Publications by authors named "Mingmin Zhang"

43 Publications

TMEM120A contains a specific coenzyme A-binding site and might not mediate poking- or stretch-induced channel activities in cells.

Elife 2021 Aug 19;10. Epub 2021 Aug 19.

National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

TMEM120A, a member of the Transmembrane protein 120 (TMEM120) family, has pivotal function in adipocyte differentiation and metabolism, and may also contribute to sensing mechanical pain by functioning as an ion channel named TACAN. Here we report that expression of TMEM120A is not sufficient in mediating poking- or stretch-induced currents in cells, and have solved cryo-EM structures of human TMEM120A (TMEM120A) in complex with an endogenous metabolic cofactor (coenzyme A, CoASH) and in the apo form. TMEM120A forms a symmetrical homodimer with each monomer containing an amino-terminal coiled-coil motif followed by a transmembrane domain with six membrane-spanning helices. Within the transmembrane domain, a CoASH molecule is hosted in a deep cavity and forms specific interactions with nearby amino acid residues. Mutation of a central tryptophan residue involved in binding CoASH dramatically reduced the binding affinity of TMEM120A with CoASH. TMEM120A exhibits distinct conformations at the states with or without CoASH bound. Our results suggest that TMEM120A may have alternative functional roles potentially involved in CoASH transport, sensing or metabolism.
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http://dx.doi.org/10.7554/eLife.71474DOI Listing
August 2021

MagicChem: a MR system based on needs theory for chemical experiments.

Virtual Real 2021 Jul 22:1-16. Epub 2021 Jul 22.

Jing Hengyi Education College, Hangzhou Normal University, Hangzhou, China.

Real chemical experiments may be dangerous or pollute the environment; meanwhile, the preparation of drugs and reagents is time-consuming. Due to the above-mentioned reasons, few experiments can be actually operated by students, which is not conducive to the chemistry learning and the phenomena principle understanding. Recently, due to the impact of Covid-19, many schools adopt online teaching, which is even more detrimental to students' learning of chemistry. Fortunately, MR(mixed reality) technology provides us with the possibility of solving the safety issues and breaking the space-time constraints, while the theory of human needs (Maslow's hierarchical needs) provides us with a way to design a comfortable and stimulant MR system with realistic visual presentation and interaction. The paper combines with the theory of human needs to propose a new needs model for virtual experiment. Based on this needs model, we design and develop a comprehensive MR system called MagicChem, which offers a robust 6-DoF interactive and illumination consistent experimental space with virtual-real occlusion, supporting realistic visual interaction, tangible interaction, gesture interaction with touching, voice interaction, temperature interaction, olfactory interaction and virtual human interaction. User study shows that MagicChem satisfies the needs model better than other MR experimental environments that partially meet the needs model. In addition, we explore the application of the needs model in VR environment.

Supplementary Information: The online version contains supplementary material available at 10.1007/s10055-021-00560-z.
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http://dx.doi.org/10.1007/s10055-021-00560-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295458PMC
July 2021

Si-Wu-Tang facilitates ovarian function through improving ovarian microenvironment and angiogenesis in a mouse model of premature ovarian failure.

J Ethnopharmacol 2021 Nov 19;280:114431. Epub 2021 Jul 19.

Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China; Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address:

Ethnopharmacological Relevance: Premature ovarian failure (POF) is a severe illness, characterized by premature menopause with a markedly decrease in ovarian function, which leads to infertility. Si-Wu-Tang (SWT), also called "the first prescription of gynecology" by medical experts in China, is widely used as the basic formula in regulating the menstrual cycle and treating infertility. However, the potential effect and underlying mechanisms of action of SWT on the treatment of POF have not yet been elucidated.

Purpose: This study aimed to explore the therapeutic effect and underlying molecular mechanism of action of SWT on the treatment of POF in C57BL/6 mice.

Materials And Methods: The main compounds of SWT were identified by high-performance liquid chromatography (HPLC). POF model groups were established by a single intraperitoneal injection of cyclophosphamide (Cy, 100 mg/kg). SWT or dehydroepiandrosterone (DHEA) were administered via oral gavage for 28 consecutive days. Ovarian function and pathological changes were evaluated by hormone levels, follicular development, and changes in angiogenesis. Furthermore, statistical analyses of fertility were also performed.

Results: Treatment with SWT significantly improved estrogen levels, the number of follicles, antioxidant defense, and microvascular formation in POF mice. Moreover, SWT significantly activated the Nrf2/HO-1 and STAT3/HIF-1α/VEGF signaling pathways to promote angiogenesis, resulting in a better fertility outcome when compared to the model group.

Conclusions: Our findings indicated that SWT protected ovarian function of Cy-induced POF mice by improving the antioxidant ability and promoting ovarian angiogenesis, thereby providing scientific evidence for the treatment of POF using SWT.
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http://dx.doi.org/10.1016/j.jep.2021.114431DOI Listing
November 2021

Single-molecule optical mapping of the distribution of DNA phosphorothioate epigenetics.

Nucleic Acids Res 2021 04;49(7):3672-3680

Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.

DNA phosphorothioate (PT) modifications, with the nonbridging phosphate oxygen replaced by sulfur, governed by DndABCDE or SspABCD, are widely distributed in prokaryotes and have a highly unusual feature of occupying only a small portion of available consensus sequences in a genome. Despite the presence of plentiful non-PT-protected consensuses, DNA PT modification is still employed as a recognition tag by the restriction cognate, for example, DndFGH or SspE, to discriminate and destroy PT-lacking foreign DNA. This raises a fundamental question about how PT modifications are distributed along DNA molecules to keep the restriction components in check. Here, we present two single-molecule strategies that take advantage of the nucleophilicity of PT in combination with fluorescent markers for optical mapping of both single- and double-stranded PT modifications across individual DNA molecules. Surprisingly, PT profiles vary markedly from molecule to molecule, with different PT locations and spacing distances between PT pairs, even in the presence of DndFGH or SspE. The results revealed unprecedented PT modification features previously obscured by ensemble averaging, providing novel insights into the riddles regarding unusual target selection by PT modification and restriction components.
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http://dx.doi.org/10.1093/nar/gkab169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053081PMC
April 2021

The mechanosensitive Piezo1 channel mediates heart mechano-chemo transduction.

Nat Commun 2021 02 8;12(1):869. Epub 2021 Feb 8.

State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, IDG/McGovern Institute for Brain Research, School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, China.

The beating heart possesses the intrinsic ability to adapt cardiac output to changes in mechanical load. The century-old Frank-Starling law and Anrep effect have documented that stretching the heart during diastolic filling increases its contractile force. However, the molecular mechanotransduction mechanism and its impact on cardiac health and disease remain elusive. Here we show that the mechanically activated Piezo1 channel converts mechanical stretch of cardiomyocytes into Ca and reactive oxygen species (ROS) signaling, which critically determines the mechanical activity of the heart. Either cardiac-specific knockout or overexpression of Piezo1 in mice results in defective Ca and ROS signaling and the development of cardiomyopathy, demonstrating a homeostatic role of Piezo1. Piezo1 is pathologically upregulated in both mouse and human diseased hearts via an autonomic response of cardiomyocytes. Thus, Piezo1 serves as a key cardiac mechanotransducer for initiating mechano-chemo transduction and consequently maintaining normal heart function, and might represent a novel therapeutic target for treating human heart diseases.
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http://dx.doi.org/10.1038/s41467-021-21178-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870949PMC
February 2021

Bushen Huoxue recipe attenuates early pregnancy loss via activating endometrial COX2-PGE2 angiogenic signaling in mice.

BMC Complement Med Ther 2021 Jan 14;21(1):36. Epub 2021 Jan 14.

Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.

Background: During the fresh cycles of in vitro fertilization and embryo transfer, a disturbance in the reproductive endocrine environment following controlled ovarian hyperstimulation (COH) is closely related to compromised endometrial receptivity. This is a major disadvantage for women during pregnancy. Based on the theory of traditional Chinese medicine, Bushen Huoxue recipe (BSHXR) has been indicated to facilitate embryo implantation.

Methods: The COH model (Kunming breed) was induced by injecting mice with pregnant mare serum gonadotrophin (0.4 IU/g) and human chorionic gonadotropin (1 IU/g), followed by treatment with BSHXR at three different concentrations (5.7, 11.4, and 22.8 g/kg), Bushen recipe (BSR) (5.7 g/kg), and Huoxue recipe (HXR) (5.7 g/kg). After successful mating, the pregnancy rate and implantation sites were examined on embryo day 8 (ED8), and the weight ratio of endometrium was calculated on ED4 midnight. Serum estrogen, progesterone, and endometrial PGE2 levels were measured using enzyme-linked immunosorbent assay. The endometrial microvasculature was evaluated using CD31 immunostaining. The protein and mRNA levels of the angiogenic factors in the endometrium were evaluated using western blot, immunohistochemistry, and polymerase chain reaction.

Results: In the COH group, the pregnancy rate and implantation sites were significantly decreased, and abnormal serum hormone levels and impaired endometrial vascular development were observed. After BSHXR treatment, the supraphysiological serum progesterone level in COH mice was restored to normalcy. Moreover, the abnormal expression of the endometrial pro-angiogenic factors, including HIF1α, COX2-PGE2 pathway, and the down-stream factors, namely, MMP2, MMP9, TIMP2, and FGF2 after subjecting mice to COH was significantly improved after BSHXR treatment.

Conclusion: BSHXR could improve embryo implantation by regulating hormonal balance and modulating endometrial angiogenesis in mice, without inducing any side effects in normal pregnancy.
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http://dx.doi.org/10.1186/s12906-021-03201-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809844PMC
January 2021

microRNA-9-5p regulates the mitochondrial function of hepatocellular carcinoma cells through suppressing PDK4.

Cancer Gene Ther 2021 Jun 30;28(6):706-718. Epub 2020 Nov 30.

Integrative Cancer Centre, Guangzhou University of Chinese Medicine First Affiliated Hospital, 510405, Guangzhou, China.

Due to the lack of early diagnostic and effective treatment modalities, hepatocellular carcinoma (HCC) is still the most lethal cancer with a high mortality on a global scale. Recent studies have highlighted the key roles of microRNAs (miRs) in HCC development. In the study, we attempted to investigate the potential role of miR-9-5p in the progression of HCC. Expression of pyruvate dehydrogenase kinase 4 (PDK4) and miR-9-5p was examined in HCC tissues collected from HCC patients and cell lines. The proliferation, migration, invasion, and apoptosis of HCC cells, and levels of oxygen consumption rate, extracellular acidification rate and reactive oxygen species (ROS) as well as the tumorigenicity of transfected cells in vivo were measured after gain- and loss-of-function experiments in HCC cells. It was revealed that miR-9-5p was upregulated, while PDK4 was poorly expressed in HCC tissues and cells, associating with a poor prognosis of HCC patients. miR-9-5p directly targeted PDK4 and could downregulate its expression, thus leading to promoted cell proliferation, invasion and migration, enhanced mitochondrial activity and energy metabolism, and suppressed apoptosis in HCC cells, along with increased tumorigenicity in mouse xenograft models. Altogether, miR-9-5p facilitated mitochondrial energy metabolism of HCC cells by downregulating PDK4, promoting the development of HCC. miR-9-5p and PDK4 may serve as potential therapeutic targets for preventing recurrence and metastasis of HCC.
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http://dx.doi.org/10.1038/s41417-020-00253-wDOI Listing
June 2021

Investigation on the mental health status of pregnant women in China during the Pandemic of COVID-19.

Arch Gynecol Obstet 2021 02 3;303(2):463-469. Epub 2020 Oct 3.

Department of Traditional Chinese Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road 1095#, Wuhan, 430030, Hubei Province, China.

Purpose: To evaluate the anxiety and depression in pregnant women in China, and its influencing factors during the corona virus disease 2019 (COVID-19) pandemic.

Methods: From February 22 to February 27, a questionnaire survey was conducted on 156 pregnant women, including demographic characteristics, a self-rating anxiety scale (SAS), and a self-depression rating scale (SDS).

Results: A total of 13 non-homologous end-joining (8.3%, 13/156) patients were anxious, 79 patients (50.6%, 79/156) were depressed, and 13 patients (8.3%, 13/156) suffered from both anxiety and depression. The SAS score of pregnant women was 40.55 ± 6.09, and the SDS score was 50.42 ± 11.64. For the SAS score, only 8.3% of all patients (13/156) were in a light anxiety state. For the SDS score, 46.79% (73/156) of patients was normal, 23.72% of patients (37/156) showed mild depression, 22.44% (35/156) showed moderate depression, and 4.49% (7/156) showed severe depression. No significant changes were observed in SAS and SDS scores between patients from different regions within China, health state, gestational week, educational background, and living condition (P > 0.05). Moreover, no significant differences were observed between diagnosed/suspected patients and the normal control group (P > 0.05), and between pregnant women in Wuhan compared to other regions (P > 0.05).

Conclusion: During the COVID-19 epidemic, the anxiety level of pregnant women was the same as that before the epidemic, while the level of depression was significantly higher. Pregnant women who lived in Wuhan, the epicenter of the epidemic, were not more anxious or depressed compared to pregnant women in other regions during the COVID-19 epidemic. Furthermore, the mental health status of pregnant women with COVID-19 was not more severe.
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http://dx.doi.org/10.1007/s00404-020-05805-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532741PMC
February 2021

Different clinical presentations of two renal transplant recipients with coronavirus disease 2019: a case report.

BMC Infect Dis 2020 Sep 25;20(1):707. Epub 2020 Sep 25.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.

Background: The Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome Coronavirus-2 has spread rapidly worldwide and disease spread is currently increasing. Data on the clinical picture of transplant recipients and management of the anti-rejection immunosuppressive therapy on COVID-19 infection are lacking.

Case Presentation: We report two cases of COVID-19 infection in renal transplant recipients with variable clinical presentations. The first patient presented with mild respiratory symptoms and a stable clinical course. The second patient had more severe clinical characteristics and presented with severe pneumonia and multi-organ failure. Both patients received a combination therapy including antiviral treatment and reduced immunosuppression therapy and finally recovered.

Conclusions: We report COVID-19 infection in two renal transplant recipients with a favorable outcome but different clinical courses, which may provide a reference value for treating such patients.
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http://dx.doi.org/10.1186/s12879-020-05434-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517783PMC
September 2020

Dream-Experiment: A MR User Interface with Natural Multi-channel Interaction for Virtual Experiments.

IEEE Trans Vis Comput Graph 2020 Dec 10;26(12):3524-3534. Epub 2020 Nov 10.

This paper studies a set of MR technologies for middle school experimental teaching environments and develops a multi-channel MR user interface called Dream-Experiment. The goal of Dream-Experiment is to improve the traditional MR user interface, so that users can get a real, natural 3D interactive experience like real experiments, but without danger and pollution. In terms of visual presentation, we design multi-camera collaborative registration to realize robust 6-DoF MR interactive space, and also define a complete rendering pipeline to provide improved processing of virtual-real objects' occlusion including translucent devices. In the virtual-real interaction, we provide six interaction modes that support visual interaction, tangible interaction, virtual-real gestures with touching, voice, thermal feeling, and olfactory feeling. After users' testing, we find that Dream-Experiment has better interactive efficiency and user experience than traditional MR environments.
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http://dx.doi.org/10.1109/TVCG.2020.3023602DOI Listing
December 2020

Advantages of a 21-loci short tandem repeat method for detection of cross-contamination in human cell lines.

Gene 2020 Dec 14;763:145048. Epub 2020 Aug 14.

College of Life Sciences, Wuhan University, Wuhan, China; China Center for Type Culture Collection, Wuhan University, Wuhan, China. Electronic address:

Cross-contamination of cell lines is a highly relevant and pervasive problem. The analysis of short tandem repeats (STR) is a simple and commercially available technique to authenticate cell lines for more than two decades. At present, STR multiple amplification kits have been developed up to 21 loci while the current STR databases only provide 9-loci STR profiles. Here, we compared the advantages of 21-loci STR methodology using the same algorithm as 9-loci method. The 21-loci method reduced the uncertainty ratio for authentications by 97.5% relative to the 9-loci method and exclude effectively false positive. We show that the additional 12 loci helped to greatly reduce sample-site marker specificity arising from genetic isolation and the occurrence of null alleles, suggesting that inclusion of additional loci in these databases will ultimately improve the efficiency and accuracy of authentication of cell lines. Taken together, we demonstrate the utility of a 21-loci method in human cells, providing a novel marker panel for use as a valuable alternative to 9-loci analyses to minimize cell line authentication errors and reduce costs due to erroneous experiments.
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http://dx.doi.org/10.1016/j.gene.2020.145048DOI Listing
December 2020

[Application of medical biomaterials in prevention and treatment of tendon adhesion].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2020 Aug;34(8):1065-1070

Department of Trauma Orthopedics, Nanfang Hospital Affiliated to Southern Medical University, Guangzhou Guangdong, 510515, P.R.China.

Objective: To review the research progress of medicine biomaterials in prevention and treatment of adhesion after tendon injury, and to provide reference for clinical treatment.

Methods: The literature on the application of medical biomaterials in the prevention and treatment of tendon adhesions in recent years was reviewed, and the biological process, treatment methods, and current status of tendon adhesions were summarized.

Results: Tendon adhesion as part of the healing process of the tendon is the biological response of the tendon to the injury and is also a common complication of joint dysfunction. Application of medical biomaterials can achieve better biological function of postoperative tendon by reducing the adhesion of peritendon tissues as far as possible without adversely affecting the tendon healing process.

Conclusion: The use of medical biomaterials is conducive to reduce the adhesion of tendon after operation, and the appropriate anti-adhesion material should be selected according to the patients' condition and surgical needs.
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http://dx.doi.org/10.7507/1002-1892.201910024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171898PMC
August 2020

Clinical characteristics of 17 patients with COVID-19 and systemic autoimmune diseases: a retrospective study.

Ann Rheum Dis 2020 09 16;79(9):1163-1169. Epub 2020 Jun 16.

Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China

Objectives: Increasing data about COVID-19 have been acquired from the general population. We aim to further evaluate the clinical characteristics of COVID-19 in patients with systemic autoimmune diseases (AIDs).

Methods: We included all confirmed inpatients with COVID-19 and systemic AIDs in Wuhan Tongji Hospital from 29 January to 8 March 2020. We retrospectively collected and analysed information on epidemiology of 1255 inpatients and additional clinical characteristics of patients with systemic AIDs. Outcomes were followed up until 16 April 2020.

Results: Of the 1255 patients with COVID-19, the median age was 64.0 years and 53.1% were male. More than half (63.0%) had chronic comorbidities. The proportions of elderly, male and patients with comorbidities were significantly higher in intensive care unit (ICU) than in the general ward (p<0.001). 17 (0.61%) patients with systemic AIDs were further screened and analysed from 2804 inpatients. The median age was 64.0 years and 82.4% were female. All patients were living in Wuhan and two family clusters were found. 1 (5.9%) patient was admitted to ICU and one died. 10 (62.5%) of 16 patients changed or stopped their anti-AIDs treatments during hospitalisation, and 5 of them felt that the disease had worsened after the quarantine.

Conclusions: Older males with chronic comorbidities are more vulnerable to severe COVID-19. The lower proportion of COVID-19 in patients with systemic AIDs needs more high-quality human clinical trials and in-depth mechanism researches. Of note, the withdrawal of anti-AIDs treatments during hospitalisation can lead to flares of diseases.
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http://dx.doi.org/10.1136/annrheumdis-2020-217425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316114PMC
September 2020

Psychological symptoms among frontline healthcare workers during COVID-19 outbreak in Wuhan.

Gen Hosp Psychiatry 2020 Nov-Dec;67:144-145. Epub 2020 Apr 3.

Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address:

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http://dx.doi.org/10.1016/j.genhosppsych.2020.03.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194721PMC
December 2020

General Issues in Clinical Research of Acupuncture and In Vitro Fertilization.

Evid Based Complement Alternat Med 2020 13;2020:3460641. Epub 2020 Apr 13.

Department of Neurology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan 430030, China.

In vitro fertilization-embryo transfer (IVF-ET), a well-developed technology, provides the last possibility or hope for infertile women. However, the live birth rate per IVF cycle is still not satisfactory. Acupuncture is a frequently used adjunctive therapy drawing wide attention on improvement of IVF. Although so many randomized controlled trials have been evaluating the effect of acupuncture on IVF in the past 20 years, the exact efficacy of acupuncture on IVF is still controversy mainly because of no consensus on placebo control and acupuncture scheme. This paper focused on the general issues in clinical research of acupuncture and IVF and gave some suggestions for future directions.
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http://dx.doi.org/10.1155/2020/3460641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174969PMC
April 2020

A Plug-and-Latch Mechanism for Gating the Mechanosensitive Piezo Channel.

Neuron 2020 05 5;106(3):438-451.e6. Epub 2020 Mar 5.

State Key Laboratory of Membrane Biology, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, IDG/McGovern Institute for Brain Research, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China. Electronic address:

The mechanosensitive Piezo1 and Piezo2 channels convert mechanical force into cation permeation. However, their precise mechanogating and regulatory mechanisms remain elusive. Here, we report that Piezo1 utilizes three lateral ion-conducting portals equipped with physical gates for cooperative gating and splicing regulation. Mutating residues lining the portal converts Piezo1 into an anion-selective channel, demonstrating the portal-based cation-permeating pathway. Intriguingly, the portal is physically blocked with a plug domain, which undergoes alternative splicing in both Piezo1 and Piezo2. The Piezo1 isoform has local openings of the portals, enlarged single-channel conductance and sensitized mechanosensitivity. Remarkably, the three plugs are strategically latched onto the central axis for coordinated gating of the three portals. Disrupting the latching induces three quantal sub-conductance states in Piezo1, but not in the isoform. Together, we propose that Piezo utilizes an elegant plug-and-latch mechanism to physically and coordinately gate the lateral portals through the spliceable plug gates.
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http://dx.doi.org/10.1016/j.neuron.2020.02.010DOI Listing
May 2020

Jiao-tai-wan inhibits inflammation of the gut-brain-axis and attenuates cognitive impairment in insomnic rats.

J Ethnopharmacol 2020 Mar 13;250:112478. Epub 2019 Dec 13.

Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR China. Electronic address:

Ethnopharmacological Relevance: Jiao-tai-wan is a well-known traditional Chinese herbal medicine formula that is used to treat insomnia and systemic inflammation. Studies indicate chronic insomnia might contribute to the prevalence of cognitive impairment. The role of systemic inflammation and intestinal permeability in the progression of neurodegenerative diseases attracts much attention.

Aim Of The Study: This study aimed to investigate if Jiao-tai-wan plays a role in promoting the repair of the intestinal epithelial barrier to suppress systemic inflammation and cognitive impairment in sleep-deprived (SD) rats.

Materials And Methods: Male obesity-resistant SD rats were partially sleep-deprived for 16 weeks. During the last 8 weeks, they were treated with Jiao-tai-wan. A Morris water maze was used to analyze their cognitive ability. Aβ42 and proinflammation cytokines in the cerebrospinal fluid, tissue, or serum were determined using enzyme-linked immunosorbent assay or polymerase chain reaction. Intestinal permeability was detected using the fluorescein isothiocyanate-dextran perfusion assay method. Plasma lipopolysaccharide (LPS) levels were detected with Tachypleus Amebocyte Lysate. Western bolt was used in the signaling pathway analysis.

Results: Sleep deprivation deteriorated the performance of rats in the Morris water maze and increased the Aβ42, caspase3, IL-6, and TNF-α levels in their brains. The intestinal TLR4/NF-κB pathway was activated with an increase in the expression of IL-6 and TNF-α. The expression of tight junction proteins was also decreased in the intestinal tissue. This increased the intestinal permeability and circulation of LPS, LPS binding protein, IL-6, and TNF-α. Treatment with Jiao-tai-wan could partly reverse these changes.

Conclusion: Jiao-tai-wan has the potential to attenuate systemic inflammation and cognitive impairment in partially sleep-deprived rats. The possible underlying mechanism is by preventing an inflammation trigger being transferred through the gut-brain-axis.
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http://dx.doi.org/10.1016/j.jep.2019.112478DOI Listing
March 2020

Structure and mechanogating of the mammalian tactile channel PIEZO2.

Nature 2019 09 21;573(7773):225-229. Epub 2019 Aug 21.

State Key Laboratory of Membrane Biology, Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, IDG/McGovern Institute for Brain Research, School of Pharmaceutical Sciences, Tsinghua University, Beijing, China.

PIEZO2 is a mechanosensitive cation channel that has a key role in sensing touch, tactile pain, breathing and blood pressure. Here we describe the cryo-electron microscopy structure of mouse PIEZO2, which is a three-bladed, propeller-like trimer that comprises 114 transmembrane helices (38 per protomer). Transmembrane helices 1-36 (TM1-36) are folded into nine tandem units of four transmembrane helices each to form the unusual non-planar blades. The three blades are collectively curved into a nano-dome of 28-nm diameter and 10-nm depth, with an extracellular cap-like structure embedded in the centre and a 9-nm-long intracellular beam connecting to the central pore. TM38 and the C-terminal domain are surrounded by the anchor domain and TM37, and enclose the central pore with both transmembrane and cytoplasmic constriction sites. Structural comparison between PIEZO2 and its homologue PIEZO1 reveals that the transmembrane constriction site might act as a transmembrane gate that is controlled by the cap domain. Together, our studies provide insights into the structure and mechanogating mechanism of Piezo channels.
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http://dx.doi.org/10.1038/s41586-019-1505-8DOI Listing
September 2019

Mechanically Activated Piezo Channels Mediate Touch and Suppress Acute Mechanical Pain Response in Mice.

Cell Rep 2019 02;26(6):1419-1431.e4

State Key Laboratory of Membrane Biology, Tsinghua-Peking Joint Center for Life Sciences, IDG/McGovern Institute for Brain Research, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China; Joint Graduate Program of Peking-Tsinghua-NIBS, Tsinghua University, Beijing 100084, China. Electronic address:

Touch and mechanical pain represent distinct, but interactive, modalities of mechanosensation. However, the molecular mechanisms underlying these mechanotransduction processes remain incompletely understood. Here, we show that deletion of the mechanically activated and rapidly adapting Piezo2 channel in a portion of the low-threshold mechanoreceptors and a majority of the IB4-positive nociceptors impairs touch but sensitizes mechanical pain in mice. Ectopic expression of the Piezo2 homolog, the intermediately adapting Piezo1 channel, in sensory neurons can sensitize touch in normal mice and rescue defective touch of the Piezo2-knockout mice. Broad expression of Piezo1 in sensory neurons decreases, rather than evokes, mechanical pain responses. Together, our data suggest that Piezo channels can mediate touch and indirectly suppress acute pain. Tuning Piezo-mediated touch sensitivity allows us to recapitulate the inhibitory effect of touch on acute pain in mouse models.
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http://dx.doi.org/10.1016/j.celrep.2019.01.056DOI Listing
February 2019

STIM1 thermosensitivity defines the optimal preference temperature for warm sensation in mice.

Cell Res 2019 02 3;29(2):95-109. Epub 2019 Jan 3.

State Key Laboratory of Membrane Biology; Tsinghua-Peking Joint Center for Life Sciences; IDG/McGovern Institute for Brain Research; School of Pharmaceutical Sciences, Tsinghua University, 100084, Beijing, China.

Mammals possess a remarkable ability to sense subtle temperature deviations from the thermoneutral skin temperature of ~33 °C, which ensures precise warm sensation. However, the underlying mechanisms remain unclear. Here we show that STIM1, an endoplasmic reticulum (ER) resident transmembrane protein that responds to both ER Ca depletion and heat, mediates temperature-induced Ca influx in skin keratinocytes via coupling to Orai Ca channels in plasma membrane. Behaviorally, the keratinocyte-specific knockout of STIM1 shifts the optimal preference temperature (OPT) of mice from ~32 °C to ~34 °C, resulting in a strikingly reversed preference between 32 °C and 34 °C. Importantly, the thermally inactive STIM1-ΔK knock-in mice show altered OPT and warm preference behaviors as well, demonstrating the requirement of STIM1 thermosensitivity for warm sensation. Furthermore, the wild-type and mutant mice prefer temperatures closer to their respective OPTs, but poorly distinguish temperatures that are equally but oppositely deviated from their OPTs. Mechanistically, keratinocyte STIM1 affects the in vivo warm responses of sensory neurons by likely involving TRPA1 as a downstream transduction channel. Collectively, our data suggest that STIM1 serves as a novel in vivo thermosensor in keratinocytes to define the OPT, which might be utilized as a peripheral reference temperature for precise warm sensation.
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http://dx.doi.org/10.1038/s41422-018-0129-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355819PMC
February 2019

Tumor Growth Assessment by Computed Tomography Perfusion Imaging (CTPI), Perfusion-Weighted Imaging (PWI), and Diffusion-Weighted Imaging (DWI) in a Rabbit Pleural Squamous Cell Carcinoma VX2-Implanted Model.

Med Sci Monit 2018 Sep 25;24:6756-6764. Epub 2018 Sep 25.

Department of Radiology, Baotou Cancer Hospital, Baotou, Inner Mongolia, China (mainland).

BACKGROUND Computed tomography perfusion imaging (CTPI) and perfusion-weighted imaging (PWI) are non-invasive technologies that can quantify tumor vascularity and blood flow. This study explored the blood flow information, tumor cell viability, and hydrothoraces in a rabbit pleural VX2-implanted model through use of CTPI, PWI, and DWI. MATERIAL AND METHODS A pleural VX2-implanted model was established in 58 New Zealand white rabbits. CTPI, PWI, and DWI were applied with a 16-slice spiral CT and an Archival 1.5 T dual-gradient MRI. RESULTS Compared with muscle tissue, PV, PEI, and BV of parietal and visceral pleural tumor implantation rabbits showed significant differences. The t values of PV, PEI, and BV between parietal and visceral pleura were 2.08, 2.29, and 2.88, respectively. Compared with muscle tissue, WIR, WOR, and MAXR of parietal and visceral pleural tumor implantation rabbits showed significant differences. In parietal pleural tumor implantation rabbits, the section surface of lesion tissues was 5.2±2.7 cm². Hydrothorax appeared 6.0±2.0 days after tumor implantation. The mean value of ADC was 1.5±0.6. In visceral pleural tumor implantation rabbits, the section surface of lesion tissues was 1.6±0.8 cm². Hydrothorax appeared 7.0±3.0 days after tumor implantation. The mean value of ADC was 1.4±0.5. The t values of the above 3 indices for the parietal and visceral pleura were 1.85, 1.83, and 1.76, respectively (P<0.05). CONCLUSIONS The combined application of CTPI, PWI, and DWI accurately and visually reflects the blood perfusion of tumor tissues and quantitatively analyzes blood flow information and the mechanism underlying hydrothorax generation in tumor tissues.
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http://dx.doi.org/10.12659/MSM.909431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247745PMC
September 2018

Bushen Huoxue Recipe Alleviates Implantation Loss in Mice by Enhancing Estrogen-Progesterone Signals and Promoting Decidual Angiogenesis Through FGF2 During Early Pregnancy.

Front Pharmacol 2018 15;9:437. Epub 2018 May 15.

Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Bushen Huoxue recipe (BSHXR) is a classic Chinese herbal prescription for nourishing the kidney and activating blood circulation. It consists of six herbs: , , , , , and , and the main active constituents of BSHXR are ferulic acid, calycosin-7-glucopyranoside, hyperoside, quercitrin, and asperosaponin VI. In clinical practice, BSHXR is traditionally used to treat failed pregnancy and its complications. However, little is known about the underlying mechanism of BSHXR for the treatment of implantation loss during early pregnancy. In the current study, controlled ovarian hyperstimulation was induced in mice as our implantation loss model, and we evaluated the effects of BSHXR on implantation, decidualization, decidual angiogenesis, and reproductive outcome. We showed that BSHXR could regulate the supraphysiological levels of serum estrogen and progesterone observed in these mice, and also act on estrogen and progesterone receptors in the stroma and epithelium. BSHXR also enhanced FGF2 expression in the vascular sinus folding area of the decidua, thus potentially reducing implantation loss during early pregnancy and contributing to placentation and survival of the fetuses. Taken together, our findings provide scientific evidence for the application of BSHXR in the clinic as a treatment for implantation loss during early pregnancy, and warrant further investigation of BSHXR as an effective treatment for failed pregnancy and its complications.
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http://dx.doi.org/10.3389/fphar.2018.00437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5962815PMC
May 2018

Effects of gas reservoir configuration and pore radius on shale gas nanoflow: A molecular dynamics study.

J Chem Phys 2018 May;148(20):204703

Key Laboratory of Earth and Planetary Physics, Institute of Geology and Geophysics, Chinese Academy of Sciences, Beijing 100029, China.

We calculated methane transport through cylindrical graphite nanopores in cyclical steady-state flows using non-equilibrium molecular dynamics simulations. First, two typical gas reservoir configurations were evaluated: open (OS) and closed (CS) systems in which pores connect to the gas reservoir without/with a graphite wall parallel to the gas flow. We found that the OS configuration, which is commonly used to study nanoflows, exhibited obvious size effects. Smaller gas reservoir cross-sectional areas were associated with faster gas flows. Because Knudsen diffusion and slip flow in pores are interrupted in a gas reservoir that does not have walls as constraints, OSs cannot be relied upon in cyclical nanoflow simulations. Although CSs eliminated size effects, they introduced surface roughness effects that stem from the junction surface between the gas reservoir and the pore. To obtain a convergent nanoflow, the length of a side of the gas reservoir cross-section should be at least 2 nm larger than the pore diameter. Second, we obtained methane flux data for various pore radii (0.5-2.5 nm) in CSs and found that they could be described accurately using the Javadpour formula. This is the first direct molecular simulation evidence to validate this formula. Finally, the radial density and flow-velocity distributions of methane in CS pores were analyzed in detail. We tested pores with a radius between 0.5 nm and 2.5 nm and determined that the maximum ratio (∼34%) of slip flow to overall flow occurred in the pore with a radius of 1.25 nm. This study will aid in the design of gas reservoir configurations for nanoflow simulations and is helpful in understanding shale gas nanoflows.
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http://dx.doi.org/10.1063/1.5021139DOI Listing
May 2018

The Neural Basis of Taste-visual Modal Conflict Control in Appetitive and Aversive Gustatory Context.

Neuroscience 2018 02 30;372:154-160. Epub 2017 Dec 30.

Faculty of Psychological Science, Southwest University, Chongqing 400715, China.

The functional magnetic resonance imaging (fMRI) technique was used to investigate brain activations related to conflict control in a taste-visual cross-modal pairing task. On each trial, participants had to decide whether the taste of a gustatory stimulus matched or did not match the expected taste of the food item depicted in an image. There were four conditions: Negative match (NM; sour gustatory stimulus and image of sour food), negative mismatch (NMM; sour gustatory stimulus and image of sweet food), positive match (PM; sweet gustatory stimulus and image of sweet food), positive mismatch (PMM; sweet gustatory stimulus and image of sour food). Blood oxygenation level-dependent (BOLD) contrasts between the NMM and the NM conditions revealed an increased activity in the middle frontal gyrus (MFG) (BA 6), the lingual gyrus (LG) (BA 18), and the postcentral gyrus. Furthermore, the NMM minus NM BOLD differences observed in the MFG were correlated with the NMM minus NM differences in response time. These activations were specifically associated with conflict control during the aversive gustatory stimulation. BOLD contrasts between the PMM and the PM condition revealed no significant positive activation, which supported the hypothesis that the human brain is especially sensitive to aversive stimuli. Altogether, these results suggest that the MFG is associated with the taste-visual cross-modal conflict control. A possible role of the LG as an information conflict detector at an early perceptual stage is further discussed, along with a possible involvement of the postcentral gyrus in the processing of the taste-visual cross-modal sensory contrast.
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http://dx.doi.org/10.1016/j.neuroscience.2017.12.042DOI Listing
February 2018

Effect of controlled ovarian hyperstimulation on puberty and estrus in mice offspring.

Reproduction 2017 10 7;154(4):433-444. Epub 2017 Jul 7.

Institute of Integrated Traditional Chinese and Western MedicineTongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China

Controlled ovarian hyperstimulation (COH) is widely used for the treatment of infertility, while the long-term effects of COH on the reproductive function in female offspring are currently unknown. Based on the fact that COH could cause high E2 levels in women throughout pregnancy and excess estrogenic exposure during fetal development is harmful to subsequent adult ovarian function, we assumed the hypothesis that COH disrupts reproductive function in female offspring. To test this hypothesis, COH was induced in mice to obtain female offspring by pregnant mare serum gonadotropin (PMSG) and HCG, and then we evaluated pubertal transition, serum levels of E2, anti-Mullerian hormone (AMH), FSH and LH, mRNA expressions of , , and in ovaries, number of follicles and ovarian histology. We also investigated the apoptosis of follicles by TUNEL; the mRNA expressions of , , , , and caspase 3, 8 and 9 by quantitative real-time PCR; and the protein expressions of cleaved-caspase (CASP) 3, 8 and 9 by Western blot. Moreover, we further observed estrous cyclicity in young adult offspring, performed follicle counting and measured the level of AMH in both serum and ovary. COH could induce detrimental pregnancy outcomes, as well as delayed pubertal transition and irregular estrous cycle due to the aberrant growth and maturation of follicles in female offspring. Our novel findings add new evidence to better understand the potential risks of COH on the reproductive function in female offspring, raising the awareness that COH could exert adverse effects on female offspring, rather than just obtain more oocytes for fertilization.
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http://dx.doi.org/10.1530/REP-16-0572DOI Listing
October 2017

Immunomodulatory mechanism of Bushen Huoxue Recipe alleviates cyclophosphamide-induced diminished ovarian reserve in mouse model.

J Ethnopharmacol 2017 Aug 21;208:44-56. Epub 2017 Jun 21.

Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical Collage, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. Electronic address:

Ethnopharmacological Relevance: Bushen Huoxue recipe (BHR) is a Chinese herbal prescription composed of ten herbs and it is widely used for the treatment of diminished ovarian reserve (DOR). This study investigates the potentially beneficial effects and underlying mechanism of BHR on a cyclophosphamide (CTX) induced model of DOR in mice.

Materials And Methods: Granules of BHR were first subjected to high performance liquid chromatography (HPLC) to determine the exact ingredients within the mixture. We then induced DOR in mice by injecting them with 90mg/kg of CTX. Following the single intraperitoneal injection, mice then received either saline or BHR for 21 days. To assess the effects of BHR on DOR, we examined splenic and ovarian morphology, estrous cycle duration, ovarian index, follicle number, body weight, and concentration of serum E and FSH. To explore the immunological mechanism behind the effects, mouse splenocytes were isolated in order to analyze the proportion of CD4, CD8 T cells and Th1, Th17 and Treg subsets by flow cytometry. The serum levels of IFN-γ, TNF-α, IL-4, IL-17A, IL-6 and IL-10 were detected using Cytometric Bead Array (CBA). Additionally, the mRNA expression levels of T-bet, RORγt and Foxp3 were measured with quantitative real-time PCR.

Results: Our results show that following treatment with BHR in DOR mice, several measures showed significant improvement. The morphology of the ovary and spleen, estrous cycle duration, body weight, ovarian index, and serum levels of E and FSH recovered to approximately normal levels and the loss of follicles at all stages was significantly attenuated. Furthermore, the elevated proportions of CD4 T cells, Th1, Th17, Treg subsets and the increased serum levels of IFN-γ, TNF-α, IL-17A, IL-6 and IL-10 as well as the mRNA expressions of T-bet, RORγt and Foxp3 in DOR mice were significantly decreased.

Conclusions: Our results show that BHR is a promising candidate to treat DOR mice and this beneficial effect may be mediated through the downregulation of augmented autoimmunity.
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http://dx.doi.org/10.1016/j.jep.2017.06.022DOI Listing
August 2017

Electroacupuncture for Functional Constipation: A Multicenter, Randomized, Control Trial.

Evid Based Complement Alternat Med 2017 31;2017:1428943. Epub 2017 Jan 31.

Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei 430030, China.

. To investigate the efficacy and safety of electroacupuncture (EA) with different current intensities for functional constipation (FC) and to assess whether the effects of EA with different current intensities are superior to the mosapride. . Patients with FC were randomly divided into low current intensity group (LCI), high current intensity group (HCI), and mosapride group (MC). The primary outcome was three or more spontaneous bowel movements (SBMs) per week and an increase of one or more SBMs from baseline during at least 3 of the 4 weeks. . The primary outcome was reached by 53.45%, 66.15%, and 52.24% of the patients who received LCI, HCI, and mosapride, respectively. EA can significantly improve the weekly SBMs and stool consistency and reduce straining severity ( < 0.0001, all). HCI improved the quality of life better than mosapride ( < 0.05) and reduced the proportion of severe constipation more than LCI and mosapride ( < 0.05, both). . EA is effective and safe at both current intensities for FC; therapeutic effects of LCI and HCI are not superior to mosapride. EA is superior to mosapride in improving patients' life quality and satisfaction level of treatment; EA has fewer adverse events than mosapride.
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http://dx.doi.org/10.1155/2017/1428943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5307003PMC
January 2017

Expression Pattern of Mouse Vasa Homologue (MVH) in the Ovaries of C57BL/6 Female Mice.

Med Sci Monit 2016 Jul 27;22:2656-63. Epub 2016 Jul 27.

Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical Collage, Huazhong University of Science and Technology, Wuhan, Hubei, China (mainland).

BACKGROUND Vasa (a DEAD-box helicase, also known as Ddx4) is an ATP-dependent RNA helicase highly conserved among all animals. Research on the presence and function of DDX4 in female mammals is limited. To gain greater insight into its distribution and role in female mice, we detected the expression of DDX4 protein in the ovaries and analyzed its expression pattern. MATERIAL AND METHODS MVH was detected in the cytoplasm of oocytes in all non-apoptotic follicles. RESULTS In the present study, we found that higher expression levels of ~55-60 kDa MVH isoform in the ovaries were followed by the accumulations of preovulatory follicles. CONCLUSIONS Higher levels of MVH protein in the ovaries might prepare oocytes for the competence to resume meiosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973802PMC
http://dx.doi.org/10.12659/msm.899830DOI Listing
July 2016

Ion Permeation and Mechanotransduction Mechanisms of Mechanosensitive Piezo Channels.

Neuron 2016 Mar 25;89(6):1248-1263. Epub 2016 Feb 25.

School of Pharmaceutical Sciences, Tsinghua-Peking Joint Center for Life Sciences, IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, 100084, China. Electronic address:

Piezo proteins have been proposed as the long-sought-after mechanosensitive cation channels in mammals that play critical roles in various mechanotransduction processes. However, the molecular bases that underlie their ion permeation and mechanotransduction have remained functionally undefined. Here we report our finding of the miniature pore-forming module of Piezo1 that resembles the pore architecture of other trimeric channels and encodes the essential pore properties. We further identified specific residues within the pore module that determine unitary conductance, pore blockage and ion selectivity for divalent and monovalent cations and anions. The non-pore-containing region of Piezo1 confers mechanosensitivity to mechano-insensitive trimeric acid-sensing ion channels, demonstrating that Piezo1 channels possess intrinsic mechanotransduction modules separate from their pore modules. In conclusion, this is the first report on the bona fide pore module and mechanotransduction components of Piezo channels, which define their ion-conducting properties and gating by mechanical stimuli, respectively.
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http://dx.doi.org/10.1016/j.neuron.2016.01.046DOI Listing
March 2016

Competitive adsorption of a binary CO2-CH4 mixture in nanoporous carbons: effects of edge-functionalization.

Nanoscale 2015 Jan;7(3):1002-12

College of Science, China University of Petroleum, Qingdao, Shandong 266580, P. R. China.

The effect of edge-functionalization on the competitive adsorption of a binary CO2-CH4 mixture in nanoporous carbons (NPCs) has been investigated for the first time by combining density functional theory (DFT) and grand canonical Monte Carlo (GCMC) simulation. Our results show that edge-functionalization has a more positive effect on the single-component adsorption of CO2 than CH4, therefore significantly enhancing the selectivity of CO2 over CH4, in the order of NH2-NPC > COOH-NPC > OH-NPC > H-NPC > NPC at low pressure. The enhanced adsorption originates essentially from the effects of (1) the conducive environment with a large pore size and an effective accessible surface area, (2) the high electronegativity/electropositivity, (3) the strong adsorption energy, and (4) the large electrostatic contribution, due to the inductive effect/direct interaction of the embedded edge-functionalized groups. The larger difference from these effects results in the higher competitive adsorption advantage of CO2 in the binary CO2-CH4 mixture. Temperature has a negative effect on the gas adsorption, but no obvious influence on the electrostatic contribution on selectivity. With the increase of pressure, the selectivity of CO2 over CH4 first decreases sharply and subsequently flattens out to a constant value. This work highlights the potential of edge-functionalized NPCs in competitive adsorption, capture, and separation for the binary CO2-CH4 mixture, and provides an effective and superior alternative strategy in the design and screening of adsorbent materials for carbon capture and storage.
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http://dx.doi.org/10.1039/c4nr05128aDOI Listing
January 2015
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