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Targeted and immunotherapy drugs for hepatocellular carcinoma (HCC) have been rapidly developed. Atezolizumab in combination with bevacizumab has been recommended as the first-line standard of care for unresectable or advanced HCC in several national and international guidelines. The combination therapies with sindilizumab and bevacizumab biosimilar, apatinib and carrilizumab, dulvalizumab and tremelimumab are also recommended as first-line standard regimens for advanced HCC in the guideline of Chinese Society of Clinical Oncology. Local therapy combined with targeted drugs (such as sorafenib and lenvatinib) or immune checkpoint inhibitors can significantly improve outcomes. Therefore, some progress has also been made in the study of single-agent or combination regimens as perioperative neoadjuvant therapy.肝细胞癌（HCC）的靶向治疗及免疫治疗药物研发迅猛，阿替利珠单抗联合贝伐珠单抗已在国内外多个指南优先推荐作为不可切除或进展期HCC的一线标准治疗方案，信迪利单抗联合贝伐珠单抗生物类似物、阿帕替尼联合卡瑞利珠单抗、度伐利尤单抗联合替西木单抗亦被我国指南推荐作为中晚期HCC一线标准方案。局部治疗联合靶向药物索拉非尼、仑伐替尼或同时联合免疫检查点抑制剂显著改善预后。单药或联合方案作为围手术期新辅助治疗的研究亦取得一定进展。.

The tumor immune microenvironment (TIME) plays crucial roles in the growth, progression, and therapeutic response of hepatocellular carcinoma(HCC) which is a prototypical inflammation-associated cancer. The efficacy of immunotherapy largely depends on the TIME. Targeting the immune microenvironment is an attractive strategy for the treatment of HCC. This review provides the characteristics of immune microenvironment of HCC,therapeutic approaches based on immune microenvironment,and information on the immune microenvironment underlying the response or resistance of HCC to immunotherapies.肝细胞癌（HCC）是典型的炎症相关性癌症，肿瘤免疫微环境（TIME）在HCC发生、发展和抗肿瘤治疗反应中发挥关键作用，尤其免疫治疗效果与TIME密切相关，因此，靶向免疫微环境是治疗肝细胞癌的一项具有吸引力的策略。现阐述HCC免疫微环境的特点，基于免疫微环境的治疗方法，以及HCC对免疫疗法产生应答或抗性背后的免疫微环境信息。.

Hevea brasiliensis is widely planted in tropical and subtropical regions and is the main source of natural rubber production. The growth of rubber trees is plagued by various leaf diseases, resulting in decreased rubber production. From January to March in 2020, a severe leaf spots disease on Hevea brasiliensis found in Agricultural Science Base in Haidian campus of Hainan University (20° 03' 31″ N, 110° 19' 07″ E), Haikou, Hainan province, China. Spots were only observed on the mature green rather than young and bronze-colored leaves. This symptom has never been reported on the leaves of Hevea brasiliensis. During the early stages of the disease, gray leaf spots were concentrated to the leaf margins, but later expanded forming irregular gray lesions with chlorotic edges (Figure 1A). Eventually, lesions became necrotic shot holed, and leaves curled, wilted, and dropped. Five small pieces were cut from the margin of spots from different infected leaves, and were surface disinfected with 75% alcohol three times for five seconds each time and 1% sodium hypochlorite solution (NaClO) for 60 s. After washing twice with sterile water, leaf pieces were placed in the center of plates with Potato Dextrose Agar (PDA) medium and incubated for one week at 28 °C. After 7 days, mycelium developed and colonies were single-spore cultured for further study. One of the strains labeled HN01 developed a yellowish-brown to reddish-brown pigment on PDA, and the colonies were gray and cottony. The colony and pigment feature very consistent with Stemphylium sp. (Figure 2) (Li et al. 2017). Conidiophore were solitary, transparent to pale, mostly 102.1-228.8 µm × 4.0-5.8 µm, with 2-3 septa and apical vesicular swellings 6.5-7.9 µm. The dimensions of conidia were 28.3-45.1 × 11.5-17.5 µm and one septum (Figure 3). Conidia of S. lycopersici were solitary, oblong with a conical end at the apex, with 1-2 septa, and constricted at the transverse septum. The internal transcribed spacer region of rDNA was amplified with primers ITS1/ITS4 (5'-TCCGTAGGTGAACCTGCGG-3'/5'-TCCTCCGCTTATTGATATGC-3'), glyceraldehyde-3-phosphate dehydrogenase (gpd) was amplified with primers GPD-F/R (5'-GCACCGACCACAAAAATC-3'/ 5'-GGGCCGTCAACGACCTTC-3'), calmodulin region (cmdA) was amplified with the primers CALDF1/CALDR2 (5'-AGCAAGTCTCCGAGTTCAAGG-3'/5'-CTTCTGCATCATCAYCTGGACG3') from genomic DNA of strain HN01 (Xie et al. 2018), and PCR products were sequenced. The ITS sequence of strain HN01 (GenBank Accession No. MZ496930) had 99.64% identity with isolates sl001, sl110, sl111, and sl112 of Stemphylium lycopersici (GenBank Accession No. KX858848.1, MF480547.1, MF480548.1, MF480549.1). Similarly GPD sequences (GenBank Accession No. MZ505106) had 100% identity with strain xiqing, HZ2114 and HZ2115 of Stemphylium lycopersici (GenBank Accession No. KR911809.1, KR911810.1, KT957742.1 and KT957743.1), and CMDA sequences (GenBank Accession No. MZ505105) had 99.85% identity with Stemphylium lycopersici strain LJ1609270201 (GenBank Accession No. MG742412.1). A phylogenetic analysis constructed by MEGA6.0 based on concatenated sequences of the HN01 and another 17 strains from GenBank by using the maximum-likelihood (ML) method showed that the HN01 was clustered and matched with Stemphylium lycopersici LJ1609270201 (Figure 4). To satisfy Koch's postulates, we inoculated mature green leaves of Hevea brasiliensis with mycelial plugs (diameter = 5 mm) of pure cultured strain HN01. All leaves of Hevea brasiliensis were wrapped in a freezer bag to maintain relative humidity85%, and the temperature of greenhouse is 28ºC. The disease developed on the inoculated leaves after 2-3 days, but not on control leaves (Figure 1B). We used the same method as before to re-isolate the pathogen, which had the same morphology and genotypes as the original isolate. S. lycopersici has been reported to infect the leaves of a variety of plants, including pepper, tomato, eggplant, watermelon, Physalis alkekengi. (Yang et al.2017; Ben et al. 2017; Yang et al. 2020). To our knowledge, this is the first record of S. lycopersici causing leaf spot of Hevea brasiliensis in China, and Hevea brasiliensis is the global new host of S. lycopersici. Hevea brasiliensis is the main source of natural rubber and is widely planted in southern China. Therefore, it is imperative to implement disease management measures to prevent potential threats.

Cucumber (Cucumis sativus L.) is one of the most important vegetables cultivated in the world. It is widely cultivated and mostly grown under greenhouse conditions (Sallam et al. 2021). Cucumber has a long growth cycle and is particularly susceptible to bacterial diseases. In May 2021, bacterial leaf spot was found on cucumbers of the variety Lyuyou NO.3 in Hainan Province, China. In the early stage of the disease, the leaves showed small yellow-brown spots in the shape of water stains. When exposed to light, a yellow halo around the disease spots could be seen. In later stages, the lesions gradually become larger and more yellow. The leaf veins around the disease site also gradually turned yellow (Figure 2a). In serious cases, the whole leaf turned yellow, resulting in leaf death. We collected plants with the same symptoms from 25 different farms in Hainan Province. Five plants were selected from each farm by the classic five-point sampling method and three leaves were selected from each plant, for a total of 15 leaves collected from each farm. Then three leaves were randomly selected from the 15 leaves on each farm for isolation of the pathogen, and a total of 75 leaves were isolated. We found that the incidence of the disease was from 20% to 30% based on a diagnostic test, which conducted on 75 cucumber leaves samples suspected of same symptom of cucumber, collected from Hainan Province. Using microscopy, bacterial streaming was observed to tentatively identify the causal agent as a bacteria. Tissue isolation was used to isolate the responsible pathogens. A 5 mm × 5 mm sample of tissue at the junction of diseased and healthy sections was collected. First, the surface of the tissue was disinfected in a 75% ethanol solution for 30 sec; then it was soaked in 2% NaOCl for 5-7 min, and finally, it was washed thrice in sterile distilled water. The tissues were inoculated onto lysogen broth culture media (LB) and cultured in a 28℃ incubator for 2 days. Bacterial colonies that emerged from the tissues were cultured in LB. Four isolated colonies were selected for verification. The colonies of isolated from the diseased leaves of cucumber are round, egg yellow and slightly sticky (Figure 2c). The isolate named PA-1 was identified by PCR amplification and sequencing of the partial 16S rRNA gene with the primer 27F/1492R (Lane 1991) and gyrB gene (Li et al. 2019). Sequences were stored in GenBank with the accession numbers OK576932.1 (16S rRNA, PA-1) and OL978577 (gyrB); BLASTn was used to compare these with other GenBank sequences. Sequencing of the 16S rRNA gene showed that PA-1 had a sequence length of 1403bp, with 99.78% genetic similarity to Pantoea ananatis strain MZ007857.1. Sequencing of the gyrB gene showed that the sequence length of PA-1 was 1136bp, with 99.29% genetic similarity to P. ananatis strain MW981331.1. Then, a pathogenicity text was conducted to verify Koch's postulates, which was done by first inoculating P. ananatis into LB liquid medium (shake culture at 28°C, 180 r/min). The log phase cell was collected by centrifugation (5,000 r/min for 2 min at 4°C), and inoculated strains were resuspended in sterile water at OD600 = 0.5. The bacterial suspension was inoculated on healthy cucumber leaves with a syringe. The control was sterile water, which was injected onto healthy cucumber leaves using the same methodology. The plants were placed in a greenhouse with a diurnal temperature difference of 21- 27°C and were observed daily. After two weeks, all bacterial inoculated plants developed symptoms of shriveling and necrosis (Figure 2b), while the control group showed no symptoms. From the symptomatic plants, the pathogen was isolated again and identified by morphological and molecular characterization. The sequences of the isolates recovered from the inoculated experiment matched 100% the sequences of the isolate PA-1. Koch's postulates were completed by following the previously described method. To our knowledge, this is the first report of P. ananatis causing leaf spot of cucumber.

In Hopkinson pressure bar experiments on ceramics, the stress inequilibrium and indentation of the specimen to bar ends are critical issues due to the brittle nature and high strength of ceramics. Theoretical analysis is employed to reconstruct the loading process for investigating the influence of the stress inequilibrium. The results indicate that it has little influence on the accuracy of stress–strain curves and accurate peak stress measurements during the dynamic test can be made. The optimized bilinear incident wave is formulated for achieving the stress equilibrium and constant strain rate loading on the specimen, and the experimental verification demonstrates the feasibility and merits of the bilinear wave in testing brittle materials. Numerical simulations are also performed to see the effect of bar indentation on stress–strain curves, and simulation results show strain concentration at both ends of the specimens resulting in premature failure. A specimen with a dogbone configuration is proposed which can greatly reduce the strain concentration and facilitate the accurate measurement of stress–strain for brittle materials.

Objective To study the influence of halogenated hydroxyl-alkanes inhalation anesthetic on the determination of ethanol content in blood. Methods Halogenated hydroxyl-alkanes were analyzed by headspace gas chromatography with double column confirmatory detection method. The influence of halogenated hydroxyl-alkanes on determination of ethanol content in blood sample by headspace gas chromatography was explored under the different detection conditions of KB-BAC1/ KB-BAC2 and JW DB-ALC1/DB-ALC2 gas chromatographic column. Results The retention time of sevoflurane and enflurane was similar to that of ethanol and tert butanol respectively when using the JW DB-ALC1/DB-ALC2 gas chromatographic column, and interfered with the detection of ethanol content in blood; only JW DB-ALC1 gas chromatographic column can separate the sevoflurane and ethanol components, so as to eliminate their influence on the detection of ethanol content in blood. When using KB-BAC1/KB-BAC2 gas chromatographic column, the retention time of sevoflurane, isoflurane and ethanol is similar, especially that of sevoflurane and ethanol, and sevoflurane obviously interferes with the determination of ethanol content in blood. Conclusion Halogenated hydroxy-alkanes interfere with determination of ethanol content in blood by headspace gas chromatography. The interference can be discriminated effectively by choosing the suitable chromatographic column and double column confirmatory detection.卤代羟基烷类吸入用麻醉剂对血液中乙醇含量检测的影响.目的 研究血液中的卤代羟基烷类吸入用全身麻醉剂对血液中乙醇含量检测的影响。 方法 利用顶空气相色谱双柱确认检测方法对卤代羟基烷类进行分析，观察其在KB-BAC1/KB-BAC2和JW DB-ALC1/DB-ALC2气相色谱柱条件下对顶空气相色谱法检测血液中乙醇含量的影响。 结果 JW DB-ALC1/DB-ALC2气相色谱柱中，七氟烷、恩氟烷分别与乙醇和叔丁醇的保留时间相近，对血液中乙醇含量的检测存在干扰；仅JW DB-ALC1气相色谱柱可分离七氟烷和乙醇成分，以排除其对血液中乙醇含量检测的影响。在KB-BAC1/KB-BAC2气相色谱柱中，七氟烷、异氟烷与乙醇的保留时间相近，尤其是七氟烷与乙醇的保留时间基本一致，对血液中乙醇含量检测存在明显干扰。 结论 卤代羟基烷类对顶空气相色谱法检测血液中乙醇含量存在干扰，选择适当的色谱柱进行双柱确认检测可有效予以甄别。.法医毒理学；卤代羟基烷；麻醉药，吸入；乙醇；顶空气相色谱法；血液.

To develop a method to screen and quantify 10 common herbicides （paraquat, diquat, glyphosate, glufosinate, cyanazine, atrazine, metazachlor, acetochlor, chlorsulfuron, and metsulfuron） in blood.With acetonitrile-water solution [All the 10 herbicides had good linearity in their linear range （coefficient of determinationThis method is easy to operate with high recovery rates. It enables rapid and accurate qualitative screening and quantitative analysis of various herbicides in blood simultaneously.血液中常见除草剂的UPLC-HRMS分析.建立一种血液中10种常见除草剂（百草枯、敌草快、草甘膦、草铵膦、氰草津、莠去津、吡草胺、乙草胺、氯磺隆、甲磺隆）的筛查及定量方法。.以乙腈-水溶液［10种除草剂在各自线性范围内线性关系良好（决定系数该方法操作简便、回收率高，可同时对血液中多种除草剂进行快速准确的定性筛选和定量分析。.法医毒理学；除草剂；超高效液相色谱-高分辨质谱；蛋白沉淀法；生物检材.

Al doped ZnO (AZO) films were prepared on glass substrates by radio frequency (RF) magnetron sputtering technology. Surface morphology, crystal structure, chemical composition, UV-visible transmittance, electrical and infrared properties of the AZO films were investigated by atomic force microscopy, scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, Spectrophotometer, Hall measurement system and Fourier Transform infrared spectroscopy, respectively. The results indicate that AZO films with strong c-axis preferred wurtzite structure were successfully prepared by RF magnetron sputtering at room temperature. The average visible transmittance and infrared reflection rate (from 1·5 to 25 μm) of the deposited films was 84·8 and 30%, respectively. The study creates a sound basis for investigating the infrared properties of AZO films for future heat shielding films.

The impact of anatomic resection (AR) as compared to non-anatomic resection (NAR) for hepatocellular carcinoma (HCC) as a factor for preventing intra-hepatic and local recurrence after the initial surgical procedure remains controversial. A systematic review and meta-analysis of nonrandomized trials comparing anatomic resection with non-anatomic resection for HCC published from 1990 to 2010 in PubMed and Medline, Cochrane Library, Embase, and Science Citation Index were therefore performed. Intra-hepatic recurrence, including early and late, and local recurrence were considered as primary outcomes. As secondary outcomes, 5 year survival and 5 year disease-free survival were considered. Pooled effects were calculated utilizing either fixed effects or random effects models. Eleven non-randomized studies including 1,576 patients were identified and analyzed, with 810 patients in the AR group and 766 in the NAR group. Patients in the AR group were characterized by lower prevalence of cirrhosis, more favorable hepatic function, and larger tumor size and higher prevalence of macrovascular invasion compared with patients in the NAR group. Anatomic resection significantly reduced the risks of local recurrence and achieved a better 5 years disease-free survival. Also, anatomic resection was marginally effective for decreasing the early intra-hepatic recurrence. However, it was not advantageous in preventing late intra-hepatic recurrence compared with non-anatomic resection. No differences were found between AR and NAR with respect to postoperative morbidity, mortality, and hospitalization. Anatomic resection can be recommended as superior to non-anatomic resection in terms of reducing the risks of local recurrence, early intra-hepatic recurrence and achieving a better 5 year disease-free survival in HCC patients.

Synthetic extracellular matrix (ECM) has been shown to be efficient to preserve the function of transplanted islets. In this study using a mouse model, we sought to determine whether subcutaneous transplantation was a convenient procedure for achieving normoglycemia.We performed in vitro tests as well as morphologic observations and Western blotting to establish that embedded islets survived better than non-embedded islets. Streptozotocin-induced diabetic mice (BALB/c) were transplanted with ECM-embedded syngeneic islets via the subcutaneous (SC; n = 5) or subrenal capsule (SRC; n = 6) routes. We measured mean blood glucose levels at various points from pretransplantation to postoperative day 14, and examined immunohistochemistry staining for insulin in the transplant grafts on day 14.Islets transplanted with ECM gel retained better structure and developed a functional vasculature. Western blotting showed more caspase-3 expressed in the non-embedded islets, which indicated more islet cells undergoing apoptosis. On the first day after transplantation, glucose levels were significantly decreased in the SRC group compared with the SC group: 383.33 ± 44.50 mg/dL to 80.67 ± 16.85 mg/dL versus 414.00 ± 92.33 mg/dL to 278.28 ± 121.80 mg/dL (P.05). Glucose levels were better maintained in the SRC group than the SC group over 14 days. Immunohistochemistry staining for insulin showed fewer islets in the SC group.Embedded islets with ECM gel functioned better than non-embedded ones in vitro. However, the subcutaneous route may not be an ideal site for islet transplantation.

We present in this report an efficient KTP-based intracavity optical parametric oscillator driven by a diode-pumped Nd:GdVO4/Cr:YAG passively Q-switched laser. For the first time, a novel folded cavity configuration was employed to set the KTP and Cr:YAG crystals separately at different fundamental beam waists. Based on the ABCD-matrix theory and by taking the thermal lens effect into account, the laser cavity was well optimized to enhance the OPO performance. A diode pump threshold as low as 1.2 W and a maximum signal (1.57 μm) average output power up to 560 mW have been achieved. Efficient energy transfer in the IOPO leads to short pulse duration (1.8–2.6 ns) and high peak power (6.8 kW) output at 1.57 μm. Additionally, the correlation dynamics between the pump laser and the OPO was analyzed in detail.

A compact small-scale intracavity optical parametric oscillator (IOPO) at 1.57 μm, driven by a diode pumped Nd:YVO4/Cr:YAG passively Q-switched laser, is experimentally presented. By optimizing the mode matching, low threshold (0.66 W) and high repetition rate (21 kHz) operation of the IOPO has been investigated. At the incident diode pump power of 1.56 W, the miniature (56 mm long) IOPO produces a signal average output power up to 86 mW. Efficient parametric conversion leads to short duration (1.8 ns) pulses and high peak power output (2.3 kW) at 1.57 μm. Moreover, near diffraction limited and Gaussian type signal beam profile is also observed.

Bombyx mori nucleopolyhedrovirus (BmNPV) ORF 51 (Bm51) is a gene present in many lepidopteran NPVs, but its function is unknown. In this study, Bm51 was characterized. Transcripts of Bm51 were detected from 4.5 through 72 hour post infection (h p.i.) by RT-PCR. The corresponding protein was detected from 6 to 72 h p.i. in BmNPV-infected BmN cells by western blot analysis using a polyclonal antibody against Bm51. Western blot assay of occlusion-derived virus and budded virus (BV) preparations revealed that Bm51 encodes a 23-kDa structural protein that is associated with BV and is located in the envelope fraction of budded virions. The protein was temporarily called BV-E23. In addition immunofluorescence microscopy demonstrated that the protein was present within the cytoplasm and nuclei in virus-infected cells. In conclusion, the available data suggest that Bm51 is a functional ORF of BmNPV and encodes a protein expressed in the early stage of the infection cycle that is associated with the BV envelope.

Based on the experiments of laser-TIG double-side welding (LTDSW) for aluminium alloys, the influence of laser radiation on the arc behaviours of the opposite side was investigated. Generally, with the variation of laser power, there are three typical arc shapes: arc column convergence, arc root constriction and arc expansion. An important point to notice is that the laser keyhole preheating will induce the arc column convergence in the LTDSW. The arc voltage in the LTDSW is lower than that in TIG welding over the entire range of the experimental currents. Moreover, with increasing welding current, the difference in arc voltage between TIG welding and LTDSW is diminished because of the self-stabilisation of the arc burning at high currents. The complex transformation of arc behaviours has a great effect on the arc current density and its stability. The laser generated hot spot or laser induced plasma will have a higher temperature and greater electron density than neighbouring regions, and will of...

To discuss the surgical methods of total knee arthroplasty (TKA) in the patients with active tuberculosis of the knee and find out its curative effect after TKA.We analyzed 10 patients with active tuberculosis of the knee who received TKA in our department from March 2006 to March 2010, whose ages were from 22 to 64 years old (average age was 40.6 ± 1 years). The following parameters were measured in the pre- and post-operation periods: HSS score, range of motion (ROM). From x-ray to find out post-operate curative effect of TKA.All cases had pain and elevated ESR. Deep vein thrombosis (DVT) and nerve damage were not found in these cases. There were 4 cases that had sinuses on the skin: the skin healed before the operation took place. Pre-operation HSS average scores were 25.0 ± 2. All patients received TKA by the para-patellar medial approach. Eight cases were followed-up for 6-28 months; the average follow-up period was 14 ± 0.5 months. Post-operation we took an HSS score and X-rays to find out its curative effect after TKA operation. There were also no patients with dislocation, aseptic loosening or fracture of prosthesis, although 1 case had recurrence. Post-operation's HSS average scores were 86.75 ± 5.45. The average ROM was improved to 95 ± 5°.Recent clinical results indicate that TKA is effective to treat the patients with active tuberculosis of the knee joint. TKA can significantly improve the function of the joint and relieve pain, improving patients' living conditions.

In order to provide a scientific basis for a strictly medical comparison (a ‘unified standard’) of local reference values for erythrocyte sedimentation rate (ESR) among the presenile population in China, the reference values for ESR of healthy persons have been collected, the assays having been performed by the method of Wintrobe. The relationship between the reference value for ESR in the presenile population and geographical factors has been examined. Altitude was found to be the most important factor affecting the reference value for ESR in the presenile population; ESR reference values decrease as the altitude gradually increased, the relationship being highly significant. The method of stepwise regression analysis was used to deduce two regression equations, so that if the geographical factor value of a particular area in China is known, the national reference value for ESR in the presenile population can be calculated by means of these equations. Based on geographical factors, China can be divided into six districts: Qingzang, Southwest, Northwest, Southeast, North and Northeast.

The mouse reelin gene (Rein} encodes a novel protein that, when mutated, results in the characteristic reeler phenotype. A key component of this phenotype is the extensive disruption of the organization of many brain structures. Reelin is believed to be an extracellular protein that controls neural cell positioning during brain development. The reelin gene is conserved in many vertebrate species, including humans. To study the role of the reelin homolog in human brain development, we have isolated and characterized the human gene [RELy. Like its murine counterpart, RELN is large, encoding an mRNA of -12 kb. Overlapping cDNA clones containing the entire open reading frame were isolated and sequenced, revealing that the predicted mouse and human proteins are similar in size (388 kD) and that the amino acid and nucleotide sequences are 94.2% and 87.2% identical, respectively. Northern hybridization analyses revealed that RELN is expressed in fetal and postnatal brain as well as liver. The expression of RELN in postnatal human brain was high in the cerebellum. RELN was mapped to human chromosome 7q22, based on both fluorescence in situ hybridization studies and localization within a well-positioned yeast artificial chromosome [YAC) contig. The YAC contig also contains a number of genetic markers. Together, these studies provide the sequence information and genetic tools for performing more detailed analyses of RELN in an attempt to define its role in human brain development and possibly in human disease. [The sequence data described in this paper have been submitted to GenBank under accession no. U79716.]

Development of the Edmonton protocol was a pivotal contribution to clinical islet transplantation (ITx). Persistent limitations to ITx include insufficient supply and posttransplant functional failure of islets. In this study, nerve growth factor (NGF) was used to enhance both cultured and transplanted beta-cell function, thus achieving prolonged graft survival.Fluorescence microscopy with ethidium bromide and SYTO green staining was used to evaluate balb/c mouse islet viability. Islets were syngeneically transplanted under the kidney capsule of recipients with streptozotocin-induced diabetes. Intraperitoneal glucose tolerance was used to test posttransplant function.Improved viability was found in murine islets cultured for 48 hours in 500 ng/mL NGF (P.05). A submarginal islet mass (260 islet equivalents/recipient) was used for ITx. The NGF-culture resulted in prolonged islet survival (24.7 days vs 5.5 days without NFG culture, n = 6). Intravenous injection of NGF (6 mug) on the day of transplant and postoperative days (POD) 1 + 2 prolonged islet survival from 4.1 days (no treatment) to 13.2 days (n = 6). Glucose tolerance testing performed at posttransplant day 4 showed improvement at 60 and 120 minutes in recipients treated intravenously with NGF (blood glucose of 95 +/- 15 vs 210 +/- 78 and 57 +/- 6 vs 176 +/- 70 mg/dL, respectively).NGF may improve beta-cell function and result in prolonged survival of both cultured and transplanted islets.

The autosomal recessive mouse mutation reeler leads to impaired motor coordination, tremors and ataxia. Neurons in affected mice fail to reach their correct locations in the developing brain, disrupting the organization of the cerebellar and cerebral cortices and other laminated regions. Here we use a previously characterized reeler allele (rl(tg)) to close a gene, reelin, deleted in two reeler alleles. Normal but not mutant mice express reelin in embryonic and postnatal neurons during periods of neuronal migration. The encoded protein resembles extracellular matrix proteins involved in cell adhesion. The reeler phenotype thus seems to reflect a failure of early events associated with brain lamination which are normally controlled by reelin.

Reeler (rl) is an autosomal recessive mutation that affects migration of postmitotic neurons in the mouse central nervous system. The reeler (rl/rl) mouse displays a disruption of laminar structures in both the cerebellum and the forebrain and it exhibits tremors, dystonia, and ataxia. The molecular basis of the reeler phenotype is unknown because the gene involved has not yet been identified. We report here the isolation and characterization of an allele of rl, reelertransgene (rltg). This allele was generated by the fortuitous insertion of a transgene, supfos (sf), into the mouse rl locus. Crosses between rl/+ and rltg/+ mice yielded offspring that exhibited the reeler phenotype, indicating that rl and rltg are allelic. We cloned the genomic sequences flanking the transgene insertion site from the rltg/rltg mouse genome. Chromosomal mapping studies revealed that the 5' flanking cellular sequence maps to a locus, D5Gmr1, that lies in a region of mouse chromosome 5 that also contains the rl locus. Southern blot analysis using a probe derived from the D5Gmr1 locus revealed no gross structural rearrangement in the rl locus. Thus, unlike the two rl alleles described previously, rltg provides a molecular probe that can now be used to identify and isolate the rl gene.

The proto-oncogene transcription factors Fos and Jun form a heterodimeric complex that binds to DNA and regulates expression of specific target genes. Continuous expression of c-fos causes transformation of cultured fibroblasts and induces osteogenic sarcoma in mice. To investigate the molecular basis of fos-mediated oncogenesis, we developed a conditional cell transformation system in which Fos expression was regulated by isopropyl-beta-D-thiogalactopyranoside (IPTG). Synthesis or repression of Fos in L1-3c-fos cells occurred rapidly, within 30 min, after the removal or addition of IPTG to the culture medium. However, there was a significant delay between the induction of Fos expression and the appearance of morphological transformation. No effect was observed after 12 h of Fos expression, partial transformation was detected after 24 h, and full transformation required approximately 3 days of continuous Fos expression. Similarly, the transformed cell morphology persisted for at least 2 days after repression of Fos, and a normal phenotype was observed only after 3 days. Fos-Jun complexes, capable of binding to AP-1 sequences, were present continuously during the delay in morphological transformation. Furthermore, increased expression of several candidate Fos target genes, including those encoding Fra-1, transin (stromelysin), collagenase, and ornithine decarboxylase, was detected shortly after Fos induction. The induction of morphological transformation was not dependent on the cell cycle, as it occurred in both cycling and noncycling cells. Thus, the Fos-Jun complexes present before L1-3c-fos cells become fully transformed are transcriptionally active. These complexes disappeared, and the Fos target genes were repressed at least 2 days prior to reversion. Our results suggest that cell transformation by Fos requires increased expression of a target gene(s) with a long-lived product(s) that must reach a critical level.

The proto-oncogene transcription factors Fos and Jun form a heterodimeric complex that binds to DNA and regulates expression of specific target genes. Continuous expression of c-fos causes transformation of cultured fibroblasts and induces osteogenic sarcoma in mice. To investigate the molecular basis of fos-mediated oncogenesis, we developed a conditional cell transformation system in which Fos expression was regulated by isopropyl-beta-D-thiogalactopyranoside (IPTG). Synthesis or repression of Fos in L1-3c-fos cells occurred rapidly, within 30 min, after the removal or addition of IPTG to the culture medium. However, there was a significant delay between the induction of Fos expression and the appearance of morphological transformation. No effect was observed after 12 h of Fos expression, partial transformation was detected after 24 h, and full transformation required approximately 3 days of continuous Fos expression. Similarly, the transformed cell morphology persisted for at least 2 days after repression of Fos, and a normal phenotype was observed only after 3 days. Fos-Jun complexes, capable of binding to AP-1 sequences, were present continuously during the delay in morphological transformation. Furthermore, increased expression of several candidate Fos target genes, including those encoding Fra-1, transin (stromelysin), collagenase, and ornithine decarboxylase, was detected shortly after Fos induction. The induction of morphological transformation was not dependent on the cell cycle, as it occurred in both cycling and noncycling cells. Thus, the Fos-Jun complexes present before L1-3c-fos cells become fully transformed are transcriptionally active. These complexes disappeared, and the Fos target genes were repressed at least 2 days prior to reversion. Our results suggest that cell transformation by Fos requires increased expression of a target gene(s) with a long-lived product(s) that must reach a critical level.

The DNA binding activity of transcription factor AP-1 is regulated in vitro by a posttranslational mechanism involving reduction/oxidation (redox). Redox regulation is mediated by a conserved cysteine residue in the DNA-binding domain of Fos and Jun. Previously, we demonstrated that a DNA repair protein, Ref-1, could stimulate the DNA binding activity of Fos-Jun dimers by reducing this cysteine residue. To examine the relationship between the redox and repair functions of Ref-1, we generated a series of deletion mutants. Analysis of the truncated proteins in vitro revealed that the redox and repair activities are encoded by distinct regions of Ref-1. Sequences in the N-terminal domain of Ref-1 that are not present in functionally related proteins from other organisms are required for the redox activity, whereas the DNA repair activity requires conserved C-terminal sequences. Chemical alkylation or oxidation of cysteine sulfhydryls inhibits the redox activity of Ref-1 without affecting its DNA repair activity. Crosslinking studies suggest that a direct cysteine-mediated interaction occurs between Ref-1 and Jun.

This paper investigates wind field and traffic pollutant dispersion at street level in a local urban area. A coupling method is employed between the mesoscale model weather research and forecast (WRF) for the atmospheric flow of whole city and the large eddy simulation (LES) method for local environmental flows. A combined model is proposed for building clusters in the urban area. The wind speed, temperature and carbon monoxide concentration fields are computed from 9 am of October 26 2009 to 8 am of the next day in a district of Beijing and the results show a good agreement with the observation.

The development of a multicellular organism involves a delicate balance among the processes of proliferation, differentiation and death. Naturally occurring cell death aids tissue remodelling, eliminates supernumerary cell populations and provides structural elements such as hair and skin. In the nervous system, selective cell death contributes to the formation and organization of the spinal cord and sympathetic ganglia, retina and corpus callosum. But cell death also occurs in several neuropathological conditions, such as amyelotrophic lateral sclerosis and Alzheimer's disease. Therefore an elucidation of the mechanisms responsible for cell death is critical for an appreciation of both normal development and neuropathological disorders. Using a fos-lacZ transgenic mouse, we provide evidence showing that the continuous expression of Fos, beginning hours or days before the morphological demise of the cell, appears to be a hallmark of terminal differentiation and a harbinger of death.

Summary Length-weight relationships (LWR) are described for eleven indigenous fishes from the upper Jinsha River, which is the upper stretch of the Yangtze River, China. This is the first record of length-weight relationships for ten of these species in FishBase and new maximum lengths are recorded for seven species.

Aim Islet transplantation is a promising treatment to cure diabetes, but is associated with a high rate of early graft failure. The isolation process leads to the loss of the surrounding extracellular matrix, resulting in eventual islet disintegration and apoptosis. The purpose of this study was to determine the effects on the viability of isolated islets of embedding islets in reconstituted basement membrane extract (BME), which is similar to the normal peri-islet BM composition in vivo. Methods Isolated mouse islets were embedded in BME gel for 24 or 48 hours. Expression of caspase-3, α3, and α5, focal adhesion kinase (FAK), phosphor-FAK, and pancreatic duodenal homeobox factor (PDX)-1 were detected with Western immunoblotting. Results Impaired aggregation of single islet cells could only be observed in non-BME medium. Islets embedded in BME gel were partially protected from anoikis showed decreased caspase-3 compared with non-BME islets. We also observed an increase of α3 integrin, FAK protein level, and FAK activity. Furthermore, expression of PDX-1 was preserved at 48 hours, suggesting a positive contribution of BME to β-cell activity. Conclusion These results indicated that embedding islets in BME can upregulate α3 integrin, which may result in preservation of viability and function of isolated islets.

For exploration in the Chepaizi area, Junggar Basin of Northwest China, lateral lithologic variations due to deltaic and fluvial sediments present major challenges to the characterization of oil sand reservoirs. The major oil reservoirs exist in so-called “sweet spots”. However, conventional P wave is not able to effectively distinguish true “bright spots” from false ones, which leads to high drilling risk. For example, a strong reflection amplitude is observed in the target layer for Che89, a highly productive oil well drilled in 2006. But only a few wells drilled on a similar reflection response turned out to be successful commercial discoveries. It is widely believed that not only the fluid content, but also lithologic variations, have led to such misleading outcomes. Effectively locating the hydrocarbon distribution by eliminating the impact of lithologic variations could be the key for successful oil exploration. In order to better characterize the reservoirs, PetroChina Xinjiang acquired a high resolution 2D-3C seismic line in 2007, intersecting two existing wells, Che89 (good producer) and Che97 (dry well), by employing DSU3 digital sensor units with advanced MEMs accelerometer technology. Both high-resolution amplitude-preserving processing and PP-PS joint inversion were employed for reservoir characterization.

More than half of transplanted beta-cells undergo apoptotic cell death triggered by nonimmunological factors within a few days after transplantation. To investigate the dynamic hypoxic responses in early transplanted islets, syngeneic islets were transplanted under the kidney capsule of balb/c mice. Hypoxia-inducible factor-1alpha (HIF-1alpha) was strongly expressed at post-transplant day (POD) 1, increased on POD 3, and gradually diminished on POD 14. Insulin secretion decreased on POD 3 in association with a significant increase of HIF-1alpha-related beta-cell death, which can be suppressed by short-term hyperbaric oxygen therapy. On POD 7, apoptosis was not further activated by continually produced HIF-1alpha. In contrast, improvement of nerve growth factor and duodenal homeobox factor-1 (PDx-1) production resulted in islet graft recovery and remodeling. In addition, significant activation of vascular endothelial growth factor in islet grafts on POD 7 correlated with development of massive newly formed microvessels, whose maturation is advanced on POD 14 with gradual diminution of HIF-1alpha. We conclude that (1) transplanted islets strongly express HIF-1alpha in association with beta-cell death and decreased insulin production until adequate revascularization is established and (2) early suppression of HIF-1alpha results in less beta-cell death thereby minimizing early graft failure.

Disruption of the reelin gene by partial deletion causes the neurological phenotype known as reeler. Here we report the cloning and sequencing of the reelin breakpoint region from the Jackson reeler strain (rl). Based on this sequence, we developed a polymerase chain reaction screen that allows the identification of mutant mice prior to the appearance of the phenotype. The assay also permits discrimination of heterozygous from wild-type mice. These findings provide a strategy for the characterization of the early anatomical and physiological consequences of the reeler mutation.

The design of a fully-integrated 10.5 to 13.5 Gbps transceiver is presented. The chip uses a half-rate architecture for both the transmitter and receiver. Duo-binary and electrical RZ pre-coding are implemented in the transmitter. The receiver uses a high-gain input buffer with a new digital offset cancellation technique to achieve 15 mVpp differential input sensitivity. Programmable phase tuning capability in the clock and data recovery (CDR) loop provides optimum data sampling instants. The transceiver occupies 8 mm/sup 2/ and dissipates 1 W in a 0.13 /spl mu/m digital CMOS process.

The design of a continuous rate octal 1.0 to 3.2 Gb/s serializer/deserializer circuit that meets SONET and XAUI requirements is presented. The performance of the SERDES surpasses stringent OC-48 jitter generation and tolerance specifications. This is achieved with the use of a master-slave PLL tuning scheme and meticulous attention to layout and isolation techniques. Implemented in a 0.13 /spl mu/m digital CMOS technology, the part exhibits less than 5 mUI r.m.s. jitter and the 1.2 mm/sup 2/ transceiver dissipates 160 mW.

A capillary electrophoresis (CE) method has been developed and validated for the quantitative determination of alginic acid, which is used as a rafting agent in complex antacid formulations. The method involves a preliminary separation of the alginic acid from the formulation by washing the sample matrix with methanol, diluted HCl and water. This is followed by electrophoresis within a fused silica capillary using borate/boric acid buffer as the electrolyte, and the quantification is performed by a UV detector monitoring at 200 nm, where the intrinsic absorption of alginic acid is measured. An assay precision of better than 3% was achieved in intra- and interday determinations. No interference was found from the matrix of the antacid formulations.

The determination of lead in water depuration agent with single-slotted quartz tube by the fuel-lean flame trapping and pulsed fuel-rich flame discharge atom-trapping atomic absorption spectrometry have been investigated. The optimum conditions for the determination and the tolerance of interfering elements are studied. A simple and rapid method is proposed. The linear relationship holds in the range 0-100 micrograms.L-1, the recovery is between 97%-103% and the relative standard deviation is 2.6%-2.8%. The proposed method has been applied to the determination of lead in water depuration agent samples with satisfactory results.

The purpose of this paper is to provide a scientific basis for a unified standard of the reference value of young people's erythrocyte sedimentation rate (ESR) in China. The reference values of healthy young people's ESR were collected according to the Wintrobe method, and the relationship between the reference value of young people's ESR and altitude was tested in this paper. It was found that the reference value of young people's ESR decreases when the altitude gradually increases, and the relationship is significant. The method of mathematical univariate regression analysis was used to deduce two regression equations: &#147 1 &#118 = &#118 10.92-0.00183X &#118 &#45 2.59 and &#147 2 &#118 = &#118 18.58-0.00319X &#118 &#45 4.37. If the altitude value of a particular area of China is known, the reference value of young people's ESR can be calculated by means of the regression equations. Furthermore, depending on the altitude, China can be divided into three districts: Qingzang, Central and Eastern districts.

A reversed-phase liquid chromatographic method has been developed and validated for the determination of the polydimethylsiloxane (PDMS) component of Simethicone, which is used as an anti-foaming agent in pharmaceutical formulations. The method involves acidification to neutralise antacid components of the formulation, then a single extraction of the PDMS with dichloromethane. This is followed by separation with a reversed-phase column using an acetonitrile-chloroform solvent gradient, and quantification by an evaporative light scattering detector. An assay precision of 3% was achieved in intraday and interday determinations. No interference was found from the aluminium and magnesium hydroxide components of antacid formulations.

There exists a rational range of artificial supplemental energy inputs in fields. In the range, the inputs can improve the yield and the output/input ratio. The rational range of energy input in total energy output is bigger than that in the output/input ratio. It is bigger in low yield fields than high yield fields, which suggests that increasing artificial supplemental energy input can increase the production of low yield fields as same as high yield fields. In the rational range of energy input, there exist high efficient lines in water and fertilizer inputs. The highest efficiency occurs when the rational inputs of water and fertilizer occur in these two lines. There also exist optimum lines of energy and economy input proportions. In the two lines, the proportions of energy and economy output/input of water and fertilizer inputs are the highest, which are the optimum of water and fertilizer inputs. Water and fertilizer may replace each other for equal yields, but would result in a decrease in the output/input ratio.

We demonstrate an all-normal-dispersion ytterbium (Yb)-doped fiber laser mode-locked by a higher modulation depth carbon nanotube saturable absorber (CNT-SA) based on an evanescent field interaction scheme. The laser cavity consists of pure normal dispersion fibers without dispersion compensation and an additional spectral filter. It is exhibited that the higher modulation depth CNT-SA could contribute to stabilize the mode-locking operation within a limited range of pump power and generate the highly chirped pulses with a high-energy level in the cavity with large normal dispersion and strong nonlinearity. Stable mode-locked pulses with a maximal energy of 29 nJ with a 5.59 MHz repetition rate at the operating wavelength around 1085 nm have been obtained. The maximal time-bandwidth product is 262.4. The temporal and spectral characteristics of pulses versus pump power are demonstrated. The experimental results suggest that the CNT-SA provides a sufficient nonlinear loss to compensate high nonlinearity and catch up the gain at a different pump power and thus leads to the stable mode locking.

In order to provide a scientific basic for a unified standard of the reference value of old people's erythrocyte sedimentation rate (ESR) in China. The reference value of healthy old people's ESR was collected according to the Wintrobe method, the relationship between the reference value of old people's ESR and altitude was tested in this paper. It was found that the reference value of old people's ESR decreases when the altitude gradually increases, the relationship is quite significant. The method of mathematical univariate regression analysis was used to deduce two regression equations: Y1 = 16.38 - 0.00301X +/- 6.53, Y2 = 25.92 - 0.00438X +/- 10.25. If the altitude value of a particular area of China is known, the reference value of old people's ESR can be calculated by means of the regression equations. Furthermore, depending on the altitude, China can be divided into three districts: Qingzang Districts, Central Districts and Eastern Districts.

In order to provide a scientific basis for the layout of a unified standard of the reference value of Chinese young people's erythrocyte sedimentation rate (ESR), the relationship between the reference values of the Chinese healthy young's ESR and five geographical factors was tested according to the Wintrobe methods. The altitude was found to be the most important factor affecting the reference value of the Chinese young's ESR. The altitude increase correlates with the decrease of the reference value of the young's ESR. The method of stepwise regression analysis was used to deduce two multivariate regression equations. If the geographical index values of a particular area of China are known, the reference value of the young's ESR of this region can be calculated by means of the regression equations. Furthermore, the depending on geographical factors, China can be divided into six districts: Qingzang, Southwest, Northwest, Southeast, North and Northeast District, according to the reference values of the Chinese young's ESR.