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1.
Bioact Mater ; 21: 1-19, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36017071

RESUMO

Although nano-immunotherapy has advanced dramatically in recent times, there remain two significant hurdles related to immune systems in cancer treatment, such as (namely) inevitable immune elimination of nanoplatforms and severely immunosuppressive microenvironment with low immunogenicity, hampering the performance of nanomedicines. To address these issues, several immune-regulating camouflaged nanocomposites have emerged as prevailing strategies due to their unique characteristics and specific functionalities. In this review, we emphasize the composition, performances, and mechanisms of various immune-regulating camouflaged nanoplatforms, including polymer-coated, cell membrane-camouflaged, and exosome-based nanoplatforms to evade the immune clearance of nanoplatforms or upregulate the immune function against the tumor. Further, we discuss the applications of these immune-regulating camouflaged nanoplatforms in directly boosting cancer immunotherapy and some immunogenic cell death-inducing immunotherapeutic modalities, such as chemotherapy, photothermal therapy, and reactive oxygen species-mediated immunotherapies, highlighting the current progress and recent advancements. Finally, we conclude the article with interesting perspectives, suggesting future tendencies of these innovative camouflaged constructs towards their translation pipeline.

2.
Chem Eng J ; 451: 138822, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36060034

RESUMO

The novel mutations attributed by the high mutagenicity of the SARS-CoV-2 makes its prevention and treatment challenging. Developing an ultra-fast, point-of-care-test (POCT) protocol is critical for responding to large-scale spread of SARS-CoV-2 in public places and in resource-poor remote areas. Here, we developed a nanoplasmonic enhanced isothermal amplification (NanoPEIA) strategy that combines a nanoplasmonic sensor with isothermal amplification. The novel strategy provides an ideal easy-to operate detection platform for obtaining accurate, ultra-fast and high-throughput (96 samples can be tested together) data. For clinical samples with viral detection at Ct value <25, the entire process (including sample preparation, virus lysis, detection, and data analysis) can be completed within six minutes. The method is also appropriate for detection of SARS-CoV-2 γ-coronavirus mutants. The NanoPEIA method was validated using clinical samples from 21 patients with SARS-CoV-2 infection and 31 healthy individuals. The detection result on the 52 clinical samples for SARS-CoV-2 showed that the NanoPEIA platform had a 100% sensitivity for N and orf1ab genes, which was higher than those obtained using RT-qPCR (88.9% and 90.0%, respectively). The specificities of 31 clinical negative samples were 92.3% and 91.7% for the N gene and the orf1ab gene, respectively. The limits of detection (LoD) of the clinical samples were 28.3 copies/mL and 23.3 copies/mL for the N gene and the orf1ab gene, respectively. The efficient NanoPEIA detection strategy facilitates real-time detection and visualization within ultrashort durations and can be applied for POCT diagnosis in resource-poor and highly populated areas.

3.
J Extracell Vesicles ; 11(9): e12264, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36068649

RESUMO

Pattern-recognition receptors (PRRs) have been shown to promote tumour metastasis via sensing tumour cell-derived small extracellular vesicles (EVs). Nucleotide-binding oligomerisation domain 1 (NOD1), a cytoplasmic PRR, plays a role in colorectal cancer (CRC) by detecting bacterial products. However, the precise mechanisms underlying the effects of NOD1, following identification of CRC cell-derived EVs (CRC-EVs), to potentiate CRC liver metastasis (CRC-LM), remain poorly understood. Here, we demonstrate that CRC-EVs activate NOD1 in macrophages to initiate secretion of inflammatory cytokines and chemokines. NOD1-activated macrophages also promote CRC cell migration, while in a murine model of liver metastasis (LM), NOD1-deficient mice exhibit reduced metastasis following CRC-EV treatment. Furthermore, cell division cycle 42 (CDC42), a small Rho guanosine-5'-triphosphate (GTP)ase, is delivered by CRC-EVs into macrophages where it activates NOD1. In addition, EVs from the plasma of patients with CRC-LM mediate NOD1 activation in human peripheral blood mononuclear cells. Moreover, high NOD1 expression in tumour tissues is associated with poor prognosis of CRC-LM. Our findings suggest that CRC-EVs activate NOD1 to promote tumour metastasis, thus, NOD1 may serve as a potential target in the diagnosis and treatment of CRC-LM.


Assuntos
Neoplasias Colorretais , Vesículas Extracelulares , Neoplasias Hepáticas , Animais , Vesículas Extracelulares/metabolismo , Humanos , Leucócitos Mononucleares/metabolismo , Neoplasias Hepáticas/metabolismo , Camundongos , Proteína Adaptadora de Sinalização NOD1/metabolismo , Transdução de Sinais
4.
Nat Commun ; 13(1): 5156, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36056046

RESUMO

How lake temperatures across large geographic regions are responding to widespread alterations in ice phenology (i.e., the timing of seasonal ice formation and loss) remains unclear. Here, we analyse satellite data and global-scale simulations to investigate the contribution of long-term variations in the seasonality of lake ice to surface water temperature trends across the Northern Hemisphere. Our analysis suggests a widespread excess lake surface warming during the months of ice-off which is, on average, 1.4 times that calculated during the open-water season. This excess warming is influenced predominantly by an 8-day advancement in the average timing of ice break-up from 1979 to 2020. Until the permanent loss of lake ice in the future, excess lake warming may be further amplified due to projected future alterations in lake ice phenology. Excess lake warming will likely alter within-lake physical and biogeochemical processes with numerous implications for lake ecosystems.


Assuntos
Gelo , Lagos , Ecossistema , Estações do Ano , Temperatura , Água
5.
Front Aging Neurosci ; 14: 940166, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36051307

RESUMO

Backgroud: Vascular dementia is the second most common cause of dementia after Alzheimer's disease, accounting for an estimated 15% of cases. Recently, Epimedium has attracted great attention for its potential neuroprotective benefit. However, the direct role and mechanism of Epimedium on vascular dementia still lack systematic research. To systematically explore the possible pharmacological mechanism of Epimedium for the treatment of vascular dementia, network pharmacology, molecular docking, combined with experiment validation were conducted. Methods: The bioactive compounds and targets of Epimedium were obtained from the TCMSP database. The potential targets of vascular dementia were identified from the DrugBank, OMIM, Genecards, Therapeutic Target Database, and DisGeNET databases. GO and KEGG pathway analyses were performed. Molecular docking was applied to validate the interaction between active components and hub targets. The bilateral common carotid artery occlusion (BCCAO) method was used for construction of a vascular dementia model in mice. The effects of Epimedium on learning and memory ability were examined by behavioral tests. The mechanisms of the cerebral protective effects of Epimedium were evaluated by WB, RT-PCR, and immunofluorescence. Results: A total of 23 Epimedium active ingredients, and 71 intersecting targets of Epimedium against vascular dementia were obtained. The top five hub targets AKT1, TNF, IL1ß, IL6, and MMP9 were identified, and molecular docking showed good binding. GO enrichment showed a total of 602 enrichment results, with 458 (80.56%) key targets mainly focused on biological processes (BP). The response to hypoxia, positive regulation of nitric oxide biosynthetic process, aging, inflammatory response, cellular response to lipopolysaccharide, negative regulation of apoptotic process were well ranked. KEGG pathway enrichment analysis identified the TNF signaling pathway as an important pathway, with the MAPK/extracellular signal-regulated kinase (ERK) and NF-κB signaling pathways as the key pathways involved. Consistently, in vivo experiments showed that Epimedium treatment improved learning and memory functions in mice with vascular dementia. In addition, Epimedium attenuated the activation of microglia and astrocytes in the hippocampal region after BCCAO. RT-qPCR and Western blot analysis showed that Epimedium not only affected the expression of AKT, TNF, IL1ß, IL6, and MMP9, but also suppressed the TNF signaling pathway. Conclusion: Epimedium may exert a protective effect against vascular dementia through the alleviation of oxidative stress, neuroinflammation, BBB dysfunction, apoptosis through TNF signaling pathway. This study explored the mechanism of Epimedium on vascular dementia systematically through network pharmacological and in vivo experiment approach, which provides insight into the treatment of vascular dementia.

6.
Perfusion ; : 2676591221122349, 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36059244

RESUMO

BACKGROUND: To explore impact of various periods of ischemia and reperfusion on the severity of myocardial injury. METHODS: Langendorff model of isolated cardiac perfusion system was established in 56 rat hearts. They were randomly assigned into four groups with four different ischemia (perfusion-pause) time and reperfusion time. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and creatine kinase-MB (CK-MB) were measured and the size of myocardial infarction was assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining. RESULTS: The levels of AST, ALT, LDH, and CK-MB in the heart tissues and perfusate were lowest in the group I (shortest time of perfusion-pause and reperfusion) followed by the groups II, III, and IV (longest time of perfusion-pause and reperfusion) (p < 0.05). The myocardial infarction size was smallest in the group I (6.63 ± 0.47) followed by group II (15.12 ± 1.03), group III (20.32 ± 2.18), and group IV (32.29 ± 5.42) (p < 0.05). Two-way ANOVA analysis revealed that period of perfusion-pause and reperfusion independently and significantly affected the levels of AST and ALT in both heart tissues and perfusate (p < 0.001). The interaction of pausing period and reperfusion significantly affected the level of AST (p = 0.046) and CK-MB (p = 0.001) in the perfusate. In addition, perfusion-pause period significantly affected levels of LDH and CK-MB only in the perfusate (p < 0.001). Neither perfusate nor heart tissue LDH level was significantly affected by the interaction of perfusion-pause and reperfusion period (p > 0.05). CONCLUSION: The severity of myocardial injury in the Langendorff model was affected by the period of perfusion-pause and reperfusion. The longer period of perfusion-pause followed by the longer the period of reperfusion, the severe myocardial injury was found.

7.
Nucleic Acids Res ; 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36062570

RESUMO

Recent advances in epitranscriptomics have unveiled functional associations between RNA modifications (RMs) and multiple human diseases, but distinguishing the functional or disease-related single nucleotide variants (SNVs) from the majority of 'silent' variants remains a major challenge. We previously developed the RMDisease database for unveiling the association between genetic variants and RMs concerning human disease pathogenesis. In this work, we present RMDisease v2.0, an updated database with expanded coverage. Using deep learning models and from 873 819 experimentally validated RM sites, we identified a total of 1 366 252 RM-associated variants that may affect (add or remove an RM site) 16 different types of RNA modifications (m6A, m5C, m1A, m5U, Ψ, m6Am, m7G, A-to-I, ac4C, Am, Cm, Um, Gm, hm5C, D and f5C) in 20 organisms (human, mouse, rat, zebrafish, maize, fruit fly, yeast, fission yeast, Arabidopsis, rice, chicken, goat, sheep, pig, cow, rhesus monkey, tomato, chimpanzee, green monkey and SARS-CoV-2). Among them, 14 749 disease- and 2441 trait-associated genetic variants may function via the perturbation of epitranscriptomic markers. RMDisease v2.0 should serve as a useful resource for studying the genetic drivers of phenotypes that lie within the epitranscriptome layer circuitry, and is freely accessible at: www.rnamd.org/rmdisease2.

8.
Artigo em Inglês | MEDLINE | ID: mdl-36046944

RESUMO

OBJECTIVE: The study aimed to identify BMI-related lipids and to explore the role of lipids linking BMI and gestational diabetes mellitus (GDM). METHODS: Plasma lipidome, height, and weight were measured in early pregnancy among 1008 women. Pearson correlation analyses and least absolute shrinkage and selection operator regression (LASSO) were performed to identify BMI-associated lipids. Based on these lipids, a lipid score was created using LASSO, and its association with GDM risk was evaluated by conditional logistic regression. The causal relationships between BMI and lipids were tested by Mendelian randomization analysis with genotyping data. Mediation analysis was conducted to evaluate the mediating effect of lipids on the association of BMI with GDM. RESULTS: Of 366 measured lipids, BMI was correlated with 28 lipids, which mainly belong to glycerophospholipids and glycerolipids. A total of 10 lipid species were associated with BMI, and a lipid score was established. A causal relationship between BMI and lysophosphatidylcholine 14:0 was observed. The lipid score was associated with a 1.69-fold increased risk of GDM per 1-point increment (95% CI: 1.33-2.15). Furthermore, BMI-associated lipids might explain 66.4% of the relationship between BMI and GDM. CONCLUSIONS: Higher BMI in early pregnancy was associated with altered lipid metabolism that may contribute to the increased risk of GDM.

9.
J Environ Manage ; 322: 116128, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36067668

RESUMO

Livestock production is greenhouse gas (GHG) emission intensive, and thus the increasing international trade of livestock products in recent decades has resulted in increased embodied emissions. Considering the varying emission intensity in production in different countries and the expected further increase in livestock product trade in the future, it becomes crucial to understand the spatial and temporal dynamics of such embodied GHG emissions for climate change mitigation in the livestock sector. In this study, we aimed to address such gaps and analyzed the spatiotemporal patterns and network characteristics of GHG emissions embodied in the international trade of seven major categories of livestock products among 228 world economies during 1986-2017. The results showed that the total volume of GHG emissions embodied in livestock product trade reached 92.0 MT in 2017, accounting for 2.6% of the total emissions from livestock production. Sheep meat has replaced cattle meat as the major contributor to embodied emissions. In 2017, the largest flows of embodied emissions were within Europe, followed by the flows from Oceania to Asia. The fluxes in intra-upper middle and intra-high-income economies accounted for most of the total embodied emissions. Although the global average emission intensity of livestock production declined in these four decades, the trade flows from high to low emission intensity economies increased, especially for cattle and sheep meat. This resulted in an overall increase of contribution from the global livestock trade in GHG emissions from the global livestock sector. Therefore, effective measures and policies must be designed from both consumption and production perspectives to ensure proper accounting of these embodied emissions and maximize the reduction potential for a sustainable food system transition.

11.
Am J Cancer Res ; 12(8): 3512-3531, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119847

RESUMO

The advancement in systemic neoadjuvant therapy has significantly increased the pathological complete response (pCR) rate in breast cancer. As surgeries inevitably affect patients physically and psychologically and the accuracy of pCR prediction and diagnosis by minimal invasive biopsy is improving, the necessity of surgery in neoadjuvant chemotherapy (NAC) patients who achieve pCR is under debate. Thus, we conducted a literature review of studies on the selective omission of breast surgery after NAC for breast cancer patients. We summarized the existing predictive models and technologies to predict and diagnose pCR after NAC. Our research indicates that, for nearly half a century, the extent of surgery on both breast and axillary lymph nodes is decreasing, while more precise systematic treatments are increasing. NAC has advanced significantly and its pCR rates have improved, so surgery may be omitted in certain patients. However, accurately predicting pCR after NAC is still a challenge. We also described the design for a randomized clinical trial and the potential problems of omitting surgical treatment after NAC. In summary, the decrease in breast cancer surgery is an unavoidable trend, and more high-quality clinical trials need to be conducted.

12.
Neural Plast ; 2022: 1500710, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36124291

RESUMO

Neuronal apoptosis is an important factor in the etiology of Alzheimer's disease (AD). Aerobic exercise (AE) enhances learning and memory, improves cognitive impairment, increases telomere binding protein expression, and decreases apoptosis regulators, but it remains unclear whether it can improve cognitive impairment caused by neuronal apoptosis in AD. Therefore, this study investigated whether an 8-week running table exercise intervention could reduce apoptosis and improve cognitive function in the hippocampal neurons of AD model mice. After the exercise intervention, we evaluated the learning memory ability (positioning, navigation, and spatial search) of mice using a Morris water labyrinth, Nissl staining, immunohistochemistry, and protein application to detect hippocampal PI3K/Akt/GSK-3ß signaling pathway protein and hippocampal neuronal cell apoptosis protein B cell lymphoma 2 (Bcl-2) and apoptosis-promoting protein bcl-2-related X (Bax) protein expression. The results showed that aerobic exercise improved the location and spatial exploration ability of mice, increased the number of PI3K- and p-Akt-positive cells, increased the expression of PI3K, p-Akt, and bcl-2 proteins, decreased the expression of GSK-3ß and Bax proteins, and increased the bcl-2/Bax ratio of mice. The results suggest that aerobic exercise can reduce apoptosis and improve cognitive function in AD mice. The molecular mechanism may involve activation of the PI3K/Akt/GSK-3ß signaling pathway.

13.
Chem Commun (Camb) ; 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36069518

RESUMO

By quenching the electronic excited state, self-aggregation of photosensitizers deteriorates the photodynamic therapy (PDT) outcome. Previously reported strategies to mitigate aggregation-caused-quenching (ACQ) involve harsh conditions and tedious synthesis processes. Moreover, failure to tune the extent of photosensitizer aggregation on-demand usually leads to a sub-optimal PDT effect. Herein, a new insight into ACQ alleviation by precisely tailoring the aggregation extent of photosensitizers via the confinement effect is unraveled by concise and facile coordination co-assembly fabrication of Pt/TCPP NCPs. Optimized meso-tetra(4-carboxyphenyl)porphine (TCPP) aggregation extent was achieved by precisely regulating the PES/TCPP feeding ratio to 12, unleashing outstanding PDT efficacy for robustly synergistic cancer PDT/chemotherapy.

14.
Ying Yong Sheng Tai Xue Bao ; 33(7): 1853-1860, 2022 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-36052788

RESUMO

Biocrusts and herbs coexist in arid and semi-arid areas, playing an important role in soil and water conservation. However, the combined effects of biocrusts and herbs on process and mechanism of runoff and infiltration on slope are still unclear. In this study, simulated rainfall experiments with four treatments, including bare soil, biocrusts, Stipa bungeana and S. bungeana+biocrusts, were designed to investigate runoff, infiltration process and hydrodynamic characteristics of herbs and biocrusts on slope. The results showed that the runoff under the two treatments with biocrusts was stable. The total runoff of four treatments was in the following order: biocrusts > S. bungeana+biocrusts > bare soil > S. bungeana, indicating that biocrusts could inhibit soil infiltration and S. bungeana could promote soil infiltration. At soil depths of 16 cm and 24 cm, the cumulative infiltration of biocrusts treatment was significantly less than that of S. bungeana+biocrusts treatment, suggesting that with the increases of soil depth, S. bungeana reduced the negative effect of biocrusts on soil infiltration. The Froude number was greater than 1 under bare soil and less than 1 under other treatments, which was subcritical flow. Compared with the runoff kinetic energy of the bare soil treatment, the treatments of biocrusts, S. bungeana, and S. bungeana+biocrusts were reduced by 83.3%, 59.5%, and 88.1%, respectively. The variations of hydrodynamic parameters indicated that the role of biocrusts is greater than S. bungeana in regulating runoff.


Assuntos
Chuva , Solo , Poaceae
15.
Sci Total Environ ; : 158648, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36096212

RESUMO

Reducing the water content of waste activated sludge (WAS) is critical for sludge treatment and disposal in wastewater treatment plants (WWTPs). In this study, a new combined conditioning processes by using lysozyme (LZM) and free nitrous acid (FNA) were proposed and demonstrated to enhance the dewaterability of WAS. The water content of sludge cake dropped from 82.82 % to 68.42 % (1 h FNA treatment + 1 h LZM treatment) and 69.52 % (6 h FNA treatment + 1 h LZM treatment) with the combined FNA and LZM treatment; and the corresponding capillary suction time (CST) reduction efficiency increased 49.29 % (1 h FNA treatment + 1 h LZM treatment) and 52.98 % (6 h FNA treatment + 1 h LZM treatment). A comprehensive investigation conducted in this study revealed the underlying mechanism of dewaterability improvement lies in the transformations of extracellular polymeric substances (EPS). The combined conditioning led to enhanced hydrophobicity in the sludge, as suggested by FTIR protein secondary structure and interfacial free energy. The reduced zeta potential and the potential barrier indicated the reduction of the repulsive force of sludge particles and the bound water content in the conditioned floc. The hydrophobicity, flow permeability and flocculability were enhanced after combined treatment, leading to the release of bound water.

16.
Artigo em Inglês | MEDLINE | ID: mdl-36097173

RESUMO

Highland birds evolve multiple adaptive abilities to cope with the harsh environments; however, how they adapt to the high-altitude habitats via the gut microbiota remains understudied. Here we integrated evidences from comparative analysis of gut microbiota to explore the adaptive mechanism of black-necked crane, a typical highland bird in the Qinghai-Tibet Plateau. Firstly, the gut microbiota diversity and function was compared among seven crane species (one high-altitude species and six low-altitude species), and then among three populations of contrasting altitudes for the black-necked crane. Microbiota community diversity in black-necked crane was significantly lower than its low-altitude relatives, but higher microbiota functional diversity was observed in black-necked crane, suggesting that unique bacteria are developed and acquired due to the selection pressure of high-altitude environments. The functional microbial genes differed significantly between the low- and high-altitude black-necked cranes, indicating that altitude significantly impacted microbial communities' composition and structure. Adaptive changes in microbiota diversity and function are observed in response to high-altitude environments. These findings provide us a new insight into the adaptation mechanism to the high-altitude environment for birds via the gut microbiota. KEY POINTS: • The diversity and function of gut microbiota differed significantly between the low- and high-altitude crane species. • Black-necked crane adapts to the high-altitude environment via specific gut microbiota. • Altitude significantly impacted microbial communities' composition and structure.

17.
Diabetes Res Clin Pract ; : 110085, 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36126799

RESUMO

AIMS: To quantify associations of different metrics of long-term glycemic variability (GV) with multiple adverse diabetes-related outcomes. METHODS: We searched PubMed and Embase from database inception to 23 August 2021. GV was based on measurements of HbA1c or fasting plasma glucose (FPG) and calculated by standard deviation (SD), coefficient of variance (CV), or other metrics. Outcomes included mortality, cardiovascular disease (CVD), renal disease, peripheral neuropathy, retinopathy, dementia, and cancer. Random-effects meta-analyses were adopted to pool the relative risks (RRs). RESULTS: Seventy-five articles with 2,051,701 participants were included. When comparing top with bottom quartiles, HbA1c variabilities were associated with all-cause mortality (RRCV=1.63, 95% CI 1.37-1.92; RRSD=1.87, 1.55-2.26), CVD (RRCV=1.38, 1.07-1.78; RRSD=1.34, 1.12-1.59), renal disease (RRCV=1.43, 1.18-1.74; RRSD=1.44, 1.24-1.67), and peripheral neuropathy (RRCV=1.84, 1.40-2.43; RRSD=1.98, 1.51-2.61), but not retinopathy. FPG variabilities were associated with all-cause mortality (RRCV=1.59, 1.43-1.78; RRSD=1.67, 1.26-2.20), renal disease (RRCV=1.77, 1.32-2.38), and retinopathy (RRCV=1.92, 1.10-3.35), but not CVD and peripheral neuropathy. Associations of GV with Alzheimer's disease (RRHbA1c-CV=1.38, 1.13-1.70; RRFPG-CV=1.32, 1.07-1.63) and cancer (RRHbA1c-SD= 2.19, 1.52-3.17; RRFPG-CV=3.64, 2.21-5.98) were each found significant in one study. CONCLUSIONS: Long-term GV was associated with multiple adverse diabetes-related outcomes, while the strength of associations varied. The findings support the use of long-term GV for diabetes management in clinical practice.

18.
Mol Carcinog ; 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36121331

RESUMO

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death, and the prognosis varies due to its high heterogeneity, systematic evaluation of HCC is mainly based on genomic and transcriptomic features, metabolomics-based classification has yet to be reported. Here we performed RNA-seq on 50 paired samples and metabolomics analysis on 72 paired samples of both normal and tumor tissues from HCC patients. Through unsupervised hierarchical cluster analysis with train and test data sets, metabolic and gene expression signatures were identified. We found that most fluxes related to glutamate are attenuated, except for the glutamate-proline pathway. Three subgroups were identified with distinct survival, clinical observations, and metabolic/gene signatures. S1 is characterized by a relatively poor prognosis, a low concentration of the degradation products of phosphatidylcholine and phosphatidylethanolamine, an enrichment of specific genes related to focal adhesion, and an upregulation of genes on chromosome 6q27. Beyond commonly downregulated metabolites, S2 tumors are largely characterized by few alterations in metabolites and genes, as well as low incidence of mutations/loss of heterozygosity, the metabolite signature of this group consists of hexoses and their phosphates, and the prognosis is the best, with a 5-year survival rate of greater than 80%. S3 is characterized by the worst survival (an approximately 20% 5-year survival rate), unsaturated fatty acid metabolites, an upregulation of specific genes involved in metastasis, and an upregulation of genes on chromosome 1q21. The metabolite-based classifications are more stable and reproducible, with each subgroup characterized by a distinct molecular signature and disease prognosis.

19.
Biosens Bioelectron ; 217: 114671, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36122469

RESUMO

microRNA (miRNA) is a kind of small non-coding RNA that has been regarded as potential biomarkers for cancers. Sensitive and specific detection of miRNA at low expression levels is highly desirable but remains challenging, especially for amplification-free and portable point of care (POC) diagnostics. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas13a has been recently discovered and used in the field of RNA detection. Nonetheless, most CRISPR/Cas13a-based methods were burdened with expensive equipment, time-consuming procedures, and complicated operations which were not suitable for POC analysis. In this work, we constructed a three-dimensional tetrahedral DNA framework based CRISPR-electrochemical biosensor (CRISPR-E). By combining tetrahedral DNA framework, CRISPR, and electrochemical biosensor, the process of activation, cleavage of Cas13a, and signal readout were all finished on the chip, and a simple, amplification-free and sensitive detection of miRNA-19b was realized. Under the optimal experimental conditions, a linear range from 10 pM to 104 pM with detection limit of 10 pM for miRNA-19b in buffer solution was achieved. Selectivity analysis indicated that our CRISPR-E had good distinguishing ability between miRNA-19b and miRNA-197. The results of miRNA-19b detection in mimic serum samples were consistent with that of the buffer solution. This all-on-chip strategy of our CRISPR-E is very suitable for POC testing.

20.
J Vector Borne Dis ; 59(2): 115-126, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36124477

RESUMO

BACKGROUND & OBJECTIVES: Weather and climate are directly linked to human health including the distribution and occurrence of vector-borne diseases which are of significant concern for public health. METHODS: In this review, studies on spatiotemporal distribution of dengue, Barmah Forest Virus (BFV) and Ross River Virus (RRV) in Australia and malaria in Papua New Guinea (PNG) under the influence of climate change and/ or human society conducted in the past two decades were analysed and summarised. Environmental factors such as temperature, rainfall, relative humidity and tides were the main contributors from climate. RESULTS: The Socio-Economic Indexes for Areas (SEIFA) index (a product from the Australian Bureau of Statistics that ranks areas in Australia according to relative socio-economic advantage and disadvantage) was important in evaluating contribution from human society. INTERPRETATION & CONCLUSION: For future studies, more emphasis on evaluation of impact of the El Niño-Southern Oscillation (ENSO) and human society on spatio-temporal distribution of vector borne diseases is recommended to highlight importance of the environmental factors in spreading mosquito-borne diseases in Australia and PNG.

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