The effect of overexpression of CyPA on gene expression in human umbilical vein endothelial cells.

The aim of this study is to screen the differentially expressed genes and genes with alternative splicing in PPIA overexpressing cells by transcriptome sequencing. Transcriptome sequencing was performed to identify differentially expressed genes and genes with altered alternative splicing in PPIA overexpressing cells and results were validated by real-time quantitative polymerase chain reaction. The biological function and pathways of those genes were further explored through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses. A total of 157 significantly upregulated genes and 171 significantly downregulated genes were identified in PPIA overexpressing cells, and the splicing pattern of LHPP, APH1A, BRD1, and ORAI3 was found to be altered. GO analyses showed that the most enriched GO terms of the 157 upregulated genes included extracellular region, protein binding, and metal ion, and the most enriched GO terms of the 171 downregulated genes included binding neuron projection, protein binding, and endoplasmic reticulum unfolded protein response. Kyoto Encyclopedia of Genes and Genomes analyses showed that the 157 upregulated genes were mainly enriched in gastric acid secretion, Mitogen-activated protein kinase signaling pathway, etc, and the 171 downregulated genes were mainly enriched in transcriptional misregulation in cancer, Tumor necrosis factor signaling pathway, etc. The overexpression of PPIA in human umbilical vein endothelial cells causes changes in the expression of downstream genes and induces alternative splicing in multiple genes. PPIA alters the expression or the alternative splicing pattern of downstream genes, leading to pathogenesis of vascular endothelial injury by high glucose mediated through CyPA.

Sildenafil-induced bilateral ciliochoroidal effusion syndrome: Case report.

PURPOSE: To report a case of bilateral ciliochoroidal effusion syndrome associated with sildenafil use. CASE REPORT: A 41-year-old male presented with a five-day history of bilateral blurred vision, elevated intraocular pressure, and myopic shift. Ultrasound biomicroscopy radial scans showed closed angles and 360 degrees of ciliochoroidal effusion in both eyes. Anterior segment coherence tomography angiography showed bilateral shallow anterior chamber. Further questioning revealed that the patient had taken sildenafil several times just a few days before symptoms appeared. Since then, the patient stopped dosing sildenafil. After treatment of anti-inflammation and shifting the lens-iris diaphragm posteriorly, the patient's visual acuity improved and intraocular pressure decreased. Follow-up ultrasound biomicroscopy and anterior segment coherence tomography angiography revealed resolution of ciliochoroidal effusion and increase of anterior chamber depth in both eyes. CONCLUSIONS: The patient demonstrated a rare case of sildenafil-induced bilateral ciliochoroidal effusion syndrome. This case report shows that sildenafil should be added to the possible causative agents of ciliochoroidal effusion syndrome.

Improvement in caffeic acid and ferulic acid extraction by oscillation-assisted mild hydrothermal pretreatment from sorghum straws.

This work investigated the effect of oscillation-assisted hydrothermal process on extraction of caffeic acid and ferulic acid from sorghum straws. The results showed that the oscillation-assisted hydrothermal process efficiently improved extraction of caffeic acid and ferulic acid. The oscillation-assisted hydrothermal process resulted in the extraction rates of 1275.48 and 1822.64 mg/L.h for caffeic acid and ferulic acid, respectively. Moreover, the oscillation-assisted hydrothermal process exerted destructive effects on hemicellulose, lignin and the amorphous regions of cellulose, contributing to the release of caffeic acid and ferulic acid in pretreated sorghum straws. The scavenging activities for hydroxyl, 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid radicals of the caffeic acid and ferulic acid extracts obtained by the oscillation-assisted hydrothermal process were determined to be 83.69 %, 84.17 % and 88.45 %, respectively.

Effects of operating conditions on the in situ control of sulfur-containing odors by using a novel alternative landfill cover and its transformation mechanism.

Sulfur-containing gases are main sources of landfill odors, which has become a big issue for pollution to environment and human health. Biocover is promising for treating landfill odors, with advantages of durability and environmental friendliness. In this study, charcoal sludge compost was utilized as the main effective component of a novel alternative landfill cover and the in situ control of sulfur-containing odors from municipal solid waste landfilling process was simulated under nine different operating conditions. Results showed that five sulfur-containing odors (hydrogen sulfide, H2S; methyl mercaptan, CH3SH; dimethyl sulfide, CH3SCH3; ethylmercaptan, CH3CH2SH; carbon disulfide, CS2) were monitored and removed by the biocover, with the highest removal efficiencies of 77.18% for H2S, 87.36% for CH3SH, and 92.19% for CH3SCH3 in reactor 8#, and 95.94% for CH3CH2SH and 94.44% for CS2 in reactor 3#. The orthogonal experiment showed that the factors influencing the removal efficiencies of sulfur-containing odors were ranked from high to low as follows: temperature > weight ratio > humidity content. The combination of parameters of 20% weight ratio, 25°C temperature, and 30% water content was more recommended based on the consideration of the removal efficiencies and economic benefits. The mechanisms of sulfur conversion inside biocover were analyzed. Most organic sulfur was firstly degraded to reduced sulfides or element sulfur, and then oxidized to sulfate which could be stable in the layer as the final state. In this process, sulfur-oxidizing bacteria play a great role, and the distribution of them in reactor 1#, 5#, and 8# was specifically monitored. Bradyrhizobiaceae and Rhodospirillaceae were the dominant species which can utilize sulfide as substance to produce sulfate and element sulfur, respectively. Based on the results of OUTs, the biodiversity of these sulfur-oxidizing bacteria, these microorganisms, was demonstrated to be affected by the different parameters. These results indicate that the novel alternative landfill cover modified with bamboo charcoal compost is effective in removing sulfur odors from landfills. Meanwhile, the findings have direct implications for addressing landfill odor problems through parameter adjustment.

Corrigendum: The prevalence, incidence, and persistence of self-reported visual impairment among Chinese population with diabetes mellitus: evaluation from a nationally representative survey, 2015-2018.

[This corrects the article DOI: 10.3389/fpubh.2023.978457.].

NHC-catalyzed formal [3 + 3] annulations of δ-acetoxy allenoates for the synthesis of 4H-pyran derivatives.

Herein, an N-heterocyclic carbene (NHC) catalyzed formal [3 + 3] annulation of δ-acetoxy allenoates with 1C,3O-bisnucleophiles for the construction of 4H-(fused)pyrans has been developed. This protocol provides a facile method to synthesize highly functionalized 4H-pyrans and has a broad substrate scope (30 examples, up to 77% yield).

The prevalence, incidence, and persistence of self-reported visual impairment among Chinese population with diabetes mellitus: evaluation from a nationally representative survey, 2015-2018.

Aims: Our aim was to investigate the prevalence, incidence, and persistence of visual impairment (VI) and their correlates among the Chinese population with diabetes mellitus (DM) over 3 years. Materials and methods: The China Health and Retirement Longitudinal Survey is the first nationally representative longitudinal survey of the Chinese population. A cross-sectional analysis of prevalent VI in 2015 consisted of 2,173 participants with DM. A longitudinal observation of incident and persistent VI consisted of 1,633 participants from 2015 to 2018. Risk factors of VI were identified via univariate and multivariate logistic regression analyses. Results: Among our study population with DM, 11.8% reported VI in 2015, 4.5% had persistent VI from 2015 to 2018, and 8.9% developed VI in 2018. Factors identified to be correlated to VI (p < 0.05) were older age, being a woman, lower educational attainment, living in a rural area, application of DM medication and non-pharmacological treatment, receiving DM-related tests, use of spectacles, and poorer health status. Conclusion: This most recent national data provides a baseline for future public health initiatives on VI among the Chinese population with DM. With multiple risk factors identified, these could provide concurrent targets for various public health strategies and interventions with the aim of reducing the burden of VI among the population with DM in China.

Associations between metabolic score for visceral fat and the risk of cardiovascular disease and all-cause mortality among populations with different glucose tolerance statuses.

AIMS: To investigate the associations between metabolic score for visceral fat (METS-VF) and clinical outcomes among populations with different glucose tolerance statuses. METHODS: We analysed 6827 participants aged ≥ 40 years with different glucose tolerance statuses from a cohort study. The associations between METS-VF and cardiovascular disease (CVD) events and all-cause mortality were assessed using Cox regression, restricted cubic spline and receiver operating characteristic curves. RESULTS: During a follow-up of 5.00 years, there were 338 CVD events and 307 subjects experienced all-cause death. The METS-VF quartile (Quartile 4 versus 1) was significantly related to CVD events [adjusted HRs and 95% CIs: 5.75 (2.67-12.42), 2.80 (1.76-4.48), and 3.31 (1.28-8.54) for subjects with normal glucose tolerance, prediabetes and diabetes, respectively] and all-cause mortality [adjusted HRs and 95% CIs: 2.80 (1.43-5.49), 4.15 (2.45-7.01), and 4.03 (1.72-9.42), respectively]. Restricted cubic spline suggested a dose-response association of METS-VF with the risk of CVD events and all-cause mortality. The area under curve for CVD events and all-cause mortality was higher for METS-VF than for the other obesity and IR indexes in subjects with different glucose tolerance statuses. CONCLUSIONS: The METS-VF was associated with an increased risk of CVD events and all-cause mortality and could be used as a predictive index of the risk of CVD events and all-cause mortality among populations with different glucose tolerance statuses.

Omicron variants escape the persistent SARS-CoV-2-specific antibody response in 2-year COVID-19 convalescents regardless of vaccination.

With the ongoing COVID-19 pandemic and the emergence of various SARS-CoV-2 variants, a comprehensive evaluation of long-term efficacy of antibody response in convalescent individuals is urgently needed. Several longitudinal studies had reported the antibody dynamics after SARS-CoV-2 acute infection, but the follow-up was mostly limited to 1 year or 18 months at the maximum. In this study, we investigated the durability, potency, and susceptibility to immune evasion of SARS-CoV-2-specific antibody in COVID-19 convalescents for 2 years after discharge. These results showed the persistent antibody-dependent immunity could protect against the WT and Delta variant to some extent. However, the Omicron variants (BA.1, BA.2, and BA.4/5) largely escaped this preexisting immunity in recovered individuals. Furthermore, we revealed that inactivated vaccines (BBIBP-CorV, CoronaVac, or KCONVAC) could improve the plasma neutralization and help to maintain the broadly neutralizing antibodies at a certain level. Notably, with the time-dependent decline of antibody, 1-dose or 2-dose vaccination strategy seemed not to be enough to provide immune protection against the emerging variants. Overall, these results facilitated our understanding of SARS-CoV-2-induced antibody memory, contributing to the development of immunization strategy against SARS-CoV-2 variants for such a large number of COVID-19 survivors.

Associations of lipid parameters with non-alcoholic fatty liver disease in type 2 diabetic patients according to obesity status and metabolic goal achievement.

Aims: Non-obese non-alcoholic fatty liver disease (NAFLD) phenotype has sparked interest and frequently occurred in type 2 diabetes mellitus (T2DM). Information on associations between lipid parameters and NAFLD in non-obese patients with diabetes has been lacking. We aimed to investigate the relationships between lipid parameters and NAFLD according to obesity status and metabolic goal achievement in T2DM patients. Methods: A total of 1,913 T2DM patients who were hospitalized between June 2018 and May 2021 were cross-sectionally assessed. We used logistic regression models to estimate the associations of lipid parameters with NAFLD risk according to obesity and metabolic goal achievement status. Results: Higher triglycerides, non-HDL-cholesterol, and all lipid ratios including (total cholesterol/HDL-cholesterol, triglyceride/HDL-cholesterol, LDL-cholesterol/HDL-cholesterol, non-HDL-cholesterol/HDL-cholesterol), and lower HDL-cholesterol were associated with NAFLD risk in both non-obese and obese patients. The associations were stronger in non-obese patients than in obese patients. Further, the inverse associations of total cholesterol and LDL-cholesterol with NAFLD risk were only detected in non-obese patients. Triglycerides, HDL-cholesterol, and all lipid ratios studied were significantly associated with NAFLD risk, irrespective of whether the patients achieved their HbA1c, blood pressure, and LDL-cholesterol goal. The presence of poor lipids and lipid ratios were more strongly associated with NAFLD in patients who attained the HbA1c, blood pressure, and/or LDL-cholesterol goal than in those who did not achieve the goal attainment. Conclusions: The associations of lipids and lipid ratios with NAFLD risk were stronger in T2DM patients who were non-obese and achieved the HbA1c, blood pressure, and/or LDL-cholesterol goal attainment.

Case report: Bilateral central serous chorioretinopathy-like abnormalities in a man with pulmonary arterial hypertension.

Background: Pulmonary arterial hypertension (PAH) leads to progressive increases in pulmonary vascular resistance, right heart failure, and death if left untreated. Ocular complications secondary to PAH were less reported. In this study, we reported a case of bilateral visual loss and metamorphopsia in a patient with PAH, who developed central serous chorioretinopathy (CSCR)-like abnormalities and optic disc atrophy. Case summary: A 45-year-old man presented with decreasing central vision and metamorphopsia in both eyes. He had a history of PAH and 6-year history of low-dose oral sildenafil treatment. Slit-lamp examination revealed prominent dilated and tortuous episcleral and conjunctival vessels. Ultrawide-field color picture showed retinal pigment epithelial mottling and atrophy in ring-like configurations. Ultrawide-field autofluorescence showed multiple irregular hyper-autofluorescence with a constellation-like pattern surrounding the optic nerve head and macular region. Optical coherence tomography angiography (OCTA) b-scan demonstrated CSCR-like changes. Swept-source optical coherence tomography (SS-OCT) analysis showed optic nerve atrophy with enlarged cup/disc ratio in right eye, which was confirmed with perimetry. Fluorescein angiography (FA) showed marked leakage of macula and optic nerve head with time, cystoid macular edema, early blocking with late staining of the flecks as shown in the backgrounds of infrared and autofluorescence, and mild leakage in peripheral retina. Indocyanine green angiography (ICGA) showed dilation, tortuosity and congestion of all vortex veins without obvious leakage. Conclusion: Undertreated PAH may cause the congestion of the choroid and induce CSCR-like abnormalities.

A fourth dose of Omicron RBD vaccine enhances broad neutralization against SARS-CoV-2 variants including BA.1 and BA.2 in vaccinated mice.

The SARS-CoV-2 vaccines have been widely used to build an immunologic barrier in the population against the COVID-19 pandemic. However, a newly emerging Omicron variant, including BA.1, BA.1.1, BA.2, and BA.3 sublineages, largely escaped the neutralization of existing neutralizing antibodies (nAbs), even those elicited by three doses of vaccines. Here, we used the Omicron BA.1 RBD as a fourth dose of vaccine to induce potent Omicron-specific nAbs and evaluated the broadly neutralizing activities against SARS-CoV-2 variants. The BA.1-based vaccine was indeed prone to induce a strain-specific antibody response substantially cross-reactive with BA.2 sublineage, and yet triggered broad neutralization against SARS-CoV-2 variants when it was used in the sequential immunization with WT and other variant vaccines. These results demonstrated that the booster of Omicron RBD vaccine could be a rational strategy to enhance the broadly nAb response.

Circulating ANGPTL8 levels and risk of kidney function decline: Results from the 4C Study.

BACKGROUND: ANGPTL8, an important regulator of lipid metabolism, was recently proven to have additional intracellular and receptor-mediated functions. This study aimed to investigate circulating levels of ANGPTL8 and its potential association with the risk of kidney function decline in a cohort study. METHODS: We analysed 2,311 participants aged 40 years old and older from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Kidney function decline was defined as an estimated glomerular filtration rate (eGFR) less than 60 mL per minute per 1.73 m2 of body surface area, a decrease in eGFR of ≥ 30% from baseline, chronic kidney disease (CKD)-related hospitalization or death, or end-stage renal disease. The association between baseline ANGPTL8 levels and kidney function decline was assessed using multivariable-adjusted Cox proportional hazards models, and inverse possibility of treatment weight (IPTW) was utilized to prevent overfitting. RESULTS: There were 136 (5.9%) cases of kidney function decline over a median of 3.8 years of follow-up. We found that serum ANGPTL8 levels at baseline were elevated in individuals with kidney function decline compared to those without kidney function decline during follow-up (718.42 ± 378.17 vs. 522.04 ± 283.07 pg/mL, p < 0.001). Compared with the first quartile, multivariable-adjusted hazard ratio (95% confidence intervals [CIs]) for kidney function decline was 2.59 (95% CI, 1.41-4.77) for the fourth ANGPTL8 quartile. Furthermore, compared with patients in the first ANGPTL8 quartile, those in the fourth ANGPTL8 quartile were more likely to report a higher stage of CKD (relative risk: 1.33; 95% CI, 1.01-1.74). The conclusions of the regression analyses were not altered in the IPTW models. Multivariable-adjusted restricted cubic spline analyses suggested a linear relationship of ANGPTL8 with kidney function decline (p for nonlinear trend = 0.66, p for linear trend < 0.001). CONCLUSIONS: Participants with higher circulating ANGPTL8 levels were at increased risk for kidney function decline, highlighting the importance of future studies addressing the pathophysiological role of ANGPTL8 in CKD.

Ubiquitin-specific peptidase 18 regulates the differentiation and function of Treg cells.

Ubiquitin-specific peptidase 18 (USP18) plays an important role in the development of CD11b+ dendritic cells (DCs) and Th17 cells, however, its role in the differentiation of other T cell subsets, especially in regulatory T (Treg) cells, is unknown. In our study, we used Usp18 KO mice to study the loss of USP18 on the impact of Treg cell differentiation and function. We found that USP18 deficiency upregulates the differentiation of Treg cells, which may lead to disrupted homeostasis of peripheral T cells, and downregulates INF-γ, IL-2, IL-17A producing CD4+ T cells and INF-γ producing CD8+ T cells. Mechanistically, we also found that the upregulation of Tregs is due to elevated expression of CD25 in Usp18 KO mice. Finally, we found that the suppressive function of Usp18 KO Tregs is downregulated. Altogether, our study was the first to identify the role of USP18 in Tregs differentiation and its suppressive function, which may provide a new reference for the treatment of Treg function in many autoimmune diseases, and USP18 can be used as a new therapeutic target for precise medical treatment.

Clinical relevance of serum immunoglobulin G4 in glucocorticoid therapy of Graves' ophthalmopathy.

OBJECTIVE: Previous study suggested IgG4 levels were associated with the development of Graves' ophthalmopathy (GO). The aims of the present study were to investigate the role of IgG4 levels in glucocorticoid (GC) treatment in GO patients. DESIGN: 69 GO patients were enrolled. Serum thyroid hormones, thyroid antibodies, IgG, IgG4, ophthalmological examinations and orbital MRI were performed. Furthermore, the clinical outcomes (a composite response endpoint including the clinical activity score (CAS), proptosis, vision, intraocular pressure, diplopia and lid width) after high-dose intravenous GC treatment in 32 active moderate-to-severe GO patients were compared. PATIENTS: 69 consecutive patients with GO were asked to participate in the study. 32 of 69 GO patients were treated with high-dose intravenous GCs. MEASUREMENTS: Measurement of serum IgG and IgG4, serum thyroid hormones and thyroid autoantibodies. An overall ophthalmic assessment was performed pretherapy (week 0) and post-therapy (week 12). RESULTS: 33.3% of GO patients (23/69) had elevated IgG4 levels. IgG4 levels were positively correlated with the severity and activity of GO. After GC therapy, IgG4, IgG4/IgG, vision and CAS were significantly improved in GO patients. Patients with high IgG4 levels had a significantly reduced extraocular muscle area (EOMs) and better clinical outcomes than patients with normal IgG4 levels. CONCLUSIONS: Our results suggest a possible subgroup of elevated IgG4 GO patients, with more severe ophthalmopathy and better response to GCs treatment compare with normal IgG4 GO patients.

Attenuation of porcine deltacoronavirus disease severity by porcine reproductive and respiratory syndrome virus coinfection in a weaning pig model.

Porcine deltacoronavirus (PDCoV) is a potentially emerging zoonotic pathogen that causes severe diarrhea in young pigs, with a risk of fatal dehydration. Its pathogenicity on neonatal piglet has been previously reported, however, it is less known if the coinfection with immunosuppressive pathogens can influence PDCoV disease manifestation. Here, a coinfection model of PDCoV and porcine reproductive and respiratory syndrome virus (PRRSV), a global-spread immunosuppressive virus, was set to study their interaction. Weaning pigs in the coinfection group were intranasally inoculated with PRRSV NADC30-like virus and latterly orally inoculated with PDCoV at three day-post-inoculation (DPI). Unexpectedly, compared with pigs in the PDCoV single-infected group, the coinfected pigs did not show any obvious diarrhea, as PDCoV fecal shedding, average daily weight gain (ADWG), gross and microscopic lesions and PDCoV IHC scores consistently indicated that PRRSV coinfection lessened PDCoV caused diarrhea. Additionally, three proinflammatory cytokines TNF-α, IL-1 and IL-6, which can be secreted by PRRSV infected macrophages, were detected to be highly expressed at the intestine from both PRRSV infected groups. By adding to PDCoV-infected cells, these three cytokines were further confirmed to be able to inhibit the PDCoV replication post its cellular entry. Meanwhile, the inhibition effect of the supernatant from PRRSV-infected PAMs could be obviously blocked by the antagonist of these three cytokines. In conclusion, PRRSV coinfection increased TNF-α, IL-1, and IL-6 in the microenvironment of intestines, which inhibits the PDCoV proliferation, leading to lessened severity of diarrhea. The findings provide some new insight into the pathogenesis and replication regulation of PDCoV.

A strain of porcine deltacoronavirus: Genomic characterization, pathogenicity and its full-length cDNA infectious clone.

As a novel enteropathogenic coronavirus, porcine deltacoronavirus (PDCoV) warrants further investigation. In this study, a Chinese PDCoV strain, designated CHN-HN-1601, was isolated from the faeces of a diarrhoeic piglet. After plaque purification, the genome was determined which shared 97.5%-99.5% nucleotide identities with 71 representative PDCoV strains available in the GenBank. The pathogenic properties of CHN-HN-1601 were evaluated using 5-day-old piglets. All inoculated piglets developed severe diarrhoea from 2 days post-infection (dpi) onwards. To our surprise, two periods of diarrhoea starting from 2 to 7 dpi and from 13 to 19 dpi were observed in affected piglets during the experiment. Faecal viral shedding of the inoculated piglets was detected by real-time RT-PCR, with viral shedding peaked at 4 and 16 dpi, respectively. At necropsy at 5 dpi, the main gross lesions included transparent, thin-walled and gas-distended intestines containing yellow watery contents. Further histopathological examinations, including haematoxylin and eosin staining, immunohistochemistry and RNAscope in situ hybridization, revealed that the virus infection caused severe villous atrophy of the small intestines, with PDCoV antigen and RNA mainly distributed in the cytoplasm of the villous epithelial cells of jejunum and ileum in piglets. The dynamic production of PDCoV-specific IgG and neutralizing antibodies in serum of the affected piglets was also assessed using a whole virus-based ELISA and an immunofluorescence assay-based neutralization test, respectively. Furthermore, a full-length cDNA infectious clone of CHN-HN-1601 was constructed using a bacterial artificial chromosome system. The rescued virus exhibited in vitro growth and pathogenic properties similar to the parental virus. Taken together, our study not only enriches the information of PDCoV, but also provides a useful reverse genetics platform for further pathogenesis exploration of the virus.