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Clinical trials of convalescent plasma therapy for coronavirus disease 2019 (COVID-19) are extensive, but the relationship between antibody titers, infused volume of plasma and virus clearance in patients remains unknown. This study proposed a possible estimating equation for clinical use of high antibody titer convalescent plasma.A total of 38 patients were recruited in the Guanggu District Maternal and Child Health Hospital of Hubei Province from March 1 to 30, 2020. COVID-19 convalescent plasma was collected and high-titer (≥1:640) anti-S-RBD units used. The SARS-CoV-2 nucleic acid viral load was measured 24 h before and 72 h after convalescent plasma infusion.Convalescent plasma therapy was associated with reduced viral load in patients with moderate and severe severity. The viral negative rate at 72 h was 65.8%. The disappearance of viral nucleic acid in study patients was positively correlated with infuscate antibody titer and volume (r = 0.3375, p = 0.04). A possible estimation equation was as follows: LogThis study proposes a potential dose-response equation that adds a convenient way to estimate the dose of convalescent plasma product. It is beneficial to facilitate the rational allocation of plasma with high antibody titers and provide an individualised use strategy for convalescent plasma therapy.

Tuberculosis (TB) treatment is plagued by liver damage, which often leads to treatment interruptions. Circular RNAs (circRNAs) are a special class of non-coding RNAs abundant in body fluids with important biological functions. However, the role of circRNA in anti-tuberculosis drug-induced liver injury (ADLI) is unclear. We explored ADLI-specific circRNAs in TB patients using circRNA microarrays and verified circMARS in a cohort of 300 individuals. In addition to the value assessment of circMARS in patients using a receiver operating characteristic (ROC) curve, cell experiments were also performed under the guidance of bioinformatics analyses. In particular, we found that circMARS acts as a miRNA sponge by binding to miRNAs. Compared with the blank group, the expressions of circMARS, KMT2C gene, and EGFR protein in the ADLI group were increased, while miR-6808-5p, miR-6874-3p, and miR-3157-5p were decreased. Furthermore, when si-circMARS was used in the ADLI groups, circMARS demotion manifested the opposite results. Subsequently, a self-controlled cohort of 35 participants was used to verify the circMARS-miR-6808-5p/-6874-3p/-3157-5p-KMT2C-EGFR function axis. Therefore, circMARS may participate in the compensatory repair mechanism of ADLI through the function axis, and may be a potential biomarker for ADLI diagnosis in TB patients.

OBJECTIVE To observe the expression of N-methyl-D-aspartate (NMDA), apoptosis and the effect on neurological function recovery in rat model with middle cerebral artery occlusion (MCAO). Diffusion kurtosis imaging (DKI) was used to evaluate crossed cerebellar diaschisis (CCD) and to provide experimental and theoretical basis for the clinical treatment. MATERIALS AND METHODS The MCAO models were established in rats. Eighty-four rats were randomly and evenly divided into 7 groups, including control group, 6-h group, 12-h group, 24-h group, 48-h group, 7-day group and 14-day group. The rats were scanned by MRI at the above time points. Then, rats were sacrificed for H&E staining, immunohistochemical staining and TUNEL staining to detect the expression of NMDA in the core infarct area and cerebellum. At the end, the discussion of relationships between molecular biology and MRI parameters (ADC derived from DWI, and MD, MK and FA derived from DKI) was performed. RESULTS The values of MD, ADC and FA in MCAO rats were all lower than those in the control group. All MRI parameters of the contralateral cerebellum were lower than those of the ipsilateral cerebellum (p

Background In this study, we have investigated the potential regulatory mechanisms of IL‐35 to relieve lupus nephritis (LN) through regulating Janus kinase (JAK)/signal transducers and activators of transcription (STAT) signaling pathway in mesangial cells. Results Among 105 significant differentially expressed proteins (DEPs) between juvenile systemic lupus erythematosus (JSLE) patients with LN and healthy controls, LAIR1, PDGFRβ, VTN, EPHB4, and EPHA4 were downregulated in JSLE‐LN. They consist of an interactive network with PTPN11 and FN1, which involved in IL‐35‐related JAK/STAT signaling pathway. Besides, urinary LAIR1 was significantly correlated with JSLE‐LN clinical parameters such as SLEDAI‐2K, %CD19+ B, and %CD3+ T cells. Through bioinformatics analysis of co‐immunoprecipitation with mass spectrometry results, including GO, KEGG, and STRING, five genes interacted with Lair1 were upregulated by IL‐35, but only Myh10 was downregulated. Therefore, we presumed an interactive network among these DEPs, JAK/STAT, and IL‐35. Moreover, the downregulated phosphorylated (p)‐STAT3, p‐p38 MAPK, and p‐ERK, and the upregulated p‐JAK2/p‐STAT1/4 in IL‐35 overexpressed mesangial cells, and RNA‐sequencing results validated the potential regulatory mechanisms of IL‐35 in alleviating JSLE‐LN disease. Moreover, the relieved histopathological features of nephritis including urine protein and leukocyte scores, a decreased %CD90+αSMA+ mesangial cells and pro‐inflammatory cytokines, the inactivated JAK/STAT signals and the significant upregulated Tregs in spleen, thymus and peripheral blood were validated in Tregs and IL‐35 overexpression plasmid‐treated lupus mice. Conclusions Our study provided a reference proteomic map of urinary biomarkers for JSLE‐LN and elucidated evidence that IL‐35 may regulate the interactive network of LAIR1‐PTPN11‐JAK‐STAT‐FN1 to affect JAK/STAT and MAPK signaling pathways to alleviate inflammation in JSLE‐LN. This finding may provide a further prospective mechanism for JSLE‐LN clinical treatment., A reference proteomic map of urinary biomarkers contributes to the diagnosis of JSLE‐LN. IL‐35 may interact with LAIR1‐PTPN11‐JAK‐STAT‐FN1 to affect JAK/STAT and MAPK signaling pathways to alleviate inflammation in vivo and in vitro. LAIR1 could be a novel potential target of IL‐35‐regulated JAK/STAT signaling pathway in JSLE‐LN.

Cardiovascular endothelial barrier dysfunction is associated with a number of cardiovascular diseases. This study aims to investigate the role of platelet endothelial cell adhesion molecule-1 (PECAM1) in the maintenance of the vascular endothelial barrier integrate. Human umbilical vein endothelial cells (HUVECs) were cultured into monolayers using as an in vitro model to assess the endothelial barrier function. Knockdown of the gene of PECAM1 markedly reduced the transendothelial resistance and increased the permeability of the HUVEC monolayers. From the wild HUVECs, we detected a complex of PECAM1, claudin1, occluding and endothelial cell selective adhesion molecule (ESAM); such a complex was not detected in the PECAM1-deficient HUVECs. Knockdown of either claudin1, or occludin, or ESAM, did not affect the formation of the tight junction (TJ) complex. Exposure to recombinant interleukin (IL)-13 inhibited the expression of PECAM1 and down-regulated the HUVEC monolayer barrier function. PECAM1 plays an important role in the formation of TJ complex.

We demonstrated an all-fiber birefringent comb filter with tunable and switchable wavelength spacing. The comb filter is based on a fiber loop mirror (FLM) with three sections of high-birefringence (HB) fibers and polarization controllers (PCs). The transmission characteristics of the birefringent FLM are dependent of the relative phase difference of the two orthogonal polarization modes and the rotational angles of the different HB fibers. By adjusting the PCs, four different wavelength spacings can be obtained; particularly, interleaving operation—halved and quartered wavelength spacing—can be effectively realized. By using a Jones matrix method, the transmission of the birefringent comb filter is analyzed. The theoretical analysis agrees with the experimental results. © 2014 Wiley Periodicals, Inc. Microwave Opt Technol Lett 56:1666–1670, 2014

Current clinically assays, such as enzyme-linked immunosorbent assay and chemiluminescence immunoassay, for hepatitis B surface antigen (HBsAg) are inferior in terms of either sensitivity and accuracy or rapid and high-throughput analysis. A novel assay based on magnetic beads and time-resolved fluoroimmunoassay was developed for the quantitative determination of HBsAg in human serum. HBsAg was captured using two types of anti-HBsAg monoclonal antibodies (B028, S015) immobilized on to magnetic beads and detected using europium-labeled anti-HBsAg polyclonal detection antibody. Finally, the assay yielded a high sensitivity (0.02 IU/mL) and a wide dynamic range (0.02-700 IU/mL) for HBsAg when performed under optimal conditions. Satisfactory accuracy, recovery and specificity were also demonstrated. The intra- and interassay coefficients of variation were 4.7-8.7% and 3.8-7.5%, respectively. The performance of this assay was further assessed against a well-established commercial chemiluminescence immunoassay kit with 399 clinical serum samples. It was revealed that the test results for the two methods were in good correlation (Y = 1.182X - 0.017, R = 0.989). In the current study, we demonstrated that this novel time-resolved fluoroimmunoassay could be used: as a highly sensitive, automated and high-throughput immunoassay for the diagnosis of acute or chronic hepatitis B virus infection; for the screening of blood or organ donors; and for the surveillance of persons at risk of acquiring or transmitting hepatitis B virus.

Background Cytokeratin 19 fragment antigen (CYFRA 21–1) is used to diagnose and monitor neoplasms. However, the main disadvantages of the currently available CYFRA 21–1 assays include heterogenous technology, being time-consuming, and having low through-put with low insensitivity. This study investigated the use of amplified luminescent proximity homogeneous immunoassay (AlphaLISA) for the quantization of CYFRA 21–1 in human serum. Methods The AlphaLISA kit was developed based on AlphaScreen detection technology with two different anti-CYFRA 21–1 monoclonal antibodies. One was coated on AlphaLISA acceptor beads and the other was biotinylated. Donor beads were coated with streptavidin. The test conditions were optimized and analytical performance was studied. Results The measurement range of AlphaLISA CYFRA 21–1 kit was 0.08–500 ng/ml. Assay detection limit was 0.08 ng/ml. The intra- and interassay coefficients of variation were 3.00–9.00% and 4.00–10.00%, respectively. There was no cross-reaction to alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cancer antigen 19–9 (CA19–9), cytokeratins 8 (CK8), and cytokeratins 18 (CK18). The correlation coefficient of blood samples involved was 0.974 between CYFRA 21–1-AlphaLISA assay and a commercial electrochemiluminescence immunoassay (ECLIA) CYFRA 21–1 kit (Roche). Conclusions The AlphaLISA CYFRA 21–1 kit developed in this study had favorable performance characteristics for clinical application with acceptable analytical sensitivity, specificity, and accuracy.

PBD is an important determinant of osteoporotic fractures. Few studies were performed to search for genes underlying PBD variation in Chinese populations. We tested linkage and/or association of the estrogen receptor alpha gene polymorphism with PBD in 401 Chinese nuclear families. This study suggests the ER-alpha gene may have some minor effects on PBM variation in the Chinese population. Low peak bone density (PBD) in adulthood is an important determinant of osteoporotic fractures in the elderly. PBD variation is mainly regulated by genetic factors. Extensive molecular genetics studies have been performed to search for genes underlying PBD variation, largely in whites. Few studies were performed in Chinese populations. In this study, we simultaneously test linkage and/or association of the estrogen receptor alpha (ER-alpha) gene polymorphism with PBD in 401 Chinese nuclear families (both parents plus their female children) of 1260 subjects, with the 458 children generally between 20 and 40 years of age. All the subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) at polymorphic PvuII and XbaI sites inside the ER-alpha gene. Bone mineral density was measured at the lumbar spine (L1-L4) and hip (femoral neck, trochanter, and intertrochanteric region). Raw bone mineral density values were adjusted by age, height, and weight as covariates. We detected marginally significant results for within-family association (transmission disequilibrium; p = 0.054) between the spine bone mineral density variation and the ER-alpha XbaI genotypes. For the hip bone mineral density variation, significant (p < 0.05) linkage results were generally found for the two intragenic markers. Analyses of the haplotypes defined by the two markers confer further evidence for linkage of the ER-alpha with the hip PBD variation. In conclusion, this study suggests that the ER-alpha gene may have minor effects on PBD variation in our Chinese population.

Total synthesis of the proposed structure (II) results in differences concerning the NMR spectra of the natural product.