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For the manned International Space Station, the more stringent requirements of the leakage performance of the rubber seal, which is located in it, is presented. The leakage is caused by the small leakage paths between contact pairs of the rubber seal. Therefore, it is necessary that the micro-leakage performance analysis between interfaces of the rubber seal is carried out. Based on this, the finite element model (FEM) of macroscopic contact performance analysis of the rubber seal is established first, and the macroscopic contact pressure and contact width of the rubber seal are calculated by the model. Then, the micro-leak path model is constructed based on the contact width and surface micro-structure, and the cross-sectional area of the micro-leakage path is obtained, when the contact pressure is acted on the model. Therefore, the fluid flow states in the micro-leakage path are determined, and the flow conductance and the seal leakage rate of rubber seal are all calculated. Finally, the micro-leakage model of the rubber seal is modified to improve the theoretical calculation accuracy by the experiment.

Leakage performance of rubber seal is a key factor of spacecraft system, which is required long life. But the degradation law of the rubber seal performance in long service period is limited to qualitative analysis for its macro contact performance, and the quantitative research of rubber seal leakage performance is rarely involved considering thermal oxygen aging effect. Therefore, the thermal oxygen aging mathematical model is firstly established to predict the life of rubber material by aging tests. Secondly, the finite element model (FEM) of rubber seal performance analysis considering thermal oxygen aging effect is built to obtain the degradation law of its macroscopic contact performance with the increase of service time. Thirdly, the micro-leakage model of rubber seal considering thermal oxygen aging effect is established based on the material surface microstructure, contact pressure, and contact width, and the leakage rate of rubber seal is calculated by the model. Finally, the micro-leakage model of rubber seal is modified based on the experimental results, so the calculation accuracy of leakage rate is improved.

The expression pattern of VEGF-D in EBV-negative and EBV-positive cell lines, cellular supernatant, and specimens

Correlation between the clinicopathological features and EBV status

Supplementary Data

Lymphatic metastasis is a common clinical symptom in nasopharyngeal carcinoma (NPC), the most common Epstein-Barr virus (EBV)-associated head and neck malignancy. However, the effect of EBV on NPC lymph node (LN) metastasis is still unclear. In this study, we demonstrated that EBV infection is strongly associated with advanced clinical N stage and lymphangiogenesis of NPC. We found that NPC cells infected with EBV promote LN metastasis by inducing cancer-associated lymphangiogenesis, whereas these changes were abolished upon clearance of EBV genomes. Mechanistically, EBV-induced VEGF-C contributed to lymphangiogenesis and LN metastasis, and PHLPP1, a target of miR-BART15, partially contributed to AKT/HIF1a hyperactivity and subsequent VEGF-C transcriptional activation. In addition, administration of anti-VEGF-C antibody or HIF1α inhibitors attenuated the lymphangiogenesis and LN metastasis induced by EBV. Finally, we verified the clinical significance of this prometastatic EBV/VEGF-C axis by determining the expression of PHLPP1, AKT, HIF1a, and VEGF-C in NPC specimens with and without EBV. These results uncover a reasonable mechanism for the EBV-modulated LN metastasis microenvironment in NPC, indicating that EBV is a potential therapeutic target for NPC with lymphatic metastasis.Implications:This research demonstrates that EBV induces lymphangiogenesis in NPC by regulating PHLPP1/p-AKT/HIF1a/VEGF-C, providing a new therapeutic target for NPC with lymphatic metastasis.

In recent years, researchers have proposed many deep learning algorithms for data representation learning. However, most deep networks require extensive training data and a lot of training time to obtain good results. In this paper, we propose a novel deep learning method based on stretching deep architectures that are composed of stacked feature learning models. Hence, the method is called “stretching deep architectures” (SDA). In the feedforward propagation of SDA, feature learning models are firstly stacked and learned layer by layer, and then the stretching technique is applied to map the last layer of the features to a high-dimensional space. Since the feature learning models are optimized effectively, and the stretching technique can be easily calculated, the training of SDA is very fast. More importantly, the learning of SDA does not need back-propagation optimization, which is quite different from most of the existing deep learning models. We have tested SDA in visual texture perception, handwritten text recognition, and natural image classification applications. Extensive experiments demonstrate the advantages of SDA over traditional feature learning models and related deep learning models.

Acute promyelocytic leukemia (APL) is a special type of acute myeloid leukemia (AML), accounting for about 5% to 10% of children with AML. At the genetic level, APL is featured by a unique chromosome translocation t(15;17) which results in the PML-RARA gene fusion. Most patients can be diagnosed by traditional karyotype analysis, Fluorescence-In-Situ Hybridization (FISH), or Reverse Transcription-Polymerase Chain Reaction (RT-PCR). We report the case of a child with acute promyelocytic leukemia (APL) who had characteristic chromosome translocation t(15;17) and rare PML-RARA gene mutation. This patient had an excellent response to chemotherapy, suggesting that this mutation will not affect the treatment and prognosis of APL.

In this study, graphdiyne (GDY) was first reported as a substrate material for sodium-ion batteries (SIBs). The creative hybridization of GDY and molybdenum disulfide (MoS2) endows the composite with unique heterostructural and morphological advantages that boost the charge transport rate and enhance the battery discharge properties. Electrochemical results indicated that the MoS2@GDY anode displays a considerable discharge capacity of up to 328 mAh g-1 at 1000 mA g-1. A capacity retention of 93% even at testing current back to 200 mA g-1 suggests superior rate characteristics. An outstanding stable cyclic performance of 217 mAh g-1 is obtained at a high testing density. The attractive results not only demonstrate that GDY could be used not only as an effective conductive substrate to prevent the host material from agglomerating in the electrochemical process but also provide a novel design for fabricating efficient electrode materials for future energy-storage systems.

Atomically ordered intermetallic nanoparticles are promising for catalytic applications but are difficult to produce because the high-temperature annealing required for atom ordering inevitably accelerates metal sintering that leads to larger crystallites. We prepared platinum intermetallics with an average particle size of5 nanometers on porous sulfur-doped carbon supports, on which the strong interaction between platinum and sulfur suppresses metal sintering up to 1000°C. We synthesized intermetallic libraries of small nanoparticles consisting of 46 combinations of platinum with 16 other metal elements and used them to study the dependence of electrocatalytic oxygen-reduction reaction activity on alloy composition and platinum skin strain. The intermetallic libraries are highly mass efficient in proton-exchange-membrane fuel cells and could achieve high activities of 1.3 to 1.8 amperes per milligram of platinum at 0.9 volts.

Investigating the efficacy and safety of noninvasive cerebellar stimulation in improving the balance and walking function of patients with stroke.We searched 7 databases for randomized controlled trials (RCTs) related to noninvasive cerebellar stimulation in the treatment of stroke. The Berg Balance Scale (BBS), 6-minute walk test (6MWT), and Barthel Index (BI) were used as the outcome indexes to evaluate balance, walking and activities of daily living (ADL). The quality of the research was evaluated using the Cochrane Risk of Bias Tool. A meta-analysis was performed to evaluate the difference between the noninvasive cerebellar stimulation and control groups. Heterogeneity tests were performed to assess differences in treatment effects across noninvasive cerebellar stimulation modalities. A sensitivity analysis was performed to evaluate the robustness of the results.Seven studies were included, and 5 articles (71.43%) were rated as having a low risk of bias. Among the primary outcome indicators, 4 of the 7 articles were combined into the fixed effect model (I2 = 38%, P = .18). Compared with the control group, noninvasive cerebellar stimulation improved the BBS score, and the difference was statistically significant (mean difference [MD]: 3.00, 95% confidence interval [CI]: 1.10-5.40, P = .03); the sensitivity analysis showed that the statistical model was still stable after sequentially eliminating each article. Compared with the control group, noninvasive cerebellar stimulation improved the 6MWT results of patients with stroke (MD: 25.29, 95% CI: 4.86-45.73, P = .02). However, noninvasive cerebellar stimulation did not improve the BI (MD: 15.61, 95% CI: -7.91 to 39.13, P = .19). No safety problems or adverse reactions to noninvasive cerebellar stimulation were observed.Noninvasive cerebellar stimulation improves balance and walking function of patients with stroke, but its effect on ADL is uncertain. Due to the methodological weaknesses in the included trials, more RCTs are needed to confirm our conclusions.

To explore the intervention effect of recombinant human interleukin-11 (rhIL-11) and recombinant human granulocyte-colony stimulating factor (rhG-CSF) on the duration and severity of agranulocytosis in patients with hematological malignancies after chemotherapy, and to analyze the influencing factors.The data of hematological malignancy patients treated with rhIL-11 and rhG-CSF after chemotherapy in the hematology department of The First Hospital of Lanzhou University from July 2017 to July 2020 were collected retrospectively. The duration and differences of agranulocytosis in differeent groups were compared by univariate analysis, and the influencing factors of agranulocytosis duration were further analyzed by multiple regression analysis.The duration of agranulocytosis in 97 patients was 6.47±2.93 days. The results of univariate analysis showed that there were no statistical differences in the duration of agranulocytosis among patients with different sex, age, height, weight, body surface area, body mass index (BMI), dose of rhG-CSF, dose of rhIL-11, spontaneous bleeding after administration of rhG-CSF and rhIL-11, and the duration of agranulocytosis in patients with different red blood cell count (RBC), hemoglobin(HGB) level, platelet count (PLT) and absolute neutrophil count (ANC), before administration of rhG-CSF and rhIL-11. There were significant differences in agranulocytosis time among patients with different disease types, chemotherapy cycle, fever after rhG-CSF and rhIL-11 administration, and different white blood cell count (WBC) baseline level before rhG-CSF and rhIL-11 administration (P＜0.05). Compared with patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL), patients with acute myeloid leukemia (AML) had the longest duration of agranulocytosis, which was 7.07±3.05 d. Compared with patients with chemotherapy cycles of 4－6 and ≥7, patients with total chemotherapy cycle of 1－3 had the shortest duration of agranulocytosis, which was 5.25±2.48 d. Compared with patients without fever, patients with fever within 1 day after administration of cytokines and patients with fever within 2-5 days after administration of cytokines, the duration of agranulocytosis was the longest in patients with fever 6 days after administration of cytokines, which was 8.85±2.85 d. Compared with patients with WBC baseline1.0×10The risk of prolonged agranulocytosis is higher in patients diagnosed with AML, with more chemotherapy cycles, lower WBC baseline before cytokines administration and fever later after cytokines administration, which should be paid more attention to.联用rhIL-11和rhG-CSF的血液恶性肿瘤患者粒细胞缺乏时间及其影响因素分析.探讨重组人白介素-11（rhIL-11）联合重组人粒细胞集落刺激因子（rhG-CSF）治疗化疗后血液肿瘤患者粒缺持续时间和严重程度的干预作用，以及对其影响因素进行分析.回顾性收集兰州大学第一医院血液科2017年7月－2020年7月收治的在化疗后联合应用rhIL-11和rhG-CSF血液肿瘤患者资料，通过单因素分析比较不同分组情况下粒缺持续时间情况及差异，多元回归分析进一步明确粒缺持续时间的影响因素.97例患者粒缺持续时间为6.47±2.93 d。单因素分析结果显示，不同性别、年龄、身高、体重、体表面积、体质量指数（BMI）、rhG-CSF剂量、rhIL-11剂量，给予rhG-CSF和rhIL-11后是否自发性出血，给予rhG-CSF和rhIL-11前不同红细胞计数（RBC）、血红蛋白（HGB）水平、血小板数（PLT）、中性粒细胞数绝对值（ANC）的患者粒缺持续时间比较，差异均无统计学意义（P＞0.05）；不同疾病类型、化疗周期、给予rhG-CSF和rhIL-11后不同发热情况、给予rhG-CSF和rhIL-11前不同白细胞数（WBC）基线的患者粒细胞缺乏时间比较，差异有统计学意义（P＜0.05）。诊断为急性髓系白血病（AML）的患者与急性淋巴细胞白血病（ALL）、非霍奇金淋巴瘤（NHL）的患者相比，粒缺持续时间最长，为7.07±3.05 d。与化疗周期为4-6和≥7的患者相比，总化疗周期为1-3的患者粒缺持续时间最短，为5.25±2.48 d。在联用二种细胞因子6 d后出现发热患者，与无发热、联用细胞因子后1 d内出现发热、联用细胞因子2-5 d内出现发热患者相比，粒缺持续时间最长，为8.85±2.85 d。在联合给予细胞因子前WBC基线为≥4.0×10对于诊断为AML，化疗周期数较多，联合应用细胞因子前WBC基线较低，在给予细胞因子后较晚出现发热的患者，粒缺持续时间过度延长的风险更高，应该予以重视.

The design and construction of advanced electrode materials is important to the development of high-performance electrochemical energy storage devices. In this paper, V-doped 1T MoS2 nanosheets with a large layer spacing are grown on carbon cloth (CC) via a one-step hydrothermal method. The resulting material features abundant edge sites and active centers, and its large layer spacing facilitates the interlayer shuttle of Na+. Doping with V buffers the volume change and maintains the integrity of MoS2. The layered structure of the composite featuring CC as a conductive substrate effectively prevents the agglomeration of MoS2 during the electrochemical process. When used as an anode material for a Na+ battery, the material displays a high first-cycle irreversible discharge specific capacity of 1234.9 mAh g−1. A specific capacity of 453.2 mAh g−1 is obtained after 100 cycles at a current density of 200 mA g−1. This work provides an effective and eco-friendly route toward obtaining superior MoS2 electrodes for high-performance Na+ storage.

There has been an explosion of interest in the use of nanomaterials for biosensing applications, and carbonaceous nanomaterials in particular are at the forefront of this explosion. Carbon dots (CDs), a new type of carbon material, have attracted extensive attention due to their fascinating properties, such as small particle size, tunable optical properties, good conductivity, low cytotoxicity, and good biocompatibility. These properties have enabled them to be highly promising candidates for the fabrication of various high-performance biosensors. In this review, we summarize the top-down and bottom-up synthesis routes of CDs, highlight their modification strategies, and discuss their applications in the fields of photoluminescence biosensors, electrochemiluminescence biosensors, chemiluminescence biosensors, electrochemical biosensors and fluorescence biosensors. In addition, the challenges and future prospects of the application of CDs for biosensors are also proposed.

Acute lymphoblastic leukemia (ALL) is one of the most common malignancies in children. Our aim was to identify a novel miRNA that can predict prognosis of childhood ALL patients and explore its potential mechanism.The miRNA expression profiles of childhood ALL were analyzed using GEO database and HiSeq instruments. The expression of miR-155 was examined by RT-PCR in 42 ALL patients. To investigate the role of miR-155 in ALL, four ALL cell lines (CEM-C1, Jurkat, MOLT-3 and MOLT-4) were transfected with miR-155 mimics, miR-155 inhibitors or corresponding controls. Dual-luciferase reporter system was applied to confirm the miR-155 target ZNF238. Moreover, proliferation and apoptosis were evaluated by MTT and flow cytometry.Dataset GSE56489 and GSE23024 demonstrated that miR-155 was up-regulated and ZNF238 was down-regulated at diagnosis status of ALL. High miR-155 expression was associated with poor outcome. Overexpressed miR-155 promoted ALL cell proliferation and inhibited apoptosis. Dual-luciferase reporter result showed that miR-155 directly regulated ZNF238. Silencing ZNF238 promoted cell proliferation in ALL cells.Our research indicating that miR-155 might possess potential value as a biomarker for predicting the prognosis of individuals. However, the role of ZNF238 in childhood ALL remain unknown. In the present study, we found the possible role of ZNF238 as a new tumor suppressor in ALL, which might be necessary for the antiproliferative functions of normal cells to counteract ALL formation.Our results propose that miR-155 is in association with poor prognosis of childhood ALL. Furthermore, miR-155 could promote cell proliferation targeting ZNF238.

Four novel coordination polymers [Cd2(oba)2(phen)2]n (1), [Mn3(oba)3(phen)2]n (2), [Zn(oba)(phen)]n (3) and [Mn(oba)(dmphen)]n (4) (H2oba = 4,4′-oxybis (benzoic acid), phen = 1,10-phenanthroline, dmphen = 2,9-dimethyl-1,10-phenanthroline) have been synthesized by the solvothermal method and then characterized by single-crystal X-ray diffraction, elemental analysis, infrared spectrum, UV–Vis spectroscopy and thermogravimetric analysis. Structural analysis suggests that complex 1 displays a 1D ribbon-like structure, which extends into a 2D supramolecular layer by intermolecular π⋯π stacking. For complex 2, the trinuclear building unit of [Mn3(oba)3(phen)2] bridged by the oba2− ligands leads to the formation of a 3D supramolecular network. Complex 3 adopts a mononuclear and 1D zigzag chain structure and also extends into a 2D supramolecular network by intermolecular π⋯π stacking. Complex 4 shows 1D infinite double-chain structures which are shaped by intermolecular π⋯π stackings. Photoluminescent properties of complexes 1 and 3 in solid state were also studied. In addition, complex 2 exhibits high performance in the selective adsorption of Congo red (CR) with an adsorption capacity of 64.4 mg g−1.

The stability of ultrathin polymer films plays a crucial role in their technological applications. Here, we systematically investigated the influence of interfacial adsorption in physical aging and the stability of thin polymer films in the solvent-induced process. We further identify the stability mechanism from the theory of thin film stability. Our results show that the aging temperature and film thickness can strongly influence the stability of thin PS films in acetone vapor. Physical aging can greatly improve the stability of thin polymer films when the aging temperature Taging1 > Tg. A thinner PS film more quickly reaches a stable state via physical aging. At short aging time, the formation of the adsorbed layer can reduce the polar interaction; however, it slightly influences the stability of thin polymer films in the solvent-induced process. At later aging stage, the conformational rearrangement of the polymer chains induced by the interfacial effect at the aging temperature Taging1 plays an important role in stabilizing the thin polymer films. However, at Taging2 < Tg, the process of physical aging slightly influences the stability of the thin polymer films. The formation of the adsorbed layer at Taging2 can reduce the short-range polar interaction of the thin film system and cannot suppress the instability of thin polymer films in the solvent-induced process. These results provide further insight into the stable mechanism of thin polymer films in the solvent-induced process.

The prognosis of patients with acute myeloid leukemia (AML) caused by the FLT3-ITD mutation is poor. Arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) can down-regulate FLT3-ITD level and selectively kill leukemia cells carrying the FLT3-ITD mutation. However, the mechanisms of action of these two compounds are unknown. Here, we found that ATO could bind FLT3-ITD at Lys91 and Asp225, whereas ATRA could bind FLT3-ITD at Lys5 and Gln6. Both compounds could not bind wild-type FLT3. Further studies revealed that ATO/ATRA may suppress the Expression of FLT3-ITD by promoting the UBE2L6-mediated ubiquitination pathway and decreasing the expression of C-MYC. However, further studies are needed to define the mechanisms of these compounds on AML. Our research provides an experimental basis for the use of ATO/ATRA in FLT3-ITD AML in clinical practice.

Hierarchical ZSM-5 zeolites were successfully prepared with one-step hydrothermal method by adding MTES to the zeolite precursor. The mesoporous structure of zeolite was formed via organosilane interacts with nanoparticles to form a covalent bond of Si–R, and then the alkyl group was removed by calcination. The influence of methyltriethoxysilane on the mesopores, acidity, morphology of the zeolites, and the catalytic performance of the samples was investigated. A mesoporous size about 6.5 nm was formed in the sample, meanwhile, the Bronsted acid density of zeolite was decreased. The yield of the aromatic compound was increased by about 10% after the introduction of the mesoporous structure. The catalyst’s carbon deposition resistance was improved due to a significant decrease of the Bronsted acid density of zeolite, and the catalyst life (methanol conversion rate > 95%) was extended from 41 to 76 h.

The characteristics of interhemispheric resting-state functional connectivity (FC) in Parkinson’s disease (PD) with fatigue remain unclear; therefore, we aimed to explore the changes in interhemispheric FC in PD patients with fatigue. Sixteen PD patients with fatigue (PDF), 16 PD patients without fatigue (PDNF) and 15 matched healthy controls (HCs) were enrolled in the retrospective cross-sectional study. We used voxel-mirrored homotopic connectivity (VMHC) to analyze the resting-state functional magnetic resonance imaging (fMRI) data of these subjects. Compared to PDNF, PDF patients had decreased VMHC values in the supramarginal gyri (SMG). Furthermore, the mean VMHC values of the SMG were negatively correlated with the mean fatigue severity scale (FSS/9) scores (r = −0.754, p = 0.001). Compared to HCs, PDF patients had decreased VMHC in the SMG and in the opercular parts of the inferior frontal gyri (IFG operc). The VMHC values in the IFG operc and middle frontal gyri (MFG) were notably decreased in PDNF patients compared with HCs. Our findings suggest that the reduced VMHC values within the bilateral SMG may be the unique imaging features of fatigue in PD, and may illuminate the neural mechanisms of fatigue in PD.

Background: Breast cancer is the most common malignant tumor in women, and its pathogenesis is very complicated. More and more studies have found that Traditional Chinese Medicine plays an important role in tumor prevention. Objective: To investigate the mechanism of arnicolide D isolated from Centipeda minima in breast cancer. Methods: Cell Counting Kit-8 (CCK-8), western blot, RT-qPCR, ELISA, flow cytometry, and Transwell were used to detect the effect of arnicolide D on the biological function of breast cancer cells. Results: Arnicolide D promoted reactive oxygen species (ROS) production and induced a decrease in mitochondrial membrane potential in breast cancer cells, thereby inhibiting cell viability and increasing lactate dehydrogenase (LDH) release. Arnicolide D activated the classical apoptosis pathway to induce cell apoptosis; it significantly promoted PARP-1 expression, enhanced the nuclear translocation of apoptosis-inducing factor (AIF), and reduced the expression of AIF in mitochondria, indicating that it can induce the occurrence of parthanatos in a ROS dependent manner. In addition, arnicolide D down-regulated glutathione peroxidase 4 (GPX4) expression and increased the accumulation of Fe2+ and malondialdehyde (MDA), thereby activating ferroptosis. Apoptosis inhibitor, ferroptosis inhibitor, PARP inhibitor, PARP-1 siRNA, AIF siRNA and GPX4 overexpression vector significantly attenuated the inhibitory effect of arnicolide D on cell viability and reduced LDH release, which indicates that arnicolide D inhibits breast cancer cell growth by inducing apoptosis, parthanatos and ferroptosis. Arnicolide D also reduced breast cancer cell invasion and inhibited the expression of matrix metallopeptidase (MMP)-2 and MMP-9. Conclusion: Arnicolide D can activate a variety of cell death modes by inducing oxidative stress, thereby inhibiting the growth and invasion of breast cancer cells, indicating that arnicolide D has a good anti-tumor effect.

Background: The poor prognosis of acute myeloid leukemia (AML) is partly due to the immunosuppressive leukemia environment. A therapeutic approach to induce pyroptosis is promising to work on this issue. Pyroptosis, a form of inflammatory cell death, is capable to release pro-immune factors and enhance the infiltration and cytotoxicity of natural killer (NK) cells. Chemical drugs have been verified to enhance anti-tumor immunity by inducing pyroptosis. Arsenic trioxide (ATO), a clinical drug in leukemia, is reported to be effective to kill AML cells, but it’s still unclear about its mechanism in AML. Our research is aimed at exploring the ATO effect on pyroptosis induction and the anti-tumor immunity of NK cells in AML.Methods: Pyroptotic phenomenon was detected by confocal microscopy, Annexin-V / propidium iodide staining, LDH release assay, and western blotting; The release of cytokines was detected by SDS-PAGE, proteomic analysis, ELISA, etc.; AML xenograft models were established to explore the ATO effect in vivo and the anti-tumor effect of ATO treatment was identified by tumor-volume measurement, HE staining and KI67 staining; The activity of NK cells was evaluated by immunofluorescence, flow cytometric analysis, etc.; The differential expressed proteins were identified by quantitative proteomic analysis and western blotting.Results: We first discovered that ATO induced pyroptosis in AML cells and activated caspase-3/gasdermin E (GSDME) pathway to induce pyroptosis, and enhances the release of LDH, HMGB1, and IL-1β. Moreover, we revealed that ATO treatment promoted the proliferation, tumor-infiltration, and degranulation of NK cells in AML and its leukemia microenvironment. The further proteomic clues indicate the potential mechanisms of the ATO anti-leukemia effect in vivo.Conclusions: These findings indicate that ATO treatment induces pyroptosis via caspase-3/GSDME pathway, enhances the release of pro-inflammatory cytokines, and activates NK cells in AML. Our data identify what is to our knowledge the first clinical drug that induces pyroptosis in AML, revealing the potential anti-leukemic and pro-immune properties of ATO treatment in the leukemia microenvironment of AML, which may be beneficial in reducing the recurrence problems associated with the leukemia microenvironment.

Our and in vitro studies had confirmed that mechanosensitive ATP release and accumulation in acupoints was elicited by acupuncture (AP), which might be a pivotal step for triggering AP analgesia. But to date, the dynamics of extracellular ATP (eATP) in the interstitial space during AP process was poorly known, mainly due to the low temporal resolution of the current detection approach. This study attempted to capture rapid eATP signals in vivo in the process of needling, and further explored the role of this eATP mobilization in initiating AP analgesic effect. Ipsilateral 20-min needling was applied on Zusanli acupoint (ST36) of complete Freund's adjuvant (CFA)-induced ankle arthritis rats. Pain thresholds were assessed in injured-side hindpaws. eATP in the interstitial space was microdialyzed and real-time quantified by luciferin-luciferase assay at 1-min interval with the aid of the microfluid chip. We revealed in behavioral tests that modulation of eATP levels in ST36 influenced AP analgesic effect on ankle arthritis. A transient eATP accumulation was induced by needling that started to mobilize at 4 min, climbed to the peak of 11.21 nM within 3.25 min and gradually recovered. Such AP-induced eATP mobilization was significantly impacted by ankle inflammation, needling depth, needle manipulation, and the presence of local ecto-nucleotidases. This work reveals that needling elicits a transient eATP mobilization in acupoints, which contributes to initiating AP analgesia. This study will help us better understand the peripheral mechanism of AP analgesia and guide clinicians to optimize the needle manipulations to improve AP efficacy.

The role of telomerase reverse transcriptase (TERT) induction and telomere maintenance in carcinogenesis including cervical cancer (CC) pathogenesis has been well established. However, it remains unclear whether they affect infection of high-risk human papillomavirus (hrHPV), an initiating event for CC development. Similarly, genetic variants at the TERT locus are shown to be associated with susceptibility to CC, but it is unclear whether these SNPs modify the risk for cervical HPV infection. Here we show that in CC-derived HeLa cells, TERT overexpression inhibits, while its depletion upregulates expression of Syndecan-1 (SDC-1), a key component for HPV entry receptors. The TCGA cohort of CC analyses reveals an inverse correlation between TERT and SDC-1 expression (R = -0.23, P = 0.001). We further recruited 1330 females (520 non-HPV and 810 hrHPV-infected) without CC or high-grade cervical intraepithelial neoplasia to analyze telomeres in cervical epithelial cells and SNPs at rs2736098, rs2736100 and rs2736108, previously identified TERT SNPs for CC risk. Non-infected females exhibited age-related telomere shortening in cervical epithelial cells and their telomeres were significantly longer than those in hrHPV-infected group (1.31 ± 0.62 vs 1.19 ± 0.48, P 0.001). There were no differences in rs2736098 and rs2736100 genotypes, but non-infected individuals had significantly a higher C-allele frequency (associated with higher TERT expression) while lower T-allele levels at rs2736108 compared with those in the hrHPV group (P = 0.020). Collectively, appropriate telomere maintenance and TERT expression in normal cervical cells may prevent CC by modulating hrHPV infection predisposition, although they are required for CC development and progression.

Biosolubilization of coal to produce non-fuel products (humic acid) has offered an alternative method for coal clean utilization. Previous studies have proved pretreating low-rank coal with surfactant can improve fugal biosolubilization. However, limited reports referred high-rank coal. In the present work, a fungus HN-1 isolated from Yanzhou coal mine soil in Shandong province, northeast China was used to biodegrade Shandong bituminous coal, and the possible degrading mechanism was analyzed. The results showed that the homology of HN-1 was 97% with the white-rot fungus Hypocrea lixii, so it was assigned as Hypocrea lixii HN-1. The fungal strain HN-1 had the ability to solubilize the bituminous coal to produce black droplets within 10 days. Furthermore, it appeared that pretreatment by the surfactant sodium dodecyl sulfate could promote coal biosolubilization. The weight losses after biosolubilization of raw coal (YM) and surfactant-treated coal (A coal) were 11.33% and 14.02%, while the humic acid of YM and A coal increased by 1.42% and 2.99%, respectively. The FT-IR showed that the raw coal almost remained unchanged after biosolubilization. However, some small molecule functional groups including disulfides, amino groups, hydroxyl groups and oxygen-containing were introduced into the coal after pretreatment with surfactant.

This review summarizes experimental evidence indicating that subcutaneous mast cells are involved in the trigger mechanism of analgesia induced by acupuncture, a traditional oriental therapy, which has gradually become accepted worldwide. The results are essentially based on work from our laboratories. Skin mast cells are present at a high density in acupuncture points where fine needles are inserted and manipulated during acupuncture intervention. Mast cells are sensitive to mechanical stimulation because they express multiple types of mechanosensitive channels, including TRPV1, TRPV2, TRPV4, receptors and chloride channels. Acupuncture manipulation generates force and torque that indirectly activate the mast cells via the collagen network. Subsequently, various mediators, for example, histamine, serotonin, adenosine triphosphate and adenosine, are released from activated mast cells to the interstitial space; they or their downstream products activate the corresponding receptors situated at local nerve terminals of sensory neurons in peripheral ganglia. The analgesic effects are thought to be generated via the reduced electrical activities of the primary sensory neurons. Alternatively, these neurons project such signals to pain-relevant regions in spinal cord and/or higher centers of the brain.

Lung transplantation is the only effective way to treat end-stage lung disease. Severe gastrointestinal complications are common after lung transplantation and are associated with increased mortality. Early identification and active intervention are necessary to avoid treatment delays. Abdominal massage belongs to the category of external treatment of traditional Chinese medicine (TCM), which is often used in the treatment of internal diseases. It has an excellent effect in treating stomachache, bloating, anorexia, and constipation.The patient developed gastrointestinal dysfunction 16 days after lung transplantation. Through the implementation of abdominal massage intervention, symptoms were significantly relieved, weight gain occurred, and the curative effect was good.Abdominal massage can relieve gastrointestinal symptoms and promote the recovery of gastrointestinal function after lung transplantation and has good curative effects. This method is worth promoting in patients who have had lung transplantation.

PurposeTo analyzed the outcome of ETV6/RUNX1-positive pediatric acute B lymphoblastic leukemia (B-ALL) with the aim of identifying prognostic value.MethodA total of 2,530 pediatric patients who were diagnosed with B-ALL were classified into two groups based on the ETV6/RUNX1 status by using a retrospective cohort study method from February 28, 2008, to June 30, 2020, at 22 participating ALL centers.ResultsIn total, 461 (18.2%) cases were ETV6/RUNX1-positive. The proportion of patients with risk factors (age 9/L) in ETV6/RUNX1-positive group was significantly lower than that in negative group (PPvs82 ± 2.36%,Pvs88.79 ± 1.87%,P=0.017). Subgroup analysis showed that chemotherapy protocol, age, prednisone response, and D15 MRD were important factors affecting the prognosis of ETV6/RUNX1-positive children.ConclusionsETV6/RUNX1-positive pediatric ALL showed an excellent outcome but lack of independent prognostic significance in South China. However, for older patients who have the ETV6/RUNX1 fusion and slow response to therapy, to opt for more intensive treatment.

The pathogen detection rate of traditional ink staining procedure (TISP) is low.A modified ink staining procedure (MISP) was created to accumulate pathogen by using cell slide centrifuge. Items of RBC, WBC, and cryptococcus were observed.There were 79.98 ± 54.94 RBC and 126.98 ± 36.39 WBC in one MISP microscopic field whereas there were only 3.35 ± 2.41 RBC and 6.15 ± 1.85 WBC in one TISP microscopic field in the same sample (*200). There was statistical difference between those two methods (p = 0.000). There were 40.78 ± 13.23 mL cryptococcus in CSF processed by MISP whereas there were only 2.10 ± 1.10 mL cryptococcus in the same CSF processed by TISP. There was statistical difference between those two methods.The modified ink staining procedure contributes to the separation of cells and pathogens (such as cryptococcus).

Hyperglycemia-induced inflammation and subsequent endothelial injuries ultimately lead to the pathogenesis of cardiovascular diseases associated with high mortality, such as atherosclerosis. Maslinic acid (MA) is a phytochemical with anti-inflammatory activity. However, it remains unknown whether it can inhibit diabetes-associated cardiovascular inflammation. The present study aimed to determine the effect of MA on high glucose-induced endothelial inflammation and apoptosis in human umbilical vein endothelial cells (HUVECs) and to explore the underlying mechanism.HUVECs were treated with high glucose to induce inflammation and apoptosis. Apoptosis was determined by flow cytometry. CCK-8 assay was used to examine cell viability. Production levels of cytokines were detected by quantitative realtime PCR (qPCR) and ELISA. Protein expression levels and signaling pathways activation were detected by Western blotting. RNA immunoprecipitation and qPCR were used to determine the NMA promoted the recruitment of RNA demethylase ALKBH5 to TXNIP mRNA, and subsequently enhanced its m6A demethylation. By this means, MA decreased the stability of TXNIP mRNA and downregulated its expression level. Subsequently, reactive oxygen species (ROS) and production of pro-inflammatory cytokines, including TNF-α, IL-6 and IL-1β, were inhibited. And high glucose-induced apoptosis in HUVECs was inhibited by MA.MA ameliorates high glucose-induced endothelial inflammation and injury, serving as a new potential therapeutic application for protecting against diabetes-associated atherosclerosis and other inflammatory diseases.

Ubiquilins (UBQLNs) are important factors for cell proteostasis maintenance. UBQLNs are involved in the modulation of the cell cycle, as well as in apoptosis, membrane receptors regulation, DNA repair, epithelial-mesenchymal transition, and miRNA activities. They also affect the selection of double-strand break repair pathways. Abnormal UBQLNs expression can lead to many diseases, including cancer. Studies have found that the expression of Ubiquilin4To investigate the expression of UBQLN4 in cervical cancer and to evaluate its correlation with disease prognosis.Immunohistochemistry was performed to examine the expression of UBQLN4 in 117 cervical cancer tissues and 32 matching pericervical tissues. Paired t-test (two-tailed) was used to compare the differences between groups. We collected patients' clinical characteristics, including age, histological grade, pathologic type, lymph node metastasis, and FIGO stage (2018) and compared them by chi-square test. All patients were followed for 5.5 to 6.8 years. Kaplan-Meier method and log-rank test were used to compare the differences in the overall survival (OS) and progression-free survival (PFS) among the different groups.Overexpression of UBQLN4 was observed in 70.9% (83/117) of all cervical cancer tissues and in 15.6% (5/32) of the paired parauterine tissues. The expression of UBQLN4 was associated with lymph node metastasis, poor differentiation, and advanced stage, but the difference was not significant. Kaplan-Meier and log-rank test results suggested the high expression of UBQLN4 was associated with short OS and PFS. Regardless of UBQLN4 expression, the patient age and FIGO stage were also associated with disease prognosis. The statistically significant variables obtained from univariate the Kaplan-Meier analysis were subjected to Cox multivariate survival regression analysis, which showed that, in addition to the FIGO stage and age, UBQLN4 was also an independent prognostic marker for OS and PFS (The overexpression of UBQLN4 was associated with poor prognosis in cervical cancer. Our study proposed a novel prognostic factor and improved the existing understanding of the pathogenesis of cervical cancer.

BACKGROUND The increased stroke risk associated with atrial fibrillation (AF) burden exceeding 5 min is a matter of debate. In addition, the potential linear or nonlinear relationship between AF burden and stroke risk has been largely unexplored. AIM To determine the association between AF burden > 5 min and the increased risk of stroke and explore the potential dose-response relationship between these two factors. METHODS Sixteen studies from six databases with 53141 subjects (mean age 65 years) were included. Fifteen studies were observational studies, and one was a randomized controlled trial study. The potential nonlinear dose-response association was characterized using a restricted cubic splines regression model. AF burden for each 1 h and 2 h was associated with an increased risk of stroke. Trial sequential analysis with a random-effect model was used to evaluate the robustness of the evidence from the included 16 studies. RESULTS AF burden > 5 min was associated with an increased risk of clinical AF [adjusted risk ratio (RR) = 4.18, 95% confidence interval (CI): 2.26-7.74]. However, no association was found with an increased risk of all-cause mortality (adjusted RR = 1.55, 95%CI: 0.87-2.75). Patients with AF burden > 5 min had an increased risk of stroke (adjusted RR = 2.49, 95%CI: 1.79-3.47). Moreover, a dose-response analysis showed that the increased stroke risk was paralleled by an increase in AF burden at a rate of 2.0% per hour (Pnonlinear = 0.656, RR = 1.02, 95%CI: 1.01-1.03). Trial sequential analysis provided robust evidence of the association between AF burden > 5 min and an increased risk of stroke. CONCLUSION AF burden was a significant risk factor for clinical AF and future stroke. A significant linear association was documented between increased AF burden and risk of future stroke.