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BACKGROUND Medication adherence is crucial to the efficacy of antitumor drugs. The wechat applet, also known as the Mini Program, similar to app but has great advantages. The development and use of wechat applet provide follow-up convenience for cancer patients. OBJECTIVE This study aimed to assess the usability and utility of a newly developed medication adherence wechat applet—DolphinCare—among cancer patients in Shanghai. METHODS A qualitative methodology was utilized to obtain an in-depth understanding of users’ experiences when using DolphinCare from the usability and utility aspects. The development phase consisted of two parts: alpha and beta testing. The medication adherence of patients was evaluated using the eight-item Morisky Medication Adherence Scale (MMAS-8). RESULTS We included participants who had an electronic health literacy scale (eHEALS) of ≥50%, and a total of 20 participants were interviewed consecutively. We used the motivation, ability and trigger categories of the Fogg behaviour model to explore why patients adopted and adhered to our applet using data from the qualitative interviews and usage data. There were usabilities and utilities that could improve the patients’ medication adherence and the management of adverse drug reactions (ADRs). CONCLUSIONS This study provides beginning evidence of the usability and utility of this type of applet in cancer patients.

PurposeOn the basis of the Thoracolumbar Injury Classification and Severity Score (TLICS), an modified TLICS classification system was presented, its reliability and repeatability were assessed, and the factors influencing classification consistency were examined.MethodsFive spinal surgeons were chosen at random. The clinical data of 120 patients with thoracolumbar fractures admitted to the Department of Spine Surgery, Ningbo Sixth Hospital from December 2019 to June 2021 were categorized using the modified TLICS system. After 6 weeks, disrupt the order of data again. Using unweighted Cohen's kappa coefficients, the consistency of the modified TLICS system was assessed in five aspects: neurofunctional status, disc injury status, fracture morphology, posterior ligament complex (PLC) integrity, and treatment plan.ResultsIn terms of reliability, the average kappa values for the subclasses of the modified TLICS system (neurofunctional status and disc injury status) were 0.920 and 0.815, respectively, reaching the category of complete confidence. Fracture morphology and treatment plan had average kappa values of 0.670 and 0.660, respectively, which were basically reliable. The average kappa value of PLC integrity was 0.453, which belonged to the category of moderate confidence. The average kappa coefficients of each subcategory (neurological status, disc injury status) had excellent consistency, and the kappa values were 0.936 and 0.879, respectively, which belonged to the completely credible category. The kappa values of fracture morphology and treatment plan repeatability were 0.772 and 0.749, respectively, reaching the basic credibility category. PLC integrity repeatability kappa value is low, 0.561, to moderate credibility category.ConclusionThe modified TLICS system is intuitive and straightforward to understand. The examination of thoracolumbar fracture injuries is more exhaustive and precise, with excellent reliability and repeatability. The examination of neurological status and disc injury status is quite reliable and consistent. The consistency of fracture morphology is slightly poor, which is basically credible; the PLC integrity consistency is poor, reaching a reliability level of moderate, which may be associated with the subjectivity of clinical evaluation of PLC.

To investigate the efficacy and safety of VDZ (Vedolizumab) in the salvage treatment of glucocorticoid resistance to gastrointestinal graft-versus-host disease (GR-GI GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children.The clinical data of 5 patients with refractory GI GVHD who received allo-HSCT in Wuhan Children's Hospital from December 2020 to December 2021 were retrospectively analyzed with VDZ salvage therapy.Among the 5 children with refractory GI GVHD, there were 1 male and 4 female, including 2 cases of extremely severe aplastic anemia, 1 case of acute myeloid leukemia (M2, high-risk), 1 case of fanconi anemia and 1 case of myelodysplastic syndrome. The median age of transplant recipients was 54.4 (12-164) months. The median treatment time from transplantation to VDZ was 1.4 (0.6-6.8) months. On average, 3.5 (2-5) doses of VDZ were received. After receiving treatment, 2 patients achieved a complete response (CR), 2 patients achieved a very good partial response (VGPR), 1 patient was non-responsive (NR) after a short-term partial response (PR). Compared with that before VDZ treatment, the amount of diarrhea, stool color, blood and traits of the children after medication were effectively improved. The median follow-up time was 9.3 (7.23-12.83) months. No disseminated or severe bacterial/fungal infections occurred during VDZ treatment and follow-up, and 2 children died of leukemia recurrence and pulmonary bronchiolitis obliterans.VDZ salvage treatment of refractory GI GVHD in children has obvious short-term efficacy and good safety.维得利珠单抗挽救性治疗儿童糖皮质激素耐药性肠道移植物抗宿主病的临床分析.探讨维得利珠单抗（Vedolizumab,VDZ）挽救性治疗儿童异基因造血干细胞移植（allo-HSCT）后糖皮质激素耐药性肠道移植物抗宿主病（GI GVHD）的有效性及安全性.回顾性分析 2020年12月至2021年12月武汉儿童医院接受allo-HSCT的5例糖皮质激素耐药性GI GVHD患儿应用VDZ挽救性治疗的临床资料.5例糖皮质激素耐药性GI GVHD患儿中，男1例，女4例，包括2例极重型再生障碍性贫血，急性髓系白血病(M2，高危)、范可尼贫血和骨髓增生异常综合征各1例；其中接受移植的中位年龄为54.4（12-164）个月。移植后至接受VDZ的中位治疗时间为1.4（0.6-6.8）个月；平均接受VDZ治疗3.5（2-5）剂。接受治疗后总体2例患者达到完全反应（CR）,2例达到非常好的部分反应（VGPR），1例在短期PR后出现无反应（NR）。用药后患儿腹泻量及大便颜色、带血情况、性状均较使用前得到有效改善。中位随访时间9.3（7.23-12.83）个月，在VDZ治疗及随访期间未出现播散性或严重细菌/真菌感染，2例患儿因原发病复发或肺部闭塞性支气管炎而死亡.VDZ挽救性治疗儿童糖皮质激素耐药性GI GVHD的近期疗效明显，安全性良好.

To observe the efficacy and prognosis of cladribine (2-CdA) combined with cytarabine (Ara-C) regimen in the treatment of relapsed refractory Langerhans cell histiocytosis (LCH) in children.Nine patients with relapsed refractory LCH treated with the 2-CdA combined with Ara-C regimen in the Department of Hematology and Oncology of Wuhan Children's Hospital from July 2014 to February 2020 were retrospectively analyzed, and the efficacy and disease status were evaluated according to the Histiocyte Society Evaluation and Treatment Guidelines (2009) and the Disease Activity Score (DAS), the drug toxicity were evaluated according to the World Health Organization（WHO） grading criteria for chemotherapy. All patients were followed up for survival status and disease-related sequelae.Before the treatment combining 2-CdA and Ara-C, 7 of 9 patients were evaluated as active disease worse (ADW), and 2 as active disease stable (ADS) with a median disease activity score of 8 (4-15). Of 9 patients, 6 cases achieved non active disease (NAD) and 3 achieved active disease better (ADB) with a median disease activity score of 0 (0 to 5) after 2-6 courses of therapy. All 9 patients experienced WHO grade IV hematologic toxicity and 3 patients had hepatobiliary adverse effects (WHO grade I～II) after treatment. The median follow-up time was 31(1 to 50) months with all 9 patients survived, 3 of the 9 patients experienced sequelae to the disease with 2 combined liver cirrhosis as well as cholestatic hepatitis and 1 with oral desmopressin acetate tablets for diabetes insipidus.2-CdA combined with Ara-C is an effective regimen for the treatment of recurrent refractory LCH in children, and the main adverse effect is hematologic toxicity, which is mostly tolerated in children. Early treatment with this regimen may be considered for patients with multisystem LCH with risky organ involvement who have failed first-line therapy and for patients with relapse.克拉屈滨联合阿糖胞苷治疗儿童复发难治性朗格汉斯细胞组织细胞增生症.观察克拉屈滨（Cladribine，2-CdA）联合阿糖胞苷（Ara-C）方案治疗儿童复发难治性朗格汉斯细胞组织细胞增生症（LCH）的疗效及预后.回顾性分析2014年7月至2020年2月于武汉儿童医院血液肿瘤科接受2-CdA联合Ara-C方案治疗的复发难治性LCH患儿9例，根据国际组织细胞协会LCH评估指南以及疾病活动度评分（DAS）对疗效以及疾病状态进行评估，根据世界卫生组织（WHO）化疗药物不良反应分级标准进行药物不良反应评估，随访患者生存状态以及疾病相关后遗症.在接受2-CdA联合Ara-C方案治疗前，9例患者中有7例评估为活动性疾病进展（ADW），2例评估为活动性疾病稳定（ADS），中位DAS为8分（4-15分）。经过（2-6）个该疗程治疗后，有6例患者达到无活动性疾病（NAD），3例达到活动性疾病好转（ADB），中位DAS为0分（0-5分）。9例患者在治疗后均出现血液系统不良反应（WHO IV级），3例患者出现肝胆系统不良反应（WHO I-II级）。中位随访时间31（1-50）个月，9例患者均存活，3例出现疾病相关后遗症，2例合并肝硬化以及胆汁淤积性肝炎、1例因中枢性尿崩症口服醋酸去氨加压素片.2-CdA联合Ara-C是治疗儿童复发难治性LCH的有效方案，主要药物不良反应为血液学毒性，儿童多可耐受。对于一线治疗失败的多系统LCH伴危险器官受累患者以及复发患者可考虑尽早使用2-CdA联合Ara-C方案治疗.

Background: Currently, there is no optimal treatment strategy for ostial left anterior descending (LAD) or ostial left circumflex artery (LCx) lesions. This study explored effectiveness and safety of drug-coated balloons (DCB) in individuals presenting with ostial LAD or LCx lesions. Methods: A total of 137 patients with de novo ostial LAD or LCx lesions scheduled for DCB treatment were prospectively recruited into the study. After mandatory lesion preparation, DCB-only or hybrid strategy [DCB + drug-eluting stent (DES)] were performed on 120 patients (87.59%). The primary endpoint was the rate of 2-year target lesion revascularization (TLR). Rates of major adverse cardiovascular events (MACE), cardiac death, target vessel myocardial infarction (TVMI), and vessel thrombosis were explored as the secondary outcomes. Quantitative coronary angiography software was used to analyze coronary angiograms. Results: Of the participants, 58 were treated with DCB-only and 62 with hybrid strategy. Relative to the DCB-only group, patients in the hybrid group had longer target lesions (15.47 ± 10.08 vs. 36.85 ± 9.46 mm, P 0.05). Treatment strategy (DCB-only or hybrid) was not a significant risk factor for TLR. Patients who underwent DCB-only exhibited less late lumen loss compared with the patients who underwent hybrid strategy (-0.26 ± 0.59 vs. 0.42 ± 0.47 mm, P

To observe the clinical characteristics, treatment and prognosis of intestinal acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children and futher evaluate the occurring risk factors.The clinical data of 136 patients undergoing allo-HSCT in Wuhan Children's Hospital Affiliated to Tongji Medical College from August 2016 to August 2020 were retrospectively analyzed, clinical characteristics of children with intestinal aGVHD were observed. The risk factors of intestinal aGVHD were assessed by logistic regression while cumulative survival were analyzed by Kaplan-Meier method.Among 136 patients intestinal aGVHD occurred in 24 (17.6%) cases, with 4 cases of grade II, 20 cases of grade III-IV, and the median occurrence time was 28(10-63) days. The clinical manifestations were diarrhea with intermittent abdominal pain, 17 cases with nausea and vomiting, 11 cases with fresh bloody stool, and 8 cases with skin rash before intestinal aGVHD. The average time for treatment was 33(11-100) days. 18 cases received electronic colonoscopy and histopathology examination. 20 out of 24 cases achieved remission after treatment, and the total effective rate was 83.3%. Finally, 9 out of 24 cases died during the follow-up time. Survival analysis showed that the cumulative survival rate of patients with intestinal aGVHD (15/24, 62.5%) were significantly lower than those without intestinal aGVHD (101/112, 90.2%) (Log-rank test, P=0.001). Univariate analysis showed that recipient age, sex, primary disease, donor age, donor sex, donor-recipient blood type, conditioning regimen, prophylaxis of GVHD, dosage of ATG, engraft time of blood platelet and neutrophils, and number of MNC/CD34+ were not risk factors for intestinal aGVHD (P0.05). Only the type of HSCT (χ2=16.020, P=0.001) and matched degree of HLA (χ2=15.502, P=0.001) had statistical significance with intestinal aGVHD (P0.05). Multivariate analysis showed that only HLA-mismatched unrelated donor was the risk factor for intestinal aGVHD for children (P=0.014，OR=16，95%CI 1.735-147.543).Intestinal aGVHD is a risk factor for cumulative survial of patients who received allo-HSCT in children and HLA-mismatched unrelated donor is its independent risk factor.儿童异基因造血干细胞移植后肠道急性移植物抗宿主病的临床研究.观察儿童异基因造血干细胞移植（allo-HSCT）后肠道急性移植物抗宿主病（aGVHD）的临床特点、治疗及转归，并分析其危险因素.回顾性分析2016年8月-2020年8月在同济医学院附属武汉儿童医院接受allo-HSCT的136例患儿的临床资料，观察肠道aGVHD患儿的临床特征，并用Logistic回归分析其危险因素及Kaplan-Meier模型分析其累积生存率.136例患儿中24例（17.6%）发生肠道aGVHD, 其中4例为II度，20例为III-IV度，发生的中位时间为28（10-63）d。临床表现为腹泻黄绿色稀水便伴间断腹痛，其中17例伴有恶心呕吐，11例伴鲜血便，8例患儿在出现肠道aGVHD前有皮疹。肠道aGVHD的平均治疗时间为33（11-100）d；18例患儿接受电子肠镜检查及组织病理学检查。经过治疗后，24例患儿中20例肠道aGVHD症状得到控制，总有效率为83.3%, 最终9例在随访期内死亡。发生肠道aGVHD组累积总生存率为62.5%（15例/24例），明显低于无肠道aGVHD组（90.2%，101例/112例）（Log-rank 检验，P=0.001）。单因素分析显示，儿童allo-HSCT后肠道aGVHD的发生与患儿年龄及性别、基础疾病、供者性别、供受者血型、预处理方案、GVHD的预防方案、ATG使用剂量、移植物单个核细胞数（MNC）和CD34+数量、中性粒细胞及血小板的植入时间无明显相关性（P0.05），与移植类型（χ2=16.020, P=0.001）及HLA相合程度（χ2=15.502, P=0.001）具有相关性（P0.05）;多因素分析显示，仅HLA不全相合（1位点不合）无关供者是儿童allo-HSCT后并发肠道aGVHD的独立危险因素（P=0.014，OR=16，95%CI 1.735-147.543）.肠道aGVHD是影响儿童allo-HSCT后总生存率的危险因素，HLA不全相合（1位点不合）无关供者为其发生的高危因素.

PWM (pulse-width modulation) voltage source inverters are used in a wide range of AC power systems where the output voltage must be controlled to follow a sinusoidal reference waveform. In order to achieve precision and fast-tracking control, restrictive sliding mode control (RSMC) provides a fast system state convergence time. However, the RSMC still suffers from the chattering problem, which leads to high harmonic distortion and slow response of the inverter output state. Furthermore, the load of the inverter may be severe load changing and the control parameters become difficult to adjust, worsening the adaptability to achieve the desired control of the inverter output. In this paper, a robust optimal control design comprised of an enhanced restrictive sliding mode control (ERSMC) and density particle swarm optimization (DPSO) algorithm is proposed, and then applied to PWM voltage source inverters. The ERSMC not only has finite time convergence but also provides chatter elimination. The DPSO is highly adaptable for acquiring the control parameters of the ERSMC and finding the best solution in the global domain. The proposed controller is realized for the actual PWM voltage source inverter controlled by a TI DSP-based development platform, so that the inverter output voltage has fast dynamic response and satisfactory steady-state behavior despite high load changing and non-linear disturbances.

Spinal cord impairment involving motor neuron degeneration and demyelination can cause lifelong disabilities, but effective clinical interventions for restoring neurological functions have yet to be developed. In early spinal cord development, neural progenitors of the motor neuron (pMN) domain, defined by the expression of oligodendrocyte transcription factor 2 (OLIG2), in the ventral spinal cord first generate motor neurons and then switch the fate to produce myelin-forming oligodendrocytes. Given their differentiation potential, pMN progenitors could be a valuable cell source for cell therapy in relevant neurological conditions such as spinal cord injury. However, fast generation and expansion of pMN progenitors in vitro while conserving their differentiation potential has so far been technically challenging. In this study, based on chemical screening, we have developed a new recipe for efficient induction of pMN progenitors from human embryonic stem cells. More importantly, these OLIG2+ pMN progenitors can be stably maintained for multiple passages without losing their ability to produce spinal motor neurons and oligodendrocytes rapidly. Our results suggest that these self-renewing pMN progenitors could potentially be useful as a renewable source of cell transplants for spinal cord injury and demyelinating disorders.

Background Liver hepatocellular carcinoma (LIHC) is a lethal cancer. This study aimed to identify the N6 -methyladenosine (m6 A)-targeted long non-coding RNA (lncRNA) related to LIHC prognosis and to develop an m6 A-targeted lncRNA model for prognosis prediction in LIHC. Methods The expression matrix of mRNA and lncRNA was obtained, and differentially expressed (DE) mRNAs and lncRNAs between tumor and normal samples were identified. Univariate Cox and pathway enrichment analyses were performed on the m6 A-targeted lncRNAs and the LIHC prognosis-related m6 A-targeted lncRNAs. Prognostic analysis, immune infiltration, and gene DE analyses were performed on LIHC subgroups, which were obtained from unsupervised clustering analysis. Additionally, a multi-factor Cox analysis was used to construct a prognostic risk model based on the lncRNAs from the LASSO Cox model. Univariate and multivariate Cox analyses were used to assess prognostic independence. Results A total of 5031 significant DEmRNAs and 292 significant DElncRNAs were screened, and 72 LIHC-specific m6 A-targeted binding lncRNAs were screened. Moreover, a total of 29 LIHC prognosis-related m6 A-targeted lncRNAs were obtained and enriched in cytoskeletal, spliceosome, and cell cycle pathways. An 11-m6 A-lncRNA prognostic model was constructed and verified; the top 10 lncRNAs included LINC00152, RP6-65G23.3, RP11-620J15.3, RP11-290F5.1, RP11-147L13.13, RP11-923I11.6, AC092171.4, KB-1460A1.5, LINC00339, and RP11-119D9.1. Additionally, the two LIHC subgroups, Cluster 1 and Cluster 2, showed significant differences in the immune microenvironment, m6 A enzyme genes, and prognosis of LIHC. Conclusion The m6 A-lncRNA prognostic model accurately and effectively predicted the prognostic survival of LIHC. Immune cells, immune checkpoints (ICs), and m6 A enzyme genes could act as novel therapeutic targets for LIHC.

BACKGROUND: The beet armyworm, Spodoptera exigua, is a serious agricultural pest that is primarily controlled using chemical insecticides. Recently, resistance to the insecticide spinosad has been described in S. exigua field populations. To date, there has been no functional evidence proving the involvement of the nicotinic acetylcholine receptor (nAChR) α6 mutation in spinosad resistance in S. exigua. RESULTS: In this study, using the CRISPR/Cas9 genome‐editing system, a homozygous strain (Seα6‐KO) with approximately 1760‐bp deletion within Seα6 in S. exigua causing a premature truncation of Seα6 was successfully constructed. Insecticide bioassays showed that Seα6‐KO exhibited 373‐fold higher resistance to spinosad and 850‐fold higher resistance to spinetoram compared to WH‐S strain with the same genetic background but showed no significant change in susceptibility to emamectin benzoate and chlorantraniliprole. Genetic analysis revealed that Seα6‐KO is inherited as an incompletely recessive trait. CONCLUSION: The results clearly demonstrated the functional role of Seα6 in resistance to spinosyn insecticides and provide an example of using genome editing to verify a target premature truncation associated with resistance.

Insect ryanodine receptors (RyRs) are the targets of diamide insecticides. Two point mutations G4946E and I4790M (numbering according to Plutella xylostella, PxRyR) in the transmembrane domain of the insect RyRs associated with diamide resistance have so far been identified in three lepidopteran pests, P. xylostella, Tuta absoluta and Chilo suppressalis. In this study, we identified one of the known RyR target site resistance mutations (I4790M) in a field-collected population of Spodoptera exigua. The field-collected WF population of S. exigua exhibited 154 fold resistance to chlorantraniliprole when compared with the susceptible WH-S strain. Sequencing the transmembrane domains of S. exigua RyR (SeRyR) revealed that the resistant WF strain was homozygous for the I4743M mutation (corresponding to I4790M in PxRyR), whereas the G4900E allele (corresponding to G4946E of PxRyR) was not detected. The 4743M allele was introgressed into the susceptible WH-S strain by crossing WF with WH-S, followed by three rounds of backcrossing with WH-S. The introgressed strain 4743M was homozygous for the mutant 4743M allele and shared about 94% of its genetic background with that of the recipient WH-S strain. Compared with WH-S, the near-isogenic 4743M strain showed moderate levels of resistance to chlorantraniliprole (21 fold), cyantraniliprole (25 fold) and flubendiamide (22 fold), suggesting that the I4743M mutation confers medium levels of resistance to all three diamides. Genetic analysis showed diamide resistance in the 4743M strain was inherited as an autosomal and recessive trait. Results from this study have direct implications for the design of appropriate resistance monitoring and management practices to sustainably control S. exigua.

Environmental lead exposure is closely related to the progression of Alzheimer's disease (AD). Our previous study has shown that exposure to lead could result in the cholesterol unbalance and increase amyloid-beta (Aβ) generation in the brain. However, the potential effect of lead exposure on Aβ transportation is poorly reported. In this study, we sought to explore whether lead exposure in developmental ages impaired the integrity of BCSFB and BBB, two highly vascularized structures in the brain in a rat model. The Aβ clearance in the liver was also assessed. Our results showed that lead treatment in developmental ages increased the number of TUNEL-positive apoptotic cells in rat choroid plexus and microvessels. Moreover, lead exposure markedly increased pro-inflammatory factors expression including TNF-α and IL-1β in rat choroid plexus and microvessels. Interestingly, lead treatment increased the expression of AQP-1 and reduced the expression of TTR, two key proteins associated with the functions of choroid plexus and microvessels. Additionally, the expressions of ABCB1, LRP-1, and RAGE, three major receptors responsible for Aβ transportation, were disturbed by developmental lead exposure. All these pathologies resulted in Aβ1-40 deposition within BCSFB and BBB and malfunctions of these two vascularized structures. Finally, we found that lead treatment remarkably inhibited the gene expression of LRP-1, which is responsible for Aβ endocytosis, in the liver tissue of the rat model. Collectively, our results provide the first evidence that developmental lead exposure induces Aβ deposition in BCSFB and BBB and impairs Aβ clearance in the liver, which would ultimately disturb Aβ transportation via choroid plexus/brain microvessels and facilitate Aβ deposition in the brain.

To summarize the long-term efficacy of cyclosporine (CsA) in the treatment of non-severe aplastic anemia (NSAA) in children, and explore the early significant indicators.Data of 36 NSAA children in Department of Hematological Oncology, Wuhan Children's Hospital, Tongji Medical College of Huazhong University of Science and Technology from January 2013 to December 2017 were analyzed retrospectively. All the children received oral CsA immunosuppressive therapy, and CsA trough concentration was checked to maintain at the rage of 200-250 μg/L after 2 weeks. The evaluation time points were at 3, 6, 12, 18 and 24 months, and assessment items were peripheral white blood cell differential count and reticulocyte's percentage and count.The 36 NSAA cases were composed of 16 males and 20 females, whose median age was 5.46 (2.92-7.99) years old, and median follow-up time was 28.00 (10.00-38.25) months. After taking oral CsA for 24 months, the number of cumulative effective cases was 21. There were 4 cases of complete remission (CR), 17 cases of partial remission (PR), and 15 cases of non-remission (NR). The total effective rate was 58.33%, and median effect-acting time of CsA was 3.0 (0.5-10.0) months. Compared with ineffective group, neutrophil (NEU) and red blood cell (RBC) of effective group (CR+PR) began to increase significantly at the 3rd month, and hemoglobin (Hb), platelet (PLT) and white blood cell (WBC) increase significantly at the 6th month after oral CsA administration (P0.05). Except for 2 cases who received component transfusion within 3-12 months after taking oral CsA for 3 months in effective group, the others did not need.The overall effective rate of oral CsA in children with NSAA was 58.33%. Stopping blood transfusion after the 3 months of treatment may be considered as a turning point for disease outcomes, and levels of NEU, RBC at the 3rd month and Hb, PLT, WBC at the 6th month as indicators for predicting disease prognosis.环孢素A治疗儿童非重型再生障碍性贫血的转归效果及预后因素分析.总结环孢素（CsA）治疗儿童非重型再生障碍性贫血（NSAA）的长期效果，并探讨与CsA治疗NSAA起效和预后相关的早期指标.回顾性分析2013年1月-2017年12月在华中科技大学同济医学院附属武汉儿童医院住院的36例NSAA患儿的病历资料，所有患儿在确诊后均接受CsA口服治疗，2周后检查CsA谷浓度以维持在200-250 μg/L范围，评估时间点为口服CsA后3、6、12、18和24个月，评估项目为外周血细胞分类计数及网织红细胞百分比与计数.36例患儿中男性16例，女性20例，中位年龄5.46（2.92-7.99）岁，中位随访时间28.00（10.00-38.25）个月。口服CsA后24个月临床治疗有效的累计病例数为21例。完全缓解4例，部分缓解17例，无效15例，总有效率58.33%，药物起效的中位时间为3.0（0.5-10.0）个月。与无效组比较，有效组（完全缓解和部分缓解）患儿表现为口服CsA后第3个月中性粒细胞和红细胞显著升高，第6个月血红蛋白、血小板、白细胞显著升高（P0.05）；口服CsA 3个月后有效组除2例患儿在3-12个月内进行成分输血外，其余19例患儿均不再需要成分输血支持治疗.NSAA患儿口服CsA总体有效率为58.33%。治疗3个月后是否停止输注血液制品可作为疾病转归的转折点，治疗3个月时的中性粒细胞、红细胞和6个月时的血红蛋白、血小板、白细胞水平可作为评估疾病转归的指标.

Background Microcirculatory disturbance is closely associated with multiple diseases such as ischemic and septic stroke. Luteolin (3,4,5,7-tetrahydroxyflavone) is a vascular protective flavonoid present in several dietary foods. However, how luteolin plays a role in microcirculatory disturbance is still unknown. The purpose of this study was to find out the influence of luteolin on the lipopolysaccharide (LPS)-induced microcirculatory disturbance, focusing on its effect on leukocyte adhesion and the underlying mechanism of this effect. Methods After injecting LPS into rats, we used an inverted intravital microscope to observe the velocity of red blood cells in venules, numbers of leukocytes adherent to and emigrated across the venular wall, hydrogen peroxide production in venular walls and mast cell degranulation. Intestinal microcirculation blood flow was measured by High-resolution Laser Doppler Perfusion Imaging. Histological changes of small intestine and mesenteric arteries were evaluated. Additionally, cell adhesion stimulated by LPS was tested on EA.hy926 and THP-1 cells. The production of pro-inflammatory cytokines, adhesion molecules and the activation of TLR4/Myd88/NF-κB signaling pathway were determined. Results The results showed luteolin significantly inhibited LPS-induced leukocyte adhesion, hydrogen peroxide production and mast cell degranulation, and increased intestinal microcirculation blood flow and ameliorated pathological changes in the mesenteric artery and the small intestine. Furthermore, luteolin inhibited the release of pro-inflammatory cytokines, the expression of TLR4, Myd88, ICAM-1, and VCAM-1, the phosphorylation of IκB-α and NF-κB/p65 in LPS stimulated EA.hy926. Conclusions Our findings revealed that it is likely that luteolin can ameliorate microcirculatory disturbance. The inhibitory effects of luteolin on the leukocyte adhesion stimulated by LPS, which participates in the development of microcirculatory disturbance, are mediated through the regulation of the TLR4/Myd88/NF-κB signaling pathway.

Most of the secure multi-party computation (MPC) machine learning methods can only afford simple gradient descent (sGD 1) optimizers, and are unable to benefit from the recent progress of adaptive GD optimizers (e.g., Adagrad, Adam and their variants), which include square-root and reciprocal operations that are hard to compute in MPC. To mitigate this issue, we introduce InvertSqrt, an efficient MPC protocol for computing 1/√x. Then we implement the Adam adaptive GD optimizer based on InvertSqrt and use it for training on different datasets. The training costs compare favorably to the sGD ones, indicating that adaptive GD optimizers in MPC have become practical.

Machine learning (ML) methods have been widely used in genomic studies. However, genomic data are often held by different stakeholders (e.g. hospitals, universities, and healthcare companies) who consider the data as sensitive information, even though they desire to collaborate. To address this issue, recent works have proposed solutions using Secure Multi-party Computation (MPC), which train on the decentralized data in a way that the participants could learn nothing from each other beyond the final trained model. We design and implement several MPC-friendly ML primitives, including class weight adjustment and parallelizable approximation of activation function. In addition, we develop the solution as an extension to TF Encrypted~\citep{dahl2018private}, enabling us to quickly experiment with enhancements of both machine learning techniques and cryptographic protocols while leveraging the advantages of TensorFlow's optimizations. Our implementation compares favorably with state-of-the-art methods, winning first place in Track IV of the iDASH2019 secure genome analysis competition., Description of the winning solution at Track IV of iDASH competition 2019, to be presented at the Trustworthy ML workshop co-located with ICLR2020

Homomorphic Encryption (HE) allows encrypted data to be processed without decryption, which could maximize the protection of user privacy without affecting the data utility. Thanks to strides made by cryptographers in the past few years, the efficiency of HE has been drastically improved, and machine learning on homomorphically encrypted data has become possible. Several works have explored machine learning based on HE, but most of them are restricted to the outsourced scenario, where all the data comes from a single data owner. We propose HomoPAI, an HE-based secure collaborative machine learning system, enabling a more promising scenario, where data from multiple data owners could be securely processed. Moreover, we integrate our system with the popular MPI framework to achieve parallel HE computations. Experiments show that our system can train a logistic regression model on millions of homomorphically encrypted data in less than two minutes.

Background/Aims: The objective of this study is to evaluate the hypouricemic and nephroprotective effects of an active fraction from Polyrhachis vicina Roger (AFPR) in potassium oxonate-induced hyperuricemic rats. Methods: Hyperuricemia was induced by potassium oxonate in male rats. AFPR was orally administered to hyperuricemic rats for 12 consecutive weeks. Serum, liver and kidney samples were collected for effects and mechanism analysis. The levels of serum uric acid (SUA) were measured by the phosphotungstic acid method, xanthine oxidase (XOD) activity in the hepatic and serum samples were measured by ultraviolet spectrophotometry, serum levels of interleukin-1 (IL-1β), interleukin-1 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by ELISA, the levels of serum creatinine (SCr), blood urea nitrogen (BUN), super oxide dismutase (SOD) and malondialdehyde (MDA) in serum were determined by colorimetric method. Protein expression of renal URAT1, GLUT9, and OAT1 were analyzed by Western blot. Results: AFPR significantly decreased the levels of SUA, serum and hepatic XOD, SCr, BUN, and MDA as well as increased SOD. In addition, AFPR treatment significantly reduced the levels of proinflammatory cytokines in serum, including IL-1β, IL-6 and TNF-α. Moreover, we found the significant decrease in protein expression of URAT1 and GLUT9, and the significant increase in protein expression of OAT1 in the kidney in AFPR treated groups compared to the model groups of hyperuricemia. Conclusion: These findings suggest that AFPR has anti-hyperuricemic activity attributed to the inhibition of uric acid generation in the liver and probably to the enhancement of urate excretion in the kidney, and possess nephroprotective effect in hyperuricemic rats due to its anti-inflammatory and antioxidant activities.

The use of electrokinetic (EK) phenomena can facilitate bioaugmentation by enhancing the mobility and redistribution of deposited soil bacteria through heterogeneous soil. In this research, batch treatments (T1-T6) were used to assess the characteristics of bacterial transportation and proliferation under a weak electric field (1 V/cm). The strain Bacillus cereus was mainly transported toward the cathode by electro-osmosis flow (EOF). The bacterial transport efficiency was 1.07 × 107 CFUs/mL from days 0–9 when deionized water was used as the electrolyte solution and was elevated by 46% when EOF was enhanced with 0.010 mol/L NaHCO3 solution containing 0.04 mol/L Na2SO4. However, in all treatments, bacterial transport efficiency decreased by 70%-95% after 9 days. The bacterial transport efficiency was closely related to the EOF effective action distance (ED) which narrowed as soil and bacterial properties changed after the EK process. Correspondingly, the bacteria in soil were transformed from loose-bound to tight-bound status due to the deepened secondary minimum depth of XDLVO interaction energy after EK treatment. In addition to bacterial transportation, the electric field stimulated the proliferation of bacteria to achieve higher counts by promoting bacterial adhesion and facilitating fluid contact between ions, dissolved organic carbon, and bacteria. The stimulatory effect of electric field on bacteria was stronger than the transportation effect of the electric field on bacteria. Improvements in both bacterial migration and proliferation contributed to bioaugmentation under EK conditions. Near-cathode sections (S3, S4) are optimal for bacterial augmentation under the EK treatment for a long duration.

Soil microorganisms would reproduce rapidly and migrate directionally under the applied electric field. In this study, tetradecane-degrading bacteria were added at different locations in soil, and 1 V·cm外加电场下土壤微生物会发生快速繁殖和定向迁移.本研究在十四烷污染土壤中不同位置投加十四烷高效降解菌,并施加1 V·cm

A novel electrochemical immunosensor was developed for E. coli assay in urban sludge based on dendrimer-encapsulated Au and enhanced gold nanoparticle labels. Initially, p-aminobenzoic acid (p-ABA) was electropolymerized on glassy carbon electrode (GCE) surface to provide abundant carboxyl groups. G4-polyamidoamine dendrimers (PAMAM) were covalently attached to electrode surface through the formation of amide bonds between amino groups of dendrimer and carboxyl groups of p-ABA. Subsequently, Au(III) ions were coordinated in the interior of dendrimer and then reduced to form gold nanoparticles (AuNPs). The resulting electrode (GCE/p-ABA/PAMAM (AuNPs)) provided numerous amino groups to allow highly dense immobilization of E. coli, and facilitated the improvement of electrochemical responses. The rabbit anti-E. coli polyclonal antibody (Ab1) specifically bound the electrode surface-confined E. coli, followed by the attachment of the enhanced gold nanoparticle labels (Ab2-Au-Th) featuring thionine (Th) as signal-generating molecule. The analysis of E. coli was performed by electrochemical detection of Th in the bound labels on the electrode surface. Under optimal experimental conditions, the peak current of Th showed a linear relationship with the logarithmic value of E. coli concentration in the range from 1.0 × 102 to 1.0 × 106 cfu mL−1 with a detection limit of 70 cfu mL−1 (S/N = 3). The proposed strategy was also used to determine E. coli in samples obtained from wastewater treatment plant, and the recoveries of standard addition experiments were 89.4%–105.8%.

The notion of covert security for secure two-party computation serves as a compromise between the traditional semi-honest and malicious security definitions. Roughly, covert security ensures that cheating behavior is detected by the honest party with reasonable probability (say, 1/2). It provides more realistic guarantees than semi-honest security with significantly less overhead than is required by malicious security.

2018, 【要旨】

We propose a novel framework for outsourced private function evaluation with privacy policy enforcement (OPFE-PPE). Suppose an evaluator evaluates a function with private data contributed by a data contributor, and a client obtains the result of the evaluation. OPFE-PPE enables a data contributor to enforce two different kinds of privacy policies to the process of function evaluation: evaluator policy and client policy. An evaluator policy restricts entities that can conduct function evaluation with the data. A client policy restricts entities that can obtain the result of function evaluation. We demonstrate our construction with three applications: personalized medication, genetic epidemiology, and prediction by machine learning. Experimental results show that the overhead caused by enforcing the two privacy policies is less than 10% compared to function evaluation by homomorphic encryption without any privacy policy enforcement.

Private comparison is about privately determining whether a > b, given two input integers a and b which are held as private information. Private comparison is an important building block for applications such as secure auction and privacy-preserving decision tree evaluation. In this paper, we consider a variant setting in which the inputs a and b as well as the result bit 1 {a > b} are encrypted. Using a ring variant of a fully homomorphic encryption scheme, our solution takes as input the ciphertexts of a and b and produces only one ciphertext which decrypts to the bit 1 {a > b} without any interaction with the secret key holder. Our approach does not encrypt the inputs bit-wisely and requires only a multiplicative depth of one, giving about 48 - 90 fold speed up over previous solutions.

Background: This study aimed to examine the clinical significance of fatty acid synthase (FASN) expression in gastric cancer (GC), and investigate any prognostic role. Materials and Methods: FASN expression was assessed in gastric cancers by immunohistochemistry using 60 paraffin-embedded tissue specimens, and clinical data were collected by retrospective chart review. Moreover, FASN mRNA expression in 15 fresh resected specimens was evaluated by the reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemical staining of PTEN was performed to assess the correlation of PTEN with FASN in gastric cancer. Results: Increased expression of FASN was noted in gastric cancers. The frequency of FASN gene amplification was also significantly higher in gastric cancer than in adjacent normal tissue. FASN expression in human gastric cancer tissues was significantly correlated with patient TNM stage and peritoneal dissemination (p

An efficient secure two-party computation protocol of matrix multiplication allows privacy-preserving cloud-aid machine learning services such as face recognition and traffic-aware navigation. We use homomorphic encryption to construct a secure matrix multiplication protocol with a small communication overhead and computation overhead on the client's side, which works particularly well when a large number of clients access to the server simultaneously. The fastest secure matrix multiplication protocols have been constructed using tools such as oblivious transfer, but a potential limitation of these methods is the needs of using a wide network bandwidth between the client and the server, e.g., 10~Gbps. This is of particular concern when thousands of clients interact with the server concurrently. Under this setting, the performance oblivious transfer-based methods will decrease significantly, since the server can only allocate a small ratio of its outgoing bandwidth for each client. With three proposed optimizations, our matrix multiplication protocol can run very fast even under the high concurrent setting. Our benchmarks show that it takes an Amazon instance (i.e., 72 CPUs and 25 Gbps outgoing bandwidth) less than 50 seconds to complete 1000 concurrent secure matrix multiplications with $128\times 128$ entries. In addition, our method reduces more than $74% - 97%$ of the precomputation time of two privacy-preserving machine learning frameworks, SecureML (S&P'17) and MiniONN (CCS'17).

Similarity joins are important database operations that can identify pairs of roughly similar records. Due to their many applications (e.g., duplicate elimination and plagiarism detection), a number of algorithms have been created to enhance similarity joins, especially in terms of performance. However, in some cases, the privacy of the data being joined also becomes an important aspect to consider, as leaking sensitive information can result in grave consequences for individuals, enterprises and governmental organizations. We propose a protocol for secure execution of similarity joins that is based on fully homomorphic cryptosystems, which are resistant to a number of attacks and provide flexibility to calculate the similarity between encrypted records. We also consider the adaptation of filter techniques to improve the efficiency of the protocol by reducing the number of record pairs that are compared. In addition, we exploit modern hardware to parallelize the solution and evaluate the performance of the proposal using real datasets.

Crowdfunding Publishing is a new publishing model, which Internet+ combined with publishing industry. Internet think reconsidered markets, users, products, enterprise value and entire business ecology. In this paper, we adopted Internet thinking to presented five marketing model that included Social marketing, Internet brand marketing, Subtracting marketing, Personalized marketing and Guide marketing.

Objective Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide; yet, the pathogenesis of the disorder is not completely understood. The nicotinic acetylcholine receptor α7 subunit (α7nAChR) plays an indispensable role in the vagus nerve-regulated cholinergic anti-inflammatory pathway. Methods In the present study, we investigated the key role of α7nAChR in NAFLD development. Male wild-type (WT) and α7nAChR knockout (α7nAChR−/−) mice were fed a normal chow or a high-fat diet (HFD) for 16 weeks to induce NAFLD. Results We found that both the mRNA and protein levels of α7nAChR in the liver tissue of NAFLD mice were significantly higher than those in mice fed normal chow. There were no differences in food intake, body weight, hepatic cholesterol and triglyceride contents, and insulin sensitivity between WT and α7nAChR−/− mice under normal condition. When the WT and α7nAChR−/− mice were challenged with HFD, the body weight of α7nAChR−/− mice became higher than that of WT mice. The oxygen consumption and energy expenditure in HFD-fed α7nAChR−/− mice were significantly lower than that in HFD-fed WT mice. The HFD-fed α7nAChR−/− mice also showed more aggravated hepatic lipid accumulation, steatosis and oxidative stress than HFD-fed WT mice. Macrophage infiltration; mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β; and liver fibrosis were significantly accelerated in HFD-fed α7nAChR−/− mice compared to that in HFD-fed WT mice. In addition, the bolus insulin injection-activated insulin signaling pathway, which was reflected by the phosphorylation of insulin receptor at Tyr1162/Tyr1163 site (p-IRTyr1162/Tyr1163), insulin receptor substrate-1 at Tyr612 site (p-IRS-1Tyr612) and Akt at Ser473 (p-AktSer473), was significantly compromised in liver tissues of HFD-fed α7nAChR−/− mice relative to HFD-fed WT mice. Finally, pharmacologically activation of α7nAChR in HFD-fed mice, with a selective agonist PNU-282987, remarkably ameliorated the hepatic steatosis, inflammatory cell infiltration and fibrosis. Conclusion In conclusion, our results demonstrate that activation of α7nAChR improves energy homeostasis and inhibits inflammation in nonalcoholic fatty liver disease.

According to the design and construction characteristics of steel box concrete girder of a large landscape tower, C40 grade non shrinkage self-compacting concrete meeting engineering requirements was produced. The fresh concrete workability, early age shrinkage are researched, construction technology and detection methods are discussed combined with the practical engineering of steel box concrete girder.

Various 11-chloro-5-methyl-5H-indolo(2,3-b)quinolines (neocryptolepines) with different substituents on the quinoline ring, key intermediates for antimalaria agents, are prepared from the substituted N-methylanilines, easily accessible by the N-methylation of anilines, and indole-3-carboxylate as a counterpart. This protocol is benign in terms of the reduced number of steps to reach the target, compared with the known method using anilines, and easy product purification. Alternatively, their 6-methyl congener is prepared by N-methylation of the indole moiety of 2-arylaminoindole-3-carboxylate followed by successive cyclization and chlorination. 11-Chloroneocryptolepines are found more reactive than their 6-methyl congener in the nucleophilic substitution at the C11 position.

We consider a situation that a large number of individuals contribute their personal data to multiple databases, and an analyst is allowed to issue a request of record linkage across any two of these databases. In such a situation, one concern is that very detailed information about individuals can be eventually obtained by analysts through sequential requests of record linkage across various database pairs. To resolve this privacy concern, we introduce a novel privacy notion for record linkage, record-wise linkage policy, with which each data contributor can individually designate database pairs that are allowed (resp. banned) to process record linkage by whitelist (resp. blacklist). We propose a secure multi-party computation to achieve record linkage with record-wise linkage policies. Also, we prove that our protocol can securely evaluate PPRL without violating given linkage policies and evaluate the efficiency of our protocol with experiments.

The research article describes the effect of an ester group on the in vitro antiproliferative activity in SAR studies of 5-methyl-5H-indolo[2,3-b]quinoline (neocryptolepine) derivatives. The C-2 and/or C-9 ester-substituted neocryptolepines were synthesized starting from indole-3-carboxylates and N-methylanilines, which were bearing an ester group. To these ester-substituted neocryptolepines, various aminoalkylamino substituents were further attached at the C-11, and an in vitro antiproliferative assay was performed by varying the substituents at the C-11 and the position of the ester group in the A and/or D ring of neocryptolepines. Results indicated that the antiproliferative activities of the agents could be improved by introducing an ester substituent at the C-9 position. Among them, the methyl 11-(3-aminopropylamino)-5-methyl-5H-indolo[2,3-b]quinoline-9-carboxylate (8b) was the most potent agent with an IC50 value of 0.044 μM against the human leukemia MV4-11 cell line. The selective cytotoxicity of the agents between the cancer cell lines and normal cell lines were also described. The antiproliferative potency of dimethyl 11-(3-aminopropylamino)-5-methyl-5H-indolo[2,3-b]quinoline-2,9-dicarboxylate (9a) against the human colon cancer cell line HCT116 is 28 times higher than against the normal mice fibroblast cell line BALB/3T3.

This report describes the synthesis and in vitro anti-malarial evaluations of certain C2 or C8 and C11-disubstituted 6-methyl-5H-indolo[2,3-b]quinoline (neocryptolepine congener) derivatives. To attain higher activities, the structure–activity relationship (SAR) studies were conducted by varying the kind of alkylamino or ω-aminoalkylamino stubstituents at C11 and with Cl at the C2 position, or CO2Me at the C9 position. The anti-malarial activities of the tested compounds were significantly increased compared to the 11-non(alkylamino) derivatives. The 3-aminopropylamino group at C11 was further modified to urea and thiourea, which improved the cytotoxicity against normal cells. The best results were achieved with compounds 8 and 9d against the NF54 strain with the IC(50)/SI values as of 86 nM/20 and 317 nM/370, respectively. Furthermore, the compounds were tested for β-haematin inhibition. Twelve were found to have IC(50) values below 100 µM and a linear correlation between the β-haematin inhibition and cell growth inhibition in the NF54 strain was found for those derivatives with basic amino side chains. A second correlation was identified between the NF54 activity and physico-chemical factors related to solvation and polarity.

The present report describes the synthesis and antiproliferative evaluation of certain 11-aminoalkylamino-substituted 5H- and 6H-indolo[2,3-b]quinolines and their methylated derivatives. These 5-Me- and 6-Me-indolo[2,3-b]quinoline derivatives 10-14, 20 were prepared by amination at the C-11 position of the 11-chloro-5-methyl-5H- and 11-chloro-6-methyl-6H-indolo[2,3-b]quinolines with different substituents on the quinoline ring. The 11-aminoalkylaminomethylated 23, the homologue of 11, was prepared from the same intermediate for a further SAR study. These intermediates are accessible from 4-substituted anilines or their N-methylated analogues and methyl indole-3-carboxylate as a counterpart. The in vitro antiproliferative assay indicated that the 5-methylated derivatives 10-14 are more cytotoxic than their respective 6-methylated 6H-indolo[2,3-b]quinoline derivatives 20. Among them, N-(3-aminopropyl)-2-bromo-5-methyl-5H-indolo[2,3-b]quinolin-11-amine 12f was the most cytotoxic with a mean IC(50) value of 0.12 μM against human leukemia MV4-11 cell line, and also exhibited selective cytotoxicities against A549 (lung cancer), HCT116 (colon cancer) cell lines and normal fibroblast BALB/3T3 with IC(50) values of 0.543, 0.274 and 0.869 μM, respectively. The binding constant of products 12f and 20f to salmon fish sperm DNA were also evaluated using UV-vis absorption spectroscopy, indicating intercalation binding with a constant of 2.93×10(5) and 3.28×10(5)Lmol(-1), respectively.

Production of artemisinin in genetically modified microorganisms is an attractive option to enable sufficient supply of the effective antimalarial agent. Although a sundry of artemisinin precursors are available from engineered bacteria or yeast, no artemisinin has been manufactured by engineering any microbial platforms due to inaccessibility to unidentified steps. To this end, it is essential to consider how to convert artemisinin precursors to artemisinin, either biochemically or chemically. To establish a novel procedure of artemisinin production, we incubate the mixture of artemisinin precursors from engineered Sacchromyces cerevisiae with the cell-free enzyme extract of Artemisia annua. For the single gene-expressing strain INVScI (pYES-ADS), amorpha-4,11-diene accumulation within 48 h or 14 days led to higher artemisinin content than the control. In the multiple gene-expressing strain YPH501 (pYES-ADS:: pESC-CYP71AV1-DBR2), artemisinin accumulation from the 14-day-induced yeast precursor mi...

In this paper, the speed control system controlled by motor speed was designed to control forward speed of underwater robot precisely. Based on the theory of double closed-loop speed control, motor control system was modeled firstly, and then regulator parameters were designed based on the engineering approaches. According to the characteristics of forward movement, the mechanical construction of sub-mini underwater robots and the comparison of various system designs, the double closed-loop regulator parameters of sub-mini underwater robots were obtained. And the propulsion system of sub-mini underwater robots was equipped with speed and current double closed-loop control. All the experimental results showed that within a certain range of motor speed, no static error could be guaranteed and the variable speed of underwater vehicle could be achieved.

Ups and downs control was one of the main contents in control of the submersible. A new ups and downs control system was used on the submersible with piston type. Its mechanism structure and experiment platform was introduced firstly in this paper. Then the theory design, underwater experiment and finite element analysis of piston cavity was made separately to verify its design reliability and stability. The results of experiment and emulation suggest that the piston type submersible design was reasonable, feasible and practical.

This paper introduced the important role of the remote sensing satellite in remote sensing field. There existed some defects for a traditional classical AZ-EL type antenna used in tracking remote sensing satellite. The design project of Stewart manipulator antenna was presented by Stewart manipulator designing theory. The singular configuration theory of Stewart manipulator introduced position singularity, attitude singularity analysis and posture ability of Stewart manipulator was studied. The theorem of nonsingular posture was presented and proved. The nonsingular workspace area of a Stewart manipulator was determined. The antenna design based on Stewart manipulator satisfied with hemisphere airspace workspace and got the theoretical basis of realizing passing zenith tracing.

2-Phenyl-1, 2, 3-triazole-4-formylhydrazine (2) was prepared by hydrazinolysis of the corresponding ester 1. Reaction of 2 with CS2/KOH gave the oxadiazole derivatives (3) which via Mannich reaction with different dialkyl amines furnished 3-N, N-dialkyl derivatives (4a–c). Also, condensation of 2 with appropriate aromatic acid in POCI3 yielded oxadiazole derivatives (5a–c), or with aldehydes and ketones afforded hydrazones (6a–c). Cyclization of (6a–c) with acetic anhydride gave the desired dihydroxadiazole derivatives (7a–c). On the other hand, reaction of dithiocarbazate (8) with hydrazine hydrate gave the corresponding triazole derivative (9) which on treatment with carboxylic acids in refluxing POCI3 yielded s-triazole [3, 4–b]-1, 3, 4-thiadiazole derivatives (10a–b). The structures of all the above compounds were confirmed by means of IR, 1H NMR, MS and elemental analysis.

To interfere with the endogenous gene encoding squalene synthase (SS) responsible for sterol biosynthesis, an antisense SS cDNA ( asSS ) was introduced into the genome of A. annua . Following the decline of SS mRNA and synchronous reduction of total sterols, mRNA coding for amorpha-4,11-diene synthase (ADS) tremendously elevated, whereas mRNAs for sesquiterpene cyclases encompassing 8-epicedrol synthase (EPS), β-caryophyllene synthase (CS) and β-farnesene synthase (FS) declined or kept homeostasis, suggesting a bias in redirection of the partially blocked metabolic flow to amorpha-4,11-diene. By phenotyping the chimeric ADS promoter-fused β-glucuronidase gene ( pADS-GUS ), overexpression of the pADS-GUS reporter was detected upon chilling exposure and ultraviolet (UV) irradiation. In transgenic plants that expose to chilling, ADS and EPS were dramatically up-regulated, but CS was down-regulated and FS and SS were unaffected, implying further chilling-induced diversion of carbon flux among sesquiterpenes. Accordingly, ADS and cytochrome P450 reductase (CPR) were also chilling-inducible, while cytochrome P450 monooxygenase (CYP71AV1) reflected a complicated chilling profile. A maximal artemisinin content was accounted for 16.6 mg/g or 3.7-fold increase in a chilled transgenic line. Fascinatingly, an extraordinarily high artemisinin content of 23.5 mg/g or 5.2-fold increase was measured after 15-month storage of the ground powder from the identical chilled transgenic tissue, demonstrating non-enzymatic conversion from a putative artemisinin precursor to artemisinin. Moreover, a relevance of chilling exposure with singlet oxygen ( 1 O 2 ) emission and artemisinin overproduction was established. These results indicated that the mevalonate pathway has been first skewed to amorpha-4, 11-diene and shunted ultimately to artemisinin through a synergy of genetic modification with environmental superinduction.

To study the chemical constituents from Macaranga denticulata Root.The chemical constituents were isolated and purified by silica-gel column chromatography and recrystallization, and their structures were identified by physicochemical properties and spectral data.Nine compounds were isolated and identified as: gheddic acid (1), aleuritolic acid-3-acetate (2), β-sitosterol (3), stigmast-4-en-6β-ol-3 -one (4), 2α-hydroxyaleuritolic acid 3-p-hydroxybenzoate (5), scopoletin (6), daucosterol (7), 2, 6-dimethoxy-1,4-benzoquinone (8) and maslinic acid(9).Compounds 1-9 are obtained from this plant for the first time.

Sunitinib based adjuvant chemotherapy combined with chloroquine (CQ) for the treatment of renal cell carcinoma (RCC) is in clinical trials; however, its anti-RCC effect and the mechanism remain unclear. In the present study, the anti-RCC effect of sunitinib with CQ and the underlying mechanism was investigated. An MTT assay demonstrated that CQ enhanced the proliferation inhibitory effect of sunitinib against the OS-RC-2 RCC cell line. CQ inhibited sunitinib-induced autophagy in OS-RC-2, which was evidenced by the inhibition of autophagic vacuoles, acidic vesicular organelle formation, light chain 3 (LC3)-II recruitment to the autophagosomes and the conversion of LC3-I to LC3-II, as induced by sunitinib. The inhibition of autophagy by CQ enhanced sunitinib-induced apoptosis, which was characterized by the activation of caspase-3, caspase-9, Bcl-2 and p53. Additionally, the exposure of OS-RC-2 cells to CQ and sunitinib resulted in the inhibition of AKT, tuberous sclerosis complex 2, mechanistic target of rapamycin and p70 ribosomal S6 kinase, which are associated with cell proliferation. In in vivo study, a combination of sunitinib with CQ in mice significantly reduced OS-RC-2 cell xenograft growth compared with the sunitinib alone group. In conclusion, the present study demonstrated that CQ may enhance the anti-RCC effect of sunitinib by inhibiting the autophagy induced by sunitinib, and enhance the rate of apoptosis. Inhibiting cell proliferation may also serve a role in the synergistic antitumor effect of sunitinib and CQ. These data suggest that combination therapy of sunitinib with CQ may be a promising strategy for adjuvant chemotherapy in RCC.