Accuracy of 11 intraocular lens calculation formulas in shallow anterior chamber eyes.

PURPOSE: To evaluate the performance of intraocular lens (IOL) calculation formulas and the effect of anterior chamber depth (ACD), axial length (AL) and lens thickness (LT) on the prediction accuracy in shallow ACD eyes. METHODS: This retrospective, consecutive case-series study included 648 eyes of 648 patients with an ACD < 3.0 mm who underwent phacoemulsification and IOL implantation. Eleven formulas were evaluated: Barrett Universal II (BUII), Emmetropia Verifying Optical (EVO) 2.0, Hill-Radial Basis Function (RBF) 3.0, Hoffer QST, Kane, Olsen, Pearl-DGS and traditional formulas (Haigis, Hoffer Q, Holladay 1 and SRK/T). Subgroup analysis was performed based on ACD, AL and LT. RESULTS: Overall, the Hoffer QST and Kane showed no systematic bias. The Kane, EVO 2.0, Hill-RBF 3.0 and Hoffer QST had relatively lower mean absolute error and higher percentages of prediction error within ±0.5 D. For the ACD of 2.5-3.0 mm and AL < 22.0 mm subgroup, the Pearl-DGS exhibited the lowest MAE (0.45 D) and MedAE (0.41 D). Most formulas had a significant myopic bias (-0.43 to -0.18 D, p < 0.05) in the LT < 4.3 mm subgroup and a significant hyperopic bias (0.09-0.29 D, p < 0.05) in the LT ≥ 5.1 mm subgroup. CONCLUSION: The Kane and Hoffer QST were recommended for shallow ACD eyes. In eyes with an ACD between 2.5 and 3.0 mm and a short AL, the Pearl-DGS showed excellent performance. Clinicians need to fine-tune the target refraction according to LT in shallow ACD eyes.

Chemical Evolution of Enzyme-Catalyzed Glycosylation.

ConspectusThe limited availability of structurally well-defined diverse glycans remains a major obstacle for deciphering biological functions as well as biomedical applications of carbohydrates. Despite tremendous progress that has been made in past decades, the synthesis of structurally well-defined complex glycans still represents one of the most challenging topics in synthetic chemistry. Chemical synthesis of glycans is a time-consuming and labor-intensive process that requires elaborate planning and skilled personnel. In contrast, glycosyltransferase-catalyzed enzymatic synthesis provides a more efficient, convenient, low-cost, and sustainable alternative to affording diverse and complex glycans. However, the existing methods are still insufficient to fulfill the increasing demand for specific synthetic glycan libraries necessary for functional glycomics research. This is mainly attributed to the inherent character of the glycan biosynthetic pathway. In nature, there are too many glycosyltransferases involved in the in vivo glycan synthesis, but only a small number of them are available for in vitro enzymatic synthesis. For instance, humans have over 200 glycosyltransferases, but only a few of them could be produced from the conventional bacterial expression system, and most of these membrane-associated enzymes could be overexpressed only in eukaryotic cells. Moreover, the glycan biosynthetic pathway is a nontemplate-driven process, which eventually ends up with heterogeneous glycan product mixtures. Therefore, it is not a practical solution for the in vitro enzymatic synthesis of complex glycans by simply copying the glycan biosynthetic pathway.In the past decade, we have tried to develop a simplified and transformable approach to the enzymatic modular assembly of a human glycan library. Despite the structural complexity of human glycans, the glycoinformatic analysis based on the known glycan structure database and the human glycosyltransferase database indicates that there are approximately 56 disaccharide patterns present in the human glycome and only 16 disaccharide linkages are required to account for over 80% of the total disaccharide fragments, while 35 disaccharide linkages are sufficient to cover over 95% of all disaccharide fragments of human glycome. Regardless of the substrate specificity, if one glycosyltransferase could be used for the synthesis of all of the same glycosidic linkages in human glycome, it will require only a few dozen glycosyltransferases for the assembly of entire human glycans. According to the glycobioinformatics analysis results, we rationally designed about two dozen enzyme modules for the synthesis of over 20 common glycosidic linkages in human glycome, in which each enzyme module contains a glycosyltransferase and a group of enzymes for the in situ generation of a nucleotide-activated sugar donor. By sequential glycosylation using orchestrated enzyme modules, we have completed the synthesis of over 200 structurally well-defined complex human glycans including blood group antigens, O-mannosyl glycans, human milk oligosaccharides, and others. To overcome the product microheterogeneity problem of enzymatic synthesis in the nontemplate-driven glycan biosynthetic pathway, we developed several substrate engineering strategies to control or manipulate the outcome of glycosyltransferase-catalyzed reactions for the precise synthesis of structurally well-defined isomeric complex glycans.

Is Astigmatism Correction Necessary for Patients With Cataract Who Have Corneal Astigmatism of Less Than 0.75 D?

PURPOSE: To investigate the proportion of patients with predicted refractive astigmatism (PRA) of 0.75 diopters (D) or greater and associated risk factors among cataract surgery candidates with low corneal astigmatism. METHODS: A retrospective cross-sectional study was conducted in Zhongshan Ophthalmic Center, Guangzhou, China. Patients with cataract who had preoperative simulated keratometric astigmatism of less than 0.75 D were recruited. The PRA was calculated by Barrett toric calculator using posterior corneal astigmatism (PCA) measured by the IOLMaster 700 (Carl Zeiss Meditec AG) and corneal surgically induced astigmatism (SIA). Two corneal incision locations (temporal [0°/180°], 135° incision) and varying magnitudes (0.10 to 0.60 D) were considered for SIA. Multiple logistic regression analysis was used to explore risk factors associated with PRA of 0.75 D or greater and build predictive model. Sensitivity analysis was performed using PRA threshold of 0.50 D. RESULTS: A total of 1,750 eyes from 1,750 patients were included (mean age: 60.14 ± 13.24 years, 42.91% male, 1,010 right eyes and 740 left eyes). The 135° incision (odds ratio [OR]: 17.86) and against-the-rule (ATR) astigmatism (OR: 37.55) are the major risk factors for PRA of 0.75 D or greater. Higher simulated keratometric astigmatism (OR: 2.03), larger PCA (OR: 1.64), and surgically induced astigmatism (OR: 1.29) also significantly increased the risk of PRA of 0.75 D or greater. Nomogram model were constructed with an area under curve of 0.90. CONCLUSIONS: For patients with corneal astigmatism of less than 0.75 D, temporal incision and measured PCA is preferred. Those patients with ATR astigmatism should be considered for astigmatism correction when using a 135° incision. [J Refract Surg. 2023;39(12):850-855.].

Blood-cerebrospinal fluid barrier permeability of metals/metalloids and its determinants in pediatric patients.

Concerns regarding adverse effects of metal/metalloids exposure on brain development and neurological disorders among children are increasing. However, the transport patterns of metals/metalloids across the blood-cerebrospinal fluid barrier (BCSFB) need to be clarified in children. A total of 99 Chinese pediatric patients were enrolled from February 2020 to August 2021, with a median age of 6.76 months. We detected 16 metal/metalloid levels in matched serum and cerebrospinal fluid (CSF) samples using inductively coupled plasma mass spectrometry. The BCSFB permeability of metals/metalloids were estimated and the potential effects of biomedical parameters were explored. Most metals/metalloids were detectable among > 80.0% of CSF samples. Significant correlations were observed between strontium (Sr, r = 0.46), molybdenum (Mo, r = 0.50), and cadmium (Cd, r = 0.24) concentrations in serum and CSF (P < 0.05). Ratios of metal/metalloid levels in CSF to serum (Rmetal) ranged from 0.02 to 0.74, and hazardous metals/metalloids including arsenic (As), Cd, lead (Pb), thallium (Tl), and manganese (Mn) showed high transfer efficiencies across the BCSFB (Rmetals > 0.5). With the adjustment of age and sex, albumin, ß2-microglobulin, and total protein levels in CSF were positively associated with copper (Cu) permeability (FDR-adjusted P < 0.05), while glucose in CSF was negatively correlated with calcium (Ca), Cu, Sr, and Mo BCSFB permeability (FDR-adjusted P < 0.05). Q-Alb promoted Cu permeability across the BCSFB (FDR-adjusted P < 0.001), while C-reactive protein levels in serum were positively associated with selenium (Se) permeability (FDR-adjusted P = 0.046). For the first time, our findings provided data for the BCSFB permeability of 16 metals/metalloids in children, and indicated that some biomedical parameters could influence the transformation of metals/metalloids from serum to CSF. Metals/metalloids with strong BCSFB permeability warrant attention for their potential neurotoxicity.

Plasma Proteomics Study Between the Frequent Exacerbation and Infrequent Exacerbation Phenotypes of Chronic Obstructive Pulmonary Disease.

Background: Frequent exacerbation (FE) and infrequent exacerbation (IE) are two phenotypes of chronic obstructive pulmonary disease (COPD), of which FE is associated with a higher incidence of exacerbation and a serious threat to human health. Because the pathogenesis mechanisms of FE are unclear, this study aims to identify FE-related proteins in the plasma via proteomics for use as predictive, diagnostic, and therapeutic biomarkers of COPD. Methods: A cross-sectional study was conducted in which plasma protein profiles were analyzed in COPD patients at stable stage, and differentially expressed proteins (DEPs) were screened out between the FE and IE patients. FE-related DEPs were identified using data-independent acquisition-based proteomics and bioinformatics analyses. In addition, FE-related candidates were verified by enzyme-linked immunosorbent assay. Results: In this study, 47 DEPs were screened out between the FE and IE groups, including 20 upregulated and 27 downregulated proteins. Key biological functions (eg, neutrophil degranulation, extracellular exosome, protein homodimerization activity) and signaling pathways (eg, arginine and proline metabolism) were enriched in association with the FE phenotype. Receiver operating characteristic (ROC) analysis of the 11 combined DEPs revealed an area under the curve of 0.985 (p <0.05) for discriminating FE from IE. Moreover, correlation and ROC curve analyses indicated that creatine kinase, M-type (CKM) and fat storage-inducing transmembrane protein 1 (FITM1) might be clinically significant in patients with the FE phenotype. In addition, plasma expression levels of CKM and FITM1 were validated to be significantly decreased in the FE group compared with the IE group (CKM: p <0.01; FITM1: p <0.05). Conclusion: In this study, novel insights into COPD pathogenesis were provided by investigating and comparing plasma protein profiles between the FE and IE patients. CKM, FITM1, and a combinative biomarker panel may serve as useful tools for assisting in the precision diagnosis and effective treatment of the FE phenotype of COPD.

Regulative Roles of Metabolic Plasticity Caused by Mitochondrial Oxidative Phosphorylation and Glycolysis on the Initiation and Progression of Tumorigenesis.

One important feature of tumour development is the regulatory role of metabolic plasticity in maintaining the balance of mitochondrial oxidative phosphorylation and glycolysis in cancer cells. In recent years, the transition and/or function of metabolic phenotypes between mitochondrial oxidative phosphorylation and glycolysis in tumour cells have been extensively studied. In this review, we aimed to elucidate the characteristics of metabolic plasticity (emphasizing their effects, such as immune escape, angiogenesis migration, invasiveness, heterogeneity, adhesion, and phenotypic properties of cancers, among others) on tumour progression, including the initiation and progression phases. Thus, this article provides an overall understanding of the influence of abnormal metabolic remodeling on malignant proliferation and pathophysiological changes in carcinoma.

Depression Promotes Gastroesophageal Reflux Disease: New Evidence Based on Mendelian Randomization.

BACKGROUND: Although observational studies have reported that depression is a risk factor for gastroesophageal reflux disease, it is difficult to determine the potential causal correlation. Thus, this study investigated the causal relevance of depression for gastroesophageal reflux disease using Mendelian randomization and provided new evidence for their association. METHODS: Based on data from the UK Biobank, we assessed the causality of the 2 diseases by analyzing 135 458 severe depressive disorder cases and 41 024 gastroesophageal reflux disease cases. The causal inference was assessed using inverse-variance weighting, weighted median, Mendelian randomization-Egger, and weighted median methods. Simultaneously, pleiotropy and sensitivity analyses were used for quality control. Finally, we also explored whether depression affects gastroesophageal reflux disease through other risk factors. RESULTS: A positive causal relationship between depression and gastroesophageal reflux disease was found in the inverse-variance weighted and weighted median methods, both of which were statistically significant [odds ratio = 1.011, 95% CI: 1.004-1.017, P =.001; odds ratio = 1.011, 95% CI: 1.004-1.020, P =.002)]. Sensitivity analyses were consistent with a causal interpretation, and the main deviation of genetic pleiotropy was not found (Intercept ß = 0.0005; SE = 0.005, P =.908). The genetic susceptibility to depression was also associated with smoking, insomnia, and sleep apnea (odds ratio = 1.166, 95% CI: 1.033-1.316, P =.013; odds ratio = 1.089, 95% CI: 1.045-1.134; and odds ratio = 1.004, 95% CI: 1.001-1.006, P =.001, respectively). CONCLUSION: Our results verified a causal correlation that depression could slightly increase the risk of gastroesophageal reflux disease.

A Redox-Controlled Substrate Engineering Strategy for Site-Specific Enzymatic Fucosylation.

Fucosylation is one of the most common modifications of oligo-N-acetyllactosamine (oligo-LacNAc) glycans. However, none of known fucosyltransferases (FucTs) could install the α1,3-linked fucose to the oligo-LacNAc substrates in a site-specific manner. Here, we report a facile and general redox-controlled substrate engineering strategy for the site-specific α1,3-fucosylation of complex glycans containing multiple LacNAc units. This strategy takes advantage of an operationally simple oxidation enzyme module by using galactose oxidase (GOase) to convert the LacNAc unit into oxidized C6'-aldehyde LacNAc sequence, which is not a good substrate for recombinant α1,3-FucT from Helicobacter pylori strain 26695 (Hpα1,3FucT), enabling the site-specific α1,3-fucosylation at intact LacNAc sites. The general applicability and robustness of this strategy were demonstrated by the synthesis of a variety of structurally well-defined fucosides of linear and branched O- and N-linked glycans.

Effects of 2,2',4'-trihydroxychalcone on the proliferation, metastasis and apoptosis of A549 human lung cancer cells.

The aim of the present study was to evaluate the antitumor effects of 2,2',4'-trihydroxychalcone (7a) on the A549 human lung cancer cell line. A549 cells were treated with different concentrations of 7a for different time periods. Cells without 7a were used as the negative control group. Cell proliferation, invasion, vasculogenic mimicry (VM) formation, heterogeneous adhesion and apoptosis were measured using Cell Counting Kit-8, Transwell invasion, VM, adhesion and flow cytometric assays, respectively. In addition, the expression of related proteins was determined using western blot analysis or ELISA. The present study found that 7a had a significant inhibitory effect on the survival rate of the A549 lung cancer cells but almost no effect on BEAS-2B human lung epithelial cells or human venous endothelial cells. The migration rate, VM length, invasion rate and heterogeneous adhesion number of cells treated with 7a significantly decreased as the concentration increased, while the apoptosis rate increased. Western blot analysis showed that 7a treatment significantly increased the expression levels of E-cadherin, cleaved poly (ADP-ribose) polymerase, Bax and caspase-3 and simultaneously decreased the expression levels of metalloproteinase-2/9, Bcl-2, phosphorylated (p)-PI3K, p-AKT, p-mTOR, vascular endothelial growth factor (VEGF), E-selectin and N-cadherin. At the same time, the ELISA results showed that the level of the pro-angiogenic factor VEGF in the culture media was reduced in the presence of 7a. In addition, 7a could also reduce the nuclear NF-κB protein expression, which could inhibit the gene transcription of tumor apoptosis and metastasis-related proteins. Therefore, 7a may exert inhibitory effects on A549 cells by inhibiting cell proliferation, migration, VM formation and heterogeneous adhesion, as well as by inducing apoptosis through the suppression of the PI3K/AKT/NF-κB signaling pathway; these findings suggested that 7a may be a promising agent for the treatment of lung cancer.

Educational attainment could be a protective factor against obstructive sleep apnea: a study based on Mendelian randomization.

BACKGROUND: Causality between education and obstructive sleep apnea (OSA) is not known. METHODS: Genetic variants, as instrumental variables for years of education, were derived from the Social Science Genetic Association Consortium. The outcome datasets related to OSA were from the FinnGen research project (www.finngen.fi/en/). Inverse variance-weighted, weighted-median, and Mendelian randomization-Egger analysis were used to estimate causal effects. To assess the robustness and horizontal pleiotropy of significant results, leave-one-out sensitivity analysis and Mendelian randomization-Egger regression analysis were conducted. The inverse variance-weighted method was undertaken to estimate the association between years of education and other known risk factors for OSA. Analyses were conducted using the Two Sample Mendelian Randomization package of R 4·0·3. RESULTS: Genetic predisposition towards 4.2 years of additional education was associated with a 27.8% lower risk of OSA [odds ratio (OR) =0.722, 95% confidence interval (CI): 0.566-0.921; P=0.009]. Sensitivity analyses were consistent with a causal interpretation in which a major bias from genetic pleiotropy was unlikely. The Mendelian randomization assumptions did not seem to be violated. Genetic predisposition towards longer education was associated with a lower body mass index, fewer cigarettes smoked per day, and greater alcohol intake per week. CONCLUSIONS: Our data indicated that education could be a protective factor against OSA. Potential mechanisms could include body mass index, tobacco smoking, and alcohol intake.

Chemoenzymatic Labeling Pathogens Containing Terminal N-Acetylneuraminic Acid-α(2-3)-Galactose Glycans.

The N-acetylneuraminic acid-α(2-3)-galactose epitope is often located at the nonreducing terminal ends of glycans on the envelopes of many pathogens, and it is believed that this structure mimics a host's oligosaccharide so as to circumvent and/or counteract the host's immune responses. A chemoenzymatic method for the rapid and sensitive detection of N-acetylneuraminic acid-α(2-3)-galactose has been built, so we planned to examine whether the chemoenzymatic method could be applied on the detection of N-acetylneuraminic acid-α(2-3)-galactose on pathogens. Our results revealed that the chemoenzymatic method was rapid and sensitive for labeling live or dead Gram-positive Streptococcus agalactiae A909 and Gram-negative Campylobacter jejuni MK104 with N-acetylneuraminic acid-α(2-3)-galactose. This study suggested that the chemoenzymatic method was a new strategy for labeling pathogens and had potential for the diagnosis of or therapeutics for pathogenic infection.

Enzymatic modular assembly of hybrid Lewis antigens.

The enzymatic synthesis of hybrid Lewis antigens including KH-1 (Lewis y-Lewis x-Lactose, Ley-Lex-Lac), Lewis a-Lewis x-Lactose (Lea-Lex-Lac), and Lewis b-Lewis x-Lactose (Leb-Lex-Lac) has been achieved using a facile enzymatic modular assembly strategy. Starting from a readily available tetrasaccharide, 3 complex hybrid Lewis antigens were achieved in over 40% total yields in less than 5 linear steps of sequential enzymatic glycosylation using 6 enzyme modules. The regio-selective fucosylation was achieved by simply controlling the donor-acceptor ratio. This strategy provides an easy access to these biologically important complex hybrid Lewis antigens at preparative scales.

Chemoenzymatic Synthesis of 9NHAc-GD2 Antigen to Overcome the Hydrolytic Instability of O-Acetylated-GD2 for Anticancer Conjugate Vaccine Development.

Ganglioside GD2 is an attractive tumor-associated carbohydrate antigen for anti-cancer vaccine development. However, its low immunogenicity and the significant side effects observed with anti-GD2 antibodies present significant obstacles for vaccines. To overcome these, a new GD2 derivative bearing an N-acetamide (NHAc) at its non-reducing end neuraminic acid (9NHAc-GD2) has been designed to mimic the 9-O-acetylated-GD2 (9OAc-GD2), a GD2 based antigen with a restricted expression on tumor cells. 9NHAc-GD2 was synthesized efficiently via a chemoenzymatic method and subsequently conjugated with a powerful carrier bacteriophage Qß. Mouse immunization with the Qß-9NHAc-GD2 conjugate elicited strong and long-lasting IgG antibodies, which were highly selective toward 9NHAc-GD2 with little cross-recognition of GD2. Immunization of canines with Qß-9NHAc-GD2 showed the construct was immunogenic in canines with little adverse effects, paving the way for future clinical translation to humans.

Linearly excited indium fluorescence imaging for temporally resolved high-precision flame thermometry.

Two-line atomic fluorescence (TLAF) is a promising technique for two-dimensional (2D) flame thermometry. However, it suffers either from a low signal-to-noise ratio (SNR) when excited in the linear regime or a quenching effect and nonlinear behavior in the nonlinear regime. This work aims to develop a new TLAF modality, which can overcome the aforementioned limitations based on a specifically designed laser source that can generate long pulses (∼400ns) with a moderate energy of ∼0.9µJ and operate at a repetition rate up to ∼22kHz. A proof-of-concept experiment was conducted and linearly excited fluorescence images with an SNR up to ∼14 were obtained within 1 ms acquisition time by synchronizing the laser with the microchannel plate (MCP) of a 10 Hz-rate intensified camera. The SNR achieved was comparable to that of a traditional nonlinear TLAF implementation and superior to a conventional linear TLAF approach. This approach offers a novel solution for recording linearly excited indium fluorescence images and is expected to make TLAF a temporally resolved and high-precision 2D thermometry for the first time.

Redox-Controlled Site-Specific α2-6-Sialylation.

The first bacterial α2-6-sialyltransferase cloned from Photobacterium damselae (Pd2,6ST) has been widely applied for the synthesis of various α2-6-linked sialosides. However, the extreme substrate flexibility of Pd2,6ST makes it unsuitable for site-specific α2-6-sialylation of complex substrates containing multiple galactose and/or N-acetylgalactosamine units. To tackle this problem, a general redox-controlled site-specific sialylation strategy using Pd2,6ST is described. This approach features site-specific enzymatic oxidation of galactose units to mask the unwanted sialylation sites and precisely controlling the site-specific α2-6-sialylation at intact galactose or N-acetylgalactosamine units.

Enzymatic synthesis of human blood group P1 pentasaccharide antigen.

The enzymatic synthesis of biologically important and structurally unique human P1PK blood group type P1 pentasaccharide antigen is described. This synthesis features a three-step sequential one-pot multienzyme (OPME) glycosylation for the stepwise enzymatic chain elongation of readily available lactoside acceptor with cheap and commercially available galactose and N-acetylglucosamine as donor precursors. This enzymatic synthesis provides an operationally simple approach to access P1 pentasaccharide and its structurally related Gb3 and P1 trisaccharide epitopes.

[Effect of perioperative goal-directed fluid therapy on clinical outcome in elective colorectal resection].

OBJECTIVE: To assess the effect of perioperative goal-directed fluid therapy (GDFT) on clinical outcomes in elective colorectal resection. METHODS: A total of 42 patients undergoing elective colorectal resection between March 2013 and December 2014 were recruited prospectively. GDFT was administrated based on corrected left ventricular ejection time and stroke volume using the esophageal Doppler monitoring. These patients were compared with a historical cohort of 58 patients managed without GDFT from January 2012 to February 2013. The primary endpoint was postoperative hospital stay and complication rate. RESULTS: There was no significant difference in the overall fluid volumes administered intraoperatively between two groups [(2657±1037) ml vs. (2846±1444) ml, P>0.05], but patients in GDFT group received higher volume of colloid fluids [(935±556) ml vs. (688±414) ml, P<0.05]. After a period of concordance at the start of operation, corrected left ventricular ejection time, stroke volume and cardiac index increased in GDFT group compared with control group (all P<0.05). No significant differences were found in postoperative hospital stay [(11.27±6.42) d vs. (12.04±7.18) d, P>0.05] and total complication rate (26.5% vs. 25.9%, P>0.05) between two groups, but GDFT group had earlier postoperative flatus [(3.52±0.84) d vs. (4.48±0.71) d, P<0.05] and faster tolerated diet [(5.92±1.18) d vs. (6.83±0.95) d, P<0.05]. CONCLUSIONS: Patients undergoing elective colorectal resection do not benefit from intraoperative GDFT. Further studies should be carried out to investigate whether GDFT can be routinely used during colorectal resection.