Hectogram-scale synthesis of [Aib8, Arg34]-GLP-1 (7–37) by liquid-phase fragment condensation

Based on small-scale synthesis (0.3 g), a 100-g scale-up synthesis of crude [Aib⁸, Arg³⁴]-glucagon-like peptide-1 (GLP-1) (7–37) was completed. The crude [Aib⁸, Arg³⁴]-GLP-1 (7–37) was purified using a dynamic axial compression column 200 (DAC-200). Approximately 61 g of [Aib⁸, Arg³⁴]-GLP-1 (7–37) with a purity of >99% was obtained through one-step reverse-phase chromatography. The purification yield was approximately 92%. The yield from the total reaction was approximately 60%. In summary, we developed an economical and environmentally friendly route to the synthesis and purification of crude [Aib⁸, Arg³⁴]-GLP-1 (7–37), laying a foundation for subsequent industrial production.     

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.     

Dieckol,a natural polyphenolic drug,inhibits the proliferation and migration of colon cancer cells by inhibiting PI3K,AKT, and mTOR phosphorylation

This study investigated that dieckol (DKL), a natural drug, inhibits colon cancer cell proliferation and migration by inhibiting phosphoinositide-3-kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) phosphorylation in HCT-116 cells. The cells were treated with DKL in various concentrations (32 and 50 μM) for 24 h and then analyzed for various experiments. MTT (tetrazolium bromide) and crystal violet assay investigated DKL-mediated cytotoxicity. Dichlorodihydrofluorescein diacetate staining was used to assess the reactive oxygen species (ROS) measurement, and apoptotic changes were studied by dual acridine orange and ethidium bromide staining. Protein expression of cell survival, cell cycle, proliferation, and apoptosis protein was evaluated by western blot analysis. Results indicated that DKL produces significant cytotoxicity in HCT-116, and the half-maximal inhibitory concentration was found to be 32 μM for 24-h incubation. Moreover, effective production of ROS and enhanced apoptotic signs were observed upon DKL treatment in HCT-116. DKL induces the expression of phosphorylated PI3K, AKT, and mToR-associated enhanced expression of cyclin-D1, proliferating cell nuclear antigen, cyclin-dependent kinase (CDK)-4, CDK-6, and Bcl-2 in HCT-116. In addition, proapoptotic proteins such as Bax, caspase-9, and caspase-3 were significantly enhanced by DKL treatment in HCT-116. Hence, DKL has been considered a chemotherapeutic drug by impeding the expression of PI3K-, AKT-, and mTOR-mediated inhibition of proliferation and cell cycle-regulating proteins.     

Metabarcoding reveals seasonal and spatial patterns of arthropod community assemblages in two contrasting habitats: Desert and oasis of the Baja California Peninsula,Mexico

Aim

Desert springs or oases are the only permanent mesic environments in highly water-limited arid regions. Oases have immense cultural, evolutionary and ecological importance for people and a high number of endemic and relic species. Nevertheless, they are also highly vulnerable ecosystems, with invasive species, overexploitation and climate change being the primary threats. We used the arthropod communities' spatiotemporal diversity and distribution patterns as a proxy to understand biodiversity dynamics in two geographically close but ecologically contrasting and highly threatened ecosystems: deserts and oases.

Location

Baja California Peninsula, Mexico.

Methods

Arthropod communities at five oases and surrounding desert scrub areas were sampled in two seasons. Using DNA metabarcoding and traditional taxonomic surveys, we tried to identify what biotic and abiotic characteristics of the habitat are important drivers of arthropod diversity and how these characteristics can change across spatial and temporal scales.

Results

Over 6200 individuals representing 23 orders were collected. In oasis samples, the community composition fluctuated more in space (i.e. among sites) than in time (i.e. seasons). Thus, seasonal changes did not affect oasis community diversity and composition, but the dissimilarity among sites increased with geographic distance. Moreover, anthropic activities negatively correlated with arthropod diversity in oases. On the other hand, the season, geography (e.g. latitude) and biotic characteristics of the habitat (e.g. sampled scrub species) significantly affected the diversity and composition of the desert arthropod communities.

Main Conclusions

Neutral dynamics (e.g. historical climatic events, dispersal limitation and spatial component) and human impact significantly influenced the biodiversity patterns of each oasis. In contrast, the habitat's seasonal variation and biotic characteristics were the most important variables influencing the diversity of the desert communities. Baja California oases harbour distinct invertebrate communities; therefore, each oasis should be conserved individually to preserve these unique assemblages.     

Purification and Characterization of a Protein Cryoprotective for Vibrio cholerae Extracted from the Prawn Shell Surface

A substance cryoprotective for Vibrio cholerae on the prawn shell surface was purified by ammonium sulfate precipitation and gel filtration. It was a protein of 81 kDa and called cryoprotective protein (CPP). The cryoprotective activity of this protein for V. cholerae was sensitive to heat at 100 C and trypsin treatment. In the presence of Mg ion the protein can bind to the bacterial cell surface. V. cholerae can adhere to the shell surface of the prawn. The number of adhered bacteria was reduced by treating the shell with anti-CPP serum, heat or by trypsin. The presence of Mg ion promoted the adherence. These results suggest that the CPP could serve as an adherence site for V. cholerae on the shell surface.     

微生物互营产甲烷过程中的种间电子传递

甲烷作为全球第二大温室气体,是典型的可再生清洁能源,也是碳循环中的重要物质组成。大气中约74%的甲烷由产甲烷古菌和其他微生物的互营产生,种间电子传递(interspecies electron transfer, IET)是微生物菌群降低热力学能垒、实现互营产甲烷的核心过程。IET可分为间接种间电子传递(mediated interspecies electron transfer,MIET)和直接种间电子传递(direct interspecies electron transfer, DIET)两种类型,其中MIET依赖氢气、甲酸等载体完成电子的远距离传输,而DIET则依赖导电菌毛、细胞色素c等膜蛋白,通过微生物的直接接触实现电子传递。本文将从IET的研究历程出发,从电子传递机制、微生物种类、生态多样性等方面对微生物互营产甲烷过程中的两种IET类型进行比较,最后对未来待探索的方向进行展望。本综述有助于加深对微生物互营产甲烷过程中IET的理解,为解决由甲烷引发的全球气候变暖等生态问题提供理论支撑。     

一株C3形态多重耐药大肠杆菌噬菌体生物学特性和基因组分析

【目的】多重耐药菌的出现对公共卫生安全构成严重威胁,本研究分离多重耐药大肠杆菌噬菌体,研究其生物学特性和基因组特征,为耐药菌的噬菌体疗法提供理论依据。【方法】使用双层平板法从污水样本中分离纯化大肠杆菌噬菌体;磷钨酸染色后通过透射电镜观察形态;测定其宿主范围,测定温度和pH稳定性、一步生长曲线和体外抑菌效果等生物学特性;体内抑菌试验评估噬菌体对多重耐药大肠杆菌N1203-1Af感染的大蜡螟幼虫的保护作用;基于全基因组测序对其基因组特点进行分析。【结果】本研究分离共得到5株大肠杆菌噬菌体,分别命名为pEC-S163-2.1、pEC-S163-2.2、pEC-M1167-5Ar.1、pEC-m1291-2Dr.1和pEC-N1203-2Af.1;电镜结果显示噬菌体pEC-N1203-2Af.1属于短尾噬菌体中罕见的C3形态型,头部较长,长是宽的2–3倍;pEC-N1203-2Af.1可裂解受试15株大肠杆菌中的3株;感染10 min后进入指数增长期,–20-50℃、pH值为4.0–10.0的环境下均能够保持稳定活性;大蜡螟幼虫感染大肠杆菌N1203-2Af后噬菌体pEC-N1203-2Af....     

Gut microbiome helps honeybee (Apis mellifera) resist the stress of toxic nectar plant (Bidens pilosa) exposure: Evidence for survival and immunity

Honeybee (Apis mellifera) ingestion of toxic nectar plants can threaten their health and survival. However, little is known about how to help honeybees mitigate the effects of toxic nectar plant poisoning. We exposed honeybees to different concentrations of Bidens pilosa flower extracts and found that B. pilosa exposure significantly reduced honeybee survival in a dose-dependent manner. By measuring changes in detoxification and antioxidant enzymes and the gut microbiome, we found that superoxide dismutase, glutathione-S-transferase and carboxylesterase activities were significantly activated with increasing concentrations of B. pilosa and that different concentrations of B. pilosa exposure changed the structure of the honeybee gut microbiome, causing a significant reduction in the abundance of Bartonella (p < 0.001) and an increase in Lactobacillus. Importantly, by using Germ-Free bees, we found that colonization by the gut microbes Bartonella apis and Apilactobacillus kunkeei (original classification as Lactobacillus kunkeei) significantly increased the resistance of honeybees to B. pilosa and significantly upregulated bee-associated immune genes. These results suggest that honeybee detoxification systems possess a level of resistance to the toxic nectar plant B. pilosa and that the gut microbes B. apis and A. kunkeei may augment resistance to B. pilosa stress by improving host immunity.     

Temporal dynamics of soil bacterial network regulate soil resistomes

Soil bacteria are diverse and form complicated ecological networks through various microbial interactions, which play important roles in soil multi-functionality. However, the seasonal effects on the bacterial network, especially the relationship between bacterial network topological features and soil resistomes remains underexplored, which impedes our ability to unveil the mechanisms of the temporal-dynamics of antibiotic resistance genes (ARGs). Here, a field investigation was conducted across four seasons at the watershed scale. We observed significant seasonal variation in bacterial networks, with lower complexity and stability in autumn, and a wider bacterial community niche in summer. Similar to bacterial communities, the co-occurrence networks among ARGs also shift with seasonal change, particularly with respect to the topological features of the node degree, which on average was higher in summer than in the other seasons. Furthermore, the nodes with higher betweenness, stress, degree, and closeness centrality in the bacterial network showed strong relationships with the 10 major classes of ARGs. These findings highlighted the changes in the topological properties of bacterial networks that could further alter antibiotic resistance in soil. Together, our results reveal the temporal dynamics of bacterial ecological networks at the watershed scale, and provide new insights into antibiotic resistance management under environmental changes.