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Background: Nasal and paranasal sinus abnormalities may be related to nasolacrimal duct obstructive disease but are strongly debated. Data of acute disease stage are lacking. Objective: The purpose of this study was to determine if there are correlations between radiologic signs of sinus inflammation and acute dacryocystitis (AD). Methods: This cross-sectional controlled study was conducted at Wenzhou, Zhejiang Province, China from February 2021 to November 2023. Forty-four consecutive patients with AD and 50 consecutive patients with orbital tumors (the control group), who completed preoperative computed tomography scans, were enrolled to evaluate the extent of their inflammatory sinonasal disease by the modified Lund-Mackay score system. Results: The inflammation signs of the paranasal sinuses (total mean sinus scores, 95% CI [0.00, 2.00]; P < 0.001), namely the anterior ethmoid sinus(95% CI [0.00, 1.00]; P < 0.001), the posterior ethmoid sinus(95% CI [0.00, 0.00]; P = 0.003), the frontal sinus (95% CI [0.00, 0.00]; P = 0.02), and the ostiomeatal complex (P < 0.001) were more extensive in patients with AD when compared with the controls. The disease course was negatively correlated with the anterior ethmoid (P = 0.03) and frontal scores (P = 0.01). The symptom of eyelid swelling was positively correlated with the anterior ethmoid (P = 0.03), ostiomeatal complex (P = 0.004), and total sinus scores (P = 0.005). Conclusion: Inflammatory sinus disease was found to be more frequent in patients with AD, which was gradually alleviated with the prolongation of the disease course. The mutual spread of inflammation particularly in the acute course may play an important role in lacrimal duct obstructive disease. [ABSTRACT FROM AUTHOR]

In this work, we proposed a method to extract the distribution of the built-in field (Eb) from the switching dynamics of the TiN/HfZrO/TiN capacitor. The relationship between reversal polarization and the distribution of Eb is established based on the classic inhomogeneous field mechanism model. Both positive and negative write pulses with different amplitudes and durations are applied to obtain the distribution parameters of Eb. The distribution of Eb is fitted by a Gaussian-type distribution, and the mean value and standard deviation are about −0.02 MV/cm and 0.28 MV/cm, respectively. This work provides an effective approach to analyze Eb directly from the electrical measurement and helps optimize the device design from the polarization switching point of view. [ABSTRACT FROM AUTHOR]

Summary: Adaptation of hepatitis C virus (HCV) to CD8+ T cell selection pressure is well described; however, it is unclear if HCV differentially adapts in different populations. Here, we studied HLA class I‐associated viral sequence polymorphisms in HCV 1b isolates in a Chinese population and compared viral substitution patterns between Chinese and German populations. We identified three HLA class I‐restricted epitopes in HCV NS3 with statistical support for selection pressure and found evidence for differential escape pathways between isolates from China and Germany depending on the HLA class I molecule. The substitution patterns particularly differed in the epitope VTLTHPITK1635‐1643, which was presented by HLA‐A*03 as well as HLA‐A*11, two alleles with highly different frequencies in the two populations. In Germany, a substitution in position seven of the epitope was the most frequent substitution in the presence of HLA‐A*03, functionally associated with immune escape and nearly absent in Chinese isolates. In contrast, the most frequent substitution in China was located at position two of the epitope and became the predominant consensus residue. Moreover, substitutions in position one of the epitope were significantly enriched in HLA‐A*11‐positive individuals in China and associated with different patterns of CD8+ T cell reactivity. Our study confirms the differential escape pathways selected by HCV that depended on different HLA class I alleles in Chinese and German populations, indicating that HCV differentially adapts to distinct HLA class I alleles in these populations. This result has important implications for vaccine design against highly variable and globally distributed pathogens, which may require matching antigen sequences to geographic regions for T cell‐based vaccine strategies. [ABSTRACT FROM AUTHOR]

CD8+ T cells are an essential component of successful adaptive immune responses against hepatitis C virus (HCV). A major obstacle to vaccine design against HCV is its inherent viral sequence diversity. Here, we test the hypothesis that different sequence variants of an immunodominant CD8+ T cell epitope, all binding with high affinity to HLA class I, target different T cell receptor repertoires and thereby influence the quality of the CD8+ T cell response. The impacts of sequence differences in the HLA-A*02-restricted HCV NS31406-1415 epitope on in vitro priming of naive CD8+ T cells from seronegative donors and cross-reactivity of primed T cells with other epitope variants were characterized. Although the six epitope variants tested were all high-affinity binders to HLA-A*02:01, substantial differences in priming and cross-reactivity of CD8+ T cells were observed. The variant associated with the most reproducible priming and induction of T cells with broad cross-reactivity was a genotype 1b variant (KLSAL GLNAV) that is more common in HCV isolates collected in Asia but is rare in sequences from Europe and North America. The superior immunogenicity and cross-reactivity of this relatively rare epitope variant were confirmed by using HCV-specific memory CD8+ T cells from people who inject drugs, who are frequently exposed to HCV. Collectively, the data suggest that sequence differences at the epitope level between HCV isolates substantially impact CD8+ T cell priming and the degree of cross-reactivity with other epitope variants. [ABSTRACT FROM AUTHOR]

Adaptation of hepatitis C virus (HCV) to CD8 + T cell selection pressure is well described; however, it is unclear if HCV differentially adapts in different populations. Here, we studied HLA class I-associated viral sequence polymorphisms in HCV 1b isolates in a Chinese population and compared viral substitution patterns between Chinese and German populations. We identified three HLA class I-restricted epitopes in HCV NS3 with statistical support for selection pressure and found evidence for differential escape pathways between isolates from China and Germany depending on the HLA class I molecule. The substitution patterns particularly differed in the epitope VTLTHPITK 1635-1643 , which was presented by HLA-A*03 as well as HLA-A*11, two alleles with highly different frequencies in the two populations. In Germany, a substitution in position seven of the epitope was the most frequent substitution in the presence of HLA-A*03, functionally associated with immune escape and nearly absent in Chinese isolates. In contrast, the most frequent substitution in China was located at position two of the epitope and became the predominant consensus residue. Moreover, substitutions in position one of the epitope were significantly enriched in HLA-A*11-positive individuals in China and associated with different patterns of CD8 + T cell reactivity. Our study confirms the differential escape pathways selected by HCV that depended on different HLA class I alleles in Chinese and German populations, indicating that HCV differentially adapts to distinct HLA class I alleles in these populations. This result has important implications for vaccine design against highly variable and globally distributed pathogens, which may require matching antigen sequences to geographic regions for T cell-based vaccine strategies., (© 2018 The Authors. Journal of Viral Hepatitis Published by John Wiley & Sons Ltd.)

Unlabelled: CD8+ T cells are an essential component of successful adaptive immune responses against hepatitis C virus (HCV). A major obstacle to vaccine design against HCV is its inherent viral sequence diversity. Here, we test the hypothesis that different sequence variants of an immunodominant CD8+ T cell epitope, all binding with high affinity to HLA class I, target different T cell receptor repertoires and thereby influence the quality of the CD8+ T cell response. The impacts of sequence differences in the HLA-A*02-restricted HCV NS31406-1415 epitope on in vitro priming of naive CD8+ T cells from seronegative donors and cross-reactivity of primed T cells with other epitope variants were characterized. Although the six epitope variants tested were all high-affinity binders to HLA-A*02:01, substantial differences in priming and cross-reactivity of CD8+ T cells were observed. The variant associated with the most reproducible priming and induction of T cells with broad cross-reactivity was a genotype 1b variant (KLSALGLNAV) that is more common in HCV isolates collected in Asia but is rare in sequences from Europe and North America. The superior immunogenicity and cross-reactivity of this relatively rare epitope variant were confirmed by using HCV-specific memory CD8+ T cells from people who inject drugs, who are frequently exposed to HCV. Collectively, the data suggest that sequence differences at the epitope level between HCV isolates substantially impact CD8+ T cell priming and the degree of cross-reactivity with other epitope variants., Importance: The results have important implications for vaccine design against highly variable pathogens and suggest that evidence-based selection of the vaccine antigen sequence may improve immunogenicity and T cell cross-reactivity. Cross-reactive CD8+ T cells are likely beneficial for immune control of transmitted viruses carrying epitope variants and for prevention of immune escape during acute infection. To this end, rare epitope variants and potentially even altered epitope sequences associated with priming of broadly cross-reactive T cell receptors should be considered for vaccine design and need further testing., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)