Therapeutic application of decellularized porcine small intestinal submucosa scaffold in conjunctiva reconstruction.

The objective of this study was to investigate the biological feasibility and surgical applicability of decellularized porcine small intestinal submucosa (DSIS) in conjunctiva reconstruction. A total of 52 Balb/c mice were included in the study. We obtained the DSIS by decellularization, evaluated the physical and biological properties of DSIS in vitro, and further evaluated the effect of surgical transplantation of DSIS scaffold in vivo. The histopathology and ultrastructural analysis results showed that the scaffold retained the integrity of the fibrous morphology while removing cells. Biomechanical analysis showed that the elongation at break of the DSIS (239.00 ± 12.51%) were better than that of natural mouse conjunctiva (170.70 ± 9.41%, P < 0.05). Moreover, in vivo experiments confirmed the excellent biocompatibility of the decellularized scaffolds. In the DSIS group, partial epithelialization occurred at day-3 after operation, and the conjunctival injury healed at day-7, which was significantly faster than that in human amniotic membrane (AM) and sham surgery (SHAM) group (P < 0.05). The number and distribution of goblet cells of transplanted DSIS were significantly better than those of the AM and SHAM groups. Consequently, the DSIS scaffold shows excellent biological characteristics and surgical applicability in the mouse conjunctival defect model, and DSIS is expected to be an alternative scaffold for conjunctival reconstruction.

Safety and Immunogenicity After Primary and Booster Inactivated SARS-Cov-2 Vaccination in Patients with Autoimmune Liver Diseases.

Background and Aims: SARS-CoV-2 vaccines-associated autoimmune liver diseases have been reported in several case reports. However, the safety and immunogenicity after primary and booster inactivated SARS-CoV-2 vaccination in patients with autoimmune liver diseases (AILD) is still unknown. Methods: Eighty-four patients with AILD were prospectively followed up after the second dose (primary) of inactivated SARS-CoV-2 vaccine. Some of them received the third dose (booster) of inactivated vaccine. Adverse events (AEs), autoimmune activation, and liver inflammation exacerbation after primary and booster vaccination were recorded. Meanwhile, dynamics of antireceptor-binding-domain IgG (anti-RBD-IgG), neutralizing antibodies (NAbs) and RBD-specific B cells responses were evaluated. Results: The overall AEs in AILD patients after primary and booster vaccination were 26.2% and 13.3%, respectively. The decrease of C3 level and increase of immunoglobulin light chain κ and λ levels were observed in AILD patients after primary vaccination, however, liver inflammation was not exacerbated, even after booster vaccination. Both the seroprevalence and titers of anti-RBD-IgG and NAbs were decreased over time in AILD patients after primary vaccination. Notably, the antibody titers were significantly elevated after booster vaccination (10-fold in anti-RBD-IgG and 7.4-fold in NAbs, respectively), which was as high as in healthy controls. Unfortunately, the inferior antibody response was not enhanced after booster vaccination in patients with immunosuppressants. Changes of atypical memory B cells were inversely related to antibody levels, which indicate that the impaired immune memory was partially restored partly by the booster vaccination. Conclusions: The well tolerability and enhanced humoral immune response of inactivated vaccine supports an additional booster vaccination in AILD patients without immunosuppressants.

The role of regulated necrosis in inflammation and ocular surface diseases.

In recent decades, numerous types of regulated cell death have been identified, including pyroptosis, ferroptosis and necroptosis. Regulated necrosis is characterized by a series of amplified inflammatory responses that result in cell death. Therefore, it has been suggested to play an essential role in the pathogenesis of ocular surface diseases. The cell morphological features and molecular mechanisms of regulated necrosis are discussed in this review. Furthermore, it summarizes the role of ocular surface diseases, such as dry eye, keratitis, and cornea alkali burn, as potential disease prevention and treatment targets.

Dynamic immunogenicity after primary and booster inactivated SARS-CoV-2 vaccination in people living with HIV: A longitudinal observational study.

People living with HIV (PLWH) have poor outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); vaccination reduces the associated mortality. The humoral immune response dynamics after booster inactivated vaccinations in PLWH remain unclear. In this longitudinal observational study, 100 PLWH after primary inactivated SARS-CoV-2 vaccination were consecutively recruited and followed up. After booster vaccination (BV), neutralizing antibodies (NAbs) were detected at 1 month from all the PLWH, and the titer increased sixfold compared to that associated with the primary vaccination (PV), similar to that in healthy controls after BV. The NAbs titer declined over time after BV, but remained higher at 6 months than after PV. The NAbs response was elevated after BV with CD4 count <200 cells/µL, it was the poorest among the different CD4 cell count subgroups. Similar results were observed for anti-RBD-IgG responses. Moreover, RBD-specific MBCs were significantly elevated after BV in PLWH. No serious AEs were observed after BV in PLWH. In conclusion, booster inactivated SARS-CoV-2 vaccination is well tolerated and can elicit robust and durable humoral responses in PLWH. PLWH may benefit from a third dose of the inactivated vaccine.

Association between poor sleep quality and an increased risk of dry eye disease in patients with obstructive sleep apnea syndrome.

Purpose: Obstructive sleep apnea (OSA) is related to an increased incidence of dry eye disease (DED). However, their exact relationship is unknown and requires further well-designed studies with advanced mechanisms detection. Patients and methods: This case-control study included 125 OSA cases and 125 age-gender-matched controls enrolled in the hospital between 1 January and 1 October 2021. OSA diagnosis and classification were performed using a polysomnography (PSG) assay. Detailed ophthalmological examinations, including the Schirmer I test, corneal staining, and ocular surface disease index (OSDI), were used to detect DED-related parameters. A comprehensive ocular surface assay was performed to measure a series of parameters, including first non-invasive first tear film break-up time (f-NIBUT), average non-invasive first tear film break-up time (av-NIBUT), tear meniscus height (TMH), and loss of meibomian gland. In addition, the Pittsburgh Sleep Quality Index (PSQI) scale was used to assess sleep quality. Results: Compared to the control, the OSA group showed an increased DED risk (P = 0.016) along with an increased PSQI score and a higher rate of poor quality sleep (P < 0.001 and P = 0.007, respectively). Stratification of OSA cases indicated that DED-related parameters were impaired in patients with severe OSA (P < 0.05). The analysis of DED-parameters-related factors showed significant correlations between OSA-related indexes and PSQI (P < 0.05). Moreover, the poor sleep quality group in the OSA cases showed worse DED-related parameters (P < 0.05), which was not observed in the control group. Conclusion: OSA, especially the severe stage OSA, was related to an increased risk of DED. Also, sleep quality was correlated with the onset of both OSA and DED, where poor sleep quality revealed a relationship between OSA and the risk of DED. Overall, our findings provided evidence for advanced management of DED and OSA in future.

Association between immunosuppressants and poor antibody responses to SARS-CoV-2 vaccines in patients with autoimmune liver diseases.

The antibody and B cell responses after inactivated SARS-CoV-2 vaccination have not been well documented in patients with autoimmune liver disease (AILD). Therefore, we conducted a prospective observational study that included AILD patients and healthy participants as controls between July 1, 2021, and September 30, 2021, at the Second Affiliated Hospital of Chongqing Medical University. All adverse events (AEs) after the COVID-19 vaccination were recorded and graded. Immunoglobulin (Ig)-G antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein (anti-RBD-IgG) and neutralizicadng antibodies (NAbs) were tested following full-course vaccination (BBIBP-CorV or CoronaVac). In addition, SARS-CoV-2-specific B cells were detected by flow cytometry. In total, 76 AILD patients and 136 healthy controls (HCs) were included. All AEs were mild and self-limiting, and the incidences were similar between the AILD and HCs. The seropositivity rates of anti-RBD-IgG and NAbs in AILD were 97.4% (100% in HCs, p = 0.13) and 63.2% (84.6% in HCs, p < 0.001), respectively. The titers of anti-RBD-IgG and NAbs were significantly lower in AILD patients than those in HCs. After adjusting for confounders, immunosuppressive therapy was an independent risk factor for low-level anti-RBD-IgG (adjusted odds ratio [aOR]: 4.7; 95% confidence interval [CI], 1.5-15.2; p = 0.01) and a reduced probability of NAbs seropositivity (aOR, 3.0; 95% CI, 1.0-8.9; p = 0.04) in AILD patients. However, regardless of immunosuppressants, the SARS-CoV-2-specific memory B cells responses were comparable between the AILD and HC groups. Our results suggest that inactivated SARS-CoV-2 vaccines (BBIBP-CorV and CoronaVac) are safe, but their immunogenicity is compromised in patients with AILD. Moreover, immunosuppressants are significantly associated with poor antibody responses to the SARS-CoV-2 vaccines. These results could inform physicians and policymakers about decisions on screening the populations at higher risk of poor antibody responses to SARS-CoV-2 vaccines and providing additional vaccinations in patients with AILD.

Insights into a new alternative method with graphene oxide/polyacrylamide/Fe3O4 nanocomposite for the extraction of six odor-active esters from Strong-aroma types of Baijiu.

Liquid-liquid extraction (LLE) is the most commonly utilized technique for the extraction of odor-active esters (OAEs) in strong-aroma types of Baijiu (SAB). However, since the contents of different OAEs in SAB vary widely, it is still a puzzle to ensure that all OAEs to be thoroughly extracted by LLE without the problem of saturated adsorption. Herein, a novel approach of magnetic solid phase extraction (MSPE), based on the magnetic graphene oxide nanocomposite modified with polyacrylamide (GO/PAM/Fe3O4), was employed for the efficient extraction of six OAEs from SAB. Compared with LLE, GO/PAM/Fe3O4 exhibited highly selective recognition properties and larger adsorption capacities for OAEs (ranging from 13.68 to 39.06 mg/g), resulting in better extraction performances for OAEs. Coupled with GC-MS, six OAEs in real SAB were successfully determined, with recoveries ranged from 70.1 âˆ¼ 90.0% and LODs at 0.08 âˆ¼ 1.35 µg/L. Overall, the MSPE-GC/MS is a promising alternative for accurate determination of OAEs in SAB.

Marker-Independent Food Identification Enabled by Combing Machine Learning Algorithms with Comprehensive GC × GC/TOF-MS.

Reliable methods are always greatly desired for the practice of food inspection. Currently, most food inspection techniques are mainly dependent on the identification of special components, which neglect the combination effects of different components and often lead to biased results. By using Chinese liquors as an example, we developed a new food identification method based on the combination of machine learning with GC × GC/TOF-MS. The sample preparation methods SPME and LLE were compared and optimized for producing repeatable and high-quality data. Then, two machine learning algorithms were tried, and the support vector machine (SVM) algorithm was finally chosen for its better performance. It is shown that the method performs well in identifying both the geographical origins and flavor types of Chinese liquors, with high accuracies of 91.86% and 97.67%, respectively. It is also reasonable to propose that combining machine learning with advanced chromatography could be used for other foods with complex components.

Quick classification of strong-aroma types of base Baijiu using potentiometric and voltammetric electronic tongue combined with chemometric techniques.

Nowadays, the classification of strong-aroma types of base Baijiu (base SAB) is mainly achieved by human sensory evaluation. However, prolonged tasting brings difficulties for sommeliers in guaranteeing the consistency of results, and may even cause health problems. Herein, an electronic tongue (E-Tongue) combined with a gas chromatography-mass spectrometry (GC-MS) method was successfully developed to grade high-alcoholic base SAB. The E-tongue was capable of identifying base SAB samples into four grades by a discriminant function analysis (DFA) model based on human sensory evaluation results. More importantly, it could effectively and rapidly predict the quality grade of unknown base SAB with an average accuracy up to 95%. The differences of chemical components between base SAB samples were studied by the GC-MS analysis and 52 aroma compounds were identified. The qualitative and quantitative results showed that with the increase of base SAB grade, the varieties and contents of aroma compounds increased. Overall, the comprehensive analysis of E-tongue data and GC-MS results could be in good agreement with human sensory evaluation results, which also proved that the newly developed method has a potential to be a useful alternative to the overall quality grading of base Baijiu.

Safety and immunogenicity of inactivated SARS-CoV-2 vaccines in people living with HIV.

It is important to know the safety and efficacy of vaccination in immunocompromised people living with HIV (PLWH), but currently, there is limited data on the inactivated SARS-CoV-2 vaccines' safety and immune responses in PLWH. In this prospective observational study, 139 PLWH and 120 healthy controls were enrolled and monitored for 21-105 days after a two-dose vaccination. The safety, anti-receptor binding domain IgG (anti-RBD-IgG) and anti-spike-IgG responses, and RBD-specific memory B cell (MBC) responses were evaluated. The overall adverse events within seven days were reported in 12.9% (18/139) of PLWH and 13.3% (16/120) of healthy controls. No serious adverse events occurred in both groups. Overall, the seroprevalence of anti-RBD-IgG in PLWH was significantly decreased (87.1% vs. 99.2%; p<0.001). The geometric mean end-point titer (GMT) of anti-RBD-IgG in PLWH was also reduced, especially in patients with CD4 counts <200 cells/µL, regardless of age, gender, or HIV viral load. GMTs of anti-RBD-IgG in both PLWH and healthy controls declined gradually over time. Similar results were also observed in the anti-spike-IgG response. The frequency of RBD-specific MBCs in PLWH decreased (p<0.05), and then remained stable over time. Lastly, through multivariate analysis, we found the factors that predicted a less robust response to inactivated vaccines in PLWH were a low CD4 count and long time interval after vaccination. In conclusion, inactivated vaccines are well-tolerated in PLWH but with low immunogenicity. Therefore, SARS-CoV-2 vaccines and booster doses should be given priority in PLWH, especially in patients with low CD4 counts.Trial registration: ClinicalTrials.gov identifier: NCT05043129..

Nicotinamide mononucleotide increases cell viability and restores tight junctions in high-glucose-treated human corneal epithelial cells via the SIRT1/Nrf2/HO-1 pathway.

BACKGROUND: Diabetes mellitus (DM)-related corneal epithelial dysfunction is a severe ocular disorder; however, the effects of nicotinamide mononucleotide (NMN) on high-glucose (HG)-treated human corneal epithelial cells (HCECs) remain unclear. METHODS: We conducted an in-vitro study to examine the effects of NMN treatment on HG-treated HCECs. Cell viability was measured using trypan blue stain, mitochondrial membrane potential was measured using JC-1 stain, and intracellular reactive oxygen species and apoptosis assays were conducted using flow cytometry. Transepithelial electrical resistance (TEER) and zonula occludens-1 (ZO-1) immunofluorescence for tight junction examinations were conducted. Immunoblot analyses were conducted to analyze the expression of silent information regulator-1 (SIRT1), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) of the SIRT1/Nrf2/HO-1 pathway. RESULTS: NMN increased cell viability by reducing cell damage, reducing apoptosis, increasing cell migration, and restoring tight junctions in HG-treated HCECs. By analyzing the expressions of SIRT1, Nrf2, HO-1, NMN demonstrated protective effects via the SIRT1/Nrf2/HO-1 pathway. CONCLUSIONS: NMN increases cell viability by reversing cell damage, reducing apoptosis, increasing cell migration, and restoring tight junctions in HG-treated HCECs, and these effects may be mediated by the SIRT1/Nrf2/HO-1 pathway.

Safety and antibody response to inactivated COVID-19 vaccine in patients with chronic hepatitis B virus infection.

BACKGROUND AND AIMS: The safety and antibody responses of coronavirus disease 2019 (COVID-19) vaccination in patients with chronic hepatitis B (CHB) virus infection is still unclear, and exploration in safety and antibody responses of COVID-19 vaccination in CHB patients is significant in clinical practice. METHODS: 362 adult CHB patients and 87 healthy controls at an interval of at least 21 days after a full-course vaccination (21-105 days) were enrolled. Adverse events (AEs) were collected by questionnaire. The antibody profiles at 1, 2 and 3 months were elucidated by determination of anti-spike IgG, anti-receptor-binding domain (RBD) IgG, and RBD-angiotensin-converting enzyme 2 blocking antibody. SARS-CoV-2 specific B cells were also analysed. RESULTS: All AEs were mild and self-limiting, and the incidence was similar between CHB patients and controls. Seropositivity rates of three antibodies were similar between CHB patients and healthy controls at 1, 2 and 3 months, but CHB patients had lower titers of three antibodies at 1 month. Compared to healthy controls, HBeAg-positive CHB patients had higher titers of three antibodies at 3 months (all P < .05) and a slower decline in antibody titers. Frequency of RBD-specific B cells was positively correlated with titers of anti-RBD IgG (OR = 1.067, P = .004), while liver cirrhosis, antiviral treatment, levels of HBV DNA, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and total bilirubin (TB) were not correlated with titers of anti-RBD IgG. CONCLUSIONS: Inactivated COVID-19 vaccines were well tolerated, and induced effective antibody response against SARS-CoV-2 in CHB patients.

Caproicibacterium amylolyticum gen. nov., sp. nov., a novel member of the family Oscillospiraceae isolated from pit clay used for making Chinese strong aroma-type liquor.

An anaerobic, Gram-stain-positive, rod-shaped, motile and spore-forming bacterium, designated strain LBM18003T, was isolated from pit clay used for making Chinese strong aroma-type liquor. Growth occurred at 20-40 °C (optimum, 30-37 °C), pH 4.5-9.5 (optimum, pH 6.5-7.0) and in the presence of 0.0-1.0 % (w/v) sodium chloride (optimum, 0 %). The predominant fatty acids were C16:0, C14:0, C14:0 DMA and C16:0 3-OH, and the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, two unidentified phospholipids and nine unidentified glycolipids. Phylogenetic analysis revealed that strain LBM18003T is a novel member of the family Oscillospiraceae. The 16S rRNA gene sequence similarities of strain LBM18003T to its two most closely related species were less than 94.5 % for distinguishing genera, i.e. closely related to Caproiciproducens galactitolivorans JCM 30532T (94.1 %) and Caproicibacter fermentans DSM 107079T (93.2 %). The genome size of strain LBM18003T was 2 996 201 bp and its DNA G+C content was 48.48 mol%. Strain LBM18003T exhibited 67.8 and 68.1% pairwise-determined whole-genome average nucleotide identity values to Caproiciproducens galactitolivorans JCM 30532T and Caproicibacter fermentans DSM 107079T, respectively; and showed 62.2 and 61.0 % the average amino acid identity values to Caproiciproducens galactitolivorans JCM 30532T and Caproicibacter fermentans DSM 107079T, respectively; and demonstrated 46.1 and 41.5 % conserved genes to Caproiciproducens galactitolivorans JCM 30532T and Caproicibacter fermentans DSM 107079T, respectively. The comparisons of 16S rRNA gene and genome sequences confirmed that strain LBM18003T represented a novel genus of the family Oscillospiraceae. Based on morphological, physiological, biochemical, chemotaxonomic, genotypic and phylogenetic results, strain LBM18003T represents a novel species of a novel genus of the family Oscillospiraceae, for which the name Caproicibacterium amylolyticum gen. nov., sp. nov. is proposed. The type strain is LBM18003T (=GDMCC 1.1626T=JCM 33783T).

Bio-Heat Is a Key Environmental Driver Shaping the Microbial Community of Medium-Temperature Daqu.

"Daqu" is a saccharifying and fermenting agent commonly used in the traditional solid-state fermentation industry (e.g., baijiu and vinegar). The patterns of microbial community succession and flavor formation are highly similar among batches, yet the mechanisms promoting temporal succession in the Daqu microbial ecology remain unclear. Here, we first correlated temporal profiles of microbial community succession with environmental variables (temperature, moisture, and titratable acidity) in medium temperature Daqu (MT-Daqu) throughout fermentation. Temperature dynamics significantly correlated (P < 0.05) with the quick succession of MT-Daqu microbiota in the first 12 d of fermentation, while the community structure was relatively stable after 12 d. Then, we explored the effect of temperature on the MT-Daqu community assembly. In the first 4 d of fermentation, the rapid propagation of most bacterial taxa and several fungal taxa, including Candida, Wickerhamomyces, and unclassified Dipodascaceae and Saccharomycetales species, significantly increased MT-Daqu temperature to 55°C. Subsequently, sustained bio-heat generated by microbial metabolism (53 to 56°C) within MT-Daqu inhibited the growth of most microbes from day 4 to day 12, while thermotolerant taxa, including Bacillus, unclassified Streptophyta, Weissella, Thermoactinomyces, Thermoascus, and Thermomyces survived or kept on growing. Furthermore, temperature as a major driving force on the shaping of MT-Daqu microbiota was validated. Lowering the fermentation temperature by placing the MT-Daqu in a 37°C incubator resulted in decreased relative abundances of thermotolerant taxa, including Bacillus, Thermoactinomyces, and Thermoascus, in the MT-Daqu microbiota. This study revealed that bio-heat functioned as a primary endogenous driver promoting the formation of functional MT-Daqu microbiota.IMPORTANCE Humans have mastered the Daqu preparation technique of cultivating functional microbiota on starchy grains over thousands of years, and it is well known that the metabolic activity of these microbes is key to the flavor production of Chinese baijiu. The pattern of microbial community succession and flavor formation remains highly similar between batches, yet mechanistic insight into these patterns and into microbial population fidelity to specific environmental conditions remains unclear. Our study revealed that bio-heat was generated within Daqu bricks in the first 4 d of fermentation, concomitant with rapid microbial propagation and metabolism. The sustained bio-heat may then function as a major endogenous driving force promoting the formation of the MT-Daqu microbiota from day 4 to day 12. The bio-heat-driven growth of thermotolerant microorganisms might contribute to the formation of flavor metabolites. This study provides useful information for the temperature-based modulation of microbiota function during the fermentation of Daqu.

Terahertz-bandwidth photonic temporal differentiator based on a silicon-on-isolator directional coupler.

We experimentally demonstrate a terahertz-bandwidth photonic differentiator employing a silicon-on-insulator directional coupler. The integrated waveguide coupler with two identical paralleled strip waveguides achieves a first-order differentiator when full energy coupling is met from one waveguide to another. The integrated waveguide coupler can offer different operation bandwidths by changing the length and gap of the strip waveguides. Due to the large 3 dB bandwidth of the directional coupler, we implement the first differentiator with an operation bandwidth of 1.25 THz. The performance of this photonic differentiator is tested using Gaussian-like pulses with a pulsewidth of 2.8 ps, 4 ps, 6 ps, 8 ps, and 10 ps, respectively. The differentiation processing errors and relative energy efficiency are also discussed. This silicon chip may have potential applications in integrated photonic computing circuits with sub-picosecond pulses.