Timely diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a prerequisite for treatment and prevention. The serology characteristics and complement diagnosis value ...of the antibody test to RNA test need to be demonstrated.
Serial sera of 80 patients with PCR-confirmed coronavirus disease 2019 (COVID-19) were collected at the First Affiliated Hospital of Zhejiang University, Hangzhou, China. Total antibody (Ab), IgM and IgG antibodies against SARS-CoV-2 were detected, and the antibody dynamics during the infection were described.
The seroconversion rates for Ab, IgM and IgG were 98.8%, 93.8% and 93.8%, respectively. The first detectible serology marker was Ab, followed by IgM and IgG, with a median seroconversion time of 15, 18 and 20 days post exposure (d.p.e.) or 9, 10 and 12 days post onset (d.p.o.), respectively. The antibody levels increased rapidly beginning at 6 d.p.o. and were accompanied by a decline in viral load. For patients in the early stage of illness (0-7 d.p.o), Ab showed the highest sensitivity (64.1%) compared with IgM and IgG (33.3% for both; p<0.001). The sensitivities of Ab, IgM and IgG increased to 100%, 96.7% and 93.3%, respectively, 2 weeks later. When the same antibody type was detected, no significant difference was observed between enzyme-linked immunosorbent assays and other forms of immunoassays.
A typical acute antibody response is induced during SARS-CoV-2 infection. Serology testing provides an important complement to RNA testing in the later stages of illness for pathogenic-specific diagnosis and helpful information to evaluate the adapted immunity status of patients.
Summary
Improving genetic resistance is a preferred method to manage Verticillium wilt of cotton and other hosts. Identifying host resistance is difficult because of the dearth of resistance genes ...against this pathogen. Previously, a novel candidate gene involved in Verticillium wilt resistance was identified by a genome‐wide association study using a panel of Gossypium hirsutum accessions. In this study, we cloned the candidate resistance gene from cotton that encodes a protein sharing homology with the TIR‐NBS‐LRR receptor‐like defence protein DSC1 in Arabidopsis thaliana (hereafter named GhDSC1). GhDSC1 expressed at higher levels in response to Verticillium wilt and jasmonic acid (JA) treatment in resistant cotton cultivars as compared to susceptible cultivars and its product was localized to nucleus. The transfer of GhDSC1 to Arabidopsis conferred Verticillium resistance in an A. thaliana dsc1 mutant. This resistance response was associated with reactive oxygen species (ROS) accumulation and increased expression of JA‐signalling‐related genes. Furthermore, the expression of GhDSC1 in response to Verticillium wilt and JA signalling in A. thaliana displayed expression patterns similar to GhCAMTA3 in cotton under identical conditions, suggesting a coordinated DSC1 and CAMTA3 response in A. thaliana to Verticillium wilt. Analyses of GhDSC1 sequence polymorphism revealed a single nucleotide polymorphism (SNP) difference between resistant and susceptible cotton accessions, within the P‐loop motif encoded by GhDSC1. This SNP difference causes ineffective activation of defence response in susceptible cultivars. These results demonstrated that GhDSC1 confers Verticillium resistance in the model plant system of A. thaliana, and therefore represents a suitable candidate for the genetic engineering of Verticillium wilt resistance in cotton.
Osmotic stress severely inhibits plant growth and development, causing huge loss of crop quality and quantity worldwide. Melatonin is an important signaling molecule that generally confers plant ...increased tolerance to various environmental stresses, however, whether and how melatonin participates in plant osmotic stress response remain elusive. Here, we report that melatonin enhances plant osmotic stress tolerance through increasing ROS-scavenging ability, and melatonin receptor CAND2 plays a key role in melatonin-mediated plant response to osmotic stress. Upon osmotic stress treatment, the expression of melatonin biosynthetic genes including
,
, and
and the accumulation of melatonin are increased in the wild-type plants. The
mutant is defective in osmotic stress-induced melatonin accumulation and thus sensitive to osmotic stress, while exogenous melatonin enhances the tolerance of the wild-type plant and rescues the sensitivity of the
mutant to osmotic stress by upregulating the expression and activity of catalase and superoxide dismutase to repress H
O
accumulation. Further study showed that the melatonin receptor mutant
exhibits reduced osmotic stress tolerance with increased ROS accumulation, but exogenous melatonin cannot revert its osmotic stress phenotype. Together, our study reveals that CADN2 functions necessarily in melatonin-conferred osmotic stress tolerance by activating ROS-scavenging ability in Arabidopsis.
Proprotein convertase subtilisin/kexin 9 (PCSK9) is the ninth member of the secretory serine protease family. It binds to low‐density lipoprotein receptor (LDLR) for endocytosis and lysosome ...degradation in the liver, resulting in an increasing in circulating LDL‐cholesterol (LDL‐c) level. Since a PCSK9 induced increase in plasma LDL‐c contributes to atherosclerosis, PCSK9 inhibition has become a new strategy in preventing and treating atherosclerosis. However, in addition to the effect of PCSK9 on elevating blood LDL‐c levels, accumulating evidence shows that PCSK9 plays an important role in inflammation, likely representing another major mechanism for PCSK9 to promote atherosclerosis. In this review, we discuss the association of PCSK9 and inflammation, and highlight the specific effects of PCSK9 on different vascular cellular components involved in the atherosclerotic inflammation. We also discuss the clinical evidence for the association between PCSK9 and inflammation in atherosclerotic cardiovascular disease. A better understanding of the direct association of PCSK9 with atherosclerotic inflammation might help establish a new role for PCSK9 in vascular biology and identify a novel molecular mechanism for PCSK9 therapy.
In this review, we discuss the association of proprotein convertase subtilisin/kexin 9 (PCSK9) and inflammation, and highlight the specific effects of PCSK9 on different vascular cellular components involved in the atherosclerotic inflammation. We also discuss the clinical evidence for the association between PCSK9 and inflammation in atherosclerotic cardiovascular disease. A better understanding of the direct association of PCSK9 with atherosclerotic inflammation might help establish a new role for PCSK9 in vascular biology and identify a novel molecular mechanism for PCSK9 therapy.
Human adenovirus (HAdV) is a major pathogen that causes acute respiratory tract infections (ARTI) and is frequently associated with outbreaks. The HAdV prevalence and the predominant types ...responsible for ARTI outbreaks remains obscure in China.
A systematic review was performed to retrieve literature that reported outbreaks or etiological surveillance of HAdV among ARTI patients in China from 2009 to 2020. Patient information was extracted from the literature to explore the epidemiological characteristics and clinical manifestations of the infection of various HAdV types. The study is registered with PROSPERO, CRD42022303015.
A total of 950 articles (91 about outbreaks and 859 about etiological surveillance) meeting the selection criteria were included. Predominant HAdV types from etiological surveillance studies differed from those in outbreak events. Among 859 hospital-based etiological surveillance studies, positive detection rates of HAdV-3 (32.73%) and HAdV-7 (27.48%) were significantly higher than other virus types. While nearly half (45.71%) of outbreaks were caused by HAdV-7 with an overall attack rate of 22.32% among the 70 outbreaks for which the HAdVs were typed by the meta-analysis. Military camp and school were main outbreak settings with significantly different seasonal pattern and attack rate, where HAdV-55 and HAdV-7 were identified as the leading type, respectively. Clinical manifestations mainly depended on the HAdV types and patient's age. HAdV-55 infection tends to develop into pneumonia with poorer prognosis, especially in children <5 years old.
This study improves the understanding of epidemiological and clinical features of HAdV infections and outbreaks with different virus types, and helps to inform future surveillance and control efforts in different settings.
Resistance to chemotherapy is a major challenge for the treatment of patients with colorectal cancer (CRC). Previous studies have found that microRNAs (miRNAs) play key roles in drug resistance; ...however, the role of miRNA‐373‐3p (miR‐375‐3p) in CRC remains unclear. The current study aimed to explore the potential function of miR‐375‐3p in 5‐fluorouracil (5‐FU) resistance. MicroRNA‐375‐3p was found to be widely downregulated in human CRC cell lines and tissues and to promote the sensitivity of CRC cells to 5‐FU by inducing colon cancer cell apoptosis and cycle arrest and by inhibiting cell growth, migration, and invasion in vitro. Thymidylate synthase (TYMS) was found to be a direct target of miR‐375‐3p, and TYMS knockdown exerted similar effects as miR‐375‐3p overexpression on the CRC cellular response to 5‐FU. Lipid‐coated calcium carbonate nanoparticles (NPs) were designed to cotransport 5‐FU and miR‐375‐3p into cells efficiently and rapidly and to release the drugs in a weakly acidic tumor microenvironment. The therapeutic effect of combined miR‐375 + 5‐FU/NPs was significantly higher than that of the individual treatments in mouse s.c. xenografts derived from HCT116 cells. Our results suggest that restoring miR‐375‐3p levels could be a future novel therapeutic strategy to enhance chemosensitivity to 5‐FU.
Resistance to chemotherapy is a major challenge for the treatment of patients with colorectal cancer (CRC). Our results suggest that the restoration of microRNA‐375‐3p levels could be a future novel therapeutic strategy to modulate and enhance chemosensitivity to 5‐fluorouracil treatment in CRC.
Anaplastic thyroid cancer is an extremely lethal malignancy without reliable treatment. BRAFV600E point mutation is common in ATCs, which leads to MAPK signaling activation and is regarded as a ...therapeutic target. Resveratrol inhibits ATC cell growth, while its impact on BRAF-MAPK signaling remains unknown. This study aims to address this issue by elucidating the statuses of BRAF-MAPK and STAT3 signaling activities in resveratrol-treated THJ-11T, THJ-16T, and THJ-21T ATC cells and Nthyori 3-1 thyroid epithelial cells. RT-PCR and Sanger sequencing revealed MKRN1-BRAF fusion mutation in THJ-16T, BRAF V600E point mutation in THJ-21T, and wild-type BRAF genes in THJ-11T and Nthyori 3-1 cells. Western blotting and immunocytochemical staining showed elevated pBRAF, pMEK, and pERK levels in THJ-16T and THJ-21T, but not in THJ-11T or Nthyori 3-1 cells. Calcein/PI, EdU, and TUNEL assays showed that compared with docetaxel and doxorubicin and MAPK-targeting dabrafenib and trametinib, resveratrol exerted more powerful inhibitory effects on mutant BRAF-harboring THJ-16T and THJ-21T cells, accompanied by reduced levels of MAPK pathway-associated proteins and pSTAT3. Trametinib- and dabrafenib-enhanced STAT3 activation was efficiently suppressed by resveratrol. In conclusion, resveratrol acts as dual BRAF-MAPK and STAT3 signaling inhibitor and a promising agent against ATCs with BRAF mutation.
The occurrence of emerging contaminants in our water resources poses potential threats to the livings. Due to the poor treatment in wastewater management, treatment technologies are needed to ...effectively remove these products for living organism safety. In this study, Graphene oxide (GO) was tested for the first time for its capacity to remove a kind of emerging wastewater contaminants, metformin. The research was conducted by using a series of systematic adsorption and kinetic experiments. The results indicated that GO could rapidly and efficiently reduce the concentration of metformin, which could provide a solution in handling this problem. The uptake of metformin on the graphene oxide was strongly dependent on temperature, pH, ionic strength, and background electrolyte. The adsorption kinetic experiments revealed that almost 80% removal of metformin was achieved within 20 min for all the doses studied, corresponding to the relatively high k1 (0.232 min−1) and k2 (0.007 g mg−1 min−1) values in the kinetic models. It indicated that the highest adsorption capacity in the investigated range (qm) of GO for metformin was at pH 6.0 and 288 K. Thermodynamic study indicated that the adsorption was a spontaneous (ΔG0 < 0) and exothermic (ΔH0 < 0) process. The adsorption of metformin increased when the pH values changed from 4.0 to 6.0, and decreased adsorption were observed at pH 6.0–11.0. GO still exhibited excellent adsorption capacity after several desorption/adsorption cycles. Besides, both so-called π–π interactions and hydrogen bonds might be mainly responsible for the adsorption of metformin onto GO.
•Rapid and efficient removal of metformin can be achieved during the adsorption process.•Sorption kinetic, isothermal and thermodynamic characteristics of metformin are explored.•The adsorption capacity of GO for metformin is influenced in the presence of NaCl and background electrolyte.•The adsorption mechanism is believed to be so-called π–π interactions and hydrogen bonds between GO and metformin.
Dysbiosis of gut microbiota are commonly reported in autism spectrum disorder (ASD) and may contribute to behavioral impairment. Vitamin A (VA) plays a role in regulation of gut microbiota. This ...study was performed to investigate the role of VA in the changes of gut microbiota and changes of autism functions in children with ASD.
Sixty four, aged 1 to 8 years old children with ASD completed a 6-month follow-up study with VA intervention. High-performance liquid chromatography was used to assess plasma retinol levels. The Autism Behaviour Checklist (ABC), Childhood Autism Rating Scale (CARS) and Social Responsiveness Scale (SRS) were used to assess autism symptoms. CD38 and acid-related orphan receptor alpha (RORA) mRNA levels were used to assess autism-related biochemical indicators' changes. Evaluations of plasma retinol, ABC, CARS, SRS, CD38 and RORA mRNA levels were performed before and after 6 months of intervention in the 64 children. Illumina MiSeq for 16S rRNA genes was used to compare the differences in gut microbiota before and after 6 months of treatment in the subset 20 of the 64 children. After 6 months of intervention, plasma retinol, CD38 and RORA mRNA levels significantly increased (all P < 0.05); the scores of ABC, CARS and SRS scales showed no significant differences (all P > 0.05) in the 64 children. Meanwhile, the proportion of Bacteroidetes/Bacteroidales significantly increased and the proportion of Bifidobacterium significantly decreased in the subgroup of 20 (all false discovery rate (FDR) q < 0.05).
Bacteroidetes/Bacteroidales were the key taxa related to VA. Moreover, VA played a role in the changes in autism biomarkers. It remains unclear whether the VA concentration is associated with autism symptoms.
The study protocol was peer reviewed and approved by the institutional review board of Children's Hospital, Chongqing Medical University in 2013 and retrospectively registered in Chinese Clinical Trial Registry (ChiCTR) on November 6, 2014 (TRN: ChiCTR-ROC-14005442 ).
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