The Sequential and Systemic Administration of BMP-2 and SDF-1α Nanocapsules for Promoting Osteoporotic Fracture Healing.

OBJECTIVE: The objective of this study was to investigate the use of the nanocapsule sequential delivery of BMP-2 and SDF-1α through the peripheral circulatory system to promote the healing of osteoporotic fractures. METHODS: Based on increased vascular permeability in the early hematoma environment around the fracture and the presence of a large number of matrix metalloproteinase MMPs in the inflammatory environment, we designed MMP-sensitive nanocapsules which were formed viain situ free-radical polymerization on the surface of grow factors with 2-(methacryloyloxy) ethyl phosphorylcholine (MPC) and the bisacryloylated VPLGVRTK peptide. The antiphagic effect and biological activity of the growth factors for the nanomicrocapsule delivery system were tested by cell experiments. The 36 SD rats with an osteoporotic fracture model were randomly divided into six groups (A, B, C, D, E, and F). In this paper, the nanocapsules loaded with BMP-2 and SDF-1 are represented as n (BMP-2) and n (SDF-1α). In the six groups, the following different combinations of growth factors were injected into the bone defect site on days 1 and 3 after bone defect surgery: in group A, n (SDF-1α) combined with n (SDF-1α); in group B, n (BMP-2) combined with n (BMP-2); in group C, n (SDF-1α) + n (BMP-2) combined with n (SDF-1α) + n (BMP-2); in group D, n (SDF-1α) combined with n (BMP-2); in group E, n (BMP-2) combined with n (SDF-1α); in group F, nanocapsules without growth factor were used as the control group. Micro-CT was used to observe the effect of n(BMP-2) and n(SDF-1α) sequential delivery inearly healing in osteoporotic fractures. Finally, in this study, we evaluated the safety of the nanocapsules delivery system by detecting ectopic osteogenesis and inflammatory responses in animals. RESULTS: Nanocapsules have low toxicity and protect the integrity and biological activity of growth factors. The results confirmed that nanocapsules could still be effectively targeted to the fracture site on days 1, 3, and 7 after intravenous administration. Growth factors encapsulated in nanocapsules have better bone repair results than natural growth factors. In particular, groups C and D had the best bone repair results than other groups.In vivo experiments confirmed that nanocapsules did not cause significant ectopic osteogenesis and inflammation. CONCLUSION: The results confirmed that the special vascular permeability and inflammatory factor microenvironment of the fracture site could be used to deliver two growth factors with a synergistic effect through venous circulation, which could better promote the healing process of osteoporotic fracture.

Haploinsufficiency of A20 caused by a novel pathogenic missense variant of TNFAIP3 and successfully treated with anti-TNF and immunosuppressive therapies.

Loss-of-function of protein A20, encoded by TNFAIP3, leads to an early-onset haploinsufficiency of A20 (HA20). This study reports one Chinese child with HA20 and explores the genetic etiology of TNFAIP3 variant. The patient exhibited transient recurrent episodes of fever, intermittent signs of arthritis, gastrointestinal symptoms and multiple colonic ulcers. Laboratory tests revealed elevated inflammatory indicators and mild to moderate anemia. Genetic analysis identified a heterozygous de novo variant in his TNFAIP3 gene (c.740C＞T, p. P247L), which had never been reported before. The novel missense variation was validated to be pathogenic through causing insufficient expression of A20, over-activation of NF-κB signaling pathway and elevated levels of proinflammatory cytokines in response to stimulation by lipopolysaccharide. A combination of oral corticosteroids, TNF-α inhibitors and thalidomide freed him from symptoms and abnormal inflammatory indicators. Furthermore, continual improvement of the patient's condition was observed during a follow-up period of five months. We demonstrate a case with a de novo missense variant resulting in a loss-of-function of TNFAIP3, which expands the clinical spectrum of HA20. Cytokine antagonists and immunosuppressants may be effective drugs.

Conversion of drylands to paddy fields on former wetlands restores soil organic carbon by accumulating labile carbon fractions in the Sanjiang Plain, northeast China.

BACKGROUND: Since the 1990s, drylands have been extensively converted to rice paddy fields on the former wetlands in the Sanjiang Plain of northeast China. However, the influence of this successiveland-use change from native wetlands to drylands to rice paddy fields on soil organic carbon (C) dynamics remains unexplored. Here, we compared the difference in soil organic C stock among native wetlands, drylands, and paddy fields, and then used a two-step acid hydrolysis approach to examine the effect of this land-use change on labile C I (LPI-C), labile C II (LPII-C), and recalcitrant C (RP-C) fractions at depths of 0-15 cm, 15-30 cm, and 30-50 cm. RESULTS: Soil organic C stock at a depth of 0-50 cm was reduced by 79% after the conversion of wetlands to drylands but increased by 24% when drylands were converted to paddy fields. Compared with wetlands, paddy fields had 74% lower soil organic C stock at a depth of 0-50 cm. The conversion of wetlands to drylands reduced the concentrations of LPI-C, LPII-C, and RP-C fractions at each soil depth. However, land-use change from drylands to paddy fields only increased the concentrations of LPI-C and LPII-C fractions at the 0-15 cm and 30-50 cm depths. CONCLUSION: The conversion of drylands to paddy lands on former wetlands enhances the soil organic C stock by promoting labile C fraction accumulation, and labile C fractions are more sensitive to this successive land-use change than recalcitrant C fractions in the Sanjiang Plain of northeast China. © 2022 Society of Chemical Industry.

Comprehensive and deep profiling of the plasma proteome with protein corona on zeolite NaY / 药物分析学报

Proteomic characterization of plasma is critical for the development of novel pharmacodynamic bio-markers.However,the vast dynamic range renders the profiling of proteomes extremely challenging.Here,we synthesized zeolite NaY and developed a simple and rapid method to achieve comprehensive and deep profiling of the plasma proteome using the plasma protein corona formed on zeolite NaY.Specifically,zeolite NaY and plasma were co-incubated to form plasma protein corona on zeolite NaY(NaY-PPC),followed by conventional protein identification using liquid chromatography-tandem mass spectrometry.NaY was able to significantly enhance the detection of low-abundance plasma proteins,minimizing the"masking"effect caused by high-abundance proteins.The relative abundance of middle-and low-abundance proteins increased substantially from 2.54％to 54.41％,and the top 20 high-abundance proteins decreased from 83.63％to 25.77％.Notably,our method can quantify approxi-mately 4000 plasma proteins with sensitivity up to pg/mL,compared to only about 600 proteins iden-tified from untreated plasma samples.A pilot study based on plasma samples from 30 lung adenocarcinoma patients and 15 healthy subjects demonstrated that our method could successfully distinguish between healthy and disease states.In summary,this work provides an advantageous tool for the exploration of plasma proteomics and its translational applications.

Anti-hepatocarcinoma HepG2 Cell Mechanism of Jaranol： Based on PI3K/Akt Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo study the in vitro anti-hepatocarcinoma HepG2 cell mechanism of Jaranol. MethodThe methyl thiazolyl tetrazolium （MTT） assay was employed to examine the inhibition of Jaranol （0， 5， 10， 25， 50， 100， 150， 300 μmol·L-1） on HepG2 cell proliferation at different time （24 ， 48 ， 72 h）， annexin V-fluorescein isothiocyante/propidium iodide （Annexin V-FITC/PI） kit to detect the effect of Jaranol （0， 3， 15， 75 μmol·L-1） on HepG2 cell apoptosis， and Western blot to determine the influence of Jaranol on the expression of B-cell lymphoma 2 （Bcl-2） and Bcl-2-associated X protein （Bax） in HepG2 cells. Transcriptome sequencing was performed to analyze the differential expression of genes and changes of related signaling pathways after the treatment of HepG2 cells with Jaranol （15 μmol·L-1）. Real-time PCR was carried out to verify the relative mRNA content of differential genes ［TEK， platelet-derived growth factor receptor α （PDGFRA）， spleen tyrosine kinase （SYK）， phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit gamma （PIK3CG）， Janus kinase 3 （JAK3）， membrane-associated guanylate kinase inverted 2 （MAGI2）］. ResultCompared with the blank group， Jaranol decreased HepG2 proliferation （P<0.05， P<0.01）， increased apoptosis rate of HepG2 cells （P<0.05， P<0.01）， raised Bax expression （P<0.05， P<0.01）， and reduced Bcl-2 expression （P<0.05， P<0.01）. Transcriptome sequencing yielded 59 000 regulated genes， 125 of which showed significantly different expression， with 47 up-regulated and 74 down-regulated. Kyoto Encyclopedia of Genes and Genomes （KEGG） analysis showed that the differential genes related to apoptosis in the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway changed significantly after drug addition. The mRNA expression of TEK， PDGFRA， SYK， PIK3CG， JAK3， and MAGI2 decreased in Jaranol （15 μmol·L-1） group compared with that in the control group （P<0.05）. ConclusionIn vitro cytological experiment verified that Jaranol inhibited the proliferation of HepG2 cells and promoted the apoptosis， possibly by influencing the expression of some differential genes in the PI3K/Akt signaling pathway. The result lays an experimental basis for the follow-up study of the anti-tumor effect of Jaranol， and the further development and utilization of flavonoids.

CXCL5 inhibits tumor immune of lung cancer via modulating PD1/PD-L1 signaling / 中华肿瘤杂志

Objective: To investigate the role of CXCL5 in tumor immune of lung cancer and to explore the potential molecular mechanisms. Methods: A total of 62 cases of patients with lung cancer admitted in the First Affiliated Hospital of Henan University from May 2018 to December 2019 were recruited as study object. Another 20 cases of patients with pulmonary infectious diseases and 20 cases of healthy control were selected as control. Enzyme-linked immunosorbent assay (ELISA) was used to determine serum levels of CXCL5 in patients with lung cancer, pulmonary infectious diseases and healthy control. Immunohistochemical staining (IHC) was used to detect the expressions of CXCL5 and PD-1/PD-L1 in tumor and paracarcinoma tissues of patients with lung cancer. Pearson correlation analysis was used to evaluate the correlation between CXCL5 and PD-1 in tumor and paracarcinoma tissues of patients with lung cancer. Lewis cells either expressing CXCL5 or vector plasmids were used to establish C57BL/6J mice model of lung cancer, and all mice were then divided into vehicle and PD-1 antibody treatment groups, 10 mice for each group. The mice survival and tumor growth curves were recorded. IHC was used to evaluate the expressions of CXCL5, PD-1 as well as the proportions of CD8(+) T and Treg cells in xenograft tumor tissues. Results: In patients with lung cancer, the serum level of CXCL5 [(351.7±51.5) ng/L] was significant higher than that in patients with pulmonary infectious diseases and healthy control [(124.7±23.4) ng/L, P<0.001]. The expression levels of CXCL5 (0.136±0.034), CXCR2 (0.255±0.050), PD-1 (0.054±0.012) and PD-L1 (0.350±0.084) in tumor were significant higher than those in paracarcinoma normal tissues [(0.074±0.022), (0.112±0.023), (0.041±0.007) and (0.270±0.043) respectively, P<0.001]. CXCL5 was significant positively correlated with PD-1 in tumor tissues of lung cancer (r=0.643, P<0.001), but not correlated with PD-1 in paracarcinoma tissues(r=0.088, P=0.496). The vector control group, CXCL5 overexpression group, vector control + anti-PD-1 antibody treatment group and CXCL5 overexpression + anti-PD-1 antibody treatment group all successfully formed tumors in mice, while CXCL5 overexpression increased the tumor growth significantly (P<0.01), which was abrogated by the treatment of anti-PD-1 antibody. CXCL5 overexpression decreased the mice survival time significantly (P<0.01), this effect was also abrogated by the treatment of anti-PD-1 antibody. The proportion of CD8(+) T cells in CXCL5 overexpression group [(10.40±2.00)%] was significant lower than that in vector control group [(21.20±3.30)%, P=0.002]. The proportion of CD4(+) Foxp3(+) Treg cells in CXCL5 overexpression group [(38.40±3.70)%] was significant higher than that in vector control group [(23.30±2.25)%, P<0.001]. After the treatment of anti-PD-1 antibody, no significant difference were observed for the proportion of CD8(+) T cells [(34.10±5.00)% and (33.40±4.00)% respectively] and Treg cells [(14.70±3.50)% and (14.50±3.30)% respectively] in xenograft tumor tissues between CXCL5 overexpression+ anti-PD-1 antibody treatment group and vector control + anti-PD-1 antibody treatment group (P>0.05). Conclusion: The expressions of CXCL5 and PD-1/PD-L1 are all increased significantly in the tumor tissues of patients with lung cancer, CXCL5 may inhibit tumor immune of lung cancer via modulating PD-1/PD-L1 signaling.

Application of nanocellulose in flexible sensors / 生物医学工程学杂志

The shortage of medical resources promotes medical treatment reform, and smart healthcare is a promising strategy to solve this problem. With the development of Internet, real-time health status is expected to be monitored at home by using flexible healthcare systems, which puts forward new demands on flexible substrates for sensors. Currently, the flexible substrates are mainly traditional petroleum-based polymers, which are not renewable. As a natural polymer, cellulose, owing to its wide range of sources, convenient processing, biodegradability and so on, is an ideal alternative. In this review, the application progress of nanocellulose in flexible sensors is summarized. The structure and the modification methods of cellulose and nanocellulose are introduced at first, and then the application of nanocellulose flexible sensors in real-time medical monitoring is summarized. Finally, the advantages and future challenges of nanocellulose in the field of flexible sensors are discussed.

Total virome characterizations of game animals in China reveals a spectrum of emerging viral pathogens

Game animals are wildlife species often traded and consumed as exotic food, and are potential reservoirs for SARS-CoV and SARS-CoV-2. We performed a meta-transcriptomic analysis of 1725 game animals, representing 16 species and five mammalian orders, sampled across China. From this we identified 71 mammalian viruses, with 45 described for the first time. Eighteen viruses were considered as potentially high risk to humans and domestic animals. Civets (Paguma larvata) carried the highest number of potentially high risk viruses. We identified the transmission of Bat coronavirus HKU8 from a bat to a civet, as well as cross-species jumps of coronaviruses from bats to hedgehogs and from birds to porcupines. We similarly identified avian Influenza A virus H9N2 in civets and Asian badgers, with the latter displaying respiratory symptoms, as well as cases of likely human-to-wildlife virus transmission. These data highlight the importance of game animals as potential drivers of disease emergence. HighlightsO_LI1725 game animals from five mammalian orders were surveyed for viruses C_LIO_LI71 mammalian viruses were discovered, 18 with a potential risk to humans C_LIO_LICivets harbored the highest number of potential high risk viruses C_LIO_LIA species jump of an alphacoronavirus from bats to a civet was identified C_LIO_LIH9N2 influenza virus was detected in a civet and an Asian badger C_LIO_LIHumans viruses were also identified in game animals C_LI

An in situ catechol functionalized ε-polylysine/polyacrylamide hydrogel formed by hydrogen bonding recombination with high mechanical property for hemostasis.

In situ hydrogel has attracted widely attention in hemostasis due to its ability to match irregular defects, but its application is limited by insufficient mechanical strength and long gelation time. Although some specifical in situ chemically cross-linked hydrogels could be fast formed and exhibit high mechanical strength, they unable to absorb blood. Hence their applications were further limited in emergency hemostasis usage. In this study, a robust hydrogel formed by hydration of powders was developed using multiple hydrogen bonds crosslinking. Here, catechol groups modified ε-polylysine (PL-CAT) and polyacrylamide (PAAM) were used to construct the PL-CAT/PAAM hydrogel. This hydrogel could be formed within 7 s to adhere and seal bleeding sites. The catechol groups endowed the hydrogel outstanding adhesive strength, which was 3.5 times of fibrin glue. Besides, the mechanical performance of in-situ PL-CAT/PAAM hydrogel was explored and the results showed that the hydrogel exhibited high compressive strength (0.47 MPa at 85% strain). Most importantly, the blood loss of wound treated with PL-CAT/PAAM hydrogel powders was 1/7 of untreated group, indicating the hydrogel's excellent hemostatic effect. And the cytotoxicity studies indicated that the PL-CAT/PAAM hydrogel had low toxicity. To summarize, this hydrogel could be a potential hemostatic material in emergency situations.

Effects of long-term nitrogen addition on dissolved organic matter characteristics in a temperate wetland of Northeast China.

Dissolved organic matter (DOM) plays an indispensable role in ecosystem services and functions in wetlands. While most wetlands have undergone increased nitrogen (N) loading due to intensive human activities, the response of DOM characteristics to long-term N addition remains unexplored. In this study, we assessed the changes in dissolved organic carbon (DOC), NH4+, NO3-, dissolved organic N (DON), dissolved total N (DTN), and dissolved total phosphorus (DTP) in surface water and soil pore water at 15 cm depth after 10 years of N addition at four levels (0, 60, 120, and 240 kg N hm-2 year-1) in a freshwater marsh of Northeast China. We also examined the effect of N addition on DOM aromaticity and humification by measuring the specific UV absorbance at 254 nm (SUVA254), the color per C unit (C/C ratio), and the fulvic acid/humic acid ratio (E4/E6 ratio). Our results showed that N addition significantly altered DOM properties, but the direction and magnitude of these changes generally did not vary with the N addition level. During the growing season, DOC, NH4+, NO3-, DON, and DTN concentrations in both surface water and soil pore water were increased by N addition. Accordingly, N addition increased the DOC/DTP and DTN/DTP ratios but decreased the DOC/DTN ratio in surface water and soil pore water. In addition, the SUVA254 value and C/C ratio increased, while the E4/E6 ratio reduced after N addition in surface water and soil pore water, indicating increases in DOM aromaticity and humification. These observations suggest that long-term N addition changes DOM characteristics by causing stoichiometric imbalances and increasing recalcitrant compounds in temperate freshwater wetlands, which may then deteriorate water quality, alter microbial-mediated ecological processes, and impact downstream aquatic ecosystem structures.

Dosimetric comparison between dIMRT and VMAT for bilateral breast cancer / 中国辐射卫生

Objective To compare the dosimetric difference of target and organs-at-risk between intensity-modulated radiotherapy (dIMRT) and volumetric modulated arc therapy (VMAT) for bilateral breast cancer, so as to discuss the clinical feasibility of radiotherapy for bilateral breast cancer. Methods The clinical data of 18 patients receiving radical or modified radical mastectomy for confirmed bilateral breast cancer were enrolled in this study. dIMRT plans and VMAT plans were designed for each patient, and discuss the dosimetric data of two radiotherapy plans. Results Both the two plans satisfied the prescription. In terms of the homogeneity index, VMAT plans (0.09 ± 0.02) were superior to dIMRT plans (0.11 ± 0.01, P < 0.05). In terms of the conformity index,VMAT plans (0.82 ± 0.52) were superior to dIMRT plans (0.71 ± 0.51, P < 0.05). Furthermore, VMAT plans (0.98 ± 0.06) were superior to dIMRT plans (1.24 ± 0.08, P < 0.05) in the dose gradient index. The V10、V20、V30 and Dmean of lungs in VMAT plans (39.07 ± 4.92，22.19 ± 4.36，12.81 ± 4.71，1309.03 ± 135.55) were higher than those in dIMRT plans (30.34 ± 4.26，17.56 ± 4.31，6.77 ± 3.93，1201.39 ± 166.77, P < 0.05).Meanwhile, the V5 of lungs in VMAT plans (63.36 ± 9.02) was higher than that in dIMRT plans (58.01 ± 7.17, P > 0.05). However, the V5、V30 and Dmean of heart in VMAT plans (51.98 ± 3.60，3.78 ± 1.76，885.89 ± 59.84) were lower than those in dIMRT plans (77.16 ± 12.11，5.22 ± 2.85，1036.96 ± 151.46, P < 0.05). The Dmax of spinal cord in VMAT plans (2150.42 ± 136.19) was significantly lower than that in dIMRT plans (3008.23 ± 304.15, P < 0.05). Monitor units in VMAT plans（792.61 ± 62.53）was significantly lower than that in dIMRT plans (3225.33 ± 498.66, P < 0.05). Conclusion Although VMAT has many advantages: achieves better homogeneity index and conformity index of target areas, reduces the irradiation dose of organs-at-risk, especially, the irradiation dose of heart and spinal cord is significantly reduced, however, it increases the irradiation dose of lungs. To reduce the recurrence of grade ≥ 2 radiation pneumonia, dIMRT should be better considered in the application of radiotherapy for bilateral breast cancer.

Practice and discussion of integrating ideological and political elements into psychiatry / 四川精神卫生

The aim of this paper is to explore the practical measures of integrating “ideological and political course” into “Psychiatry”. “Ideological and political course” is a key measure to foster character and civic virtue in colleges and universities， and a crucial link of “three -full education”. Based on the characteristics of the course “Psychiatry” and the practical experience of the course “ideological and political work” in the faculty of mental health， North Sichuan Medical College， this paper puts forward the strategies of implementing “ideological and political course” from four aspects： improving teachers’ understanding and practical ability of “ideological and political course”， constructing the integration point of ideological and political course in “Psychiatry”， choosing the teaching methods of “ideological and political course” and evaluating the teaching effect， thus providing references for the implementation of “ideological and political course” in the follow-up professional courses.

Evaluation of intervention effect of aerobic combined with resistance exercise on adolescents with moderate mental retardation / 中国学校卫生

Objective@#To explore the effect of aerobic plus resistance training on the intervention of adolescents with moderate mental retardation and to provide reference for healthy development among specific need population.@*Methods@#Totally 29 adolescents with moderate mental retardation, aged 12-17 years from one middle school in Shunde district of Foshan, were divided into intervention group and control group (16/13) with random number table. The intervention group was subjected to aerobic combined resistance exercise for 11 weeks. The control group maintained the original activities. The changes in body composition, muscle strength, cardiorespiratory endurance and balance ability of the two groups of subjects before and after intervention were compared.@*Results@#After the intervention, the intervention group s skeletal muscle (22.90±3.63)kg, muscle mass (39.75±5.57)kg, lean body mass (41.52±6.79)kg, sitting arm support (49.19±35.28)s, standing timing test (22.13±6.01)s, half crunches (20.12±6.48), grip strength [left (15.98±4.86)kg; right (16.37±5.46)kg], heart rate immediately after 2 min stepping exercise (91.43±13.44)frequency/min, Standing on one foot with eyes closed [left (5.82±5.20)s; right (6.02±5.56)s] compared with before exercise, the body fat decreased(t=2.57,2.72,2.07,2.10,3.31,2.92,2.76,3.44, 2.86,2.04,2.38, -2.92,P<0.05); after the intervention, the sitting arm support and closed eyes standing(right) improved(P<0.05).@*Conclusion@#Aerobic combined resistance exercise can improve muscle strength and endurance, aerobic endurance and balance ability in adolescents with moderate mental retardation and adaptability of teenagers with moderate mental retardation.

Effects of Adjuvant Chinese Patent Medicine Therapy on Prevention of Variceal Rebleeding: A Retrospective Cohort Study / 中国结合医学杂志

OBJECTIVE@#To assess whether adjuvant Chinese patent medicines (CPMs) to standard treatment could reduce recurrent bleeding after variceal bleeding in cirrhotic patients.@*METHODS@#This study retrospectively collected 555 consecutive patients who recovered from variceal bleeding. A population-based cohort study was established depending on if adjuvant CPMs were administered to prevent rebleeding. A total of 139 patients who had taken ⩾28 cumulative defined daily doses (cDDDs) of CPMs were included in the CPMs cohort, and 416 patients who used 180 cDDDs of CPMs, respectively. The median rebleeding interval in the CPMs cohort was significantly larger compared with the non-CPMs cohort (113.5 vs. 93.0 days; P=0.008).@*CONCLUSION@#Adjuvant CPMs to standard therapy can significantly reduce the incidence of variceal rebleeding and delay the time to rebleeding.

The change pattern and significance of IgM and IgG in the progress of COVID-19 disease

BackgroundTo investigate the significance of IgM and IgG in the progress of COVID-19. MethodA multicenter cross-sectional study conducted in suspected and confirmed patients from four hospitals of China and a cohort study to identify the change pattern and significance in the process of COVID-19 disease. ResultsA total of 571 patients were enrolled in the cross-sectional study, including 235 confirmed SARS-CoV-2 infection with 91.9% patients IgG positive and 92.3% IgM positive. 30 patients diagnosed with SARS-CoV-2 infection were enrolled in the cohort study for flowing-up in 20 days. The peak of IgM and IgG reached in 10th and 20 th day separately after symptom onset. The relationship between clinical classification and serological antibodies were analysed. The positive rate of COVID-19 IgG and IgM increased along with the clinical classification and the delay of treatment time. ConclusionWe demonstrated the kinetics of IgM and IgG SARS-CoV-2 antibody in COVID-19 patients, which may contribute to explain the results of IgM and IgG SARS-CoV-2 antibody test and predict the prognosis of COVID-19.

Serum protein profiling reveals a landscape of inflammation and immune signaling in early-stage COVID-19 infection

Coronavirus disease 2019 (COVID-19) is a highly contagious infection and threating the human lives in the world. The elevation of cytokines in blood is crucial to induce cytokine storm and immunosuppression in the transition of severity in COVID-19 patients. However, the comprehensive changes of serum proteins in COVID-19 patients throughout the SARS-CoV-2 infection is unknown. In this work, we developed a high-density antibody microarray and performed an in-depth proteomics analysis of serum samples collected from early COVID-19 (n=15) and influenza (n=13) patients. We identified a large set of differentially expressed proteins (n=125) that participate in a landscape of inflammation and immune signaling related to the SARS-CoV-2 infection. Furthermore, the significant correlations of neutrophil and lymphocyte with the CCL2 and CXCL10 mediated cytokine signaling pathways was identified. These information are valuable for the understanding of COVID-19 pathogenesis, identification of biomarkers and development of the optimal anti-inflammation therapy.

Proteome-wide analysis of differentially-expressed SARS-CoV-2 antibodies in early COVID-19 infection

Rapid and accurate tests that detect IgM and IgG antibodies to SARS-CoV-2 proteins are essential in slowing the spread of COVID-19 by identifying patients who are infected with COVID-19. Using a SARS-CoV-2 proteome microarray developed in our lab, we comprehensively profiled both IgM and IgG antibodies in forty patients with early-stage COVID-19, influenza, or non-influenza who had similar symptoms. The results revealed that the SARS-CoV-2 N protein is not an ideal biomarker for COVID-19 diagnosis because of its low immunogenicity, thus tests that rely on this marker alone will have a high false negative rate. Our data further suggest that the S protein subunit 1 receptor binding domain (S1-RBD) might be the optimal antigen for IgM antibody detection, while the S protein extracellular domain (S1+S2ECD) would be the optimal antigen for both IgM and IgG antibody detection. Notably, the combination of all IgM and IgG biomarkers can identify 87% and 73.3% COVID-19 patients, respectively. Finally, the COVID-19-specific antibodies are significantly correlated with the clinical indices of viral infection and acute myocardial injury (p[≤]0.05). Our data may help understand the function of anti-SARS-CoV-2 antibodies and improve serology tests for rapid COVID-19 screening.

SARS-CoV-2 proteome microarray for mapping COVID-19 antibody interactions at amino acid resolution

COVID-19 has quickly become a worldwide pandemic, which has significantly impacted the economy, education, and social interactions. Understanding the humoral antibody response to SARS-CoV-2 proteins may help identify biomarkers that can be used to detect and treat COVID-19 infection. However, no immuno-proteomics platform exists that can perform such proteome-wide analysis. To address this need, we created a SARS-CoV-2 proteome microarray to analyze antibody interactions at amino acid resolution by spotting peptides 15 amino acids long with 5-amino acid offsets representing full-length SARS-CoV-2 proteins. Moreover, the array processing time is short (1.5 hours), the dynamic range is ~2 orders of magnitude, and the lowest limit of detection is 94 pg/mL. Here, the SARS-CoV-2 proteome array reveals that antibodies commercially available for SARS-CoV-1 proteins can also target SARS-CoV-2 proteins. These readily available reagents could be used immediately in COVID-19 research. Second, IgM and IgG immunogenic epitopes of SARS-CoV-2 proteins were profiled in the serum of ten COVID-19 patients. Such epitope biomarkers provide insight into the immune response to COVID-19 and are potential targets for COVID-19 diagnosis and vaccine development. Finally, serological antibodies that may neutralize viral entry into host cells via the ACE2 receptor were identified. Further investigation into whether these antibodies can inhibit the propagation of SARS-CoV-2 is warranted. Antibody and epitope profiling in response to COVID-19 is possible with our peptide-based SARS-COV-2 proteome microarray. The data gleaned from the array could provide invaluable information to the scientific community to understand, detect, and treat COVID-19.

Chronic nitrogen addition promotes dissolved organic carbon accumulation in a temperate freshwater wetland.

Temperate wetlands have been undergoing increased nitrogen (N) inputs in the past decades, yet its influence on dissolved organic carbon (DOC) dynamics is still elusive in these ecosystems. Here, using a field multi-level N addition (0, 6, 12, and 24 g N m-2 year-1) experiment, we investigated the changes in aboveground plant biomass, DOC production from plant litters, DOC biodegradation, and DOC concentration in surface water and soil pore water (0-15 cm depth) following 10 years of N addition in a freshwater marsh of Northeast China. We observed that, irrespective of N addition levels, N addition caused an increase in DOC production from plant litters under both non-flooded and flooded conditions. Conversely, DOC biodegradation was inhibited by N addition in both surface water and soil pore water. Because of enhanced DOC production from plant litters and declined DOC biodegradation, N addition elevated DOC concentration in surface water and soil pore water across the growing season. In addition, long-term N addition increased aboveground plant biomass, but decreased species richness. Our results suggest that long-term N enrichment promotes DOC accumulation through the contrasting effects on litter-derived DOC production and microbial decomposition of DOC in temperate wetlands.

Recent advances in the discovery of dengue virus inhibitors / 药学学报

Dengue fever is one of the most important vector-borne human diseases caused by mosquito vector Aedes aegypti and Aedes albopictus. Dengue virus can cause dengue fever, dengue hemorrhagic fever and dengue shock syndrome. There are no approved drugs for the treatment of dengue disease so far. In this paper, combined with the latest progress in the research of anti-dengue virus, the new progress in the research of anti-dengue virus drugs was reviewed from the aspects of protease inhibitors, virus polymerase inhibitors, entry inhibitors, virus replication-related host factor inhibitors, capsid protein inhibitors and nucleic acid inhibitors.