Around 4000 cal yr BP, Scots pine (Pinus sylvestris) suffered a widespread demise across the British Isles. This paper presents new information about P. sylvestris populations found in the Welsh ...Marches (western central Britain), for which the long-term history and origins are poorly known. Two new pollen records were produced from the Lin Can Moss ombrotrophic bog (LM18) and the Breidden Hill pond (BH18). The LM18 peat core is supported by loss-on-ignition, humification analysis and radiocarbon dating. Lead concentrations were used to provide an estimated timeframe for the recent BH18 record. In contrast to many other Holocene pollen records from the British Isles, analysis of LM18 reveals that Scots pine grains were deposited continuously between c. 6900–300 cal yr BP, at frequencies of 0.3–5.4%. It is possible that individual Scots pine trees persisted through the wider demise on thin soils of steep drought-prone crags of hills or the fringes of lowland bogs in the Welsh Marches. At BH18, the record indicates a transition from broadleaved to mixed woodland, including conifer species introduced around AD 1850 including Picea and Pinus. The insights from BH18 suggest that the current populations may largely be the result of planting. Comparison of the LM18 findings with other regional pollen records highlights consistent patterns, including a Mid-Holocene maximum (ca. 7000 cal yr BP), long-term persistence at low pollen percentages and a Late-Holocene minimum (ca. 3000 cal yr BP). These distinctive trends encourage further studies on refugial areas for Scots pine in this region and elsewhere.
•Thrombin inhibitory peptides from casein were screened by bioinformatics analysis.•Thirty-five peptides from casein digestion by trypsin were identified by UPLC-Q-TOF.•One novel peptide with strong ...thrombin inhibitory activity was identified.•The antithrombotic mechanism underlying the peptides by molecular docking was explored.
Casein has been recognized as a good source of bioactive peptides that can be used for the production of functional food. In this study, thrombin inhibitory peptides from casein were screened by bioinformatics based on sequences predicted from in silico enzymatic digestion with trypsin, and identified by UPLC-Q-TOF-MS/MS with Mascot analysis. Molecular docking was conducted using the software of Discovery Studio 2017 to provide the potential mechanism underlying the thrombin inhibitory activity of the peptides. A total of 35 novel peptides with thrombin inhibitory activity were identified. Moreover, FQSEEQQQTEDELQDK, derived from beta-casein (fragment 33–48), showed a remarkable sequence similarity with fragment 54–65 of hirudin, and exhibited strong inhibitory activity against thrombin. FQSEEQQQTEDELQDK had similar target domain (Lys36-Gln38-Arg73-Thr74-Lys81-Ile82-Lys110) on the stereo structure of thrombin compared with hirudin. This domain belongs to the partial structure of the active site 2 of thrombin (PDB: 2BVR), and it also located at the exosite I motif buried in the external surface of thrombin molecule, with potential inhibitory activity of the peptide.
Potato (
Solanum tuberosum
L.) is an important food crop but its production is affected by potato spindle tuber viroid (PSTVd). In this study, five potato cultivars, including Jizhangshu 12, Kexin 1, ...Jizhangshu 8, Shepody, and Minfenghong, were inoculated with PSTVd, and RNA-seq was carried out to analyse gene expression profiles during PSTVd infection. We also conducted a time-course investigation of three different stages of Jizhangshu 8 infected with PSTVd and control individuals. The results showed that the different cultivars have different genes and pathways to response against PSTVd infection, and most of the upregulated genes were related to biosynthesis and developmental processes, including the development of the stomatal complex, tissues, and the epidermis. The
RPP13
gene was upregulated during PSTVd infection in all five cultivars and may play important roles in the PSTVd response process. This study provides insight into the tolerant mechanism against PSTVd and facilitates the mining of PSTVd-tolerant genes in potatoes for innovating germplasm resources. In addition, this study presents valuable genomic data from different potato cultivars and development stages for further studies.
Pulmonary nodules are usually considered to be associated with malignant tumors and benign lesions, such as granuloma, pulmonary lymph nodes, fibrosis, and inflammatory lesions. Clinical cases of ...pulmonary nodules associated with hemophagocytic lymphohistiocytosis have rarely been reported. Therefore, when patients develop pulmonary nodules, the possibility of developing hemophagocytic lymphohistiocytosis is often not considered. We report the first case of familial hemophagocytic lymphohistiocytosis with recurrent pulmonary nodules as the first symptom. Our findings will hopefully provide new ideas for the diagnosis and treatment of pulmonary nodules in the future.
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•BFO can protect the liver to maintain mice cholesterol homeostasis.•BFO can balance inflammatory response to protect the blood vessels.•Treatment with BFO inhibited the proliferation ...of foam cells induced by ox-LDL.•BFO can reduce the risk of the occurrence and development of hypercholesterolemia.
Burdock fructooligosaccharide (BFO) is a type of linear inulin extracted from burdock root. In this study, we studied the effect of BFO in hypercholesterolemic mice model and found that BFO could decrease the total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and oxidized LDL (ox-LDL). BFO also reduce the hepatocyte damage, improve the antioxidant enzymes activity and regulate genes related to the cholesterol homeostasis in liver. Besides, we found that BFO protected the blood vessels by significantly balancing inflammatory cytokines and alleviating the up-regulation of TLR4/MyD88/NF-κB pathway in aorta. Furthermore, we established a foam cells model induced by ox-LDL in vitro and found that 500 and 1000 μg/mL BFO could effectively inhibit cell proliferation and reduce the production of intracellular lipids and inflammatory cytokines. Therefore, BFO can reduce the risk of hypercholesterolemia by maintaining cholesterol homeostasis, reducing vascular inflammation and alleviating macrophage foaming to prevent its further development into cardiovascular diseases.
Sonodynamic therapy (SDT) induces immunogenic cell death (ICD) in tumors and promises to play an assistive role in immunotherapy in pancreatic cancer. However, the short half-life and limited ...diffusion distance of reactive oxygen species (ROS) impair ICD induction, especially in tumors with relatively poor blood perfusion and dense stroma.
To address this problem, we fabricated cavitation-assisted endoplasmic reticulum (ER) targeted sonodynamic nanodroplets (PMPS NDs, 329 nm). The good sonodynamic effect and precise endoplasmic reticulum target effect was verified. After intravenous injection, the cRGD peptide modified nanodroplets initially aggregated around the tumor vascular endothelial cells. Stimulated by ultrasound, the liquid-to-gas bubbles began to oscillate and cavitate. This acoustic droplet evaporation strategy facilitated transport of the nanoparticle across the vessel, with deep penetration. This loosened the tumor stroma and facilitated accumulation and penetration of loaded sonosensitizer after 6 h. The modified sonosensitizer can selectively accumulate in the ER to generate a large amount of ROS in situ, inducing potent ER stress, amplified ICD and dendritic cell maturation in vitro and in vivo. Furthermore, the elevated antitumor effect of SDT plus anti-PD-L1 immunotherapy was verified using an orthotopic tumor model.
This study reports a cavitation assisted ER targeted sonodynamic therapy that can enhance the effect of anti-PD-L1 immunotherapy effectively in orthotopic and distant pancreatic cancer.
This study aimed to explore the sentinel lymph node (SLN) identification rate in breast cancer by subcutaneous and intradermal injection of ultrasound contrast agent in the mammary areola region, ...compared to the results achieved with methylene blue (MB).
A total of 390 breast cancer patients with planned sentinel lymph node biopsy from our breast surgery department from July 2017 to February 2019 were enrolled. All patients were subjected to preoperative contrast-enhanced ultrasound (CEUS), that involved an intracutaneous injection of 1 mL ultrasonic contrast agent (UCA) at 3 and 6 o 'clock, as well as a subcutaneous injection of 1 mL UCA at 9 and 12 o'clock. The enhanced lymph nodes along the enhanced lymphatic vessels from the mammary areola were traced. The number of enhanced lymph nodes were recorded, and an ultrasound-guided injection of 1:10 diluted carbon nanoparticles were used to mark all first site enhanced lymph nodes (i.e., SLNs). An intraoperative dye method (MB) was used to track the SLNs and the results were compared with the CEUS findings.
Among the 390 cases of breast cancer, enhanced SLNs were observed in 373 patients after an injection of UCA with an identification rate of 95.64 % (373/390), compared to the identification rate of 92.05 % (359/390) using the intraoperative MB. The difference between the two methods was statistically significant (P = 0.016). And among the 390 patients, a total of 808 enhanced lymph nodes were traced by preoperative CEUS, with a median of 2 (1,3). A total of 971 blue-stained lymph nodes were traced using the intraoperative MB, with a median of 2 (2,3), indicating a statistically significant difference (p < 0.001).
Intradermal and subcutaneous injections of UCA in the mammary areola region may have clinical application value for the identification and localization of SLNs in breast cancer patients. The identification rate is higher than that of blue dye method, which can be used as a new tracer of sentinel lymph node biopsy and complement other staining methods to improve the success rate.
Background
An increasing proportion of patients with diabetic kidney disease (DKD) has been observed among incident hemodialysis patients in large cities, which is consistent with the continuous ...growth of diabetes in the past 20 years.
Purpose
In this multicenter retrospective study, we developed a deep learning (DL)-based automatic segmentation and radiomics technology to stratify patients with DKD and evaluate the possibility of clinical application across centers.
Materials and Methods
The research participants were enrolled retrospectively and separated into three parts: training, validation, and independent test datasets for further analysis. DeepLabV3+ network, PyRadiomics package, and least absolute shrinkage and selection operator were used for segmentation, extraction of radiomics variables, and regression, respectively.
Results
A total of 499 patients from three centers were enrolled in this study including 246 patients with type II diabetes mellitus (T2DM) and 253 patients with DKD. The mean intersection-over-union (Miou) and mean pixel accuracy (mPA) of automatic segmentation of the data from the three medical centers were 0.812 ± 0.003, 0.781 ± 0.009, 0.805 ± 0.020 and 0.890 ± 0.004, 0.870 ± 0.002, 0.893 ± 0.007, respectively. The variables from the renal parenchyma and sinus provided different information for the diagnosis and follow-up of DKD. The area under the curve (AUC) of the radiomics model for differentiating between DKD and T2DM patients was 0.674 ± 0.074 and for differentiating between the high and low stages of DKD was 0.803 ± 0.037.
Conclusion
In this study, we developed a DL-based automatic segmentation, radiomics technology to stratify patients with DKD. The DL technology was proposed to achieve fast and accurate anatomical-level segmentation in the kidney, and an ultrasound-based radiomics model can achieve high diagnostic performance in the diagnosis and follow-up of patients with DKD.
Objective
To investigate the prevalence of hypertension and circadian blood pressure (BP) variations in patients with obstructive sleep apnoea–hypopnoea syndrome (OSAHS).
Methods
Patients referred to ...a sleep clinic underwent polysomnography with measurement of BP at four time points. They were classified into four groups (control, and mild, moderate or severe sleep apnoea) using the apnoea–hypopnoea index (AHI). Circadian variation was assessed using night-time to daytime mean BP (RN/D) and morning to evening mean BP (RM/E) ratios.
Results
Hypertension was significantly more common in patients with OSAHS (50.5%) than in controls (30.4%). AHI was positively correlated with hypertension after controlling for related confounders. Mean BP values at all four time points rose with increasing AHI. The increase in night-time and morning values was more pronounced than the increase in daytime and evening values in patients with OSAHS, resulting in loss of the normal BP diurnal rhythm. The RN/D and RM/E ratios increased with increasing AHI. Daytime BP was significantly correlated with AHI and the lowest oxygen saturation value.
Conclusion
OSAHS was shown to be an independent risk factor for hypertension. It was also associated with loss of the normal BP diurnal rhythm.
Aims
To study the effects of mixed culture fermentation (MCF) of Bacillus amyloliquefaciens and Trichoderma longibrachiatum on its constituent strains and the application values for agricultural ...production, with the intention of developing efficient and environmentally friendly biocontrol agents.
Methods and results
In this study, an in vitro antifungal growth experiment showed that the inhibitory rate of the MCF broth on pathogenic fungi (Fusarium oxysporum f. sp. lycopersici, Botrytis cinerea, Trichothecium roseum and Colletotrichum gloeosporioides) was less than that of B. amyloliquefaciens culture fermentation (BCF). Moreover, the content and gene expression of lipopeptide antibiotics were also lower than that in the BCF group. However, the pot experiments based on irrigation with appropriately diluted fermentation broth showed that the biocontrol effect of MCF on tomato Fusarium wilt was significantly higher than that of TCF (T. longibrachiatum culture fermentation) and BCF, and was approximately 15.79% higher than that of the BTF group which made by mixing equivalent amounts of BCF and TCF. In MCF broth, two micro‐organisms antagonized and coexisted, and the growth of T. longibrachiatum was inhibited. Using transcriptomic analysis, we speculated that MCF can upregulate the expression of genes related to carbon and nitrogen metabolism, oxidation–reduction activity, sporulation, environmental information response and chemotaxis, and biosynthesis of secondary metabolites of B. amyloliquefaciens, which might enhance the nutrient substances metabolism and competitiveness, survival ability, colonization and adaptability to the environment to increase its biocontrol potential.
Conclusions
Mixed culture fermentation could promote the more reasonable and effective utilization of biocontrol micro‐organisms though improving biocontrol effect, enhancing strains survival and competitiveness, increasing beneficial metabolites, combined with resistance induction or synergistic control.
Significance and Impact of the Study
Using MCF agronomically utilizes biocontrol agents in an efficient way, which has a good potential for commercial implementation and could reduce production costs.
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