The aim of this study was to evaluate the efficacy and safety of transepithelial corneal collagen crosslinking (transepithelial CXL) versus standard corneal collagen crosslinking (epithelium-off CXL) ...on keratoconus.
Eligible studies were identified by systematically searching PubMed, the Cochrane Library and Embase. Topographic parameters, corrected distant visual acuity (CDVA), uncorrected distant visual acuity (UDVA), and corneal thickness (CT) were assessed by the pooled weighted mean differences (WMDs) of the change from baseline to the end of follow up. Quality was assessed according to Cochrane handbook. And we used Review Manager to analysis the included trials.
Three trials involving 244 eyes were evaluated, with 111 eyes in the standard CXL group and 133 eyes in the transepithelial CXL group. The pooled results showed that there were significant differences between the two groups in maximum keratometry (mean difference = 1.05D, 95% CI 0.19 to 1.92, P = 0.02)),and the standard CXL is more effective in decreasing the maximum keratometry at least 12 months after operation; the transepithelial CXL group gained more improvement in CDVA (mean difference = -0.07, 95% CI -0.12 to -0.02, P = 0.007);there were no significant differences in uncorrected distant visual acuity (UDVA) between the two groups (mean difference = -0.03, 95% CI -0.20 to 0.15, P = 0.75). A similar change was found in corneal thickness (mean difference = 4.35, 95% CI -0.43 to 9.13, P = 0.07)).
The standard CXL is more effective in decreasing the maximum keratometry than the transepithelial CXL; the transepithelial CXL provided favorable visual outcomes; they both exhibit similar safety.
Abstract
Background
This study is aimed to assess the association between asthma and cataract in a representative sample in the United States.
Methods
The National Health Interview Survey (NHIS) is ...the principal source of information on the health of the civilian noninstitutionalized population of the United States. Ten years (2010-2019) of NHIS were analyzed in this study. Asthma and cataract status were collected from relevant questionnaires among participants aged 40 years and older. Multivariate regression analyses were applied to explore the association between asthma and cataract.
Results
From 40,457 participants included, those with asthma had higher prevalence of cataract than those without asthma (29.41% vs 25.87%,
p
< 0.001). Participants who had asthma had 40% higher odds of cataract compared to those without, after adjusting for potential confounding covariates (Odds Ratio OR = 1.40, 95% Confidence Interval CI: 1.29-1.52,
p
< 0.001). When viewing asthma as the outcome, participants who had cataract had 36% higher odds of asthma compared to those without, after adjusting for potential confounding covariates (Odds Ratio OR = 1.36, 95% Confidence Interval CI: 1.25-1.47,
p
< 0.001).
Conclusions
With our study, we demonstrated that individuals with asthma were more likely to develop cataract compared with those without asthma. Further RCTs are needed to confirm this potential impact of asthma on cataract and to investigate the underlying mechanisms.
Invading viral DNA can be recognized by the host cytosolic DNA sensor, cyclic GMP-AMP (cGAMP) synthase (cGAS), resulting in production of the second messenger cGAMP, which directs the adaptor protein ...STING to stimulate production of type I interferons (IFNs). Although several DNA viruses are sensed by cGAS, viral strategies targeting cGAS are virtually unknown. We report here that Kaposi’s sarcoma-associated herpesvirus (KSHV) ORF52, an abundant gammaherpesvirus-specific tegument protein, subverts cytosolic DNA sensing by directly inhibiting cGAS enzymatic activity through a mechanism involving both cGAS binding and DNA binding. Moreover, ORF52 homologs in other gammaherpesviruses also inhibit cGAS activity and similarly bind cGAS and DNA, suggesting conserved inhibitory mechanisms. Furthermore, KSHV infection evokes cGAS-dependent responses that can limit the infection, and an ORF52 null mutant exhibits increased cGAS signaling. Our findings reveal a mechanism through which gammaherpesviruses antagonize host cGAS DNA sensing.
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•KSHV ORF52 prevents cGAS DNA sensing by directly inhibiting cGAS enzymatic activity•The inhibition of cGAS by ORF52 requires binding to both DNA and cGAS•The inhibition of cGAS by ORF52 is conserved among gammaherpesviruses•KSHV can elicit cGAS-dependent immune responses that are counteracted by ORF52
cGAS is the principal cytosolic DNA sensor that detects invading viral DNA and triggers antiviral responses. Wu et al. reveal that a gammaherpesvirus-conserved protein, ORF52, binds to DNA and cGAS and directly inhibits cGAS enzymatic activity, thereby antagonizing host cGAS-dependent DNA sensing.
Type III protein secretion systems are essential virulence factors for many important pathogenic bacteria. The entire protein secretion machine is composed of several substructures that organize into ...a holostructure or injectisome. The core component of the injectisome is the needle complex, which houses the export apparatus that serves as a gate for the passage of the secreted proteins through the bacterial inner membrane. Here, we describe a high-resolution structure of the export apparatus of the Salmonella type III secretion system in association with the needle complex and the underlying bacterial membrane, both in isolation and in situ. We show the precise location of the core export apparatus components within the injectisome and bacterial envelope and demonstrate that their deployment results in major membrane remodeling and thinning, which may be central for the protein translocation process. We also show that InvA, a critical export apparatus component, forms a multiring cytoplasmic conduit that provides a pathway for the type III secretion substrates to reach the entrance of the export gate. Combined with structure-guided mutagenesis, our studies provide major insight into potential mechanisms of protein translocation and injectisome assembly.
Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Research has recently found that both animal models and patients with PD have circadian dysfunction, accompanied by ...abnormal expression of circadian genes and proteins, which implies that the circadian clock plays a crucial role in PD etiopathogenesis. In addition, a strong relationship between NLRP3 inflammasome signaling and PD has been observed. Meanwhile, the activation of the NLRP3 inflammasome is highly relevant to dysfunctions of the molecular clock. Therefore, alleviating the neuroinflammation caused by NLRP3 inflammasome signaling by adjusting the abnormal molecular clock may be a potential strategy for preventing and treating PD. In this article, we have reviewed the potential or direct relationship between abnormalities of the circadian clock and NLRP3 inflammasome signaling in PD.
RSK1, a downstream kinase of the MAPK pathway, has been shown to regulate multiple cellular processes and is essential for lytic replication of a variety of viruses, including Kaposi's ...sarcoma-associated herpesvirus (KSHV). Besides phosphorylation, it is not known whether other post-translational modifications play an important role in regulating RSK1 function. We demonstrate that RSK1 undergoes robust SUMOylation during KSHV lytic replication at lysine residues K110, K335, and K421. SUMO modification does not alter RSK1 activation and kinase activity upon KSHV ORF45 co-expression, but affects RSK1 downstream substrate phosphorylation. Compared to wild-type RSK1, the overall phosphorylation level of RxRxxS*/T* motif is significantly declined in RSK1K110/335/421R expressing cells. Specifically, SUMOylation deficient RSK1 cannot efficiently phosphorylate eIF4B. Sequence analysis showed that eIF4B has one SUMO-interacting motif (SIM) between the amino acid position 166 and 170 (166IRVDV170), which mediates the association between eIF4B and RSK1 through SUMO-SIM interaction. These results indicate that SUMOylation regulates the phosphorylation of RSK1 downstream substrates, which is required for efficient KSHV lytic replication.
Magnesium oxysulfate (MOS) cement is a typical eco-friendly cementitious material, which presents excellent performances. In this work, a novel multiscale modeling strategy is proposed to simulate ...the hydration and pore structure of MOS cement system. This work collected and evaluated the Gibbs free energy of formation for main hydrates and equilibrium constant of main reactions in MOS cement system based on a first principle calculation using Material Studio. Followingly, the equilibrium phase compositions of MOS cement system were simulated through PHREEQC to investigate the molar ratio dependence of equilibrium phase compositions. Results showed that large M (MgO/MgSO4) was beneficial for the formation of 5Mg(OH)2·MgSO4·7H2O (Phase 517) and large H (H2O/MgSO4) tended to decompose MOS cement paste and cause leaching. The microstructure-based method visualized the hydration status of MOS cement systems at initial and ultimate stages via MATLAB and the results showed that large M was significant to reduce porosity, and similar results for the case of small H. Fractal analysis confirms that fractal dimension of pore structure (Df) was significantly decreased after the hydration of MOS and was positively correlated to the porosity of the paste. In addition, it can be referred that large M and small H were beneficial for modifying the microstructure of MOS paste by decreasing the value of Df.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) mediates viral entry into cells and is critical for vaccine development against coronavirus disease 2019 (COVID-19). ...Structural studies have revealed distinct conformations of S, but real-time information that connects these structures is lacking. Here we apply single-molecule fluorescence (Förster) resonance energy transfer (smFRET) imaging to observe conformational dynamics of S on virus particles. Virus-associated S dynamically samples at least four distinct conformational states. In response to human receptor angiotensin-converting enzyme 2 (hACE2), S opens sequentially into the hACE2-bound S conformation through at least one on-path intermediate. Conformational preferences observed upon exposure to convalescent plasma or antibodies suggest mechanisms of neutralization involving either competition with hACE2 for binding to the receptor-binding domain (RBD) or allosteric interference with conformational changes required for entry. Our findings inform on mechanisms of S recognition and conformations for immunogen design.
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•SARS-CoV-2 S protein dynamically samples at least 4 distinct conformational states•hACE2 activates S from the ground state to the activated state via an intermediate•Proteolytic processing of S accelerates hACE2-dependent activation•Antibodies can antagonize S by two different mechanisms of neutralization
The SARS-CoV-2 spike protein has been observed to adopt different structural states. Lu et al. directly visualize the conformational dynamics of spike protein on the surface of virus particles and describe how the conformational landscape changes upon activation by the host receptor or antagonism by antibodies.
A novel fluorescent probe (C460@Tb-MOFs) was designed and synthesized by encapsulating the fluorescent dye 7-diethylamino-4-methyl coumarin (C460) into a terbium-based metal-organic framework using a ...simple ultrasonic impregnation method. It is impressive that this dye-modified metal-organic framework can specifically detect styrene and temperature upon luminescence quenching. The sensing platform of this material exhibits great selectivity, fast response, and good cyclability toward styrene detection. It is worth mentioning that the sensing process undergoes a distinct color change from blue to colorless, providing conditions for the accurate visual detection of styrene liquid and gas. The significant fluorescence quenching mechanism of styrene toward C460@Tb-MOFs is explored in detail. Moreover, the dye-modified metal-organic framework can also achieve temperature sensing from 298 to 498 K with high relative sensitivity at 498 K. The preparation of functionalized MOF composites with fluorescent dyes provides an effective strategy for the construction of sensors for multifunctional applications.
This paper presents a cement-content controlled method for quality assessment and quality control of the deep soil mixing (DSM) columns in slope reinforcement. The ethylene diamine tetraacetic acid ...(EDTA) titration method was modified and used for the cement content measurement of core samples, and the effects of curing conditions and curing period on the titration results were investigated. 35 DSM columns with different construction parameters were installed in the test section, and cement content and unconfined compression tests of field core samples were conducted. The relationship between the unconfined compressive strength (UCS) and cement content of DSM columns was formulated, and the quality of DSM columns with different construction parameters was assessed. The test results suggested that the failure strength of the field cores was approximately 15-55% lower than that of laboratory samples with the same cement content. In single columns, the coefficient of variation (CV) of cement content had a negative correlation with the average failure strength and a positive correlation with the coefficient of variation of failure strength. Bidirectional mixing method, lower penetration and withdrawal velocity, more mixing blades and larger number of mixings could improve the uniformity of the DSM columns.
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