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In the treatment of transverse olecranon fractures, complicated tension band wiring (TBW) has high rates of re-operations. Besides, plate fixation (PF) and TBW both have large surgical incisions and soft-tissue irritation. Therefore, the new cross-locking intramedullary nail (CIN) with easy handling and minimally invasive features is significantly advantageous. The goal of this study was to biomechanically compare CIN with TBW for fixing transverse olecranon fracture.The transverse olecranon fracture models were created with 15 fresh-frozen cadaveric ulnae which were randomly divided into 3 groups: one group for TBW fixation, another for CIN fixation with 1 conical locking screw (CIN-1), and the last for CIN fixation with 3 conical locking screws (CIN-3). The stiffness, cyclic stability, and failure strength of the fixed fracture models were compared after the corresponding experimental tests.The failure strength of TBW, CIN-1 and CIN-3 were (313.38±27.68) N, (528.56±53.58) N and (871.04±94.95) N. There was a significant difference between them. However, as for dynamic stability and stiffness, CIN-3 was higher and TBW was lower, with no significant differences between the groups.The biomechanical properties of CIN were superior to those of TBW, and CIN was more stable and solid for fixing transverse olecranon fracture, of which CIN-3 was the strongest. more...

A novel near-infrared probe (IC-V) for detecting viscosity is constructed with NIR fluorescent emission, large Stokes shift and high response signal. IC-V can be used to monitor the level of viscosity in cells and mice. more...

The booming development of DIW technology present an unprecedented prospect in energetic materials field and has attracted great interest due to its relative simplicity and high flexibility of manufacturing. Herein, a novel CL-20 based explosive ink formulation have been developed successfully for MEMS initiation systems via DIW technology. We designed PVA/GAP into an oil-in-water(O/W)emulsion, in the way that the aqueous solution of PVA as water phase, the ethyl acetate solution of GAP as oil phase, the combination of Tween 80 and SDS as emulsifier, BPS as a curing agent of GAP. The ideal formulation with good shear-thinning rheology properties and clear gel point was prepared using only 10 wt% emulsion. The dual-cured network formed during the curing process made the printed sample have good mechanical properties. The printed samples had satisfactory molding effect without cracks or fractures, the crystal form of CL-20 not changed and the thermal stability have improved. Deposition of explosive inks via DIW in micro-scale grooves had excellent detonation performances, which critical detonation size was 1 × 0.045 mm, detonation velocity was 7129 m/s and when the corner reaching 150° can still detonated stably. This study may open new avenues for developing binder systems in explosive ink formulations. more...

Remote ischemic postconditioning (RIPostC) is a protective procedure for brain damage caused by ischemia/reperfusion (IR), yet the mechanism of this treatment remains to be elucidated. Circular RNAs (circRNAs) are endogenous non-coding RNAs that have recently been recognized to play vital roles in ischemic brain injury. The aim of this study was to explore the role of circRNAs in the protective mechanism of RIPostC and to analyze the circRNA-microRNA (miRNA) regulation network in RIPostC. Nine rats were assigned randomly into three groups (three rats per group): sham, IR, and RIPostC. Their brain tissues were extracted for next-generation RNA sequencing and bioinformatics analysis was performed for two comparisons: sham vs. IR and IR vs. RIPostC. The expression patterns of selected circRNAs and miRNAs were validated by quantitative real-time PCR (qPCR). We detected 82 upregulated and 51 downregulated circRNAs and 137 upregulated and 127 downregulated miRNAs in the IR group compared with the sham group, and 41 upregulated and 100 downregulated circRNAs and 45 upregulated and 64 downregulated miRNAs in the RIPostC group compared with the IR group. The proposed competitive endogenous RNA (ceRNA) network, which included 24 circRNAs, 20 miRNAs, and 145 mRNAs, indicated that the dysregulated circRNAs played important roles in brain IR injury. On the basis of the expression patterns of selected circRNAs, miRNAs, and mRNAs obtained by qPCR, we proposed a circRNA_0002286-miR-124-3p-VLCAD pathway. In PC12 cell, the expression level of miR-124-3p was significantly upregulated when the expression of circRNA_0002286 was repressed and the expression level of VLCAD (very-long chain acyl-CoA dehydrogenase) was significantly downregulated, which suggested that circRNA_0002286 may act as a miRNA sponge for miR-124-3p to regulate the expression of VLCAD. We found that upregulation of circRNA_0002286 attenuated IR injury and was associated with downregulation of miR-124-3p and upregulation of VLCAD. This is the first time that circRNAs have been shown to be closely related to brain IR injury and RIPostC and suggests that targeting the circRNA_0002286-miR-124-3p-VLCAD pathway might attenuate brain IR injury. more...

A novel nitrobenzoxadiazole-based near-infrared fluorescent probe (CX-N) is synthesized for the specific detection of H2S. CX-N has been successfully applied to real-time imaging of H2S in inflammatory and tumor mice. more...

A new type of explosive ink formulation that can be quickly cured was prepared with unsaturated polyester as binder, styrene as active monomer, 2,4,6-trimethylbenzoyl-diphenylphosphine oxide as photoinitiator, and hexanitrohexaazaisowurtzitane (CL-20) as the main explosive. Then the explosive ink direct writing technology was used to charge the micro-sized energetic devices, the curing mechanism of the explosive ink was discussed, and the microstructure, safety performance and explosive transfer performance of the explosive ink molded samples were tested and analyzed. Results indicate that the composite material has a fast curing molding speed, its hardness can reach 2H within 8 min. The crystal form of CL-20 in the molded sample is still e type. The CL-20 based UV-curing explosive ink formulation has good compatibility, its apparent activation energy is increased by about 3.5 kJ/mol. The composite presents a significant reduction in impact sensitivity and its characteristic drop height can reach 39.8 cm, which is about 3 times higher than the raw material. When the line width of charge is 1.0 mm, the critical thickness of the explosion can reach 0.015 mm, and the explosion velocity is 7129 m/s when the charge density is 1.612 g/cm3. more...

Adenosine triphosphate (ATP), as an indispensable biomolecule, is the main energy source of cells and is used as a marker for diseases such as cancer and fatty liver. It is of great significance to design a near-infrared fluorescent nanoprobe with excellent performance and apply it to various disease models. Here, a near-infrared fluorescent nanoprobe (ZIF-90@SiR) based on a zeolitic imidazole framework is proposed. The fluorescent nanoprobes are synthesized by encapsulating the dye (SiR) into the framework of ZIF-90. Upon the addition of ATP, the structure of the ZIF-90@SiR nanoprobe is disrupted and SiR is released to generate near-infrared fluorescence at 670 nm. In the process of ATP detection, ZIF-90@SiR shows high sensitivity and good selectivity. Moreover, the ZIF-90@SiR nanoprobe has good biocompatibility due to its low toxicity to cells. It is used for fluorescence imaging of ATP in living cells and thus distinguishing normal cells and cancer cells, as well as distinguishing fatty liver cells. Due to excellent near-infrared fluorescence properties, the ZIF-90@SiR nanoprobe can not only distinguish normal mice and tumor mice but also differentiate normal mice and fatty liver mice for the first time. more...

The sofosbuvir-velpatasvir single-tablet regimen (Epclusa) is a newly FDA-approved inhibitor of hepatitis C virus (HCV). This meta-analysis aimed to investigate the safety and efficacy of velpatasvir-sofosbuvir in the treatment of chronic HCV infection.A comprehensive literature search of PubMed, Cochrane CENTRAL, EMBASE and Web of Science was conducted. Data from eligible studies were pooled in a fixed-effect meta-analysis model, using Open-Meta and RevMan software's.Pooled data showed that velpatasvir-sofosbuvir achieved sustained virological response (SVR12) rates of 94.2% (95% CI 90.7-97.7%, P .001) in 1277 patients. The addition of ribavirin did not significantly increase the SVR12 (RR = 1.03, 95%CI [0.95, 1.11]) in HCV genotype-1 patients and the SVR12 (RR = 1.09, 95%CI [0.86, 1.38]) in HCV genotype-2 patients. However, adding ribavirin significantly increased SVR12 (RR = 1.13, 95% CI [1.04, 1.23]) in genotype-3 patients.In conclusion, the 12-week regimen of sofosbuvir-velpatasvir was highly effective in HCV patients. Except for genotype-3, adding ribavirin was not associated with significant improvements in SVR12 rates. more...

Cancer is one of the biggest public enemies of global health with its high morbidity and mortality. Achieving early diagnosis is the most effective means of reducing cancer harm, which requires the use of powerful tools to accurately identify biomarkers. However, most of the reported fluorescent probes for cancer diagnosis can only detect one substance, which makes it difficult to meet the requirements of high accuracy. Here, a fluorescent nanoprobe (CPQ@ZIF-90) for sequential detection of ATP and ONOOsup-/supis constructed by encapsulating the ONOOsup-/supsensitive unit CPQ within ZIF-90. CPQ@ZIF-90 first reacts with ATP to release CPQ, which greatly enhances the fluorescence at 740 nm. Then, the released CPQ continues to react with ONOOsup-/supand is oxidatively cleaved by ONOOsup-/supto form a coumarin product with a small π-conjugated structure, which significantly enhances the fluorescence at 510 nm. CPQ@ZIF-90 shows high sensitivity and selectivity for the detection of ATP and then ONOOsup-/sup. Moreover, CPQ@ZIF-90 has good biocompatibility and successfully realizes the sequential detection of a dual-channel fluorescence change of ATP and ONOOsup-/supin living cells and zebrafish and accurately distinguishes normal cells from cancer cells. CPQ@ZIF-90 is expected to be a potential tool for accurate cancer diagnosis through sequential detection of two cancer markers. more...

Tai Chi martial arts education is one of the components of school education. Its educational value is not only to require students to master basic Tai movement technical skills and improve their physical fitness but also to bring students’ ideological progress and cultivate students to respect teachers and lectures. Excellent moral qualities such as politeness, keeping promises, observing the rules, and acting bravely, as well as the cultivation of the spirit of unity and cooperation, and the quality of will also have a certain meaning. However, the scientific Tai Chi ideological and political courses and the construction of Wude education interactive classrooms lack relevant research. Therefore, this article builds a Tai Chi ideological and political interactive classroom system based on big data technology and graph neural network. First, the spatio-temporal graph convolutional neural network is used to reason about the relationship between Tai Chi action categories and strengthen the low-dimensional features of semantic categories and their co-occurrence expressions used for semantic enhancement of current image features. In addition, in order to ensure the efficiency of the Tai Chi scene analysis network, an efficient dual feature extraction basic module is proposed to construct the backbone network, reducing the number of parameters of the entire network and the computational complexity. Experiments show that this method can obtain approximate results, while reducing the amount of floating-point operations by 42.5% and the amount of parameters by 50.2% compared with the work of the same period, and achieves a better balance of efficiency and performance. Secondly, based on the big data of historical Tai Chi classrooms, this article constructs an interactive classroom system that can effectively improve the quality of Tai Chi ideological and political courses. more...

Autism spectrum disorders (ASD) are highly heterogeneous neurodevelopmental disorders characterized by impaired social interaction skills. Whole exome sequencing has identified loss-of-function mutations in lysine methyltransferase 2E (KMT2E, also named MLL5) in ASD patients and it is listed as an ASD high-risk gene in humans. However, experimental evidence of KMT2E in association with ASD-like manifestations or neuronal function is still missing. Relying on KMT2E more...

Diabetes is one of the metabolic diseases marked by hyperglycemia and is often accompanied by the occurrence of some complications. As a biomarker of oxidative stress, hydrogen peroxide (H2O2) has close association with the occurrence and development of diabetes and its complications. Unfortunately, there is no fluorescent probe reported for imaging H2O2 in diabetic mice. Here, a novel near-infrared (NIR) fluorescent probe named QX-B was designed and synthesized to detect H2O2. For the probe, the quinolinium-xanthene dye is used as the fluorophore and borate ester is chosen as the response group. After the addition of H2O2, a strong NIR fluorescence signal at 772 nm is observed. The probe not only shows high sensitivity with 10-fold enhancement but also displays excellent selectivity to H2O2 over other possible interfering species. In the meantime, the possible response mechanism of QX-B toward H2O2 was proposed and verified by the high-performance liquid chromatography (HPLC) experiment, mass spectra (MS) experiment, and density functional theory (DFT) calculation. Furthermore, based on the low cell cytotoxicity of QX-B, it has been applied in imaging exogenous and endogenous H2O2 in HeLa cells, HCT116 cells, 4T1 cells, and zebrafish successfully. More importantly, inspired by the performance of NIR fluorescence, QX-B has been used in monitoring H2O2 in diabetic mice for the first time. This provides very important information for the diagnosis and treatment of diabetes and its complications. more...

A novel water-soluble near-infrared fluorescent probe named QX-P with simple synthesis is developed. QX-P has high sensitivity and selectivity to ALP. Moreover, the probe can not only visualize ALP activity in four cell lines, but also real-time image ALP activity during the diagnosis and treatment of diabetes in mice. more...

A novel theranostic probe called CX-B-DF is constructed for precise chemotherapy guided by near-infrared (NIR) fluorescence imaging. Moreover, the theranostic probe shows high cytotoxicity to cancer cells under dual activation (H2O2 and TP), which causes the accuracy of drug release to be improved and the toxic side effects to be reduced. more...

Stem cells have been confirmed to be involved in the occurrence and development of diabetic retinopathy; however, the underlying mechanisms remain unclear. In this study, we used Citespace software to visually analyze 552 articles exploring the stem cell-based treatment of diabetic retinopathy over the past 20 years, which were included in the Web of Science Core Collection. We found the following: (1) a co-citation analysis of the references cited by all 552 articles indicated 15 clusters. In cluster #0, representing the stem cell field, some highly cited landmark studies emerged between 2009–2013. For example, endothelial progenitor cells and diabetic retinopathy gradually received the full attention of scholars, in terms of their relationship and therapeutic prospects. Some researchers also verified the potential of adipose-derived stem cells to differentiate into stable retinal perivascular cells, using a variety of animal models of retinal vascular disease. All of these achievements provided references for the subsequent stem cell research. (2) An analysis of popular keywords among the 552 articles revealed that, during the past 20 years, a relative increase in basic research articles examining stem cells and endothelial progenitor cells for the treatment of diabetic retinopathy was observed. The contents of these articles primarily involved the expression of vascular endothelial growth factor, vascular regeneration, oxidative stress, and inflammatory response. (3) A burst analysis of keywords used in the 552 articles indicated that genetic and cytological research regarding the promotion of angiogenesis was an issue of concern from 2001 to 2012, including several studies addressing the expression of various growth factor genes; from 2014 to 2020, mouse models of diabetic retinopathy were recognized as mature animal models, and the most recent research has focused on macular degeneration, macular edema, neurodegeneration, and inflammatory changes in diabetic animal models. (4) Globally, the current authoritative studies have focused on basic research towards the stem cell treatment of diabetic retinopathy. Existing clinical studies are of low quality and have insufficient evidence levels, and their findings have not yet been widely accepted in clinical practice. Major challenges during stem cell transplantation remain, including stem cell heterogeneity, cell delivery, and the effective homing of stem cells to damaged tissue. However, clinical trials examining potential stem cell-based treatments of diabetic retinopathy, including the use of pluripotent stem cells, retinal pigment epithelial cells, bone marrow mesenchymal stem cells, and endothelial progenitor cells, are currently ongoing, and high-quality clinical evidence is likely to appear in the future, to promote clinical transformation. more...

Objective Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients’ medical records. Multivariable logistic regression models were used to estimate the odds ratio (OR) and 95% confidence interval (95% CI) of the associations between comorbidities (cardiometabolic or non-cardiometabolic diseases), clinical severity, and treatment outcomes of COVID-19. Results Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30–6.32), type 2 diabetes (T2DM) (3.57, 2.32–5.49), cardiovascular disease (CVD) (3.78, 1.81–7.89), fatty liver disease (7.53, 1.96–28.96), hyperlipidemia (2.15, 1.26–3.67), other lung diseases (6.00, 3.01–11.96), and electrolyte imbalance (10.40, 3.00–26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89–12.75), CVD (8.47, 6.03–11.89), and electrolyte imbalance (19.44, 11.47–32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25–9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46–29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes. more...

Grain number is crucial for analysis of yield components and assessment of effects of cultivation measures. The grain number per spike and thousand-grain weight can be measured by counting grains manually, but it is time-consuming, tedious and error-prone. Previous image processing algorithms cannot work well with different backgrounds and different sizes. This study used deep learning methods to resolve the limitations of traditional image processing algorithms. Wheat grain image datasets were collected in the scenarios of three varieties, six background and two image acquisition devices with different heights, angles and grain numbers, 1 748 images in total. All images were processed through color space conversion, image flipping and rotation. The grain was manually annotated, and the datasets were divided into training set, validation set and test set. We used the TensorFlow framework to construct the Faster Region-based Convolutional Neural Network Model. Using the transfer learning method, we optimized the wheat grain detection and enumeration model. The total loss of the model was less than 0.5 and the mean average precision was 0.91. Compared with previous grain counting algorithms, the grain counting error rate of this model was less than 3% and the running time was less than 2 s. The model can be effectively applied under a variety of backgrounds, image sizes, grain sizes, shooting angles, and shooting heights, as well as different levels of grain crowding. It constitutes an effective detection and enumeration tool for wheat grain. This study provides a reference for further grain testing and enumeration applications. more...

Effect of various silicon sources, such as TEOS, MTES mixed with TEOS and 1,3,5-tris(triethoxymethyl) on SiO2 films was investigated. The synthesized solutions were used as silicon sources to prepare silica-like backbone films. The investigation showed that all precursors can able to produce the flat and uniform films. An FTIR spectrum confirmed the formation of SiO2 in film matrix. The results indicated that the internal microstructure of each film is different. The incorporation of less polar bonds such as F and C was carried out using various Si sources, while the introduction of these sources confirmed through FTIR spectra. Optical properties of the films were carried out by using ellipsometric porosometry (EP) measurement. The leakage current density for the films prepared by using TEOS, MTES and 135TTEB was observed to be 2.8 × 10-7 A/cm2, 2.9 × 10-8 A / cm2, and 4.1 × 10-6 A / cm2, respectively, at 1 MV/cm electric field strength by the IV curves obtained by semiconductor characterization after fabricating MIS devices. The calculated dielectric constants from RI of the deposited SiO2 films were 2.0, 1.9 and 2.5 respectively. When the microstructure of the precursor solution changed, the introduction of atomic morphology or terminal inerted group ratio changed the internal bridging mode of SiO2, and thereby significantly reduced the dielectric constant and improved insulation. more...

The influence of Al addition on the microstructure of Cu−B alloys and Cu−ZrB2 composites was investigated using scanning electron microscopy, X-ray diffraction and first-principles calculation. The results show that the eutectic B in Cu−B alloys can be modified by Al from coarse needles to fine fibrous structure and primary B will form in hypoeutectic Cu−B alloys. As for Cu−ZrB2 composites, Al can significantly refine and modify the morphology of ZrB2 as well as improve its distribution, which should be due to its selective adsorption on ZrB2 surfaces. The first-principles calculation results indicate that Al is preferentially adsobed on ZrB2 (12(__)10), then on ZrB2 (101(__)0), and finally on ZrB2 (0001). As a result, smaller sized ZrB2 with a polyhedron-like, even nearly sphere-like morphology, can form. Due to Al addition, the hardness of Cu−ZrB2 composites is greatly enhanced, but the electrical conductivity of the composites is seriously reduced. more...

There has been ample research showing that insomnia is a potential trigger of depression as well as a symptom of depression. These two factors contribute to behavioural problems and are closely related to the plasticity of hippocampal synapses. Although depression and insomnia impair hippocampal synaptic plasticity, the mechanism by which this happens remains a mystery. This study aimed to investigate the pathogenesis of insomnia comorbidity in depression and the regulatory effect of venlafaxine combined with melatonin on hippocampal synaptic plasticity in chronic unpredictable mild stress (CUMS) with sleep deprivation (SD) rats. Thus, rats were subjected to 14 days of chronic mild unpredictable stress, gradually acclimated to sleep deprivation on days 12-14. Followed by 21 consecutive days of sleep deprivation, 18 h per day, with daily gavage of venlafaxine (13.5 mg/kg) + melatonin (72 mg/kg) on days 15-36. Venlafaxine + melatonin treatment improves depression-like behaviour, pentobarbital sodium experimental sleep latency, and sleep duration in CUMS +SD rats. In addition to improving depressive-like behaviors, sleep deprivation also upregulates the expression of caspase-specific cysteine protein 3 (Caspase 3) in the pineal glial cells of chronic mild rats, as well as in hippocampal microglia. Expression of ionic calcium-binding adaptor 1 (iba-1), downregulates the secretion of several synaptic plasticity-related proteins, notably cAMP response element binding protein (CREB), glial cell line-derived neurotrophic factor (GDNF), and the synaptic scaffolding protein Spinophiline (Spinophiline). Hematoxylin-eosin staining showed that the structure of the pineal gland and hippocampus was damaged, and Golgi staining showed that the dendrites and spines in the DG area of the hippocampus were destroyed, vaguely aggregated or even disappeared, and the connection network could not be established. Western blot analysis further revealed a positive correlation between low melatonin levels and reduced Spinophiline protein. Interestingly, venlafaxine + melatonin reversed these events by promoting hippocampal synaptic plasticity by regulating melatonin secretion from the pineal gland. Therefore, it exerted an antidepressant effect in sleep deprivation combined with CUMS model rats. Overall, the results of this study suggest that the pathophysiology of depressive insomnia comorbidity is mediated by impaired pineal melatonin secretion and impaired hippocampal synaptic plasticity. In addition, these responses are associated with melatonin secretion from the pineal gland. more...

Autophagy plays a vital role in maintaining intracellular homeostasis through a lysosome-dependent intracellular degradation pathway, which is closely related to the polarity and ATP. Herein, the first example of the dual-response fluorescent probe Lyso-NRB was reported for visualizing the fluctuation of polarity and ATP in lysosomes during autophagy. Probe Lyso-NRB is non-fluorescent. After the decrease of polarity, Lyso-NRB exhibits significant green emission due to the unique intramolecular charge transfer (ICT) effect. Upon the addition of ATP, the probe can react with ATP to rapidly open the spirocycle of rhodamine and a strong red emission can be observed. Moreover, Lyso-NRB exhibits a high sensitivity and selectivity toward polarity and ATP. Most importantly, the probe possesses a good lysosome-targeting ability and is used for the real-time monitoring of lysosome polarity and ATP fluctuations during H more...

Enhancer is a DNA sequence, and mainly acts in cis to regulate gene transcription. Due to the uncertainty in both location and distance between enhancers and their target genes, it is more complex and difficult to study the underlying regulatory mechanism of enhancers. Accumulating evidences indicate that enhancers are closely associated with the occurrence and development of diseases, such as cancer. Therefore, the studies of enhancers in cancer will be helpful to deeply unravel cancer pathogenesis and to promote the development of antitumor drugs. The related research is with great social significance and economic value. Currently, the identification of enhancers is insufficient. The regulatory mechanisms by enhancers during the initiation and progression of cancer and other diseases have not been fully delineated. In this review, we provide an overview of enhancers, super enhancers and their properties, followed by a description of enhancer prediction and identification at the genome-wide level. Finally, we summarize the regulatory roles of enhancers during diseases such as cancer in recent years, thereby providing a reference for the future exploration on enhancer regulatory mechanisms as well as cancer diagnosis and treatment.增强子是一段具有转录调控功能的DNA序列,主要通过顺式调控方式发挥作用。由于增强子及其调控基因在位置和距离上的不确定性,大大增加了研究增强子作用机制的复杂性和困难性。越来越多的证据表明,增强子与癌症等疾病的发生发展密切相关,因此开展癌症相关增强子的研究,将有助于全面解析癌症发病机制,并推动抗肿瘤药物的高效研发,具有重要的社会意义和经济价值。目前对于增强子的鉴定不充分,增强子在癌症和其他疾病中的发生发展调控机制尚未得到完整的解析。本文主要对增强子和超级增强子及其特性进行介绍,并在全基因组水平上对增强子的预测和鉴定进行了描述,最后总结了近年来增强子在癌症等疾病发生过程中所发挥的调控作用,从而为未来解析增强子调控机制以及癌症的诊断和治疗提供参考。. more...

Deep learning is widely used in the fields of information technology and education innovation but there are few studies for young children in the preschool stage. Therefore, we aimed to explore factors that affect children’s learning ability through collecting relevant information from teachers in the kindergarten. Literature review, interview, and questionnaire survey methods were used to determine the influencing factors of deep learning. There were five dimensions for these factors: the level of difficulty of academic, communication skills, level of active collaboration, level of in-depth processing, and reflection level evaluation. Reliability and validity tests were used to analyze the data from questionnaires. In total, 100 valid questionnaires were collected. The Cronbach coefficients for academic challenge, communication, active cooperation, deep processing, and reflective evaluation were 0.801, 0.689, 0.770, 0.758, and 0.665, respectively. Principal component analysis revealed that there were three main factors that affect children’s learning depth: the level of deep processing (maximum KMO: 0.908), the level of reflective evaluation (maximum KMO: 0.542), and the active level of collaboration (maximum KMO: 0.410). In conclusion, there were several factors affecting deep learning in children and further studies are warranted to promote the development of this field. more...

Hydrogen sulfide (H

Background The high heritability and heterogeneity of autism spectrum disorder (ASD) are fundamentally determined by its varying genetic alterations including over 100 confident ASD-risk genes/genomic regions. Lysine Methyltransferase 2E (KMT2E, also named MLL5), a distinct chromatin/transcription regulator, is recently identified as a confident ASD-risk gene with germline de novo mutations in ASD probands. Clarifying the function and mechanism of KMT2E haploinsufficiency in ASD-like behaviours is important for the comprehensive understanding of ASD pathogenesis. Methods A CRISPR/Cas9-based mouse model of KMT2E (i.e., MLL5) deficiency (reading frame shift followed by a stop codon induction in exon 3) was used to characterize and define behavioural, metabolic and neuroanatomical phenotypes of ASD-linked loss-of-function mutation in KMT2E. Social/motor/repetitive behaviours and anxiety/anhedonia-like behaviours were determined in adult KMT2E+/− mice. Small-animal PET/CT was used to measure and analyse regional glycometabolic alterations in whole brain. Cerebral Cortical sizes and neuronal size/number in cortex/amygdala were measured. Spatial-temporal expression of KMT2E in developing human brain was analysed by using RNA-seq data from BrainSpan Atlas of Developing Human Brain. Results Adult KMT2E+/− haploinsufficiency mice exhibited robust social deficits in two/three-chamber behavioural paradigms, increased repetitive grooming/jumping behaviour, anxiety in open-field test and anhedonia in sucrose-preference test. 18F-FDG-PET/CT identified a selective reduction of glucose metabolism in amygdala and striatum in KMT2E+/− mice. Morphologically, cerebral cortical size was decreased while neuronal soma size/numbers in amygdala subregions were prominently increased in KMT2E+/− mice. Female and male mice were affected similarly by KMT2E haploinsufficiency. Bioinformatics showed that KMT2E mRNA levels were significantly decreased after birth in human brain overall and various subregions including amygdala and striatum. Limitations: The behaviour, metabolic and morphological analyses were performed in adult mice but not in other developmental stages due to the low fertility of KMT2E+/− mice. The effect of KMT2E knockdown or knockout on neuronal development is not verified at cellular level in vitro. Conclusions KMT2E haploinsufficiency is sufficient for causing sustained ASD-like social behaviours that is highly associated to amygdala malfunction. KMT2E+/− mice may serve as a valuable diagnostic/therapeutic ASD-model for related ASD subgroups. more...

The globally increasing annual incidence of chronic obstructive pulmonary disease (COPD), a common chronic disease, poses a serious risk to public health. Although the exact mechanism underlying the pathogenesis of COPD remains unclear, a large number of studies have shown that its pathophysiology and disease course are closely related to oxidative stress, inflammation, apoptosis, autophagy, and aging. The key players involved in COPD include the sirtuin family of NAD-dependent deacetylases that comprise seven members (SIRT1–7) in mammals. Sirtuins play an important role in metabolic diseases, cell cycle control, proliferation, apoptosis, and senescence. Owing to differences in subcellular localization, sirtuins exhibit anisotropy. In this narrative review, we discuss the roles and molecular pathways of each member of the sirtuin family involved in COPD to provide novel insights into the prevention and treatment of COPD and how sirtuins may serve as adjuvants for COPD treatment. more...

Coronavirus disease 2019 (COVID-19) remains a global public health threat. Hence, more effective and specific antivirals are urgently needed. Here, COVID-19 hyperimmune globulin (COVID-HIG), a passive immunotherapy, is prepared from the plasma of healthy donors vaccinated with BBIBP-CorV (Sinopharm COVID-19 vaccine). COVID-HIG shows high-affinity binding to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein, the receptor-binding domain (RBD), the N-terminal domain of the S protein, and the nucleocapsid protein; and blocks RBD binding to human angiotensin-converting enzyme 2 (hACE2). Pseudotyped and authentic virus-based assays show that COVID-HIG displays broad-spectrum neutralization effects on a wide variety of SARS-CoV-2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Kappa (B.1.617.1), Delta (B.1.617.2), and Omicron (B.1.1.529) in vitro. However, a significant reduction in the neutralization titer is detected against Beta, Delta, and Omicron variants. Additionally, assessments of the prophylactic and treatment efficacy of COVID-HIG in an Adv5-hACE2-transduced IFNAR more...

Cancer is a major public health problem worldwide, and traditional chemotherapy or a single therapeutic strategy often fails to achieve expected results in cancer treatment. Thus, the development of a method to realize controlled drug delivery and synergistic therapy is required. Herein, MOF-based nanoparticles named RhI-DOX-GOD@ZIF-90 are synthesized using RhI (a near-infrared fluorescent dye), DOX (an anti-cancer drug) and GOD (glucose oxidase). RhI and DOX are encapsulated inside the ZIF-90 framework and GOD is loaded on the surface of ZIF-90. Owing to the fact that the ATP level in cancer cells is abnormally higher than that in normal cells, RhI-DOX-GOD@ZIF-90 nanoparticles are destructed only in cancer cells. RhI is released to give outstanding NIR emission and realize controlled drug delivery. DOX is released and cancer cells are killed by chemotherapy. Also, GOD is released to consume glucose and achieve the purpose of starving the cancer cells. By making full use of the advantages of near-infrared emission, RhI-DOX-GOD@ZIF-90 nanoparticles can be used to image ATP in tumor-bearing mice. At the same time, DOX and GOD can be released accurately at tumor sites of mice and excellent anti-tumor efficiency by synergistic chemotherapy and starvation therapy is achieved. more...