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1.
Oxidative medicine and cellular longevity ; 2022, 2022.
Article in English | EuropePMC | ID: covidwho-1823348

ABSTRACT

Acute respiratory distress syndrome (ARDS) causes uncontrolled pulmonary inflammation, resulting in high morbidity and mortality in severe cases. Given the antioxidative effect of molecular hydrogen, some recent studies suggest the potential use of molecular hydrogen as a biomedicine for the treatment of ARDS. In this study, we aimed to explore the protective effects of magnesium hydride (MgH2) on two types of ARDS models and its underlying mechanism in a lipopolysaccharide (LPS)-induced ARDS model of the A549 cell line. The results showed that LPS successfully induced oxidative stress, inflammatory reaction, apoptosis, and barrier breakdown in alveolar epithelial cells (AEC). MgH2 can exert an anti-inflammatory effect by down-regulating the expressions of inflammatory cytokines (IL-1β, IL-6, and TNF-α). In addition, MgH2 decreased oxidative stress by eliminating intracellular ROS, inhibited apoptosis by regulating the expressions of cytochrome c, Bax, and Bcl-2, and suppressed barrier breakdown by up-regulating the expression of ZO-1 and occludin. Mechanistically, the expressions of p-AKT, p-mTOR, p-P65, NLRP3, and cleaved-caspase-1 were decreased after MgH2 treatment, indicating that AKT/mTOR and NF-κB/NLRP3/IL-1β pathways participated in the protective effects of MgH2. Furthermore, the in vivo study also demonstrated that MgH2-treated mice had a better survival rate and weaker pathological damage. All these findings demonstrated that MgH2 could exert an ARDS-protective effect by regulating the AKT/mTOR and NF-κB/NLRP3/IL-1β pathways to suppress LPS-induced inflammatory reaction, oxidative stress injury, apoptosis, and barrier breakdown, which may provide a potential strategy for the prevention and treatment of ARDS.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-330905

ABSTRACT

The biopharmaceutical industry is capable of rapid responses in the face of unprecedent challenges, such as the COVID-19 pandemic;safe and efficacious vaccines were developed in record times. However, additional hurdles, including raw materials shortages, need be overcome to improve further the industry’s agility. During the development of a SARS-CoV-2 vaccine candidate, such supply limitations necessitated the determination of a cleaning in place (CIP) strategy for a multimodal core-shell resin both rapidly and efficiently. This is a challenging task with its complexity depending on the nature of the resin and the composition of the feed stream. Here, we describe the deployment of high throughput (HT) techniques to screen CIP conditions for cleaning Capto™ Core 700 resin exposed to clarified cell culture harvest of a SARS-CoV-2 vaccine candidate produced in Vero adherent cell culture. The best performing conditions, comprised of 30% n-propanol and ≥0.75 N NaOH, were deployed in cycling experiments, completed with miniature chromatography columns, to demonstrate their effectiveness. The success of the CIP strategy was ultimately verified at laboratory scale. Here, its impact was assessed across the entire purification process which also included an ultrafiltration/diafiltration step. It is shown that the implementation of the CIP strategy enabled the re-use of the Capto Core 700 resin for up to ten cycles without any negative impact on the purified product. Hence, the strategic combination of HT and laboratory scale experiments can lead rapidly to robust CIP procedures, even for a challenging to clean resin, and thus help to overcome supply shortages.

3.
Chin Med J (Engl) ; 133(9): 1039-1043, 2020 May 05.
Article in English | MEDLINE | ID: covidwho-1722619

ABSTRACT

BACKGROUND: A patient's infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence. METHODS: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients' oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed. RESULTS: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0-62.0) years were analyzed. After in-hospital treatment, patients' inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0-11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients' stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0-16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0-4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients' urine specimens after throat swabs were negative. Using a multiple linear regression model (F = 2.669, P = 0.044, and adjusted R = 0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients' stools (t = -2.699, P = 0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs. 8.0 days, respectively; t = 2.550, P = 0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs. 11 days, respectively; t = 4.631, P < 0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results (P > 0.05). CONCLUSIONS: In brief, as the clearance of viral RNA in patients' stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/genetics , Pneumonia, Viral/genetics , RNA, Viral/genetics , Adult , Aged , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/rehabilitation , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/rehabilitation , Real-Time Polymerase Chain Reaction , Retrospective Studies , SARS-CoV-2
4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324115

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic, and little is known regarding the gut microbiota dynamics of the disease that often features a drastic and swift progression. Here we employed analyses of 16S rRNA gene sequencing and metatranscriptome to investigate the gut microbiome characteristics of a group of COVID-19 patients over the course of a probiotics-assisted therapy. Results: The COVID-19 patients exhibited apparent microbiota alterations characterized by prominent compositional and functional shifts, which included taxonomic changes (e.g., increased relative abundance of Enterococcus and Rhodococcus , and decreased relative abundance of Faecalibacterium and Clostridium XlVa) and transcriptional changes (e.g., increased transcriptional activities of Escherichia coli and Klebsiella pneumoniae , virulence factors, and antibiotic resistance genes, and decreased activities of Faecalibacterium prausnitzii ). Importantly, there were great interpersonal heterogeneity and intertimepoint fluctuations, as the most abundant or transcriptionally active taxa often greatly differed among individual patients and timepoints. Coincided with the resolution of respiratory symptoms, after the therapy some patients showed signs of recovery in the gut microbiome abnormalities. Associations were identified between gut and airway taxa and serum factors. Conclusion: Our findings suggested that there is a lack of gut microbiota stability in COVID-19 patients and that measures are needed to ameliorate the gut microbiome perturbations in the patients to improve the prognosis. In addition, inclusion of probiotics is safe for treating COVID-19 patients and may improve their prognosis. Trial registration ISRCTN, ChiCTR2000029999. Registered 19 February 2020, http://www.chictr.org.cn/showprojen.aspx?proj=49717

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323699

ABSTRACT

Despite a high prevalence of dementia in older adults hospitalized with severe acute respiratory syndrome coronavirus 2 infection (COVID-19), research investigating association between preexisting diagnoses of dementia and prognosis of COVID-19 is scarce. We explored a nationwide cohort with a total of 2,800 subjects older than 50 years who were diagnosed with COVID-19 between January and April 2020. Among them, 223 patients had underlying dementia (dementia group). We matched 1:1 for each dementia-non-dementia group pair yielding 223 patients without dementia (no dementia group) using propensity score matching. The primary outcome measure was group difference in mortality after COVID-19. Mortality rate after COVID-19 were significantly higher in dementia group than in no dementia group (33.6% vs. 20.2%, p=0.002). In addition, dementia group had higher proportion of patients requiring invasive ventilatory support than no dementia group (34.1% vs. 22.0%, p=0.006). Multivariable analysis showed that dementia group had a higher risk of mortality than no dementia group (odds ratio=3.05, p <0.001). We also found that patients in dementia group had a higher risk of needing invasive ventilatory support than those in no dementia group. Our results suggest that system including strengthen quarantines are required for patients with dementia during the COVID-19 pandemic.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-322273

ABSTRACT

The inferior electrical contact to two-dimensional (2D) materials is a critical challenge for their application in post-silicon very large-scale integrated circuits. Electrical contacts were generally related to their resistive effect, quantified as contact resistance. With a systematic investigation, this work demonstrates a capacitive metal-insulator-semiconductor (MIS) field-effect at the electrical contacts to 2D materials: the field-effect depletes or accumulates charge carriers, redistributes the voltage potential, and give rise to abnormal current saturation and nonlinearity. On the one hand, the current saturation hinders the devices' driving ability, which can be eliminated with carefully engineered contact configurations. On the other hand, by introducing the nonlinearity to monolithic analog artificial neural network circuits, the circuits' perception ability can be significantly enhanced, as evidenced using a COVID-19 critical illness prediction model. This work provides a comprehension of the field-effect at the electrical contacts to 2D materials, which is fundamental to the design, simulation, and fabrication of electronics based on 2D material.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315773

ABSTRACT

Italy was the first, among all the European countries, to be strongly hit by the Covid-19 pandemic outbreak caused by the severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2). The virus, proven to be very contagious, infected more than 9 million people worldwide (in June 2020). Nevertheless, it is not clear the role of air pollution and meteorological conditions on virus transmission. In this study, we quantitatively assessed how the meteorological and air quality parameters are correlated to the Covid-19 transmission in Lombardy (Northern Italy), the region epicenter of the virus outbreak. Our main findings highlight that temperature and humidity related variables are negatively correlated to the virus transmission, whereas air pollution (PM 2.5 ) shows a positive correlation. In other words, Covid-19 pandemic transmission prefers dry and cool environmental conditions, as well as polluted air. For these reasons, the virus might easier spread in unfiltered air-conditioned environments. Those results will be supporting decision makers to contain new possible outbreaks.

8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315772

ABSTRACT

Italy was the first, among all the European countries, to be strongly hit by the Covid-19 pandemic outbreak caused by the severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2). The virus, proven to be very contagious, infected more than 9 million people worldwide (in June 2020). Nevertheless, it is not clear the role of air pollution and meteorological conditions on virus transmission. In this study, we quantitatively assessed how the meteorological and air quality parameters are correlated to the Covid-19 transmission in Lombardy (Northern Italy), the region epicenter of the virus outbreak. Our main findings highlight that temperature and humidity related variables are negatively correlated to the virus transmission, whereas air pollution (PM2.5) shows a positive correlation. In other words, Covid-19 pandemic transmission prefers dry and cool environmental conditions, as well as polluted air. For these reasons, the virus might easier spread in unfiltered air-conditioned environments. Those results will be supporting decision makers to contain new possible outbreaks.

9.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308426

ABSTRACT

COVID-19 caused by SARS-CoV-2 has rapidly spread to more than 160 countries worldwide since 2020. Despite the tremendous efforts and resources spent around the world trying to explore antiviral drugs, there is still no effective clinical treatment for COVID-19. Approximately 15% of COVID-19 cases progress to pneumonia, patients with severe pneumonia may die from acute respiratory distress syndrome (ARDS). In addition, further pulmonary fibrosis from SARS-CoV-2 infection causes ARDS that often leads to irreversible impairment of lung function. If the mechanisms by which SARS-CoV-2 infection primarily cause immune responses or immune cell infiltration can be identified, it is possible to alleviate or prevent severe lung damage by modulating the infiltration and activation of specific immune cells to mitigate excessive immunity response.The extent to which subsets of immune cells are significantly altered in the lung tissue of COVID-19 patients remains unclear. This study applied the CIBERSORT method to comprehensively evaluate the immune infiltration landscape in lung tissues of COVID-19 patients, and further compared with the one from lung tissue of patients with idiopathic pulmonary fibrosis (IPF). We found several immune cell subtypes;particularly naïve B cells are highly infiltrated in COVID-19 group. A comparison of functional gene set analysis revealed that non-differentiated naïve B cells may be the main cause of the overactive humoral immune response. We further compared several specific COVID-19 cases receiving therapies targeting B cells and found that appropriate suppression of naïve B cells might be a new strategy to alleviate severe symptoms of COVID-19.

10.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325349

ABSTRACT

COVID-19 outbreak first reported in Wuhan has been officially declared as a global pandemic. Considering the fecal shedding of SARS-CoV-2 has been proven by the viral strains isolated from COVID-19 patient’s stool specimens, it proposed the possibility that contaminated wastewater and fomites might involve in the disease transmission in outbreak cities. In this study, we collected the wastewater samples collected from COVID-19 designated hospitals, Fangcang shelter hospitals, quarantine spots and wastewater treatment plants in Wuhan, China, and performed RT-qPCR and droplet digital PCR (ddPCR) for the detection of SARS-CoV-2. Although high concentration of residual chlorine for disinfection of SARS-CoV-2 is persisted, low level SARS-CoV-2 RNA can be detected by qPCR and droplet digital PCR (ddPCR) in the wastewater samples during the COVID-19 outbreak. This preliminary data firstly described in China implies the potential transmission risk of SARS-CoV-2 through medical wastewater in the cities during the COVID-19 outbreak, which calls particular attention for the surveillance and efficient disinfection of wastewater from COVID-19 related facilities.

11.
Processes ; 10(2):326, 2022.
Article in English | MDPI | ID: covidwho-1674763

ABSTRACT

The coronavirus disease 19 (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has a rapidly increasing prevalence and has caused significant morbidity/mortality. Despite the availability of many vaccines that can offer widespread immunization, it is also important to reach effective treatment for COVID-19 patients. However, the development of novel drug therapeutics is usually a time-consuming and costly process, and therefore, repositioning drugs that were previously approved for other purposes could have a major impact on the fight against COVID-19. Here, we first identified lung-specific gene regulatory/interaction subnetworks (COVID-19-related genes modules) enriched for COVID-19-associated genes obtained from GWAS and text mining. We then screened the targets of 220 approved drugs from DrugBank, obtained their drug-induced gene expression profiles in the LINCS database, and constructed lung-specific drug-related gene modules. By applying an integrated network-based approach to quantify the interactions of the COVID-19-related gene modules and drug-related gene modules, we prioritized 13 approved drugs (e.g., alitretinoin, clocortolone, terazosin, doconexent, and pergolide) that could potentially be repurposed for the treatment of COVID-19. These findings provide important and timely insights into alternative therapeutic options that should be further explored as COVID-19 continues to spread.

12.
J Nanobiotechnology ; 20(1): 6, 2022 Jan 04.
Article in English | MEDLINE | ID: covidwho-1608546

ABSTRACT

BACKGROUND: Gold nanoparticles (AuNPs) have been widely used in local surface plasmon resonance (LSPR) immunoassays for biomolecule sensing, which is primarily based on two conventional methods: absorption spectra analysis and colorimetry. The low figure of merit (FoM) of the LSPR and high-concentration AuNP requirement restrict their limit of detection (LOD), which is approximately ng to µg mL-1 in antibody detection if there is no other signal or analyte amplification. Improvements in sensitivity have been slow in recent for a long time, and pushing the boundary of the current LOD is a great challenge of current LSPR immunoassays in biosensing. RESULTS: In this work, we developed spectral image contrast-based flow digital nanoplasmon-metry (Flow DiNM) to push the LOD boundary. Comparing the scattering image brightness of AuNPs in two neighboring wavelength bands near the LSPR peak, the peak shift signal is strongly amplified and quickly detected. Introducing digital analysis, the Flow DiNM provides an ultrahigh signal-to-noise ratio and has a lower sample volume requirement. Compared to the conventional analog LSPR immunoassay, Flow DiNM for anti-BSA detection in pure samples has an LOD as low as 1 pg mL-1 within only a 15-min detection time and 500 µL sample volume. Antibody assays against spike proteins of SARS-CoV-2 in artificial saliva that contained various proteins were also conducted to validate the detection of Flow DiNM in complicated samples. Flow DiNM shows significant discrimination in detection with an LOD of 10 pg mL-1 and a broad dynamic detection range of five orders of magnitude. CONCLUSION: Together with the quick readout time and simple operation, this work clearly demonstrated the high sensitivity and selectivity of the developed Flow DiNM in rapid antibody detection. Spectral image contrast and digital analysis further provide a new generation of LSPR immunoassay with AuNPs.


Subject(s)
COVID-19 Serological Testing/methods , COVID-19/diagnosis , SARS-CoV-2/isolation & purification , Surface Plasmon Resonance/methods , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19 Serological Testing/instrumentation , Equipment Design , Gold/chemistry , Humans , Immunoassay/instrumentation , Immunoassay/methods , Metal Nanoparticles/chemistry , SARS-CoV-2/immunology , Saliva/virology , Spike Glycoprotein, Coronavirus/immunology , Surface Plasmon Resonance/instrumentation
14.
Biosaf Health ; 4(1): 38-44, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1588181

ABSTRACT

The coronavirus disease 2019 (COVID-19) is still causing a wide range of infections and deaths due to the high variability of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, it is necessary to establish a reliable and convenient pseudovirus-based neutralization assay to develop drug targeted variants of SARS-CoV-2. Based on the HIV-1 backbone, we generated a high titer luciferase (Luc)-expressing pseudovirus packaging system. Three dominant S mutant substitution pseudovirus were also established and identified compared to wide type in hACE2-overexpressing HEK-293T cells (293T-ACE2 cells). Compared to serine protease inhibitor camostat mesylate, the cysteine protease inhibitor E-64d could significantly block all SARS-CoV-2 mutant S pseudovirus infection in 293T-ACE2 cells. Furthermore, the neutralization ability of two antibodies targeted receptor-binding domain (RBD) of SARS-CoV-2 spike protein (S) was evaluated, which showed different inhibition dose-effect curves among four types of S pseudovirus. Overall, we developed a pseudovirus-based neutralization assay for SARS-CoV-2, which would be readily adapted to SARS-CoV-2 variants for evaluating antibodies.

15.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296274

ABSTRACT

Background: Gold nanoparticles (AuNPs) have been widely used as local surface plasmon resonance (LSPR) immunoassay for biomolecule sensings. It is primarily based on two conventional methods - absorption spectra and colorimetric. While the low figure of merit (FoM) of the LSPR and high-concentration AuNPs requirement restrict their limit of detection (LOD), which is around ng to μg per mL in antibody detection if there is no other signal or analytes amplification. By now, the improvement of sensitivity has bogged down for years. It also reveals a great challenge of the current LSPR immunoassay in biosensing - pushing the boundary of the current LOD. Results: : In this work, we developed a spectral image contrast-based flow digital nanoplasmon-metry(FDNM) to push the LOD boundary. Comparing the scattering image brightness of AuNPs in two neighboring wavelength bands near the LSPR peak, the signal of peak shift is extremely amplified and quickly detected. Introducing the digital analysis, the FDNM provides an ultra-high signal-to-noise ratio and less sample volume requirement. Compared to conventional analog LSPR immunoassay, FDNM has a LOD down to 1 pg mL -1 within only a 15-minute detection time and 500 μL sample volume. Antibody against spike proteins of SARS-CoV-2 in artificial saliva that contained various proteins was also conducted to validate the detection of FDNM in complicated samples. Of the detection, FDNM shows significant discrimination with a LOD of 10 pg mL -1 and a broad dynamic detecting range of five orders of magnitude. Conclusion: Together with the quick readout time and simple operation, this work outstandingly demonstrated the high sensitivity and selectivity of the developed FDNM in rapid antibody detection. The spectral image contrast and digital analysis further provide a new generation LSPR immunoassay of AuNPs.

16.
Sci Rep ; 11(1): 23223, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1553757

ABSTRACT

Low pathogenic avian influenza viruses (LPAIVs) have been widespread in poultry and wild birds throughout the world for many decades. LPAIV infections are usually asymptomatic or cause subclinical symptoms. However, the genetic reassortment of LPAIVs may generate novel viruses with increased virulence and cross-species transmission, posing potential risks to public health. To evaluate the epidemic potential and infection landscape of LPAIVs in Guangxi Province, China, we collected and analyzed throat and cloacal swab samples from chickens, ducks and geese from the live poultry markets on a regular basis from 2016 to 2019. Among the 7,567 samples, 974 (12.87%) were LPAIVs-positive, with 890 single and 84 mixed infections. Higher yearly isolation rates were observed in 2017 and 2018. Additionally, geese had the highest isolation rate, followed by ducks and chickens. Seasonally, spring had the highest isolation rate. Subtype H3, H4, H6 and H9 viruses were detected over prolonged periods, while H1 and H11 viruses were detected transiently. The predominant subtypes in chickens, ducks and geese were H9, H3, and H6, respectively. The 84 mixed infection samples contained 22 combinations. Most mixed infections involved two subtypes, with H3 + H4 as the most common combination. Our study provides important epidemiological data regarding the isolation rates, distributions of prevalent subtypes and mixed infections of LPAIVs. These results will improve our knowledge and ability to control epidemics, guide disease management strategies and provide early awareness of newly emerged AIV reassortants with pandemic potential.


Subject(s)
Influenza A virus/isolation & purification , Influenza in Birds/epidemiology , Influenza in Birds/virology , Poultry/virology , Animals , Chickens/virology , China/epidemiology , Ducks/virology , Epidemiological Monitoring , Geese/virology , Influenza A virus/genetics
17.
J Ultrasound Med ; 2021 Nov 05.
Article in English | MEDLINE | ID: covidwho-1499289
18.
Nano Res ; 14(12): 4894-4900, 2021.
Article in English | MEDLINE | ID: covidwho-1491411

ABSTRACT

The inferior electrical contact to two-dimensional (2D) materials is a critical challenge for their application in post-silicon very large-scale integrated circuits. Electrical contacts were generally related to their resistive effect, quantified as contact resistance. With a systematic investigation, this work demonstrates a capacitive metal-insulator-semiconductor (MIS) field-effect at the electrical contacts to 2D materials: The field-effect depletes or accumulates charge carriers, redistributes the voltage potential, and gives rise to abnormal current saturation and nonlinearity. On one hand, the current saturation hinders the devices' driving ability, which can be eliminated with carefully engineered contact configurations. On the other hand, by introducing the nonlinearity to monolithic analog artificial neural network circuits, the circuits' perception ability can be significantly enhanced, as evidenced using a coronavirus disease 2019 (COVID-19) critical illness prediction model. This work provides a comprehension of the field-effect at the electrical contacts to 2D materials, which is fundamental to the design, simulation, and fabrication of electronics based on 2D materials. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material (results of the simulation and SEM) is available in the online version of this article at 10.1007/s12274-021-3670-y.

19.
Cancers (Basel) ; 13(10)2021 May 18.
Article in English | MEDLINE | ID: covidwho-1468386

ABSTRACT

Hepatitis B virus (HBV) infection is one of the important risk factors for hepatocellular carcinoma (HCC) worldwide, accounting for around 50% of cases. Chronic hepatitis B infection generates an inflammatory microenvironment, in which hepatocytes undergoing repeated cycles of damage and regeneration accumulate genetic mutations predisposing them to cancer. A striking male dominance in HBV-related HCC highlights the influence of sex hormones which interact with viral factors to influence carcinogenesis. HBV is also considered an oncogenic virus since its X and surface mutant proteins showed tumorigenic activity in mouse models. The other unique mechanism is the insertional mutagenesis by integration of HBV genome into hepatocyte chromosomes to activate oncogenes. HCC survival largely depends on tumor stages at diagnosis and effective treatment. However, early diagnosis by the conventional protein biomarkers achieves limited success. A new biomarker, the circulating virus-host chimera DNA from HBV integration sites in HCC, provides a liquid biopsy approach for monitoring the tumor load in the majority of HBV-HCC patients. To maximize the efficacy of new immunotherapies or molecular target therapies, it requires better classification of HCC based on the tumor microenvironment and specific carcinogenic pathways. An in-depth study may benefit both the diagnosis and treatment of HBV-related HCC.

20.
Atmos Environ (1994) ; 266: 118750, 2021 Dec 01.
Article in English | MEDLINE | ID: covidwho-1432963

ABSTRACT

The coronavirus disease (COVID-19) spread rapidly worldwide in the first half of 2020. Stringent national lockdown policies imposed by China to prevent the spread of the virus reduced anthropogenic emissions and improved air quality. A weather research and forecasting model coupled with chemistry was applied to evaluate the impact of meteorology and emissions on air quality during the COVID-19 outbreak (from January 23 to February 29, 2020) in mid-eastern China. The results show that air pollution episodes still occurred on polluted days and accounted for 31.6%-60.5% of the total number of outbreak days in mid-eastern China from January 23 to February 29, 2020. However, anthropogenic emissions decreased significantly, indicating that anthropogenic emission reduction cannot completely offset the impact of unfavorable meteorological conditions on air quality. Favorable meteorological conditions in 2019 improved the overall air quality for a COVID-19 outbreak in 2019 instead of 2020. PM2.5 concentrations decreased by 4.2%-29.2% in Beijing, Tianjin, Shijiazhuang, and Taiyuan, and increased by 6.1%-11.5% in Jinan and Zhengzhou. PM2.5 concentrations increased by 10.9%-20.5% without the COVID-19 outbreak of 2020 in mid-eastern China, and the frequency of polluted days increased by 5.3%-18.4%. Source apportionment of PM2.5 during the COVID-19 outbreak showed that industry and residential emissions were the dominant PM2.5 contributors (32.7%-49.6% and 26.0%-44.5%, respectively) followed by agriculture (18.7%-24.0%), transportation (7.7%-15.5%), and power (4.1%-5.9%). In Beijing, industrial and residential contributions to PM2.5 concentrations were lower (32.7%) and higher (44.5%), respectively, than in other cities (38.7%-49.6% for industry and 26.0%-36.2% for residential). Therefore, enhancing regional cooperation and implementing a united air pollution control are effective emission mitigation measures for future air quality improvement, especially the development of new technologies for industrial and cooking fumes.

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