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1.
J Inorg Biochem ; 234: 111880, 2022 Jun 02.
Article in English | MEDLINE | ID: covidwho-1882224

ABSTRACT

Inhibitors of type 1 human immunodeficiency virus (HIV-1) reverse transcriptase are central to anti-HIV therapy. Most of their targets are enzymes, while very few could bind to viral RNA. Here we designed four new polypyridyl Ru(II) complexes, which could bind HIV-1 TAR RNA tightly and selectively by molecular recognition of hydrogen bonds, further stabilize the Ru(II)-RNA bound system by electrostatic attraction, and efficiently inhibit the Moloney murine leukemia virus (M-MuLV) and HIV-1 reverse transcriptase. The polypyridyl Ru(II) complexes also have physical and chemical advantages, including high chemical stability and photostability, sensitive spectroscopic responses to HIV TAR RNA, and low toxicity to normal cells. This work also provides valuable drug design strategies for acquired immune deficiency syndrome (AIDS) and other reverse transcriptase related disease research, such as hepatitis C virus (HCV), Ebola virus (EBOV), influenza A virus, and most recently the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-334378

ABSTRACT

Background: This study investigated the effects of nutritional status at the time of admission on clinical outcomes in patients with Coronavirus disease 2019 (COVID-19). Methods A retrospective analysis was performed on 54 patients diagnosed with COVID-19. Clinical data of admitted patients, albumin and pre-serum albumin levels, gastrointestinal intolerance, and general information were collected and analyzed. The primary clinical outcomes were length of hospital stay and hospitalization costs. Results The results showed that albumin and pre-serum albumin levels of patients at admission were negatively associated with the length of hospital stay and hospitalization costs (P < 0.001). Patients with poor appetite had longer hospital stays (P < 0.001) and higher hospital costs (P = 0.022). Conclusion These results indicated that the nutritional status at admission can directly influence the clinical outcomes of COVID-19.

3.
Nanoscale ; 14(16): 5942-5959, 2022 Apr 21.
Article in English | MEDLINE | ID: covidwho-1778650

ABSTRACT

Filamentous bacteriophages are natural nanoparticles formed by the self-assembly of structural proteins that have the capability of replication and infection. They are used as a highly efficient vaccine platform to enhance immunogenicity and effectively stimulate the innate and adaptive immune response. Compared with traditional vaccines, phage-based vaccines offer thermodynamic stability, biocompatibility, homogeneity, high carrying capacity, self-assembly, scalability, and low toxicity. This review summarizes recent research on phage-based vaccines in virus prevention. In addition, the expression systems of filamentous phage-based virus vaccines and their application principles are discussed. Moreover, the prospect of the prevention of emerging infectious diseases, such as coronavirus 2019 (COVID-19), is also discussed.


Subject(s)
Bacteriophages , COVID-19 , Inovirus , Nanoparticles , Viral Vaccines , COVID-19/prevention & control , Humans , Inovirus/metabolism , Viral Vaccines/metabolism
5.
Front Public Health ; 10: 841345, 2022.
Article in English | MEDLINE | ID: covidwho-1776048

ABSTRACT

Background: Although positive safety leadership has attracted increasingly academic and practical attention due to its critical effects on followers' safety compliance behavior, far fewer steps have been taken to study the safety impact of laissez-faire leadership. Objective: This study examines the relationships between safety-specific leader reward and punishment omission (laissez-faire leadership) and followers' safety compliance, and the mediations of safety-specific distributive justice and role ambiguity. Methods: On a two-wave online survey of 307 workers from high-risk enterprises in China, these relationships were tested by structural equations modeling and bootstrapping procedures. Results: Findings show that safety-specific leader reward omission was negatively associated with followers' safety compliance through the mediating effects of safety-specific distributive justice and role ambiguity. Safety-specific leader punishment omission was also negatively associated with followers' safety compliance through the mediating effect of safety-specific role ambiguity, while safety-specific distributive justice was an insignificant mediator. Originality: The study addresses and closes more gaps by explaining how two contextualized laissez-faire leadership measures relate to followers' safety behaviors, following the contextualization and matching principles between predictors, mediators and criteria, and by revealing two mechanisms behind the detrimental effects of laissez-faire leadership on safety outcomes.


Subject(s)
Leadership , Punishment , Reward , Safety , China , Guideline Adherence , Humans , Social Justice
6.
Front Public Health ; 9: 743087, 2021.
Article in English | MEDLINE | ID: covidwho-1775903

ABSTRACT

Background: With the development of the social economy, air pollution has resulted in increased social costs. Medical costs and health issues due to air pollution are important aspects of environmental governance in various countries. Methods: This study uses daily air pollution monitoring data from 122 cities in China to empirically investigate the impact of air pollution on residents' medical expenses using the Heckman two-stage and instrumental variable methods, matching data from the 2018 China Health and Retirement Longitudinal Study (CHARLS) survey. Results: The study found that poor air quality, measured by the air quality index (AQI), significantly increased the probability of chronic lung disease, heart disease, and self-rated poor health. Additionally, the AQI (with an effect of 4.51%) significantly impacted health-seeking behavior and medical expenses. The medical expenditure effects of mild, moderate, severe, and serious pollution days were 3.27, 7.21, 8.62, and 42.66%, respectively. Conclusion: In the long run, residents' health in areas with a higher air pollution index, indicating poor air quality, is negatively impacted. The more extreme the pollution, the higher the probability of residents' medical treatment and the subsequent increase in medical expenses. Group and regional heterogeneity also play a role in the impact of air pollution on medical expenses. Compared with the existing literature, this study is based on individuals aged 15 years and above and produces reliable research conclusions.


Subject(s)
Air Pollution , Adolescent , Air Pollution/analysis , China , Cities , Conservation of Natural Resources , Environmental Policy , Humans , Longitudinal Studies
7.
Front Public Health ; 9: 740800, 2021.
Article in English | MEDLINE | ID: covidwho-1775894

ABSTRACT

Background: Exposure to ambient particulate matter pollution (APMP) is a global health issue that directly affects the human respiratory system. Thus, we estimated the spatiotemporal trends in the burden of APMP-related respiratory diseases from 1990 to 2019. Methods: Based on the Global Burden of Disease Study 2019, data on the burden of APMP-related respiratory diseases were analyzed by age, sex, cause, and location. Joinpoint regression analysis was used to analyze the temporal trends in the burden of different respiratory diseases over the 30 years. Results: Globally, in 2019, APMP contributed the most to chronic obstructive pulmonary disease (COPD), with 695.1 thousand deaths and 15.4 million disability-adjusted life years (DALYs); however, the corresponding age-standardized death and DALY rates declined from 1990 to 2019. Similarly, although age-standardized death and DALY rates since 1990 decreased by 24% and 40%, respectively, lower respiratory infections (LRIs) still had the second highest number of deaths and DALYs attributable to APMP. This was followed by tracheal, bronchus, and lung (TBL) cancer, which showed increased age-standardized death and DALY rates during the past 30 years and reached 3.78 deaths per 100,000 persons and 84.22 DALYs per 100,000 persons in 2019. Among children aged < 5 years, LRIs had a huge burden attributable to APMP, whereas for older people, COPD was the leading cause of death and DALYs attributable to APMP. The APMP-related burdens of LRIs and COPD were relatively higher among countries with low and low-middle socio-demographic index (SDI), while countries with high-middle SDI showed the highest burden of TBL cancer attributable to APMP. Conclusions: APMP contributed substantially to the global burden of respiratory diseases, posing a significant threat to human health. Effective actions aimed at air pollution can potentially avoid an increase in the PM2.5-associated disease burden, especially in highly polluted areas.


Subject(s)
Air Pollution , Respiratory Tract Diseases , Adult , Aged , Air Pollution/adverse effects , Child , Child, Preschool , Global Burden of Disease , Humans , Particulate Matter/adverse effects , Quality-Adjusted Life Years , Respiratory Tract Diseases/epidemiology
8.
Journal of Medical Virology ; 94(5):i-i, 2022.
Article in English | Wiley | ID: covidwho-1750403

ABSTRACT

Front Cover Caption: The cover image is based on the Research Article Aggregation of high-frequency RBD mutations of SARS-CoV-2 with three VOCs did not cause significant antigenic drift by Tao Li et al., https://doi.org/10.1002/jmv.27596.

9.
Reprod Biol Endocrinol ; 20(1): 46, 2022 Mar 08.
Article in English | MEDLINE | ID: covidwho-1736421

ABSTRACT

BACKGROUND: This study aimed to evaluate the influences of SARS-CoV-2 infection on semen parameters and investigate the impact of the infection on in vitro fertilization (IVF) outcomes. METHODS: This retrospective study enrolled couples undergoing IVF cycles between May 2020 and February 2021 at Tongji Hospital, Wuhan. Baseline characteristics were matched using propensity score matching. Participants were categorized into an unexposed group (SARS-COV-2 negative) and exposed group (SARS-COV-2 positive) based on a history of SARS-CoV-2 infection, and the populations were 148 and 50 after matching, respectively. IVF data were compared between the matched cohorts. Moreover, semen parameters were compared before and after infection among the infected males. The main measures were semen parameters and IVF outcomes, including laboratory and clinical outcomes. RESULTS: Generally, the concentration and motility of sperm did not significantly differ before and after infection. Infected males seemed to have fewer sperm with normal morphology, while all values were above the limits. Notably, the blastocyst formation rate and available blastocyst rate in the exposed group were lower than those in the control group, despite similar mature oocytes rates, normal fertilization rates, cleavage rates, and high-quality embryo rates. Moreover, no significant differences were exhibited between the matched cohorts regarding the implantation rate, biochemical pregnancy rate, clinical pregnancy rate, or early miscarriage rate. CONCLUSIONS: The results of this retrospective cohort study suggested that the semen quality and the chance of pregnancy in terms of IVF outcomes were comparable between the males with a history of SARS-CoV-2 infection and controls, although a decreased blastocyst formation rate and available blastocyst rate was observed in the exposed group, which needs to be reinforced by a multicenter long-term investigation with a larger sample size.


Subject(s)
COVID-19/physiopathology , Fertilization in Vitro/methods , Semen/physiology , Sperm Injections, Intracytoplasmic/methods , Sperm Motility/physiology , Adult , Blastocyst/cytology , Blastocyst/physiology , COVID-19/virology , Embryo Implantation , Embryo Transfer , Female , Humans , Male , Pregnancy , Pregnancy Rate , Retrospective Studies , SARS-CoV-2/physiology , Semen/cytology , Sperm Count , Treatment Outcome
10.
J Infect Dis ; 225(10): 1701-1709, 2022 05 16.
Article in English | MEDLINE | ID: covidwho-1704225

ABSTRACT

BACKGROUND: Control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic needs effective vaccines. METHODS: In a phase 2 randomized, double-blind, placebo-controlled trial, 500 adults aged 18-59 years or ≥60 years were randomized in 2:2:1 ratio to receive 3 doses of 5 µg or 10 µg of a SARS-CoV-2 inactivated vaccine, or placebo separated by 28 days. Adverse events (AEs) were recorded through day 28 after each dosing. Live virus or pseudovirus neutralizing antibodies, and receptor binding domain immunoglobulin G (RBD-IgG) antibody were tested after the second and third doses. RESULTS: Two doses of the vaccine elicited geometric mean titers (GMTs) of 102-119, 170-176, and 1449-1617 for the 3 antibodies in younger adults. Pseudovirus neutralizing and RBD-IgG GMTs were similar between older and younger adults. The third dose slightly (<1.5 fold) increased GMTs. Seroconversion percentages were 94% or more after 2 doses, which were generally similar after 3 doses. The predominant AEs were injection-site pain. All the AEs were grade 1 or 2 in intensity. No serious AE was deemed related to study vaccination. CONCLUSIONS: Two doses of this vaccine induced robust immune response and had good safety profile. A third dose given 28 days after the second dose elicited limited boosting antibody response.


Subject(s)
COVID-19 Vaccines , COVID-19 , Immunogenicity, Vaccine , Adolescent , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Double-Blind Method , Humans , Immunoglobulin G/blood , Middle Aged , SARS-CoV-2 , Vaccines, Inactivated/adverse effects , Vaccines, Inactivated/immunology , Young Adult
11.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-317971

ABSTRACT

Jianhui Nie, Qianqian Li, and Jiajing Wu contributed equally to this work. Pseudotyped viruses are useful virological tools due to their safety and versatility. Based on a VSV pseudotyped virus production system, we developed a pseudotyped virus-based neutralization assay against SARS-CoV-2 in biosafety level 2 facilities. This protocol includes production, titration of the SARS-CoV-2 S pseudotyped virus and neutralization assay based on it. Various types of samples targeting virus attachment and entry could be evaluated for their potency, including serum samples derived from animals and humans, monoclonal antibodies, fusion inhibitors (peptides or small molecules). If the pseudotyped virus stock has been prepared in advance, it will take 2 days to get the potency data for the candidate samples. Experience of handling cells is needed before implementing this protocol.

12.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327528

ABSTRACT

ABSTRACT Wearable sensors can continuously and passively detect potential respiratory infections, before or absent symptoms. However, the population-level impact of deploying these devices during pandemics is unclear. We built a compartmental model of Canada’s second COVID-19 wave and simulated wearable sensor deployment scenarios, systematically varying detection algorithm accuracy, uptake, and adherence. With current detection algorithms and 4% uptake, we found that deploying wearable sensors could have averted 9% of second wave SARS-CoV-2 infections, though 29% of this reduction is attributed to incorrectly quarantining uninfected device users. Improving detection specificity and offering confirmatory rapid tests each minimized incorrect quarantines and associated costs. With a sufficiently low false positive rate, increasing uptake and adherence became effective strategies for scaling averted infections. We concluded that wearable sensor deployment can meaningfully contribute to pandemic mitigation;in the case of COVID-19, technology improvements or supporting measures are required to reduce social and economic costs to acceptable levels.

13.
J Med Virol ; 94(5): 2108-2125, 2022 05.
Article in English | MEDLINE | ID: covidwho-1627779

ABSTRACT

Variants of SARS-CoV-2 continue to emerge, posing great challenges in outbreak prevention and control. It is important to understand in advance the impact of possible variants of concern (VOCs) on infectivity and antigenicity. Here, we constructed one or more of the 15 high-frequency naturally occurring amino acid changes in the receptor-binding domain (RBD) of Alpha, Beta, and Gamma variants. A single mutant of A520S, V367F, and S494P in the above three VOCs enhanced infectivity in ACE2-overexpressing 293T cells of different species, LLC-MK2 and Vero cells. Aggregation of multiple RBD mutations significantly reduces the infectivity of the possible three VOCs. Regarding neutralization, it is noteworthy that E484K, N501Y, K417N, and N439K predispose to monoclonal antibodies (mAbs) protection failure in the 15 high-frequency mutations. Most importantly, almost all possible VOCs (single RBD mutation or aggregation of multiple mutations) showed no more than a fourfold decrease in neutralizing activity with convalescent sera, vaccine sera, and immune sera of guinea pigs with different immunogens, and no significant antigenic drift was formed. In conclusion, our pseudovirus results could reduce the concern that the aggregation of multiple high-frequency mutations in the RBD of the spike protein of the three VOCs would lead to severe antigenic drift, and this would provide value for vaccine development strategies.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antibodies, Neutralizing , COVID-19/therapy , Chlorocebus aethiops , Guinea Pigs , Humans , Immunization, Passive , Mutation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus , Vero Cells
14.
Vaccines (Basel) ; 10(1)2021 Dec 29.
Article in English | MEDLINE | ID: covidwho-1580346

ABSTRACT

Equitable and efficient distribution of COVID-19 vaccines continues to be a key issue in global health, and a targeted approach is needed to meet the World Health Organization's world vaccination targets. Although some low- and middle-income countries (LMICs) are developing their own vaccines to address the distribution problem, legal and technical challenges have had a negative impact on productivity. This article explores relevant international legal instruments that can enable faster research and development of COVID-19 vaccines in LMICs, focusing on the role of biosafety standards, biological materials transfer, and key knowledge sharing. Our analysis has established that the potential of existing global health legal instruments has yet to be realized in order to close the productivity gap in LMICs and strengthen their vaccine manufacturing capacity. Additionally, mutual recognition of vaccine efficacy has become a new challenge for achieving global vaccination targets. We argue that the World Health Organization should continue its leading position by developing a more practical and targeted framework to help LMICs overcome challenges arising from technology transfer, knowledge sharing, and politics.

15.
Nat Med ; 28(1): 175-184, 2022 01.
Article in English | MEDLINE | ID: covidwho-1541244

ABSTRACT

Early detection of infectious diseases is crucial for reducing transmission and facilitating early intervention. In this study, we built a real-time smartwatch-based alerting system that detects aberrant physiological and activity signals (heart rates and steps) associated with the onset of early infection and implemented this system in a prospective study. In a cohort of 3,318 participants, of whom 84 were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), this system generated alerts for pre-symptomatic and asymptomatic SARS-CoV-2 infection in 67 (80%) of the infected individuals. Pre-symptomatic signals were observed at a median of 3 days before symptom onset. Examination of detailed survey responses provided by the participants revealed that other respiratory infections as well as events not associated with infection, such as stress, alcohol consumption and travel, could also trigger alerts, albeit at a much lower mean frequency (1.15 alert days per person compared to 3.42 alert days per person for coronavirus disease 2019 cases). Thus, analysis of smartwatch signals by an online detection algorithm provides advance warning of SARS-CoV-2 infection in a high percentage of cases. This study shows that a real-time alerting system can be used for early detection of infection and other stressors and employed on an open-source platform that is scalable to millions of users.


Subject(s)
COVID-19/diagnosis , Carrier State/diagnosis , Exercise , Heart Rate/physiology , Wearable Electronic Devices , Accelerometry , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/physiopathology , Carrier State/physiopathology , Early Diagnosis , Female , Fitness Trackers , Humans , Male , Middle Aged , SARS-CoV-2 , Sleep , Young Adult
16.
Chinese Journal of School Health ; 42(6):863-866, 2021.
Article in Chinese | CAB Abstracts | ID: covidwho-1502925

ABSTRACT

Objective: To analyze knowledge, attitudes and practice regarding protection against COVID-19 among primary and middle school students in Hangzhou and to provide a scientific basis for schools to carry out targeted prevention and control measures.

17.
Lab Med ; 2021 Oct 27.
Article in English | MEDLINE | ID: covidwho-1493878

ABSTRACT

OBJECTIVE: Real-time reverse transcription-polymerase chain reaction is the gold standard for the diagnosis of COVID-19, but it is necessary to utilize other tests to determine the burden of the disease and the spread of the outbreak such as IgG-, IgM-, and IgA-based antibody detection using enzyme-linked immunosorbent assay (ELISA). MATERIALS AND METHODS: We developed an indirect ELISA assay to quantitatively measure the amount of COVID-19 IgG, IgM, and IgA antibodies present in patient serum, dried blood, and plasma. RESULTS: The population cutoff values for positivity were determined by receiver operating characteristic curves to be 1.23 U/mL, 23.09 U/mL, and 6.36 U/mL for IgG, IgM, and IgA, respectively. After albumin subtraction, the specificity remained >98% and the sensitivity was 95.72%, 83.47%, and 82.60%, respectively, for IgG, IgM, and IgA antibodies to the combined spike subunit 1 receptor binding domain and N proteins in serum. Plasma and dried blood spot specimens were also validated on this assay. CONCLUSION: This assay may be used for determining the seroprevalence of SARS-CoV-2 in a population exposed to the virus or in vaccinated individuals.

18.
Pediatr Pulmonol ; 57(1): 20-25, 2022 01.
Article in English | MEDLINE | ID: covidwho-1473909

ABSTRACT

BACKGROUND: With the onset of the coronavirus disease 2019 (COVID-19) pandemic, many experts expected that asthma-associated morbidity because of severe acute respiratory syndrome coronavirus 2 infection would dramatically increase. However, some studies suggested that there was no apparent increasing in asthma-related morbidity in children with asthma, it is even possible children may have improved outcomes. To understand the relationship between the COVID-19 pandemic and asthma outcomes, we performed this article. METHODS: We searched PubMed, Embase, and Cochrane Library to find literature from December 2019 to June 2021 related to COVID-19 and children's asthma control, among which results such as abstracts, comments, letters, reviews, and case reports were excluded. The level of asthma control during the COVID-19 pandemic was synthesized and discussed by outcomes of asthma exacerbation, emergency room visit, asthma admission, and childhood asthma control test (c-ACT). RESULTS: A total of 22,159 subjects were included in 10 studies. Random effect model was used to account for the data. Compared with the same period before the COVID-19 pandemic, asthma exacerbation reduced (odds ratio [OR] = 0.26, 95% confidence interval [CI] = [0.14-0.48], Z = 4.32, p < 0.0001), the odds of emergency room visit decreased as well (OR = 0.11, 95% CI = [0.04-0.26], Z = 4.98, p < 0.00001). The outcome of asthma admission showed no significant difference (OR = 0.84, 95% CI = [0.32-2.20], Z = 0.36, p = 0.72). The outcome of c-ACT scores were not analyzed because of the different manifestations used. Overall, c-ACT scores reduced during the pandemic. CONCLUSION: Compared to the same period before the COVID-19 pandemic, the level of asthma control has been significantly improved. We need to understand the exact factors leading to these improvements and find methods to sustain it.


Subject(s)
Asthma , COVID-19 , Asthma/epidemiology , Asthma/prevention & control , Child , Hospitalization , Humans , Pandemics , SARS-CoV-2
19.
Front Immunol ; 12: 753558, 2021.
Article in English | MEDLINE | ID: covidwho-1463476

ABSTRACT

To date there is limited data on the immune profile and outcomes of solid organ transplant recipients who encounter COVID-19 infection early post-transplant. Here we present a unique case where the kidney recipient's transplant surgery coincided with a positive SARS-CoV-2 test and the patient subsequently developed symptomatic COVID-19 perioperatively. We performed comprehensive immunological monitoring of cellular, proteomic, and serological changes during the first 4 critical months post-infection. We showed that continuation of basiliximab induction and maintenance of triple immunosuppression did not significantly impair the host's ability to mount a robust immune response against symptomatic COVID-19 infection diagnosed within the first week post-transplant.


Subject(s)
Basiliximab/therapeutic use , COVID-19/immunology , Glomerulonephritis, IGA/therapy , Graft Rejection/immunology , Immunosuppressive Agents/therapeutic use , Kidney Transplantation , SARS-CoV-2/physiology , Adult , Humans , Immune Tolerance , Immunity , Male , Perioperative Period , Transcriptome
20.
Front Immunol ; 12: 748566, 2021.
Article in English | MEDLINE | ID: covidwho-1463474

ABSTRACT

Coronavirus disease 2019 (COVID-19) remains a major health challenge globally. Previous studies have suggested that changes in the glycosylation of IgG are closely associated with the severity of COVID-19. This study aimed to compare the profiles of IgG N-glycome between COVID-19 patients and healthy controls. A case-control study was conducted, in which 104 COVID-19 patients and 104 age- and sex-matched healthy individuals were recruited. Serum IgG N-glycome composition was analyzed by hydrophilic interaction liquid chromatography with the ultra-high-performance liquid chromatography (HILIC-UPLC) approach. COVID-19 patients have a decreased level of IgG fucosylation, which upregulates antibody-dependent cell cytotoxicity (ADCC) in acute immune responses. In severe cases, a low level of IgG sialylation contributes to the ADCC-regulated enhancement of inflammatory cytokines. The decreases in sialylation and galactosylation play a role in COVID-19 pathogenesis via the activation of the lectin-initiated alternative complement pathway. IgG N-glycosylation underlines the complex clinical phenotypes of SARS-CoV-2 infection.


Subject(s)
COVID-19/metabolism , Immunoglobulin G/metabolism , SARS-CoV-2/physiology , Adult , Antibody-Dependent Cell Cytotoxicity , Case-Control Studies , Chromatography, High Pressure Liquid , Complement Pathway, Mannose-Binding Lectin , Female , Glycosylation , Humans , Male , Middle Aged , Phenotype
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