Tetrahydroxy stilbene glucoside rejuvenates aging hematopoietic stem cells with predilection for lymphoid differentiation via AMPK and Tet2.

INTRODUCTION: Aging of hematopoietic stem cells (HSCs) has emerged as an important challenge to human health. Recent advances have raised the prospect of rejuvenating aging HSCs via specific medical interventions, including pharmacological treatments. Nonetheless, efforts to develop such drugs are still in infancy until now. OBJECTIVES: We aimed to screen the prospective agents that can rejuvenate aging HSCs and explore the potential mechanisms. METHODS: We screened a set of natural anti-aging compounds through oral administration to sub-lethally irradiated mice, and identified 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (TSG) as a potent rejuvenating agent for aging HSCs. Then naturally aged mice were used for the follow-up assessment to determine the HSC rejuvenating potential of TSG. Finally, based on the transcriptome and DNA methylation analysis, we validated the role of the AMP-activated protein kinase (AMPK)-ten-eleven-translocation 2 (Tet2) axis (the AMPK-Tet2 axis) as the underlying mechanisms of TSG for ameliorating HSCs aging. RESULTS: TSG treatment not only significantly increased the absolute number of common lymphoid progenitors (CLPs) along with B lymphocytes, but also boosted the HSCs/CLPs repopulation potential of aging mice. Further elaborated mechanism research demonstrated that TSG supplementation restored the stemness of aging HSCs, as well as promoted an epigenetic reprograming that was associated with an improved regenerative capacity and an increased rate of lymphopoiesis. Such effects were diminished when the mice were co-treated with an AMPK inhibitor, or when it was performed in Tet2 knockout mice as well as senescent cells assay. CONCLUSION: TSG is effective in rejuvenating aging HSCs by modulating the AMPK- Tet2 axis and thus represents a potential candidate for developing effective HSC rejuvenating therapies.

[The Effect of SIRT5 Deletion on Recovery of Hematopoietic Stem Cells after Injury in Mouse].

OBJECTIVE: To investigate the effect of deacylase Sirtuin 5 in the recovery of hematopoietic stem cells (HSCs) after treated by 5-FU in mouse. METHODS: Flow cytometry was used to analyze the effect of SIRT5 deletion on the proportion of hematopoietic stem/progenitor cells (HSPCs) in bone marrow (BM), the proportion of T cells, B cells and myeloid cells (TBM) in peripheral blood (PB) and spleen, and the development of T cells in thymus. Mouse were treated with 5-FU to study the effect of SIRT5 deletion on the cell cycle, apoptosis and the proportion of HSPCs in BM. The effect of SIRT5 deletion on the proliferation of HSCs was analyzed by flow sorting in vitro. RESULTS: SIRT5 deletion did not affect the development of T cells in thymus and the proportion of TBM cells in PB and spleen compared with wild type mice. SIRT5 deletion increased proportion of HSPCs in BM. After 5-FU treatment, the proportion of HSCs in SIRT5 deletion mice was significant decreased (P < 0.05), the HSPC in SIRT5 deletion mice was activated from G0 to G1 phase (P < 0.05), and the proportion of early apoptosis increased (P < 0.05). By monoclonal culture in vitro, the ability of HSCs to form clones in SIRT5 deletion mice was decreased significantly (P < 0.05). CONCLUSION: SIRT5 deletion lead to a decreased the ability of HSCs to clone in vitro. SIRT5 deletion is not conducive to the recovery of HSPCs injury in mice under hematopoietic stress.

JCcirc: circRNA full-length sequence assembly through integrated junction contigs.

Recent studies have shed light on the potential of circular RNA (circRNA) as a biomarker for disease diagnosis and as a nucleic acid vaccine. The exploration of these functionalities requires correct circRNA full-length sequences; however, existing assembly tools can only correctly assemble some circRNAs, and their performance can be further improved. Here, we introduce a novel feature known as the junction contig (JC), which is an extension of the back-splice junction (BSJ). Leveraging the strengths of both BSJ and JC, we present a novel method called JCcirc (https://github.com/cbbzhang/JCcirc). It enables efficient reconstruction of all types of circRNA full-length sequences and their alternative isoforms using splice graphs and fragment coverage. Our findings demonstrate the superiority of JCcirc over existing methods on human simulation datasets, and its average F1 score surpasses CircAST by 0.40 and outperforms both CIRI-full and circRNAfull by 0.13. For circRNAs below 400 bp, 400-800 bp, 800 bp-1200 bp and above 1200 bp, the correct assembly rates are 0.13, 0.09, 0.04 and 0.03 higher, respectively, than those achieved by existing methods. Moreover, JCcirc also outperforms existing assembly tools on other five model species datasets and real sequencing datasets. These results show that JCcirc is a robust tool for accurately assembling circRNA full-length sequences, laying the foundation for the functional analysis of circRNAs.

Prussian-Blue-Analogue-Derived Ultrathin Co2P-Fe2P Nanosheets for Universal-pH Overall Water Splitting.

The great interest in large-scale electrochemical water splitting toward clean hydrogen has spurred large numbers of studies on developing cost-efficient and high-performance bifunctional electrocatalysts. Here, a Prussian-blue-analogue-derived method is proposed to prepare honeycomb-like ultrathin and heterogeneous Co2P-Fe2P nanosheets on nickel foam, showing low overpotentials of 0.080, 0.088, and 0.109 V for the hydrogen evolution reaction (HER) at 10 mA cm-2 as well as 0.290, 0.370, and 0.730 V for the oxygen evolution reaction (OER) at 50 mA cm-2 in alkaline, acidic, and neutral electrolytes, respectively. When directly applied for universal-pH water electrolysis, excellent performances are achieved especially at ultralow voltages of 1.45 V at 10 mA cm-2, 1.66 V at 100 mA cm-2, and 1.79 V at 500 mA cm-2 under alkaline conditions. In situ Raman spectroscopy measurements demonstrate that the excellent HER performance can be attributed to heterogeneous Co2P-Fe2P while the ultrahigh alkaline OER performance originates from reconstruction-induced oxyhydroxides.

[Intervention effect of Chuanxiong-Chishao herb pair on circRNA/lncRNA expression profile in a myocardial infarction-atherosclerosis model].

This study aimed to explore the intervention effect of Chuanxiong-Chishao herb pair(CX-CS) on a myocardial infarction-atherosclerosis(MI-AS) mouse model and investigate its effect on the expression profile of circular RNAs(circRNAs)/long non-coding RNAs(lncRNAs) in ischemic myocardium and aorta. Sixty male ApoE~(-/-) mice were randomly assigned to a model group, high-, medium-, and low-dose CX-CS groups(7.8, 3.9, and 1.95 g·kg~(-1)), and a positive drug group(metoprolol 26 mg·kg~(-1) and simvastatin 5.2 mg·kg~(-1)), with 12 mice in each group. Male C57BL/6J mice were assigned to the sham group. The mice in the model group and the groups with drug intervention were fed on a high-fat diet for 10 weeks, followed by anterior descending coronary artery ligation. After that, the mice were fed on a high-fat diet for another two weeks to induce the MI-AS model. The mice in the sham group received normal feed, followed by sham surgery without coronary artery ligation. Mice in the groups with drug intervention received CX-CS or positive drug by gavage for four weeks from the 9th week of high-fat feeding, and those in the model group and the sham group received an equal volume of normal saline. Whole transcriptome sequencing was performed on the heart and aorta tissues of the medium-dose CX-CS group, the model group, and the sham group after administration. The results showed that the medium-and high-dose CX-CS groups showed improved cardiac function and reduced myocardial fibrosis area, and the medium-dose CX-CS group showed significantly reduced plaque area. CX-CS treatment could reverse the expression of circRNA＿07227 and circRNA＿11464 in the aorta of AS model and circRNA expression(such as circRNA＿11505) in the heart of the MI model. Differentially expressed circRNAs between the CX-CS-treated mice and the model mice were mainly enriched in lipid synthesis, lipid metabolism, lipid transport, inflammation, and angiogenesis in the aorta, and in angiogenesis, blood pressure regulation, and other processes in the heart. CX-CS treatment could reverse the expression of lncRNAs such as ENSMUST00000162209 in the aorta of the AS model and TCONS＿00002123 in the heart of the MI model. Differentially expressed lncRNAs between the CX-CS-treated mice and model mice were mainly enriched in lipid metabolism, angiogenesis, autophagy, apoptosis, and iron death in the aorta, and in angiogenesis, autophagy, and iron death in the heart. In summary, CX-CS can regulate the expression of a variety of circRNAs and lncRNAs, and its intervention mechanism in coronary heart disease may be related to the regulation of angiogenesis and inflammation in ischemic myocardium, as well as lipid metabolism, lipid transport, inflammation, angiogenesis in AS aorta.

Inter-Residue Distance Prediction From Duet Deep Learning Models.

Residue distance prediction from the sequence is critical for many biological applications such as protein structure reconstruction, protein-protein interaction prediction, and protein design. However, prediction of fine-grained distances between residues with long sequence separations still remains challenging. In this study, we propose DuetDis, a method based on duet feature sets and deep residual network with squeeze-and-excitation (SE), for protein inter-residue distance prediction. DuetDis embraces the ability to learn and fuse features directly or indirectly extracted from the whole-genome/metagenomic databases and, therefore, minimize the information loss through ensembling models trained on different feature sets. We evaluate DuetDis and 11 widely used peer methods on a large-scale test set (610 proteins chains). The experimental results suggest that 1) prediction results from different feature sets show obvious differences; 2) ensembling different feature sets can improve the prediction performance; 3) high-quality multiple sequence alignment (MSA) used for both training and testing can greatly improve the prediction performance; and 4) DuetDis is more accurate than peer methods for the overall prediction, more reliable in terms of model prediction score, and more robust against shallow multiple sequence alignment (MSA).

COVID19db: a comprehensive database platform to discover potential drugs and targets of COVID-19 at whole transcriptomic scale.

Many open access transcriptomic data of coronavirus disease 2019 (COVID-19) were generated, they have great heterogeneity and are difficult to analyze. To utilize these invaluable data for better understanding of COVID-19, additional software should be developed. Especially for researchers without bioinformatic skills, a user-friendly platform is mandatory. We developed the COVID19db platform (http://hpcc.siat.ac.cn/covid19db & http://www.biomedical-web.com/covid19db) that provides 39 930 drug-target-pathway interactions and 95 COVID-19 related datasets, which include transcriptomes of 4127 human samples across 13 body sites associated with the exposure of 33 microbes and 33 drugs/agents. To facilitate data application, each dataset was standardized and annotated with rich clinical information. The platform further provides 14 different analytical applications to analyze various mechanisms underlying COVID-19. Moreover, the 14 applications enable researchers to customize grouping and setting for different analyses and allow them to perform analyses using their own data. Furthermore, a Drug Discovery tool is designed to identify potential drugs and targets at whole transcriptomic scale. For proof of concept, we used COVID19db and identified multiple potential drugs and targets for COVID-19. In summary, COVID19db provides user-friendly web interfaces to freely analyze, download data, and submit new data for further integration, it can accelerate the identification of effective strategies against COVID-19.

circMine: a comprehensive database to integrate, analyze and visualize human disease-related circRNA transcriptome.

Many circRNA transcriptome data were deposited in public resources, but these data show great heterogeneity. Researchers without bioinformatics skills have difficulty in investigating these invaluable data or their own data. Here, we specifically designed circMine (http://hpcc.siat.ac.cn/circmine and http://www.biomedical-web.com/circmine/) that provides 1 821 448 entries formed by 136 871 circRNAs, 87 diseases and 120 circRNA transcriptome datasets of 1107 samples across 31 human body sites. circMine further provides 13 online analytical functions to comprehensively investigate these datasets to evaluate the clinical and biological significance of circRNA. To improve the data applicability, each dataset was standardized and annotated with relevant clinical information. All of the 13 analytic functions allow users to group samples based on their clinical data and assign different parameters for different analyses, and enable them to perform these analyses using their own circRNA transcriptomes. Moreover, three additional tools were developed in circMine to systematically discover the circRNA-miRNA interaction and circRNA translatability. For example, we systematically discovered five potential translatable circRNAs associated with prostate cancer progression using circMine. In summary, circMine provides user-friendly web interfaces to browse, search, analyze and download data freely, and submit new data for further integration, and it can be an important resource to discover significant circRNA in different diseases.

[Effect of Laptm4b Deletion on Hematopoietic Stem and Progenitor Cells Homeostasis in Mice].

OBJECTIVE: To investigate the effect of lysosomal-associated protein transmembrane-4 Beta(Laptm4b) deletion on hematopoietic stem/progenitor cells (HSPCs) homeostasis in mice. METHODS: The hematopoietic system specific Laptm4b-deficient mice were constructed. The number and proportion of HSPCs (LSK, LT, ST, MPP, etc) in Laptm4b-deficient mice were analyzed by flow cytometry. Single SLAM-HSC cell was sorted by flow sorter and cultured in vitro to measure the effect of Laptm4b deletion on the colony forming ability of hematopoietic stem cells (HSCs). The effect of Laptm4b-deficient on the reconstitution ability of HSCs in mice was detected by competitive transplantation experiment of SLAM-HSC cells. RESULTS: Laptm4b deficiency could moderately upregulate the proportion of T cells in the peripheral blood of the mice, but showed no significant effect on the proportion and number of HSPCs. Laptm4b deletion showed no effect on the reconstruction ability of HSCs after competitive transplantation, but it could inhibit the colony formation of HSCs in vitro. CONCLUSION: LAPTM4B may play a role in HSCs under the proliferation stress. Laptm4b-deficient in mice hematopoietic system showed no significant effect on the HSPCs homeostasis maintenance and reconstruction ability.

Evaluation of residue-residue contact prediction methods: From retrospective to prospective.

Sequence-based residue contact prediction plays a crucial role in protein structure reconstruction. In recent years, the combination of evolutionary coupling analysis (ECA) and deep learning (DL) techniques has made tremendous progress for residue contact prediction, thus a comprehensive assessment of current methods based on a large-scale benchmark data set is very needed. In this study, we evaluate 18 contact predictors on 610 non-redundant proteins and 32 CASP13 targets according to a wide range of perspectives. The results show that different methods have different application scenarios: (1) DL methods based on multi-categories of inputs and large training sets are the best choices for low-contact-density proteins such as the intrinsically disordered ones and proteins with shallow multi-sequence alignments (MSAs). (2) With at least 5L (L is sequence length) effective sequences in the MSA, all the methods show the best performance, and methods that rely only on MSA as input can reach comparable achievements as methods that adopt multi-source inputs. (3) For top L/5 and L/2 predictions, DL methods can predict more hydrophobic interactions while ECA methods predict more salt bridges and disulfide bonds. (4) ECA methods can detect more secondary structure interactions, while DL methods can accurately excavate more contact patterns and prune isolated false positives. In general, multi-input DL methods with large training sets dominate current approaches with the best overall performance. Despite the great success of current DL methods must be stated the fact that there is still much room left for further improvement: (1) With shallow MSAs, the performance will be greatly affected. (2) Current methods show lower precisions for inter-domain compared with intra-domain contact predictions, as well as very high imbalances in precisions between intra-domains. (3) Strong prediction similarities between DL methods indicating more feature types and diversified models need to be developed. (4) The runtime of most methods can be further optimized.

Negative emotions and their management in Chinese convalescent cervical cancer patients: a qualitative study.

OBJECTIVE: The aim of the study was to understand the experience of negative emotions and coping styles of patients with cervical cancer during the rehabilitation period. METHODS: A descriptive qualitative research method was used. Purposive sampling was used to recruit participants. Semi-structured interviews were conducted with 18 cervical cancer patients and the data were analysed using content analysis. RESULTS: The analysis identified three relevant themes. Theme 1: Negative emotions in convalescent cervical cancer patients mainly comprised fear of recurrence, worries about sex and feelings of inferiority. Theme 2: Patients used positive and negative coping styles to manage negative emotions. Theme 3: Patients expressed a strong need for rehabilitation information. CONCLUSIONS: Patients with cervical cancer exhibited negative emotions during the rehabilitation period. To help these patients, medical staff should develop an understanding of their needs by communicating more with patients and providing them with targeted care to help them return to society more quickly.

Injectable and bioactive methylcellulose hydrogel carrying bone mesenchymal stem cells as a filler for critical-size defects with enhanced bone regeneration.

As a soluble cellulose derivative, methylcellulose (MC), can be used to construct thermosensitive hydrogels. However, a pure MC gel is generally considered an inert material that is inadequate for cell survival. We adopted an environmentally friendly method to fabricate a nano-hydroxyapatite (nHA) hybrid MC hydrogel. Rheology results showed that the addition of nHA increased the gelation temperature. Furthermore, the live/dead assay confirmed that the addition of nHA improved the survival of bone marrow-derived mesenchymal stem cells (BMSCs) inside the gel. In addition, ARS staining indicated that the presence of nHA stimulated osteogenic differentiation. Finally, in vivo cranial defect experiments showed improved remediation efficiency when using the nHA hybrid MC hydrogel to carry BMSCs.

Long-circulating zein-polysulfobetaine conjugate-based nanocarriers for enhancing the stability and pharmacokinetics of curcumin.

Though curcumin has potential treatment value for most chronic diseases, it exerts little potency in the clinic because of its low aqueous solubility, high chemical instability and poor pharmacokinetics. To enhance its potency, we developed a zein-based micelle as a nanocarrier to encapsulate curcumin. Herein, superhydrophilic zwitterionic polymers, poly(sulfobetaine methacrylate) (PSBMA), were conjugated to zein to obtain an amphiphilic zein-PSBMA conjugate. These conjugates could self-assemble into micelles composed of antifouling PSBMA shells and zein cores. The results from the cytokine secretion assay showed that the micelles induced a low level of macrophage activation. Moreover, the results from the in vivo fluorescence imaging experiment confirmed their long-circulating property, exceeding 72 h in mice. In comparison with native curcumin, micelle-encapsulated curcumin had a 230-fold increase in stability in vitro, and its half-life was 22-fold longer, according to a pharmacokinetic study on mice. Overall, this work presents a zein-PSBMA micelle with a long circulation time as a useful nanocarrier for effective curcumin delivery.

Light-Enhanced Ion Migration in Two-Dimensional Perovskite Single Crystals Revealed in Carbon Nanotubes/Two-Dimensional Perovskite Heterostructure and Its Photomemory Application.

Two-dimensional (2D) hybrid perovskite sandwiched between two long-chain organic layers is an emerging class of low-cost semiconductor materials with unique optical properties and improved moisture stability. Unlike conventional semiconductors, ion migration in perovskite is a unique phenomenon possibly responsible for long carrier lifetime, current-voltage hysteresis, and low-frequency giant dielectric response. While there are many studies of ion migration in bulk hybrid perovskite, not much is known for its 2D counterparts, especially for ion migration induced by light excitation. Here, we construct an exfoliated 2D perovskite/carbon nanotube (CNT) heterostructure field effect transistor (FET), not only to demonstrate its potential in photomemory applications, but also to study the light induced ion migration mechanisms. We show that the FET I-V characteristic curve can be regulated by light and shows two opposite trends under different CNT oxygen doping conditions. Our temperature-dependent study indicates that the change in the I-V curve is probably caused by ion redistribution in the 2D hybrid perovskite. The first principle calculation shows the reduction of the migration barrier of I vacancy under light excitation. The device simulation shows that the increase of 2D hybrid perovskite dielectric constant (enabled by the increased ion migration) can change the I-V curve in the trends observed experimentally. Finally, the so synthesized FET shows the multilevel photomemory function. Our work shows that not only we could understand the unique ion migration behavior in 2D hybrid perovskite, it might also be used for many future memory function related applications not realizable in traditional semiconductors.

Flexible Two-Dimensional Ti3C2 MXene Films as Thermoacoustic Devices.

MXenes have attracted great attention for their potential applications in electrochemical and electronic devices due to their excellent characteristics. Traditional sound sources based on the thermoacoustic effect demonstrated that a conductor needs to have an extremely low heat capacity and high thermal conductivity. Hence, a thin MXene film with a low heat capacity per unit area (HCPUA) and special layered structure is emerging as a promising candidate to build loudspeakers. However, the use of MXenes in a sound source device has not been explored. Herein, we have successfully prepared sound source devices on an anodic aluminum oxide (AAO) and a flexible polyimide (PI) substrates by using the prepared Ti3C2 MXene nanoflakes. Due to the larger interlayer distance of MXene, the MXene-based sound source device has a higher sound pressure level (SPL) than that of graphene of the same thickness. High-quality Ti3C2 MXene nanoflakes were fabricated by selectively etching the Ti3AlC2 powder. The as-fabricated MXene sound source device on an AAO substrate exhibits a higher SPL of 68.2 dB (f = 15 kHz) and has a very stable sound spectrum output with frequency varying from 100 Hz to 20 kHz. A theoretical model has been built to explain the mechanism of the sound source device on an AAO substrate, matching well with the experimental results. Furthermore, the MXene sound source device based on a flexible PI substrate has been attached to the arms, back of the hand, and fingers, indicating an excellent acoustic wearability. Then, the MXene film is packaged successfully into a commercial earphone case and shows an excellent performance at high frequencies, which is very suitable for human audio equipment.

Enhancing the mechanical and thermal properties of polypropylene composite by encapsulating styrene acrylonitrile with ammonium polyphosphate.

BACKGROUNDS: In recent decades, incorporating polypropylene (PP) within flame retardants has proved to be an effective method of improving the thermal stabilities of PP, but too much adversely affects the mechanical properties of this polymer materials. Herein we report a novel multifunctional flame retardant, (styrene acrylonitrile)-(titanate-modified ammonium polyphosphate) (SAN-TAPP), to simultaneously improve the mechanical properties and thermal stability of PP composites. METHODS: SAN-TAPP was synthesized by encapsulating SAN resins with functional titanate-modified APP (TAPP) and subsequently was incorporated into PP by a melt-blending process. The phase characteristics and morphology of SAN-TAPP were investigated, and the mechanical properties and thermal stability of different content of PP/SAN-TAPP composites were studied. RESULTS: The results showed that the TAPP was almost entirely wrapped in the SAN resins and PP/SAN-TAPP composites exhibited the sea-island morphology. For the mechanical properties, the impact strength of PP/SAN-TAPP composite was significantly improved, especially 15 wt% SAN-TAPP filled PP/SAN-TAPP composite exhibiting 2.17 times higher than that of pure PP. And the tensile strength and modulus also increased by addition of SAN-TAPP. For the thermal stabilities, melting temperatures (Tm) and residual char yield were improved. Furthermore, the LOI value of PP/SAN-TAPP composites increased from 19.8 to 27.5%; The 15 and 20 wt% SAN-TAPP filled in PP/SAN-TAPP composites passed the V-2 test of UL-94, and exerted the similar effect on the flame retardancy to TAPP with the same loading. CONCLUSIONS: These results revealed that a novel PP/SAN-TAPP composites with synthetically enhancement on the mechanical properties, thermal stabilities and flame retardancy, suggesting a strong correlation between the phase structure, mechanical and thermal properties.

Combined Toxicity of 2,4-Dichlorophenoxyacetic Acid and Its Metabolites 2,4-Dichlorophenol (2,4-DCP) on Two Nontarget Organisms.

2,4-Dichlorophenoxyacetic acid (2,4-D), a phenoxyalkanoic acid herbicide, is among the most widely distributed pollutants in the environment. 2,4-Dichlorophenol (2,4-DCP), as the main metabolite of 2,4-D, always accompanies 2,4-D. In this paper, we did research on the combined toxicities of 2,4-D and 2,4-DCP to Vibrio qinghaiensis sp.-Q67 (Q67) and Caenorhabditis elegans. It was found that the toxicity of 2,4-DCP is more severe than that of its parent 2,4-D at any concentration levels whether to Q67 or to C. elegans. Furthermore, 2,4-DCP to Q67 has the time-dependent toxicity. The toxicity of the mixture of 2,4-D and 2,4-DCP to Q67 is increasing with the exposure time, but that to C. elegans does not change over time. There is a good linear relationship between the pEC50/pLC50 value of binary mixture ray of 2,4-D and 2,4-DCP and the mixture ratio of 2,4-DCP, which implies the predictability of mixture toxicity of 2,4-D and 2,4-DCP. The toxicological interactions of the binary mixtures to Q67 are basically additive actions whether at 0.25 or at 12 h. However, most mixtures have antagonistic interactions against C. elegans.

Millimeter-Scale Nonlocal Photo-Sensing Based on Single-Crystal Perovskite Photodetector.

Organometal trihalide perovskites (OTPs) are promising optoelectronic materials for high-performance photodetectors. However, up to now, traditional polycrystal OTP-based photodetectors have demonstrated limited effective photo-sensing range. Recently, bulk perovskite single crystals have been seen to have the potential for position-sensitive photodetection. Herein, for the first time, we demonstrate a position-dependent photodetector based on perovskite single crystals by scanning a focused laser beam over the device perpendicular to the channel. The photodetector shows the best-ever effective photo-sensing distance up to the millimeter range. The photoresponsivity and photocurrent decrease by nearly an order of magnitude when the beam position varies from 0 to 950 µm and the tunability of carrier diffusion length in CH3NH2PbBr3 with the variation of the exciting laser intensity is demonstrated. Furthermore, a numerical model based on transport of photoexcited carriers is proposed to explain the position dependence. This photodetector shows excellent potential for application in future nanoelectronics and optoelectronics systems.

An ultrasensitive strain sensor with a wide strain range based on graphene armour scales.

An ultrasensitive strain sensor with a wide strain range based on graphene armour scales is demonstrated in this paper. The sensor shows an ultra-high gauge factor (GF, up to 1054) and a wide strain range (ε = 26%), both of which present an advantage compared to most other flexible sensors. Moreover, the sensor is developed by a simple fabrication process. Due to the excellent performance, this strain sensor can meet the demands of subtle, large and complex human motion monitoring, which indicates its tremendous application potential in health monitoring, mechanical control, real-time motion monitoring and so on.

[Upregulation of miR-498 suppresses Th17 cell differentiation by targeting STAT3 in rheumatoid arthritis patients].

To investigate the effect and mechanism of miR-498 on Th17 cell differentiation of peripheral blood mononuclear cells (PMBCs) in rheumatoid arthritis (RA) patients, peripheral blood samples were collected from RA patients and healthy controls, respectively. The proportion of CD4+IL-17+ T cells (Th17 cells) or CD4+FOXP3+ T cells (Tregs) in T cells and the Th17/Treg ratio were identified by the flow cytometer. The STAT3 and miR-498 expression were measured by Western blot and real-time PCR, respectively. ELISA was used to detect IL-17 concentrations. Luciferase assay was performed to confirm that miR-498 directly targeted the 3' untranslated region (3'UTR) of STAT3 in CD4+ T cells. The effect of miR-498 on Th17 cell differentiation was explored by transfection of miR-498 mimic and/or pcDNA-STAT3 into CD4+ T cells. In PMBCs of RA patients, the Th17/CD4+ T cell ratio was significantly increased, while the Tregs/CD4+ T cell ratio was obviously decreased, leading to a higher Th17/Treg ratio. The results showed a reduced miR-498 expression and an increased STAT3 protein expression in PMBCs, and an increased IL-17 concentration in serum of RA patients. In cells transfected with wild-type-STAT3-LU, miR-498 mimic significantly reduced the luciferase activity, STAT3 gene and protein expression, and miR-498 inhibitor had an opposite function. While the miR-498 mimic/inhibitor had no effect on the luciferase activity and STAT3 expression in cells transfected with mutant-STAT3-LU. CD4+ T cells transfected with miR-498 mimic had a lower Th17/CD4+ T cell ratio and IL-17 concentration, however, transfection of pcDNA-STAT3 reversed the effect of miR-498 mimic on Th17/CD4+ T cell ratio and IL-17 concentration. These results suggest that overexpression of miR-498 suppresses Th17 cell differentiation by targeting STAT3 in RA patients.