It is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly infect human kidney, thus leading to acute kidney injury (AKI). Here, we perform a retrospective ...analysis of clinical parameters from 85 patients with laboratory-confirmed coronavirus disease 2019 (COVID-19); moreover, kidney histopathology from six additional COVID-19 patients with post-mortem examinations was performed. We find that 27% (23/85) of patients exhibited AKI. The elderly patients and cases with comorbidities (hypertension and heart failure) are more prone to develop AKI. Haematoxylin & eosin staining shows that the kidneys from COVID-19 autopsies have moderate to severe tubular damage. In situ hybridization assays illustrate that viral RNA accumulates in tubules. Immunohistochemistry shows nucleocapsid and spike protein deposits in the tubules, and immunofluorescence double staining shows that both antigens are restricted to the angiotensin converting enzyme-II-positive tubules. SARS-CoV-2 infection triggers the expression of hypoxic damage-associated molecules, including DP2 and prostaglandin D synthase in infected tubules. Moreover, it enhances CD68+ macrophages infiltration into the tubulointerstitium, and complement C5b-9 deposition on tubules is also observed. These results suggest that SARS-CoV-2 directly infects human kidney to mediate tubular pathogenesis and AKI.
Given China’ rapid transformation, its economy is currently experiencing a change from a rugged development style to a sustainable development style with green development being critical to this ...transformation. Increasing green total factor productivity (GTFP) is now considered one of the significant signs of economic growth. With increasingly stricter environmental laws and regulations and a broad application of innovation capability (ICY) in modern life, this research investigates the impact mechanisms of both environmental regulations (ER) and ICY on GTFP, offering robust empirical results from panel data of 30 provinces in China covering the period 2006–2017. The results indicate that both ICY and ER effectively promote GTFP, but compared to ER, ICY has a heterogeneous effect on GTFP. Moreover, ICY plays a mediating role in ER and GTFP, while ER promotes GTFP through ICY. Accordingly, the paper puts forward some suggestions, such as to optimize and improve the ER policy, enact an innovation-driven development strategy, widely use ICY technology, and strengthen monitoring and supervision.
Metabolic reprogramming is frequently identified in hepatocellular carcinoma (HCC), which is the most common type of liver malignancy. The reprogrammed cellular metabolisms promote tumor cell ...survival, proliferation, angiogenesis, and metastasis. However, the mechanisms of this process remain unclear in HCC.
The global nontargeted metabolic study in 69 paired hepatic carcinomas and adjacent tissue specimens was performed using capillary electrophoresis-time of flight mass spectrometry-based approach. Key findings were validated by targeted metabolomic approach. Biological studies were also performed to investigate the role of proline biosynthesis in HCC pathogenesis.
Proline metabolism was markedly changed in HCC tumor tissue, characterized with accelerated consumption of proline and accumulation of hydroxyproline, which significantly correlated with α-fetoprotein levels and poor prognosis in HCC. In addition, we found that hydroxyproline promoted hypoxia- and HIF-dependent phenotype in HCC. Moreover, we demonstrated that hypoxia activated proline biosynthesis via upregulation of
, subsequently leading to accumulation of hydroxyproline via attenuated
activity. More importantly, we showed that glutamine, proline, and hydroxyproline metabolic axis supported HCC cell survival through modulating HIF1α stability in response to hypoxia. Finally, inhibition of proline biosynthesis significantly enhanced cytotoxicity of sorafenib
and
Our results demonstrate that hypoxic microenvironment activates proline metabolism, resulting in accumulation of hydroxyproline that promotes HCC tumor progression and sorafenib resistance through modulating HIF1α. These findings provide the proof of concept for targeting proline metabolism as a potential therapeutic strategy for HCC.
.
The pandemic of COVID-19, which forced cinema theaters to close and left exhibitors without revenue over a long period, may have dramatically changed the film business and its future. This paper ...seeks to examine the changing dynamic of film distribution through video streaming in the Southeast Asia region as a result of the impact of the pandemic. Some films may be chosen for video streaming media platforms as their alternative option for release into theatrical distribution. This pandemic also has changed film-viewing habits and behaviors among audiences. Several news reports have substantiated that Southeast Asian viewers are streaming more online video content due to COVID-19. As a result of the pandemic it appears that there is an accelerated shift to streaming media platforms across Southeast Asia countries. Local streaming platforms feed users their unique and culturally distinctive locally produced content which could be distinguished from that offered by global players. In 2020, some new streaming media platforms were launched for distributing film content to their targeted markets locally and internationally. Through the use of a review of trade and business press as well as interview, this paper attempts to identify and present areas of regional change and regional players which deserve systematic discussion and analysis.
While lymphocytopenia is a common characteristic of coronavirus disease 2019 (COVID-19), the mechanisms responsible for this lymphocyte depletion are unclear. Here, we retrospectively reviewed the ...clinical and immunological data from 18 fatal COVID-19 cases, results showed that these patients had severe lymphocytopenia, together with high serum levels of inflammatory cytokines (IL-6, IL-8 and IL-10), and elevation of many other mediators in routine laboratory tests, including C-reactive protein, lactate dehydrogenase, α-hydroxybutyrate dehydrogenase and natriuretic peptide type B. The spleens and hilar lymph nodes (LNs) from six additional COVID-19 patients with post-mortem examinations were also collected, histopathologic detection showed that both organs manifested severe tissue damage and lymphocyte apoptosis in these six cases.
hybridization assays illustrated that SARS-CoV-2 viral RNA accumulates in these tissues, and transmission electronic microscopy confirmed that coronavirus-like particles were visible in the LNs. SARS-CoV-2 Spike and Nucleocapsid protein (NP) accumulated in the spleens and LNs, and the NP antigen restricted in angiotensin-converting enzyme 2 (ACE2) positive macrophages and dendritic cells (DCs). Furthermore, SARS-CoV-2 triggered the transcription of
,
and
genes in infected primary macrophages and DCs
, and SARS-CoV-2-NP
macrophages and DCs also manifested high levels of IL-6 and IL-1β, which might directly decimate human spleens and LNs and subsequently lead to lymphocytopenia
. Collectively, these results demonstrated that SARS-CoV-2 induced lymphocytopenia by promoting systemic inflammation and direct neutralization in human spleen and LNs.
There has been growing interest in exhaled breath analysis for cancer screening and disease monitoring; however, limited breath biomarker information exists regarding colorectal cancer (CRC). The ...objective of this study was to screen for breath biomarkers of CRC. Exhaled breath was collected from 20 CRC patients and 20 healthy controls; subsequently, solid-phase microextraction–gas chromatography/mass spectrometry (SPME-GC/MS) was used to assess the exhaled volatile organic compounds (VOCs) of the study participants. The statistical methods of principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were performed to process the final data. The VOCs in the exhalations of CRC patients exhibited significant differences from the VOCs in the exhalations of healthy controls; in particular, relative to the latter exhalations, the former exhalations contain significantly higher levels of cyclohexanone, 2,2-dimethyldecane, dodecane, 4-ethyl-1-octyn-3-ol, ethylaniline, cyclooctylmethanol, trans-2-dodecen-1-ol, and 3-hydroxy-2,4,4-trimethylpentyl 2-methylpropanoate but significantly lower levels of 6-t-butyl-2,2,9,9-tetramethyl-3,5-decadien-7-yne (
P
< 0.05). Analyses of breath VOCs provide a related model of CRC exhalation that could represent an effective and convenient screening method for this disease.
Figure
Partial least-squares discriminant analysis scores plot (with the three components of R2X=0.583, R2Y=0.806, and Q2=0.565), which reveals that a considerable separation was achieved between colorectal cancer breath samples and normal controls
PDF
