在中国壮族家系中发现的一例-α~T/-α~Q复合β~0β~0珠蛋白基因型

本文报道在我国广西隆林壮族中发现一个罕見的HbQ复合α,β地中海贫血家系。先证者女,18岁,贫血面容,肝脾肿大。化学结构分析确证本Hb变异体为HbQ Thailand[α74(EF3)Asp→His]。血红蛋白组成以及α和β珠蛋白基因分析结果表明,先证者的珠蛋白基因型为-α~Q/-α~T复合β°/β°(IVSI-1G→T/Codon17A→T);先证者父的基因型为-‘α~Q/-复合β~O/β~A(IVSI-1G→T/β~A);先证母的基因型为-α~T/αα复合β~O/β~A(Codon17A→T/β~A)。     

岭南垛基果林湿地土壤碳组分特征

岭南垛基果林湿地是珠三角地区典型的湿地类型之一,其对土壤碳汇的贡献值得关注。为探讨果林种植类型对土壤有机碳的影响,对广州垛基果林湿地内种植黄皮(Clausenalansium)(HP),龙眼(Dimocarpuslongan)(LY)、杨桃(Averrhoa carambola)(YT),龙眼和黄皮间种(LH),杨桃、龙眼和黄皮间种(YLH)共5种种植类型下的表层(0～20 cm)土壤碳组分进行研究。结果表明,不同的植被类型对土壤的总有机碳(SOC)、可溶性有机碳(DOC)、微生物生物量碳(MBC)、易氧化有机碳(ROC)、惰性碳(NLC)含量都有影响,LY的SOC含量最高(22.6 g/kg),显著高于YLH (P<0.05),且NLC含量显著高于LH和YLH (P<0.05)。NLC含量与土壤养分呈正相关,与土壤容重呈负相关。YT的MBC含量显著高于LY、HP、LH (P<0.05),且MBC/SOC显著高于HP、LY(P<0.05)。YLH模式下,土壤DOC含量和DOC/SOC显著高于其他植被类型(P<0.05)。LH的ROC/SOC显著高于HP和L...     

崖椒茎的化学成分

从崖椒（Zanthoxglum schinifolutm Sieb.et Zucc.)茎的石油醚、二氯甲烷提取物中分离得到8个化合物。经物理常数测定及光谱（UV,IR,MS,NMR)分析鉴定其为（1）白鲜碱（dictamning),（2）茵芋碱（skimmianine),(3)滨蒿内酯（scoparone),(4)崖椒内酯（schinifolin),(5)莨菪亭（scopoletin),（6）7-羟基-8-甲氧基香豆素（7-hydroxy-8-methoxycoumarin),（7）N-甲基弗林辛（N-methylflindersine),（8）β-谷甾醇（β-sitosterol),其中化合物（5）、（6）和（7）为首次从该植物中分离。     

A real-world exploratory study on the feasibility of vonoprazan and tetracycline dual therapy for the treatment of Helicobacter pylori infection in special populations with penicillin allergy or failed in previous amoxicillin-containing therapies

Background

The treatment of Helicobacter pylori (H. pylori) infection is a challenge for those who cannot use amoxicillin.

Objective

To evaluate the eradication rate and adverse effects of vonoprazan and tetracycline dual therapy as first-line and rescue treatment regimens used in special populations with penicillin allergy or failed in previous amoxicillin-containing therapies.

Design

Patients enrolled were those who were H. pylori-positive with selected conditions: (1) allergic to penicillin, either naïve to treatment or had failed before; or (2) failed in previous amoxicillin-containing therapies. All enrolled patients accepted 14-day vonoprazan and tetracycline dual therapy (VT dual therapy) as follows: vonoprazan (20 mg b.i.d.) and tetracycline (500 mg t.i.d. [body weight < 70 kg] or 500 mg q.i.d. [body weight ≥ 70 kg]). H. pylori status was evaluated by ¹³C-urease breath test 6 weeks after treatment. All adverse effects were recorded. Some patients underwent bacterial culture and antibiotic susceptibility testing.

Results

A total of 62 patients were enrolled; 18 of them received VT dual therapy as first-line treatment, 44 patients received VT dual therapy as rescue treatment. Overall, 58 of 62 patients achieved successful eradication (93.5%), while all involved (100%,18/18) succeeded in the first-line treatment group and 40 cases (90.9%, 40/44) succeeded in the rescue treatment group. Sixty-one (61/62, 98.4%) patients completed the whole course of treatment. Adverse events occurred in 6 patients (6/62, 9.7%), while one patient quit because of skin rash. All adverse effects were mild and relieved spontaneously after H. pylori treatment. Five patients achieved successful H. pylori culture, and all strains isolated were sensitive to tetracycline.

Conclusions

For the treatment of H. pylori infection in special populations with penicillin allergy or failed in previous amoxicillin-containing therapies, a 14-day vonoprazan and tetracycline dual therapy was effective and safe as first-line and rescue treatment in our study. Further study is warranted to verify its efficacy, especially for those who cannot use amoxicillin.     

Intratumoral interleukin-2 immunotherapy: Activation of tumor-infiltrating and splenic lymphocytes in vivo

Direct intratumoral injection of interleukin-2 (IL-2) was evaluated in a murine model. Balb/c mice received 5 × 10⁴ Line 1 alveolar carcinoma cells (L1C2) by subcutaneous injection. On the third day following tumor implantation, mice received injections of IL-2 (5 × 10³–5 × 10⁴ units) or diluent twice daily, either by i. p. or intratumoral injection, 5 days/week for 3 weeks. Intratumoral injection of 5 × 10⁴ units IL-2 significantly reduced tumor volume (P <0.05 versus control), increased median survival time (P = 0.0001), and resulted in a 23.5% cure rate (P = 0.008). There were no long-term survivors in the other treatment groups. Both tumor-infiltrating lymphocytes (TIL) and splenic lymphocytes isolated directly from IL-2-treated mice demonstrated enhanced cytolytic activity compared to diluent-treated controls. To determine whether non-T-cell-mediated antitumor responses were active in our model, intratumoral immunotherapy was evaluated in athymic Balb/cnu/nu mice. In order to decrease the recruitment of lymphocyte precursors, nude mice were splenectomized and received cyclophosphamide prior to tumor injection and IL-2 therapy. Intratumoral IL-2 immunotherapy also significantly decreased tumor volume in these immunodeficient mice (P <0.02), but did not lead to long-term survival. We conclude that both TIL and splenic lymphocytes are activated in vivo in response to intratumoral IL-2 immunotherapy, suggesting that intratumoral therapy with IL-2 activates both local and systemic antitumor responses.Supported by the Tobacco-Related Disease Research Program of the University of California, the Cancer Research Coordinating Committee, the Jonsson Cancer Center Foundation, and Veterans Administration Medical Research Funds     

Genomic insights into selection for heterozygous alleles and woody traits in Populus tomentosa

Heterozygous alleles are widespread in outcrossing and clonally propagated woody plants. The variation in heterozygosity that underlies population adaptive evolution and phenotypic variation, however, remains largely unknown. Here, we describe a de novo chromosome-level genome assembly of Populus tomentosa, an economic and ecologically important native tree in northern China. By resequencing 302 natural accessions, we determined that the South subpopulation (Pop_S) encompasses the ancestral strains of P. tomentosa, while the Northwest subpopulation (Pop_NW) and Northeast subpopulation (Pop_NE) experienced different selection pressures during population evolution, resulting in significant population differentiation and a decrease in the extent of heterozygosity. Analysis of heterozygous selective sweep regions (HSSR) suggested that selection for lower heterozygosity contributed to the local adaptation of P. tomentosa by dwindling gene expression and genetic load in the Pop_NW and Pop_NE subpopulations. Genome-wide association studies (GWAS) revealed that 88 single nucleotide polymorphisms (SNPs) within 63 genes are associated with nine wood composition traits. Among them, the selection for the homozygous AA allele in PtoARF8 is associated with reductions in cellulose and hemicellulose contents by attenuating PtoARF8 expression, and the increase in lignin content is attributable to the selection for decreases in exon heterozygosity in PtoLOX3 during adaptive evolution of natural populations. This study provides novel insights into allelic variations in heterozygosity associated with adaptive evolution of P. tomentosa in response to the local environment and identifies a series of key genes for wood component traits, thereby facilitating genomic-based breeding of important traits in perennial woody plants.     

Avicularin alleviates acute liver failure by regulation of the TLR4/MyD88/NF-κB and Nrf2/HO-1/GPX4 pathways to reduce inflammation and ferroptosis

Acute liver failure (ALF) is an inflammation-mediated hepatocyte death process associated with ferroptosis. Avicularin (AL), a Chinese herbal medicine, exerts anti-inflammatory and antioxidative effects. However, the protective effect of AL and the mechanism on ALF have not been reported. Our in vivo results suggest that AL significantly alleviated lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced hepatic pathological injury, liver enzymes, inflammatory cytokines, reactive oxygen species and iron levels and increased the antioxidant enzyme activities (malondialdehyde and glutathione). Our further in vitro experiments demonstrated that AL suppressed inflammatory response in LPS-stimulated RAW 264.7 cells via blocking the toll-like receptor 4 (TLR4)/myeloid differentiation protein-88 (MyD88)/nuclear factor kappa B (NF-κB) pathway. Moreover, AL attenuated ferroptosis in D-GalN-induced HepG2 cells by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1)/glutathione peroxidase 4 (GPX4) pathway. Therefore, AL can alleviate inflammatory response and ferroptosis in LPS/D-GalN-induced ALF, and its protective effects are associated with blocking TLR4/MyD88/NF-κB pathway and activating Nrf2/HO-1/GPX4 pathway. Moreover, AL is a promising therapeutic option for ALF and should be clinically explored.     

低碳发展背景下北京市土地利用与生态系统服务多情景模拟研究

在全球气候变化的背景下,合理协调低碳减排与经济效益之间的关系,进而指导土地利用优化配置,对于推动经济社会低碳转型与生态系统服务价值的提升具有重要意义。通过耦合多目标规划(MOP)与斑块生成土地利用模拟模型(PLUS),针对北京市构建了自然演变、经济优先与低碳发展这3种未来发展情景,并对不同情景下2030年土地利用与生态系统服务价值进行模拟评估。在此基础上,进一步对北京市未来生态系统服务提升区域进行识别,将传统的多情景土地利用模拟研究进行了延伸与扩展。结果表明：(1)3种情景下的土地利用结构与空间布局存在差异,低碳发展情景下东南部平原区建设用地的扩张与耕地面积的减少趋势得到了有效控制,西北部山区的林地面积有较大幅度的增长。(2)低碳发展情景下的生态系统服务价值总量约为590亿元,高于另外两种情景,且从空间分布上来看,该情景下服务价值提升区域的面积也显著高于其他情景。(3)低碳发展情景下,北京市生态系统服务提升潜力较大的区域面积占比约7.98%、潜力中等区域的面积占比约26.57%,潜力较低区域的面积占比约65.45%。     

基于水足迹的山东省农业水土资源匹配特征及短缺压力分析

高强度农业开发引起的农业水土资源生态问题日益增多,探究粮食及蔬菜（粮蔬）生产中水土资源空间配置及短缺压力对农业资源的可持续利用具有重要意义。从水足迹视角出发,分析了山东省3种主要粮食作物（冬小麦、玉米及大豆）和两种不同种植模式蔬菜（设施蔬菜和露地蔬菜）的生产水足迹空间特征;同时将资源数量及资源质量的概念纳入研究框架,分析了农业水土资源数量及质量匹配格局差异,并进一步探究了农业水土资源短缺压力及其影响因素。研究结果表明：（1）2019年,山东省粮食和蔬菜的生产总水足迹为811亿m³,其中粮食生产总水足迹占比78.50%,蔬菜生产总水足迹占比21.50%;粮蔬生产水足迹受地势影响明显,鲁西北及鲁西南平原地区的粮蔬生产水足迹占比较大。（2）考虑资源数量的水土资源匹配系数均值为0.622×10⁴ m³/hm²,考虑资源质量的匹配系数均值为0.416×10⁴ m³/hm²;水土资源数量及质量匹配系数在空间上呈现出一致性,表明山东省农业生产水土资源空间配置水平高的地区同时面临着较大的农业面源污染压力。（3）整体上,土地资源短缺压力略高于水资源短缺压力;基于生产视角的水土资源短缺压力受生产环境因素制约显著,受经济发展因素的影响具有差异性,社会因素对水土资源短缺压力无显著影响。研究可为农业资源可持续管理提供数据基础,为全面理解粮蔬生产所产生的水土资源短缺提供案例参考。