| 1. |
|
|
| 2. |
|
|
| 3. |
- Chen, DS, et al.
(author)
-
Single cell atlas for 11 non-model mammals, reptiles and birds
- 2021
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 7083-
-
Journal article (peer-reviewed)abstract
- The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Zhang, JR, et al.
(author)
-
Systematic bias between blinded independent central review and local assessment: literature review and analyses of 76 phase III randomised controlled trials in 45 688 patients with advanced solid tumour
- 2018
-
In: BMJ open. - : BMJ. - 2044-6055. ; 8:9, s. e017240-
-
Journal article (peer-reviewed)abstract
- Unbiased assessment of tumour response is crucial in randomised controlled trials (RCTs). Blinded independent central review is usually used as a supplemental or monitor to local assessment but is costly. The aim of this study is to investigate whether systematic bias existed in RCTs by comparing the treatment effects of efficacy endpoints between central and local assessments.DesignLiterature review, pooling analysis and correlation analysis.Data sourcesPubMed, from 1 January 2010 to 30 June 2017.Eligibility criteria for selecting studiesEligible articles are phase III RCTs comparing anticancer agents for advanced solid tumours. Additionally, the articles should report objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) or time to progression (TTP); the treatment effect of these endpoints, OR or HR, should be based on central and local assessments.ResultsOf 76 included trials involving 45 688 patients, 17 (22%) trials reported their endpoints with statistically inconsistent inferences (p value lower/higher than the probability of type I error) between central and local assessments; among them, 9 (53%) trials had statistically significant inference based on central assessment. Pooling analysis presented no systematic bias when comparing treatment effects of both assessments (ORR: OR=1.02 (95% CI 0.97 to 1.07), p=0.42, I2=0%; DCR: OR=0.97 (95% CI 0.92 to 1.03), p=0.32, I2=0%); PFS: HR=1.01 (95% CI 0.99 to 1.02), p=0.32, I2=0%; TTP: HR=1.04 (95% CI 0.95 to 1.14), p=0.37, I2=0%), regardless of funding source, mask, region, tumour type, study design, number of enrolled patients, response assessment criteria, primary endpoint and trials with statistically consistent/inconsistent inferences. Correlation analysis also presented no sign of systematic bias between central and local assessments (ORR, DCR, PFS: r>0.90, p<0.01; TTP: r=0.90, p=0.29).ConclusionsNo systematic bias could be found between local and central assessments in phase III RCTs on solid tumours. However, statistically inconsistent inferences could be made in many trials between both assessments.
|
|
| 9. |
- Thomas, HS, et al.
(author)
-
- 2019
-
swepub:Mat__t
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Chen, XD, et al.
(author)
-
Non-invasive early detection of cancer four years before conventional diagnosis using a blood test
- 2020
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 3475-
-
Journal article (peer-reviewed)abstract
- Early detection has the potential to reduce cancer mortality, but an effective screening test must demonstrate asymptomatic cancer detection years before conventional diagnosis in a longitudinal study. In the Taizhou Longitudinal Study (TZL), 123,115 healthy subjects provided plasma samples for long-term storage and were then monitored for cancer occurrence. Here we report the preliminary results of PanSeer, a noninvasive blood test based on circulating tumor DNA methylation, on TZL plasma samples from 605 asymptomatic individuals, 191 of whom were later diagnosed with stomach, esophageal, colorectal, lung or liver cancer within four years of blood draw. We also assay plasma samples from an additional 223 cancer patients, plus 200 primary tumor and normal tissues. We show that PanSeer detects five common types of cancer in 88% (95% CI: 80–93%) of post-diagnosis patients with a specificity of 96% (95% CI: 93–98%), We also demonstrate that PanSeer detects cancer in 95% (95% CI: 89–98%) of asymptomatic individuals who were later diagnosed, though future longitudinal studies are required to confirm this result. These results demonstrate that cancer can be non-invasively detected up to four years before current standard of care.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
- La Manno, G, et al.
(author)
-
RNA velocity of single cells
- 2018
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 560:7719, s. 494-
-
Journal article (peer-reviewed)
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
- Ma, Q, et al.
(author)
-
ZnT8 loss-of-function accelerates functional maturation of hESC-derived β cells and resists metabolic stress in diabetes
- 2022
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4142-
-
Journal article (peer-reviewed)abstract
- Human embryonic stem cell-derived β cells (SC-β cells) hold great promise for treatment of diabetes, yet how to achieve functional maturation and protect them against metabolic stresses such as glucotoxicity and lipotoxicity remains elusive. Our single-cell RNA-seq analysis reveals that ZnT8 loss of function (LOF) accelerates the functional maturation of SC-β cells. As a result, ZnT8 LOF improves glucose-stimulated insulin secretion (GSIS) by releasing the negative feedback of zinc inhibition on insulin secretion. Furthermore, we demonstrate that ZnT8 LOF mutations endow SC-β cells with resistance to lipotoxicity/glucotoxicity-triggered cell death by alleviating endoplasmic reticulum (ER) stress through modulation of zinc levels. Importantly, transplantation of SC-β cells with ZnT8 LOF into mice with preexisting diabetes significantly improves glycemia restoration and glucose tolerance. These findings highlight the beneficial effect of ZnT8 LOF on the functional maturation and survival of SC-β cells that are useful as a potential source for cell replacement therapies.
|
|
| 26. |
- Sarri, Gianluca, et al.
(author)
-
A table-top laser-based source of short, collimated, ultra-relativistic positron beams
- 2013
-
In: Laser Acceleration of Electrons, Protons, and Ions II; and Medical Applications of Laser-Generated Beams of Particles II; and Harnessing Relativistic Plasma Waves III. - : SPIE - International Society for Optical Engineering. - 9780819495815 - 0819495816 ; , s. 87790Z-1-87790Z-7
-
Conference paper (peer-reviewed)abstract
- An ultra-relativistic electron beam passing through a thick, high-Z solid target triggers an electromagnetic cascade, whereby a large number of high energy photons and electron-positron pairs are produced. By exploiting this physical process, we present here the first experimental evidence of the generation of ultra-short, highly collimated and ultra-relativistic positron beams following the interaction of a laser-wakefield accelerated electron beam with high-Z solid targets. Clear evidence has also been obtained of the generation of GeV electron-positron jets with variable composition depending on the solid target material and thickness. The percentage of positrons in the overall leptonic beam has been observed to vary from a few per cent up to almost fifty per cent, implying a quasi-neutral electron-positron beam. We anticipate that these beams will be of direct relevance to the laboratory study of astrophysical leptonic jets and their interaction with the interstellar medium
|
|
| 27. |
- Sarri, Gianluca, et al.
(author)
-
Laser-driven generation of collimated ultra-relativistic positron beams
- 2013
-
In: Plasma Physics and Controlled Fusion. - London : Institute of Physics (IOP). - 0741-3335 .- 1361-6587. ; 55:12
-
Journal article (peer-reviewed)abstract
- We report on recent experimental results concerning the generation of collimated (divergence of the order of a few mrad) ultra-relativistic positron beams using a fully optical system. The positron beams are generated exploiting a quantum-electrodynamic cascade initiated by the propagation of a laser-accelerated, ultra-relativistic electron beam through high-Z solid targets. As long as the target thickness is comparable to or smaller than the radiation length of the material, the divergence of the escaping positron beam is of the order of the inverse of its Lorentz factor. For thicker solid targets the divergence is seen to gradually increase, due to the increased number of fundamental steps in the cascade, but it is still kept of the order of few tens of mrad, depending on the spectral components in the beam. This high degree of collimation will be fundamental for further injection into plasma-wakefield afterburners.
|
|
| 28. |
- Su, GB, et al.
(author)
-
Association of Kidney Function with Infections by Multidrug-Resistant Organisms: An Electronic Medical Record Analysis
- 2018
-
In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 13372-
-
Journal article (peer-reviewed)abstract
- Antibiotic resistance is a major global health threat. High prevalences of colonization and infection with multi-drug resistance organisms (MDROs) have been reported in patients undergoing dialysis. It is unknown if this finding extends to patients with mild and moderate/severe kidney disease. An observational study included all adult incident patients hospitalized with a discharge diagnosis of infection in four hospitals from Guangzhou, China. Inclusion criteria: Serum creatinine measurement at admission together with microbial culture confirmed infections. Exclusion criterion: Undergoing renal replacement therapy. Four categories of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (eGFR) were compared: eGFR ≥ 105, 60–104 (reference), 30–59, and <30 ml/min/1.73 m2. The odds ratio of MDROs, defined as specific pathogens (Staphylococcus aureus, Enterococcus spp., Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp.) resistant to three or more antibiotic classes, were calculated using a multivariable logistic regression model across eGFR strata. Of 94,445 total microbial culture records, 7,288 first positive cultures matched to infection diagnosis were selected. Among them, 5,028 (68.9%) were potential MDROs. The odds of infections by MDROs was 19% and 41% higher in those with eGFR between 30–59 ml/min/1.73 m2 (Adjusted odds ratio, AOR): 1.19, 95% CI:1.02–1.38, P = 0.022) and eGFR < 30 ml/min/1.73 m2 (AOR: 1.41, 95% CI:1.12–1.78, P = 0.004), respectively. Patients with impaired renal function have a higher risk of infections by MDROs. Kidney dysfunction at admission may be an indicator for need of closer attention to microbial culture results requiring subsequent change of antibiotics.
|
|
| 29. |
- Sun, XT, et al.
(author)
-
Inflammatory cell-derived CXCL3 promotes pancreatic cancer metastasis through a novel myofibroblast-hijacked cancer escape mechanism
- 2022
-
In: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 71:1, s. 129-147
-
Journal article (peer-reviewed)abstract
- Pancreatic ductal adenocarcinoma (PDAC) is the most lethal malignancy and lacks effective treatment. We aimed to understand molecular mechanisms of the intertwined interactions between tumour stromal components in metastasis and to provide a new paradigm for PDAC therapy.DesignTwo unselected cohorts of 154 and 20 patients with PDAC were subjected to correlation between interleukin (IL)-33 and CXCL3 levels and survivals. Unbiased expression profiling, and genetic and pharmacological gain-of-function and loss-of-function approaches were employed to identify molecular signalling in tumour-associated macrophages (TAMs) and myofibroblastic cancer-associated fibroblasts (myoCAFs). The role of the IL-33–ST2–CXCL3–CXCR2 axis in PDAC metastasis was evaluated in three clinically relevant mouse PDAC models.ResultsIL-33 was specifically elevated in human PDACs and positively correlated with tumour inflammation in human patients with PDAC. CXCL3 was highly upregulated in IL-33-stimulated macrophages that were the primary source of CXCL3. CXCL3 was correlated with poor survival in human patients with PDAC. Mechanistically, activation of the IL-33–ST2–MYC pathway attributed to high CXCL3 production. The highest level of CXCL3 was found in PDAC relative to other cancer types and its receptor CXCR2 was almost exclusively expressed in CAFs. Activation of CXCR2 by CXCL3 induced a CAF-to-myoCAF transition and α-smooth muscle actin (α-SMA) was uniquely upregulated by the CXCL3–CXCR2 signalling. Type III collagen was identified as the CXCL3–CXCR2-targeted adhesive molecule responsible for myoCAF-driven PDAC metastasis.ConclusionsOur work provides novel mechanistic insights into understanding PDAC metastasis by the TAM-CAF interaction and targeting each of these signalling components would provide an attractive and new paradigm for treating pancreatic cancer.
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
- Xiong, Y, et al.
(author)
-
Removal of formic acid from wastewater using three-phase three-dimensional electrode reactor
- 2003
-
In: Water, Air and Soil Pollution. - 1573-2932. ; 144:1, s. 67-79
-
Journal article (peer-reviewed)abstract
- A new electrochemical reactor, three-phase three-dimensional electrode reactor, was designed and used to investigate the removal of formic acid from simulated wastewater. The experimental results were assessed in term of Chemical Oxygen Demand (COD) removal efficiency. The results showed that the three-phase three-dimensional electrodes could effectively remove formic acid. Its COD removal efficiency was much higher than those of two-dimensional electrodes and common three-dimensional electrodes, respectively. The COD removal efficiency of the three-phase three-dimensional electrodes using air as a sparge gas increased 13.5% relative to that using nitrogen as a sparge gas. The observation indicated that the sparged air in the three-phase three-dimensional electrodes not only participated in some physical processes but also played an important role in electrochemical reactions to assist COD removal.
|
|
| 34. |
|
|
| 35. |
|
|
| 36. |
- Yang, YY, et al.
(author)
-
Prenatal exposure to concentrated ambient PM2.5 results in spatial memory defects regulated by DNA methylation in male mice offspring
- 2023
-
In: Environmental science and pollution research international. - : Springer Science and Business Media LLC. - 1614-7499. ; 30:4912, s. 35142-35152
-
Journal article (peer-reviewed)abstract
- Ambient fine particulate matter (PM2.5) exposures during pregnancy could lead to adverse birth outcomes, including neurobehavioral development defects. However, limited studies explored the effects and potential epigenetic mechanisms of maternal PM2.5 exposure on offspring spatial memory defects. This study aims to explore the effects and underlying epigenetic mechanisms of maternal concentrated ambient PM2.5 exposure in male mice offspring with spatial memory defects. Pregnant female C57BL/6 mice were exposed daily to concentrated ambient PM2.5 (CAP) or filtered air (FA) throughout gestation, with the concentration of particulates (102.99 ± 78.74 μg/m3) and (2.78 ± 1.19 μg/m3), respectively. Adult male mice offspring were subsequently assessed for spatial learning and memory ability using Morris Water Maze tests and locomotor activities in open field tests. The hippocampus of the male mice offspring was harvested to test mRNA expression and DNA methylation. Results from the probe test of Morris Water Maze showed that the mice offspring in the CAP group had shorter swimming distance travelled in the target quadrant, shorter duration in the target quadrant, and less number of entries into the target quadrant (p < 0.05), suggesting spatial memory impairments. The acquisition trials of Morris Water Maze did not show a significant difference in learning ability between the groups. The mRNA level of interleukin 6 (IL-6) in the CAP group hippocampus (10.80 ± 7.03) increased significantly compared to the FA group (1.08 ± 0.43). Interestingly, the methylation levels of the CpG sites in the IL-6 promoter region declined significantly in the CAP group, (5.66 ± 0.83)% vs. (4.79 ± 0.48)%. Prenatal exposure to concentrated ambient PM2.5 induced long-lasting spatial memory defects in male mice offspring. The underlying biological mechanism might be mediated by an inflammatory reaction which is regulated by DNA methylation.
|
|
| 37. |
|
|
| 38. |
|
|
