Sex- and age-specific clinical and immunological features of coronavirus disease 2019.

To simultaneously determine clinical and immunological responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young and old females and males, 681 coronavirus disease 2019 (COVID-19) patients and 369 normal controls (NCs) were analyzed based on age and sex classifications using multiple linear regression analysis. Compared to the age-matched NCs, both young and old male and female non-comorbid COVID-19 patients had lower lymphocyte counts and alanine aminotransferase (ALT) concentration, and only young male and female patients had lower neutrophil counts. Compared to young patients, both old males and females had significantly higher plasma ALT and AST concentrations. Compared to young and old females, age-matched males had higher plasma ALT and AST concentrations, but only young males had higher C-reactive protein (CRP) concentration. Compared to females, old males, but not young males, showed higher incidence of critical illness. Compared to young patients, old females had more leukocyte and neutrophil counts above the normal upper limit and B cell count below the normal lower limit (NLL), while old males had more lymphocyte and natural killer (NK) cell counts below the NLL. No sex or age associations with B cell and NK cell counts were observed. However, there were age-dependent decreases in CD8+ T-cell counts in both male and female COVID-19 patients. Age was negatively associated with CD8+ T cell counts but positively associated with neutrophil count, CRP, ALT, and AST concentrations, and sex (females) was negatively associated with neutrophil count, CRP, ALT, and AST concentrations. The present study suggests that SARS-CoV-2 infection mainly induced 1) beneficial sex (female)-related differences regarding reduced COVID-19 disease severity and negative associations with inflammatory responses and liver damage, and 2) harmful age-related differences relating to negative associations with CD8+ T cell count and positive associations with inflammatory responses and liver damage. Thus, sex and age are biological variables that should be considered in the prevention and treatment of COVID-19.

Assessment of the Corneal Biomechanical Features of Sturge-Weber Syndrome Using Dynamic Ultrahigh-speed Scheimpflug Imaging.

PURPOSE: To evaluate the corneal biomechanical characteristics of eyes with Sturge-Weber syndrome (SWS) secondary glaucoma (SSG) by analyzing corneal biomechanical parameters obtained using the Corneal Visualization Scheimpflug Technology instrument (Corvis ST). METHODS: In patients with SWS, eyes affected by SSG were designated as the SSG group while the contralateral eyes were designated as the SWS contralateral group (SC group). Patients from the myopia clinic served as the control group. Dynamic corneal response parameters (DCRs) including the stress-strain index (SSI)-a critical material stiffness parameter that excludes interference from IOP and central corneal thickness (CCT)-were analyzed. RESULTS: For CCT, no significant difference was observed between the SSG and SC groups. However, significant differences were found between the SSG and control groups and between the SC and control groups. Parameters such as HC Time, A1 Deformation Amp., A2 Deformation Amp., length of Whole Eye Movement (WEM), DA Ratio Max (2 mm), PachySlope, DA Ratio Max (1 mm), and ARTh showed significant differences between the SSG group and control group. In the SSG group, 4 of night eyes had an SSI of less than 0.85. CONCLUSIONS: Some DCRs indicated a stiffer cornea in the SSG group, possibly due to a thicker cornea in this group. On analyzing SSI, it was found that corneal material properties change, becoming less stiff in some of the patients with SSG. In conclusion, our study provides a preliminary exploration of the biomechanical properties of SWS secondary glaucoma.

Sustained and Efficient Delivery of Antivascular Endothelial Growth Factor by the Adeno-associated Virus for the Treatment of Corneal Neovascularization: An Outlook for Its Clinical Translation.

Corneal diseases represent 5.1% of all eye defects and are the fourth leading cause of blindness globally. Corneal neovascularization can arise from all conditions of chronic irritation or hypoxia, which disrupts the immune-privileged state of the healthy cornea, increases the risk of rejection after keratoplasty, and leads to opacity. In the past decades, significant progress has been made for neovascular diseases of the retina and choroid, with plenty of drugs getting commercialized. In addition, to overcome the barriers of the short duration and inadequate penetration of conventional formulations of antivascular endothelial growth factor (VEGF), multiple novel drug delivery systems, including adeno-associated virus (AAV)-mediated transfer have gone through the full process of bench-to-bedside translation. Like retina neovascular diseases, corneal neovascularization also suffers from chronicity and a high risk of recurrence, necessitating sustained and efficient delivery across the epithelial barrier to reach deep layers of the corneal stroma. Among the explored methods, adeno-associated virus-mediated delivery of anti-VEGF to treat corneal neovascularization is the most extensively researched and most promising strategy for clinical translation although currently although, it remains predominantly at the preclinical stage. This review comprehensively examines the necessity, benefits, and risks of applying AAV vectors for anti-VEGF drug delivery in corneal vascularization, including its current progress and challenges in clinical translation.

Stromal lenticule addition keratoplasty with corneal crosslinking for corneal ectasia secondary to FS-LASIK: a case series.

AIM: To explore the clinical efficacy and safety of stromal lenticule addition keratoplasty (SLAK) with corneal crosslinking (CXL) on patients with corneal ectasia secondary to femtosecond laser-assisted in situ keratomileusis (FS-LASIK). METHODS: A series of 5 patients undertaking SLAK with CXL for the treatment of corneal ectasia secondary to FS-LASIK were followed for 4-9mo. The lenticules were collected from patients undertaking small incision lenticule extraction (SMILE) for the correction of myopia. Adding a stromal lenticule was aimed at improving the corneal thickness for the safe application of crosslinking and compensating for the thin cornea to improve its mechanical strength. RESULTS: All surgeries were conducted successfully with no significant complications. Their best corrected visual acuity (BCVA) ranged from 0.05 to 0.8-2 before surgery. The pre-operational total corneal thickness ranged from 345-404 µm and maximum keratometry (Kmax) ranged from 50.8 to 86.3. After the combination surgery, both the corneal keratometry (range 55.9 to 92.8) and total corneal thickness (range 413-482 µm) significantly increased. Four out of 5 patients had improvement of corneal biomechanical parameters (reflected by stiffness parameter A1 in Corvis ST). However, 3 patients showed decreased BCVA after surgery due to the development of irregular astigmatism and transient haze. Despite the onset of corneal edema right after SLAK, the corneal topography and thickness generally stabilized after 3mo. CONCLUSION: SLAK with CXL is a potentially beneficial and safe therapy for advanced corneal ectasia. Future work needs to address the poor predictability of corneal refractometry and compare the outcomes of different surgical modes.

Triple-crosslinked double-network alginate/dextran/dendrimer hydrogel with tunable mechanical and adhesive properties: A potential candidate for sutureless keratoplasty.

An ideal adhesive hydrogel must possess high adhesion to the native tissue, biocompatibility, eligible biodegradability, and good mechanical compliance with the substrate tissues. We constructed an interpenetrating double-network hydrogel containing polysaccharides (alginate and dextran) and nanosized spherical dendrimer by both physical and chemical crosslinking, thus endowing the hydrogel with a broad range of mechanical properties, adhesive properties, and biological functions. The double-network hydrogel has moderate pore sizes and swelling properties. The chelation of calcium ions significantly enhances the tensile and compressive properties. The incorporation of dendrimer improves both the mechanical and adhesive properties. This multicomponent interpenetrating network hydrogel has excellent biocompatibility, tunable mechanical and adhesive properties, and satisfied multi-functions to meet the complex requirements of wound healing and tissue engineering. The hydrogel exhibits promising corneal adhesion capabilities in vitro, potentially supplanting the need for sutures in corneal stromal surgery and mitigating the risks associated with donor corneal damage and graft rejection during corneal transplantation. This novel polysaccharide and dendrimer hydrogel also shows good results in sutureless keratoplasty, with high efficiency and reliability. Based on the clinical requirements for tissue bonding and wound closure, the hydrogel provides insight into solving the mechanical properties and adhesive strength of tissue adhesives.

Higher-order aberrations and visual quality after incision lenticule extraction surgery with intraoperative angle kappa adjustments between small and large kappa patients: A 2-year follow-up.

Purpose: To evaluate the postoperative visual outcomes, that is, corneal higher-order aberrations (HOAs) and visual quality, of patients with an angle kappa greater than 0.30 mm who underwent angle kappa adjustment during small-incision lenticule extraction (SMILE) 2 years after surgery compared to eyes with an angle kappa less than 0.30 mm. Methods: This was a retrospective study and included 12 patients from October 2019 to December 2019 who underwent the SMILE procedure for correction of myopia and myopic astigmatism and had one eye with a large kappa angle and another eye with a small kappa angle. Twenty-four months after surgery, an optical quality analysis system (OQAS II; Visiometrics, Terrassa, Spain) was used to measure the modulation transfer function cutoff frequency (MTFcutoff), Strehl2D ratio, and objective scatter index (OSI). HOAs were measured with a Tracey iTrace Visual Function Analyzer (Tracey version 6.1.0; Tracey Technologies, Houston, TX, USA). Assessment of subjective visual quality was achieved using the quality of vision (QOV) questionnaire. Results: At 24 months postoperatively, the mean spherical equivalent (SE) refraction was - 0.32 ± 0.40 and - 0.31 ± 0.35 in the S-kappa group (kappa <0.3 mm) and the L-kappa group (kappa ≥0.3 mm), respectively (P > 0.05). The mean OSI was 0.73 ± 0.32 and 0.81 ± 0.47, respectively (P > 0.05). There was no significant difference in MTFcutoff and Strehl2D ratio between the two groups (P > 0.05). Total HOA, coma, spherical, trefoil, and secondary astigmatism were not significantly different (P > 0.05) between the two groups. Conclusion: Adjustment of angle kappa during SMILE helps reduce the decentration, results in less HOAs, and promotes visual quality. It provides a reliable method to optimize the treatment concentration in SMILE.

Retrospective analysis of the impact of dose delay and reduction on outcomes of colorectal cancer patients treated with FOLFIRI­based treatment.

Objectives: To determine the relationship between chemotherapy dose delay/reduction with progression-free survival (PFS) and overall survival (OS) in colorectal cancer patients treated with FOLFIRI based first-line chemotherapy in real-world retrospectively study. Methods: We identified 144 eligible patients with advanced CRC who received FOLFIRI as first-line based treatment. The study protocol was submitted to the institutional review board and was exempted. Dose delay was defined as an average delay of more than 3 days (>3 days vs. ≤3 days) from the intended date. Dose reduction (actual dose/standard dose * 100%) ≤85% was considered as chemotherapy reduction in the chemotherapy dose relative to the standard (mg/m2) regimen for all cycles. Relative dose intensity (RDI) ≤80% was described as chemotherapy reduction. OS and PFS were measured using Kaplan-Meier and Cox proportional hazard models. Results: There were 114 patients with chemotherapy dose delay (dose delay >3 days). PFS of patients without dose delay had better survival than patients with dose delay (p = 0.002). There were 28.47% patients treated with dose reduction of 5-Fu. PFS and OS were better in patients without 5-Fu dose reduction than in patients with 5-Fu dose reduction with p values of 0.024 and <0.001, respectively. Patients with high 5-FU RDI had better PFS than patients with low 5-FU RDI (p < 0.001). While, there was no statistical difference in OS between the two groups. Then we stratified the analysis by age. In <65 years cohort, both PFS and OS were better in patients with high 5-Fu RDI than in those with low 5-Fu RDI (p < 0.001, p = 0.005, respectively). But, in ≥65 years cohort, OS were better in patients with low 5-Fu RDI than in those with high 5-Fu RDI (p = 0.025). Moreover, both dose reduction and RDI of irinotecan had no statistically significant difference in both PFS and OS. Conclusion: In the advanced colorectal cancer patients who received FOLFIRI based treatment as first-line regimen, chemotherapy dose delay and reduction dose of 5-Fu were associated with worse survival, especially among patients younger than 65 years.

Chemosensory Gene Families in the Oligophagous Pear Pest Cacopsylla chinensis (Hemiptera: Psyllidae).

Chemosensory systems play an important role in insect behavior, and some key associated genes have potential as novel targets for pest control. Cacopsylla chinensis is an oligophagous pest and has become one of the main pests of pear trees, but little is known about the molecular-level means by which it locates its hosts. In this study, we assembled the head transcriptome of C. chinensis using Illumina sequencing, and 63,052 Unigenes were identified. A total of 36 candidate chemosensory genes were identified, including five different families: 12 odorant binding proteins (OBPs), 11 chemosensory proteins (CSPs), 7 odorant receptors (ORs), 4 ionotropic receptors (IRs), and 2 gustatory receptors (GRs). The number of chemosensory gene families is consistent with that found in other Hemipteran species, indicating that our approach successfully obtained the chemosensory genes of C. chinensis. The tissue expression of all genes using quantitative real-time PCR (qRT-PCR) found that some genes displayed male head, female head, or nymph-biased specific/expression. Our results enrich the gene inventory of C. chinensis and provide valuable resources for the analysis of the functions of some key genes. This will help in developing molecular targets for disrupting feeding behavior in C. chinensis.

Glutathione prevents chronic oscillating glucose intake-induced ß-cell dedifferentiation and failure.

Modern lifestyles have altered diet and metabolic homeostasis, with increased sugar intake, glycemic index, and prediabetes. A strong positive correlation between sugar consumption and diabetic incidence is revealed, but the underlying mechanisms remain obscure. Here we show that oral intake of long-term oscillating glucose (LOsG) (4 times/day) for 38 days, which produces physiological glycemic variability in rats, can lead to ß-cells gaining metabolic memory in reactive oxygen species (ROS) stress. This stress leads to suppression of forkhead box O1 (FoxO1) signaling and subsequent upregulation of thioredoxin interacting protein, inhibition of insulin and SOD-2 expression, re-expression of Neurog3, and ß-cell dedifferentiation and functional failure. LOsG-treated animals develop prediabetes exhibiting hypoinsulinemia and glucose intolerance. Dynamic and timely administration of antioxidant glutathione prevents LOsG/ROS-induced ß-cell failure and prediabetes. We propose that ROS stress is the initial step in LOsG-inducing prediabetes. Manipulating glutathione-related pathways may offer novel options for preventing the occurrence and development of diabetes.