides contractility-based biomechanical readout for phenotypic drug screening with expanded and profiled targets.

Lab Chip 2015 Sep 29;15(17):3481-94. Epub 2015 Jul 29.

School of Life Sciences, Tsinghua University, Beijing, 10084, China.

Phenotypic screening has regained momentum in the pharmaceutical industry owing to its success over target-based screening. Most phenotypic screening relies on nonspecific biochemical readouts regarding cellular viability, which hampers the discovery of novel drug mechanisms of action (MOAs). Here we present a Contractility-based bi-Content micro-Collagen Chip (3CChip), which establishes cellular contractility as a biomechanics-related phenotype for drug screening. Bi-content analysis of cell contractility (imaged by iPhone) and viability suggests that the label-free contractility-based analysis exhibits superior sensitivity to compounds targeting contractile elements (e.g. focal adhesion, cytoskeleton), resulting in a enlarged target pool for drug assessment. Six typical readout patterns of drug response are summarized according to the relative positions of the contraction/viability curves, and drug targets are profiled into three categories (biomechanical, biochemical and housekeeping) by 3CChip, which will benefit subsequent target identification. The simple-to-use and effective 3CChip offers a robust platform for micro-tissue-based functional screening and may lead to a new era of mechanism-informed phenotypic drug discovery.
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http://dx.doi.org/10.1039/c5lc00589bDOI Listing
September 2015

Sch9 regulates intracellular protein ubiquitination by controlling stress responses.

Redox Biol 2015 Aug 9;5:290-300. Epub 2015 Jun 9.

Key Laboratory of Bio-Resources and Eco-Environment of Ministry of Education, College of Life Science, Sichuan University, Chengdu, Sichuan 610064, China. Electronic address:

Protein ubiquitination and the subsequent degradation are important means by which aberrant proteins are removed from cells, a key requirement for long-term survival. In this study, we found that the overall level of ubiquitinated proteins dramatically decreased as yeast cell grew from log to stationary phase. Deletion of SCH9, a gene encoding a key protein kinase for longevity control, decreased the level of ubiquitinated proteins in log phase and this effect could be reversed by restoring Sch9 function. We demonstrate here that the decrease of ubiquitinated proteins in sch9Δ cells in log phase is not caused by changes in ubiquitin expression, proteasome activity, or autophagy, but by enhanced expression of stress response factors and a decreased level of oxidative stress. Our results revealed for the first time how Sch9 regulates the level of ubiquitinated proteins and provides new insight into how Sch9 controls longevity.
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http://dx.doi.org/10.1016/j.redox.2015.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4477112PMC
August 2015

Technical note: Development of Hemipyrellia ligurriens (Wiedemann) (Diptera: Calliphoridae) at constant temperatures: Applications in estimating postmortem interval.

Forensic Sci Int 2015 Aug 14;253:48-54. Epub 2015 May 14.

Department of Forensic Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China. Electronic address:

Blowflies (Calliphoridae) are recognized as a powerful tool for estimating the minimum postmortem interval (PMImin). The times for blowflies to develop from oviposition to eclosion is mainly controlled by temperature, which can differ between even closely related species. Hemipyrellia ligurriens (Wiedemann) (Diptera: Calliphoridae) is a blowfly distributed throughout Asia and Australia. However, a systematic determination of the developmental times of H. ligurriens under constant temperature, necessary for estimating the PMImin, is lacking. Such an examination would broaden the forensic importance of the species. Thus, this study explored the growth curves of larval H. ligurriens at 7 constant temperatures (16, 19, 22, 25, 28, 31, and 34°C). Isomegalen and isomorphen diagrams were successfully constructed, depicting the time of larval length or developmental event, respectively, at different temperatures. A thermal summation model was also constructed via regression analysis, by estimating the developmental threshold temperature t and thermal summation constant K. The thermal summation model indicated that t at 8.3°C and K at 5747.5 degree-hours (°Ch) are required for complete development from oviposition to eclosion, and suggested an optimum temperature range of 16-28°C for the development of H. ligurriens. These data establish for the first time the temperature-dependent developmental time of H. ligurriens for forensic entomology application. The 3 developmental models are provided.
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http://dx.doi.org/10.1016/j.forsciint.2015.05.006DOI Listing
August 2015
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