Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health
. Despite intense research efforts, how, when and where ...new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing
of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here 'WH-Human 1' coronavirus (and has also been referred to as '2019-nCoV'). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China
. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.
This study aimed to determine the levels of health-related behaviours (physical activity, screen exposure and sleep status) among Chinese students from primary, secondary and high schools during the ...pandemic of COVID-19, as well as their changes compared with their status before the pandemic. A cross-sectional online survey of 10,933 students was conducted among 10 schools in Guangzhou, China, between 8th and 15th March, 2020. After getting the informed consent from student's caregivers, an online questionnaire was designed and used to obtain time spending on health-related behaviours during the pandemic of COVID-19, as well as the changes compared with 3 months before the pandemic, which was completed by students themselves or their caregivers. Students were stratified by regions (urban, suburban, exurban), gender (boys and girls), and grades (lower grades of primary school, higher grades of primary schools, secondary schools and high schools). Data were expressed as number and percentages and Chi-square test was used to analyse difference between groups. Overall, the response rate of questionnaire was 95.3% (10,416/10,933). The median age of included students was 13.0 (10.0, 16.0) years and 50.1% (n = 5,219) were boys. 41.4%, 53.6% and 53.7% of total students reported less than 15 min per day in light, moderate and vigorous activities and 58.7% (n = 6,113) reported decreased participation in physical activity compared with the time before pandemic. Over 5 h of screen time spending on online study was reported by 44.6% (n = 4,649) of respondents, particular among high school students (81.0%). 76.9% of students reported increased screen time compared with the time before pandemic. Inadequate sleep was identified among 38.5% of students and the proportion was highest in high school students (56.9%). Our study indicated that, during the COVID-19 pandemic, the school closure exerted tremendous negative effects on school-aged children's health habits, including less physical activity, longer screen exposure and irregular sleeping pattern.
Esophageal squamous cell carcinoma (ESCC) is among the most common malignancies, but little is known about its spatial intratumoral heterogeneity (ITH) and temporal clonal evolutionary processes. To ...address this, we performed multiregion whole-exome sequencing on 51 tumor regions from 13 ESCC cases and multiregion global methylation profiling for 3 of these 13 cases. We found an average of 35.8% heterogeneous somatic mutations with strong evidence of ITH. Half of the driver mutations located on the branches of tumor phylogenetic trees targeted oncogenes, including PIK3CA, NFE2L2 and MTOR, among others. By contrast, the majority of truncal and clonal driver mutations occurred in tumor-suppressor genes, including TP53, KMT2D and ZNF750, among others. Interestingly, phyloepigenetic trees robustly recapitulated the topological structures of the phylogenetic trees, indicating a possible relationship between genetic and epigenetic alterations. Our integrated investigations of spatial ITH and clonal evolution provide an important molecular foundation for enhanced understanding of tumorigenesis and progression in ESCC.
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•Cobalt ferrite/graphene oxide (CoFe2O4/GO) were prepared by a facile sonochemical method.•GO nanosheets were fully exfoliated and decorated homogeneously with CoFe2O4 ...nanoparticles.•CoFe2O4/GO showed superparamagnetic behavior, hydrophilic character and negligible cytotoxicity.•Significant T2-weighted enhancement effect with relaxivity coefficient of 92.71mM−1s−1.•Drug loading capacity was as high as 1.08mg/mg and drug release showed pH-sensitive feature.
Developing multifunctional theranostic platforms with complementary roles has drawn considerable attention in recent years. In this study, superparamagnetic cobalt ferrite/graphene oxide (CoFe2O4/GO) nanocomposites with integrated characteristics of magnetic resonance imaging and controlled drug delivery were prepared by sonochemical method. The morphology, microstructure and physical properties of as-prepared CoFe2O4/GO were investigated in detail by transmission electron microscope (TEM), scanning electron microscope (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), Raman spectra, N2 adsorption/desorption isotherm, thermogravimetric analysis (TGA), superconducting quantum interference device (SQUID) and zeta potential measurements. The obtained CoFe2O4/GO exhibited superparamagnetic property and dose-dependent T2-weighted enhancement effect with relaxivity coefficient of 92.71mM−1s−1. Furthermore, the CoFe2O4/GO showed negligible cytotoxicity even at a high concentration after being treated for 96h. Doxorubicin hydrochloride (DOX) as an anti-tumor model drug was loaded on CoFe2O4/GO. The nanocomposites were found to be able to efficiently transport DOX into the cancer cells and then cause cell death. The drug loading capacity of this nanocarrier was as high as 1.08mg/mg and the drug release behavior demonstrated a sustained and pH-responsive way. The results suggested that the as-prepared CoFe2O4/GO showed great potential as an effective multifunctional nanoplatform for magnetic resonance imaging and controlled drug delivery for simultaneous cancer diagnosis and chemotherapy.
In this paper, the X-ray micro-computed tomography (X-ray µCT), spherical harmonical-based principal component analysis (SH-PCA), and discrete element method (DEM) were incorporated to generate ...virtual samples with morphological gene mutation at different length scales. All samples were subjected to axial compression and constant confining stress. The effects of multiscale particle morphology on the stress-strain and energy storage/dissipation responses of granular soils were investigated. It is found that: (a) the effects of particle morphology on the initial stiffness, stress-strain, volumetric strain, and frictional energy dissipation behaviours are more pronounced for looser samples than for denser ones; (b) among different length scales, the particle morphology at the local roundness-level outperforms the one at the general form-level in dictating the macro-scale responses of granular soils; (c) the energy dissipation of a granular assemblage is a result of competition between particle morphology and initial void ratio.
Chronic Obstructive Pulmonary Disease (COPD) is a growing public health problem in the southern United States, particularly in Alabama. However, very little is known about specific health risk ...factors disproportionately impacting Alabamians with COPD. We conducted a latent class analysis of 2015–2019 Behavioral Risk Factor Surveillance System data from 4057 Alabamians with COPD (White = 2947, Black = 873, Other = 237). Eighteen risk indicators were examined across three health-related domains: (1) comorbidities, (2) limited healthcare access, and (3) substance use/abuse. Racial disparities between Black and white Alabamians with COPD were assessed using configural similarity analysis. Findings showed that almost one-third (31%) of Alabamians with COPD were in the high-risk class for eight comorbidities, and nearly one-half (48.88%) belonged to the high-risk class for limited healthcare access. Black Alabamians with COPD who did not have health insurance were much more likely to be at high risk for limited healthcare access (94.44%) when compared to their counterparts with insurance (5.56%), χ2(df = 2) = 1389.94, p < 0.0001. Furthermore, the proportion of high-risk, uninsured Black Alabamians with COPD (94.44%) substantially exceeded the percentage of high-risk, uninsured white Alabamians with COPD (59.70%). Most Alabamians with COPD (82.97%) were at low risk for substance use/abuse. Future research should explore new mechanisms for facilitating better healthcare access among high-risk Alabamians living with COPD and other prevalent comorbidities. Greater attention should be focused on Black Alabamians with COPD who cannot afford adequate health insurance.
Metastasis and chemotherapy resistance are the key factors affecting the effectiveness of osteosarcoma (OS) treatments. CXCR1 overexpression is found to be closely related to chemotherapy resistance ...and anoikis resistance in OS cell subtypes with high metastasis potential. Further study demonstrates that CXCR1 is highly expressed on circulating tumor cell (CTC)‐derived cells with cancer stem cell characteristics. Then, a CXCR1 targeting peptide is designed and synthesized to competitively inhibit the IL‐8/CXCR1 pathway and to improve the cisplatin sensitivity of CTCs. Fluorescence‐labeled magnetic nanoparticles (NPs) with pH‐responsive cisplatin release are fabricated and linked with the CXCR1 targeting peptide (Cis@MFPPC). Results demonstrate that CTC survival could be inhibited effectively by the targeting nanoparticles in vivo. Cis@MFPPC can also inhibit OS growth and pulmonary metastasis in an orthotopic model and patient‐derived tumor xenograft model. This study verifies the clinical significance of CXCR1 as a therapeutic target and provides a drug delivery NP system for precise treatment of OS.
Fluorescence‐labeled magnetic nanoparticles with pH‐responsive cisplatin release are fabricated and linked with the CXCR1 targeting peptide (Cis@MFPPC). Circulating tumor cells could be inhibited effectively by Cis@MFPPC in vivo. Cis@MFPPC can also inhibit osteosarcoma growth and pulmonary metastasis in an orthotopic model and patient‐derived tumor xenograft model.
We investigated the correlation between the beneficial effect of Lactobacillus acidophilus on gut microbiota composition, metabolic activities, and reducing cow's milk protein allergy. Mice ...sensitized with β‐lactoglobulin (β‐Lg) were treated with different doses of L. acidophilus KLDS 1.0738 for 4 weeks, starting 1 week before allergen induction. The results showed that intake of L. acidophilus significantly suppressed the hypersensitivity responses, together with increased fecal microbiota diversity and short‐chain fatty acids (SCFAs) concentration (including propionate, butyrate, isobutyrate, and isovalerate) when compared with the allergic group. Moreover, treatment with L. acidophilus induced the expression of SCFAs receptors, G‐protein–coupled receptors 41 (GPR41) and 43 (GPR43), in the spleen and colon of the allergic mice. Further analysis revealed that the GPR41 and GPR43 messenger RNA expression both positively correlated with the serum concentrations of transforming growth factor‐β and IFN‐γ (p < .05), but negatively with the serum concentrations of IL‐17, IL‐4, and IL‐6 in the L. acidophilus–treated group compared with the allergic group (p < .05). These results suggested that L. acidophilus protected against the development of allergic inflammation by improving the intestinal flora, as well as upregulating SCFAs and their receptors GPR41/43.
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