Fe based MOF encapsulating triethylenediamine cobalt complex to prepare a FeN3-CoN3 dual-atom catalyst for efficient ORR in Zn-air batteries.

Single-atom catalysts show good oxygen reduction reaction (ORR) performance in metal-air battery. However, the symmetric electron distribution results in discontented adsorption energy of ORR intermediates and a lower ORR activity. Herein, Fe-Co dual-atom catalyst with FeN3-CoN3 configuration was prepared by encapsulating nitrogen-rich ion (triethylenediamine cobalt complex, [Co(en)3]3+) in Fe based MOF cage to greatly enhance ORR performance. Due to the confinement effect of the MOF cage, the encapsulated [Co(en)3]3+ is closer to Fe of MOF, thus easily generating FeN3-CoN3 sites. The FeN3-CoN3 sites can break the symmetric electron distribution of single-atom sites, optimizing adsorption energy of oxygen intermediate. Thus, FeCo-NC exhibits extraordinary ORR activity with a high half-wave potential of 0.915 V and 0.789 V in alkaline and acidic electrolyte, respectively, while it was 0.874 V and 0.79 V for Pt/C. The liquid and solid Zn-air batteries with FeCo-NC as cathode show higher peak power density and specific capacity. DFT results indicate that FeN3-CoN3 site can reduce the reaction energy barrier of the rate-determining step resulting in an excellent ORR performance.

Relationship between plasma brain-derived neurotrophic factor levels and neurological disorders: An investigation using Mendelian randomisation.

Background: Altered brain-derived neurotrophic factor (BDNF) concentrations have been detected in the central nervous system tissues and peripheral blood. These alterations are associated with a series of neurological disorders. Objective: To investigate the potential causal relationships between genetically determined plasma BDNF levels and various neurological diseases using a two-sample Mendelian randomisation study. Methods: We selected single nucleotide polymorphisms strongly related to plasma BDNF levels as instrumental variables. Within the Mendelian randomisation framework, we used summary-level statistics for exposure (plasma BDNF levels) and outcomes (neurological disorders). Results: We observed suggestive evidence of a relation between higher plasma BDNF levels and less risk of nontraumatic intracranial haemorrhage (nITH) (odds ratio [OR] = 0.861, 95 % confidence interval [CI]: 0.774-0.958, P = 0.006, PFDR = 0.078), epilepsy (OR = 0.927, 95 % CI: 0.880-0.976, P = 0.004, PFDR = 0.078), focal epilepsy (OR = 0.928, 95 % CI: 0.874-0.986, P = 0.016, PFDR = 0.139), and non-lesional focal epilepsy (OR = 0.981, 95 % CI: 0.964-0.999, P = 0.041, PFDR = 0.267). Combined with the UK Biobank dataset, the association of plasma BDNF levels with nITH remained significant (OR = 0.88, 95 % CI: 0.81-0.96, P < 0.01). The combined analysis of three consortium datasets demonstrated a considerable impact of plasma BDNF on epilepsy (OR = 0.94, 95 % CI: 0.90-0.98, P < 0.01) and a suggestive impact on focal epilepsy (OR = 0.94, 95 % CI: 0.89-0.99, P = 0.02). However, there was no apparent correlation between plasma BDNF levels and other neurological disorders or related subtypes. Conclusions: Our study supports a possible causal relationship between elevated plasma BDNF levels and a reduced risk of nITH, epilepsy, and focal epilepsy.

Completely Methylene-Free Side Chain Enables Significant Microphase Separation at Medium IECs for Fuel-Cell Anion Exchange Membranes.

The introduction of hydrophobic side chain structures in anion exchange membranes (AEMs) to facilitate ion transport has been widely studied; however, low or moderate hydrophobic hydrocarbon and semifluorinated side chains are insufficient to induce a high degree of microphase separation. Herein, we design and prepare poly(aryl piperidinium) AEMs with completely methylene-free perfluorinated side chains, which can maximize the thermodynamic incompatibility between main- and side chains, thus enhancing microphase separation at medium ion exchange capacities (IECs). According to the molecular dynamics study, the methylene-free perfluorinated side chain leads to better hydration of cations. The hydroxide conductivity of the methylene-free perfluorinated side chain-grafted PAP-pF-1 membrane reaches 124.9 mS cm-1 at 80 °C, and the PAP-sF-1 with semifluorinated side chains and PAP-CH-1 with hydrocarbon side chains show lower conductivity (116.8 and 104.0 mS cm-1). The H2/O2 fuel cell using the PAP-pF-1 membrane demonstrates a remarkable peak power density (1651 mW cm-2 at 80 °C) and durability (greater than 300 h). This work provides a novel insight into enhancing microphase separation in AEMs; it opens up new possibilities for developing high-performance AEMs.

Insulin eye drops improve corneal wound healing in STZ-induced diabetic mice by regulating corneal inflammation and neuropeptide release.

INTRODUCTION: In recent years, insulin eye drops have attracted increasing attention from researchers and ophthalmologists. The aim of this study was to investigate the efficacy and possible mechanism of action of insulin eye drops in diabetic mice with corneal wounds. METHODS: A type 1 diabetes model was induced, and a corneal epithelial injury model of 2.5 mm was established. We used corneal fluorescein staining, hematoxylin-eosin (H-E) staining and the Cochet-Bonnet esthesiometer to examine the process of wound healing. Subsequently, the expression levels of Ki-67, IL-1ß, ß3-tubulin and neuropeptides, including substance P (SP) and calcitonin gene-related peptide (CGRP), were examined at 72 h after corneal injury. RESULTS: Fluorescein staining demonstrated an acceleration of the recovery of corneal epithelial injury in diabetic mice compared with the saline treatment, which was further evidenced by the overexpression of Ki-67. Moreover, 72 h of insulin application attenuated the expression of inflammatory cytokines and neutrophil infiltration. Remarkably, the results demonstrated that topical insulin treatment enhanced the density of corneal epithelial nerves, as well as neuropeptide SP and CGRP release, in the healing cornea via immunofluorescence staining. CONCLUSIONS: Our results indicated that insulin eye drops may accelerate corneal wound healing and decrease inflammatory responses in diabetic mice by promoting nerve regeneration and increasing levels of neuropeptides SP and CGRP.

Balanced activation of Nrf-2/ARE mediates the protective effect of sulforaphane on keratoconus in the cell mechanical microenvironment.

Keratoconus (KC) is a progressive degenerative disease that usually occurs bilaterally and is characterized by corneal thinning and apical protrusion of the cornea. Oxidative stress is an indicator of the accumulation of reactive oxygen species (ROS), and KC keratocytes exhibit increased ROS production compared with that of normal keratocytes. Therefore, oxidative stress in KC keratocytes may play a major role in the development and progression of KC. Here, we investigated the protective effect of sulforaphane (SF) antioxidants using a hydrogel-simulated model of the cell mechanical microenvironment of KC. The stiffness of the KC matrix microenvironment in vitro was 16.70 kPa and the stiffness of the normal matrix microenvironment was 34.88 kPa. Human keratocytes (HKs) were cultured for 24 h before observation or drug treatment with H2O2 in the presence or absence of SF. The levels of oxidative stress, nuclear factor E2-related factor 2 (Nrf-2) and antioxidant response element (ARE) were detected. The high-stress state of HKs in the mechanical microenvironment of KC cells compensates for the activation of the Nrf-2/ARE signaling pathway. H2O2 leads to increased oxidative stress and decreased levels of antioxidant proteins in KC. In summary, SF can reduce endogenous and exogenous oxidative stress and increase the antioxidant capacity of cells.

Water-Free Cyclosporine Ophthalmic Solution vs Vehicle for Dry Eye Disease: A Randomized Clinical Trial.

Importance: Dry eye disease (DED) is a prevalent eye disorder. Cyclosporine is an effective immunomodulator that is widely used in DED; however, due to its highly hydrophobic nature, delivery of cyclosporine to the ocular surface is challenging. Objective: To evaluate the efficacy and safety of SHR8028, a water-free cyclosporine ophthalmic solution, 0.1%, compared with vehicle in Chinese participants with DED. Design, Setting, and Participants: This was a multicenter, double-blind, vehicle-controlled, phase 3 randomized clinical trial conducted from March 4, 2021, to July 22, 2022. Adult participants with moderate to severe DED were recruited from 12 hospitals in China. Study data were analyzed April 2, 2022, for the primary analysis. Interventions: Following a 14-day run-in period with an artificial tear, participants were randomly assigned (1:1) to receive water-free cyclosporine or vehicle (1 eye drop in each eye twice daily). After a 29-day treatment, participants of both groups were given the option to receive water-free cyclosporine for an additional 12 weeks for longer-term safety assessment. Main Outcomes and Measures: The primary end points were changes from baseline in total corneal fluorescein staining (tCFS) using the National Eye Institute scale and in dryness score on a visual analog scale at day 29. Results: A total of 206 participants (mean [SD] age, 47.8 [14.2] years; 185 female [90%]) were enrolled, with 103 each in the cyclosporine group and the vehicle group. At day 29, the cyclosporine group experienced improved tCFS compared with vehicle (change [Δ] = -1.8; 95% CI, -2.7 to -1.0; P < .001), with a tCFS score decrease from baseline of -4.8 in the cyclosporine group and -3.0 in the vehicle group. Dryness score decreased from baseline in both groups (-19.2 vs -15.4; Δ = -3.8; 95% CI, -9.2 to 1.6; P = .17). During the 29-day treatment, treatment-related adverse events were reported in 15 participants (14.6%) in the cyclosporine group and 11 participants (10.7%) in the vehicle group. Conclusions And Relevance: Results demonstrated superiority of a water-free cyclosporine, 0.1%, eye solution over vehicle in improving tCFS score at day 29 in Chinese participants with DED. However, dryness score (VAS) was not improved at day 29. Trial Registration: ClinicalTrials.gov Identifier: NCT05841043.

Reactive cutaneous capillary endothelial proliferations of the eyelids induced by camrelizumab: A case report.

With the widespread application of immune checkpoint inhibitors, a series of adverse events (AEs) related to treatment resulting from alterations in the immune system have emerged that warrant attention. The present study report the case of a patient with reactive cutaneous capillary endothelial proliferations (RCCEPs) on the eye lid, following treatment with the programmed cell death protein 1 inhibitor camrelizumab (SHR-1210) for stage IIa2 well- to moderately differentiated squamous cell carcinoma of the cervix. Although RCCEPs have been revealed to be the most common AEs of SHR-1210, they are usually distributed on the head, neck, trunk and extremities. The current study presents a rare case of ocular RCCEPs induced by SHR-1210. Prompt diagnosis and treatment of immune-related AEs is crucial for the optimal management of patients. Although RCCEPs are usually slight-risk toxicities that pose no threat to the continuity of treatment, lesions with unusual distributions that cause disturbances in normal life require proper treatment, such as surgical excision.

Comprehensive bioinformation analysis of homeodomain-leucine zipper gene family and expression pattern of HD-Zip I under abiotic stress in Salix suchowensis.

BACKGROUND: Homeodomain-leucine zipper (HD-Zip) transcription factors are plant-specific and play important roles in plant defense against environmental stresses. Identification and functional studies have been carried out in model plants such as rice, Arabidopsis thaliana, and poplar, but comprehensive analysis on the HD-Zip family of Salix suchowensis have not been reported. RESULTS: A total of 55 HD-Zip genes were identified in the willow genome, unevenly distributed on 18 chromosomes except for chromosome 19. And segmental duplication events containing SsHD-Zip were detected on all chromosomes except chromosomes 13 and 19. The SsHD-Zip were classified into 4 subfamilies subfamilies (I-IV) according to the evolutionary analysis, and members of each subfamily shared similar domain structure and gene structure. The combination of GO annotation and promoter analysis showed that SsHD-Zip genes responded to multiple abiotic stresses. Furthermore, the results of qPCR analysis showed that the SsHD-Zip I gene exhibited different degrees of expression under salt stress, PEG treatment and heat treatment. Moreover, there was a synergistic effect between SsHD-Zip I genes under stress conditions based on coregulatory networks analysis. CONCLUSIONS: In this study, HD-Zip transcription factors were systematically identified and analyzed at the whole genome level. These results preliminarily clarified the structural characteristics and related functions of willow HD-Zip family members, and it was found that SsHox34, SsHox36 and SsHox51 genes were significantly involved in the response to various stresses. Together, these findings laid the foundation for further research on the resistance functions of willow HD-Zip genes.

Association between dyslipidaemia and dry eye disease: a systematic review and meta-analysis.

PURPOSE: To report a systematic review and meta-analysis of the association between dry eye disease (DED) and dyslipidaemia. METHODS: PubMed, Embase, Web of Science and Cochrane Library were systematically searched from January 2000 to December 2021. We included observational studies to assess the correlation of DED with meibomian gland dysfunction and dyslipidaemia without any language restrictions. The pooled OR with 95% CI was calculated in Stata V.15. RESULTS: Of 6727 identified studies, 18 studies (21 databases) with a total of 2 663 126 patients were analysed in our meta-analysis. The results showed that DED risk was associated with dyslipidaemia (OR=1.53, 95% CI: 1.41 to 1.66, p=0.001), especially elevated total cholesterol levels (OR=1.57, 95% CI: 1.25 to 1.99, p<0.001), elevated low-density lipoprotein cholesterol levels (OR=1.13, 95% CI: 1.06 to 1.20, p<0.001) and high-density lipoprotein cholesterol levels (OR=1.06, 95% CI: 1.01 to 1.11, p<0.001), but not with serum triglyceride levels. Moreover, having a history of lipid-lowering drug use (OR=1.41, 95% CI: 1.19 to 1.67, p<0.001) was also found to be positively associated with DED risk. CONCLUSIONS: The findings suggested that dyslipidaemia and lipid-lowering drug use might be associated with an increased risk of DED. More evidence is needed to confirm the findings by prospective studies. PROSPERO REGISTRATION NUMBER: CRD42022296664.

Functional connectomic profile correlates with effective anterior thalamic stimulation for refractory epilepsy.

BACKGROUND: Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) is an effective treatment for refractory epilepsy; however, seizure outcome varies among individuals. Identifying a reliable noninvasive biomarker to predict good responders would be helpful. OBJECTIVES: To test whether the functional connectivity between the ANT-DBS sites and the seizure foci correlates with effective seizure control in refractory epilepsy. METHODS: We performed a proof-of-concept pilot study of patients with focal refractory epilepsy receiving ANT-DBS. Using normative human connectome data derived from 1000 healthy participants, we investigated whether intrinsic functional connectivity between the seizure foci and the DBS site was associated with seizure outcome. We repeated this analysis controlling for the extent of seizure foci, distance between the seizure foci and DBS site, and using functional connectivity of the ANT instead of the DBS site to test the contribution of variance in DBS sites. RESULTS: Eighteen patients with two or more seizure foci were included. Greater functional connectivity between the seizure foci and the DBS site correlated with more favorable outcome. The degree of functional connectivity accounted for significant variance in clinical outcomes (DBS site: |r| = 0.773, p < 0.001 vs ANT-atlas: |r| = 0.715, p = 0.001), which remained significant when controlling for the extent of the seizure foci (|r| = 0.773, p < 0.001) and the distance between the seizure foci and DBS site (|r| = 0.777, p < 0.001). Significant correlations were independent of variance in the DBS sites (|r| = 0.148, p = 0.57). CONCLUSION: These findings suggest that functional connectomic profile is a potential reliable non-invasive biomarker to predict ANT-DBS outcomes. Accordingly, the identification of ANT responders could decrease the surgical risk for patients who may not benefit and optimize the cost-effective allocation of health care resources.

Advances in the pharmacological study of Chinese herbal medicine to alleviate diabetic nephropathy by improving mitochondrial oxidative stress.

Diabetic nephropathy (DN) is one of the serious complications of diabetes mellitus, primarily arising from type 2 diabetes (T2DM), and can progress to chronic kidney disease (CKD) and end stage renal disease (ESRD). The pathogenesis of DN involves various factors such as hemodynamic changes, oxidative stress, inflammatory response, and lipid metabolism disorders. Increasing attention is being given to DN caused by oxidative stress in the mitochondrial pathway, prompting researchers to explore drugs that can regulate these target pathways. Chinese herbal medicine, known for its accessibility, rich historical usage, and remarkable efficacy, has shown promise in ameliorating renal injury caused by DN by modulating oxidative stress in the mitochondrial pathway. This review aims to provide a reference for the prevention and treatment of DN. Firstly, we outline the mechanisms by which mitochondrial dysfunction impairs DN, focusing on outlining the damage to mitochondria by oxidative stress. Subsequently, we describe the process by which formulas, herbs and monomeric compounds protect the kidney by ameliorating oxidative stress in the mitochondrial pathway. Finally, the rich variety of Chinese herbal medicine, combined with modern extraction techniques, has great potential, and as we gradually understand the pathogenesis of DN and research techniques are constantly updated, there will be more and more promising therapeutic targets and herbal drug candidates. This paper aims to provide a reference for the prevention and treatment of DN.

Radiomics features from 3D-MPRAGE imaging can differentiate temporal-plus epilepsy from temporal lobe epilepsy.

OBJECTIVE: This study aimed to differentiate temporal-plus epilepsy (TPE) from temporal lobe epilepsy (TLE) using extraction of radiomics features from three-dimensional magnetization-prepared rapid acquisition gradient echo (3D-MPRAGE) imaging data. METHODS: Data from patients with TLE or TPE who underwent epilepsy surgery between January 2019 and January 2021 were retrospectively analyzed. Thirty-three regions of interest in the affected hemisphere of each patient were defined on 3D-MPRAGE images. A total of 3531 image features were extracted from each patient. Four feature selection methods and 10 machine learning algorithms were used to build 40 differentiation models. Model performance was evaluated using receiver operating characteristic analysis. RESULTS: Eighty-two patients were included for analysis, 47 with TLE and 35 with TPE. The model combining logistic regression and the relief selection method had the best performance (area under the receiver operating characteristic curve, .779; accuracy, .875; sensitivity, .800; specificity, .929; positive predictive value, .889; negative predictive value, .867). SIGNIFICANCE: Radiomics analysis can differentiate TPE from TLE. The logistic regression classifier trained with radiomics features extracted from 3D-MPRAGE images had the highest accuracy and best performance.

Continuous Covalent Organic Frameworks Membranes: From Preparation Strategies to Applications.

Covalent organic frameworks (COFs) are porous crystalline polymeric materials formed by the covalent bonding of organic units. The abundant organic units library gives the COFs species diversity, easily tuned pore channels, and pore sizes. In addition, the periodic arrangement of organic units endows COFs regular and highly connected pore channels, which has led to the rapid development of COFs in membrane separations. Continuous defect-free and high crystallinity of COF membranes is the key to their application in separations, which is the most important issue to be addressed in the research. This review article describes the linkage types of covalent bonds, synthesis methods, and pore size regulation strategies of COFs materials. Further, the preparation strategies of continuous COFs membranes are highlighted, including layer-by-layer (LBL) stacking, in situ growth, interfacial polymerization (IP), and solvent casting. The applications in separation fields of continuous COFs membranes are also discussed, including gas separation, water treatment, organic solvent nanofiltration, ion conduction, and energy battery membranes. Finally, the research results are summarized and the future prospect for the development of COFs membranes are outlined. More attention may be paid to the large-scale preparation of COFs membranes and the development of conductive COFs membranes in future research.

3% diquafosol sodium eye drops in Chinese patients with dry eye: a phase IV study.

Introduction: The efficacy and safety of 3% diquafosol sodium eye drops in Chinese patients with dry eye in the real-world setting remains unclear. Methods: 3099 patients with dry eye symptoms were screened according to Asia Dry Eye Society latest recommendation. Among them, 3000 patients were enrolled for a phase IV study. We followed up with multiple clinical characteristics including corneal fluorescein staining, tear break up time, Schirmer's tests, visual acuity, intraocular pressure, and others. The follow ups were performed at baseline, 2 weeks and 4 weeks after treatment. Results: Based on the results of corneal fluorescein staining and tear break up time, all age and gender subgroups exhibited obvious alleviation of the symptoms among the patients with dry eye, and the data in elderly group showed the most significant alleviation. All the adverse drug reactions (ADRs, 6.17%) were recorded, among which 6% local ocular ADRs were included. Meanwhile, mild ADRs (91.8%) accounted for the most. Most of the ADRs (89.75%) got a quick and full recovery, with an average time at 15.6 days. 1.37% of patients dropped out of the study due to ADRs. Discussion: The use of 3% diquafosol sodium eye drop is effective and safe in the treatment of dry eye, with a low incidence of ADRs showing mild symptoms. This trial was registered at Chinese Clinical Trial Registry ID: ChiCTR1900021999 (Registration Date: 19/03/2019).

Association of malnutrition with all-cause and cardiovascular mortality in patients with mild to severe chronic kidney disease undergoing coronary angiography: a large multicenter longitudinal study.

PURPOSE: Evidence on the prognostic impact of malnutrition was focused on patients with advanced kidney disease. The relationships between malnutrition and all-cause and cardiovascular mortality in patients with different severity of chronic kidney disease (CKD) have not been adequately addressed. We aimed to reveal the prevalence of malnutrition and its prognostic value in patients with different severity of CKD undergoing coronary angiography (CAG). METHODS: This was a multicenter, longitudinal, and retrospective cohort study of 12,652 patients with non-dialysis dependent CKD (defined as estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2) undergoing CAG from five tertiary hospitals between January 2007 and December 2020. The controlling nutritional status (CONUT) score was applied to assess nutritional status. Cox regression models and competing risk Fine and Gray models were used to examine the relationships between malnutrition, all-cause and cardiovascular mortality. Further stratified analysis was performed according to baseline CKD severity (mild, moderate and severe, defined by eGFR < 30, 30-44 and 45-59 ml/min/1.73 m2). RESULTS: During a median follow-up of 5.5 years (interquartile range: 3.2 to 8.6 years), 3801 patients (30.0%) died, and 2150 (17.0%) definitely died of cardiovascular disease. After controlling for confounders, patients had higher all-cause mortality (mild, moderate, and severe vs. absent: HR 1.27, 95 CI % [1.17-1.39]; HR 1.54, 95 CI % [1.39-1.71]; HR 2.22, 95 CI % [1.78-2.77], respectively; P for trend < 0.001) and cardiovascular mortality (mild, moderate and severe vs. absent: HR 1.35, 95 CI % [1.21-1.52]; HR 1.67, 95 CI % [1.45-1.92]; HR 2.10, 95 CI % [1.55-2.85], respectively; P for trend < 0.001) with the severity of malnutrition. In further stratified analysis, a similar prognostic impact of malnutrition was observed in patients with mild to moderate CKD, while mild malnutrition did not seem to have a consistent effect on severe CKD patients. CONCLUSION: Malnutrition is common among patients with mild to severe CKD undergoing CAG and is strongly associated with increased risk of all-cause and cardiovascular mortality. Malnutrition seems to have a modestly stronger impact on mortality in patients with mild to moderate CKD. This study was registered at Clinicaltrials.gov as NCT05050877.

Effect of Urinary Albumin Creatinine Ratio on Cardiovascular Morbidity and Mortality in Diabetes Patients with Atherosclerotic Disease.

Background: Diabetes mellitus (DM) patients with increased urinary albumin creatinine ratio (uACR) have higher risk of mortality, while it is unclear in DM patients with atherosclerotic cardiovascular disease (ASCVD). Methods: We analysed 2832 DM patients with ASCVD in this multi-center registry cohort study Cardiorenal ImprovemeNt II (CIN-II) in 5 Chinese tertiary hospitals from 2007 to 2020. Patients were divided into 3 groups according to their uACR level (normal group: uACR <30mg/g, moderately increased group: 30mg/g≤ uACR <300mg/g, severely increased group: 300mg/g≤ uACR). The main outcome of the study was cardiovascular mortality and all-cause mortality. Results: During a median follow-up of 2.1 years, among 2832 patients (mean age: 63.3 ± 9.9 years, 29.1% women), 434 patients (15.3%) had moderately increased uACR, and 203 patients (7.2%) had severely increased uACR. Compared to patients in normal group, patients had higher cardiovascular mortality in moderately increased group and severely increased group (2.5% vs 9.9% vs 16.7%, P < 0.001), as well as all-cause mortality. After adjusting confounders, the risk of cardiovascular mortality remained higher in moderately increased group (adjusted hazard ratio [aHR]: 3.13; 95% confidence interval [CI]: 2.04-4.81) and severely increased group (aHR: 4.54; 95% CI: 2.58-8.01) than in normal group, as well as all-cause mortality. Conclusion: In our study, we found nearly a quarter of DM patients with ASCVD had increased uACR, and they have over 2- or 3-fold risk of cardiovascular mortality than those with normal uACR. UACR is a helpful indicator for risk stratification and treatment target for DM patients with ASCVD.

Efficacy and safety of microbial transglutaminase-induced scleral stiffening invivo.

The purpose of this study was to investigate the efficacy and safety of microbial transglutaminases (mTGases) during scleral collagen cross-linking (CXL) in vivo. Sixteen New Zealand white albino rabbits were treated with sub-Tenon's injections of 2 ml of 1 U/ml mTGases in the right eye and 2 ml of phosphate buffer saline (PBS) in the left eye. The rabbits were killed 2 weeks after the injection, and all eyeballs, including some scleral strips, were processed. The elastic modulus was measured with a biomaterials tester. Histopathological analysis and transmission electron microscopy (TEM) were used for the morphological observations. The elastic modulus of the mTGase-treated sclera was 15.79 ± 2.93 MPa, and that of the control was 6.91 ± 2.23 MPa, indicating an increase of 129% after the mTGases treatment (P < 0.05). The density of the scleral collagen bundles and diameter of the collagen fibrils increased compared with those in the control group. No apoptosis was detected in the retina or posterior sclera by TUNEL staining, and no histological damage was observed on the TEM scan. This study is based on a short-term study on animal models. These results indicate that mTGase-mediated scleral CXL is a promising approach to effectively stiffen the sclera and safe enough for retina, and may be a useful treatment modality for strengthening scleral tissue.

Shaping droplet by semiflexible micro crystallizer for high quality crystal harvest.

Droplet crystallization behavior held great potential in crystal preparation, micromaterial engineering, and molecular assembly. However, restricted by natural surface tension, the intrinsic crystallization regulation and efficient harvest of high quality crystal in diverse droplet features were still a great challenge. Herein, we developed a 3D printed semiflexible micro crystallizer with two aspectant sessile platforms that could simultaneously construct a series of heteromorphic droplets (HDs) and controllable HD shape. By shaping HD on the interface of the platform, central-converging micro-flows were generated by coordinating the gas-liquid interface and flow intensity (i.e., Ra/Ma) during HD crystallization from 'barrel', 'can', to 'sand clock' shape, which was validated via simulative and experimental research. Therefore, HDs, constructed in semiflexible micro crystallizer, exhibited efficient screening (>70 %) of single cubic crystal just at the center zone of platform, even under wide ranges of concentration and volume, manifesting excellent repeatability on high quality crystal harvest and relevant interfacial science research.

Fibrinogen-to-Albumin Ratio and Long-Term Mortality in Coronary Artery Disease Patients with Different Glucose Metabolism Status.

Background: Abnormal glucose metabolism is present in most patients with coronary artery disease (CAD). Inflammation is considered to be a common risk factor for CAD and diabetes. Fibrinogen-to-albumin ratio (FAR), a novel inflammation biomarker, has been proposed as a predictor for cardiovascular disease. However, the relationship between the level of FAR and long-term mortality including all-cause, cardiovascular and cancer mortality, remains unknown in CAD patients, especially those with prediabetes. Methods: We enrolled 66,761 CAD patients from 2007 to 2020 from a multi-center registry cohort study. The primary outcomes were the all-cause, cardiovascular and cancer mortality. FAR was calculated using the following formula: Fibrinogen (g/L)/Albumin (g/L). Patients were divided into three groups by FAR tertile (low FAR (FAR-L), median FAR (FAR-M), high FAR (FAR-H)), and further categorized into 9 groups according to FAR and glucose metabolism status (normal glucose regulation (NGR), prediabetes mellitus (PreDM), diabetes mellitus (DM)). Cox regression models and competing risk models were used to examine the relationships between FAR and clinical outcomes. Results: 66,761 patients (63.1 ± 11.0 years, 75.3% male) were enrolled. During the follow-up, 10,534 patients died, including 4991 cardiovascular deaths and 1092 cancer deaths. After adjusting for confounders, higher FAR was associated with increased risk of all-cause and cause-specific mortality in CAD patients with NGR, PreDM and DM. The risk of all-cause and cardiovascular mortality was highest in FAR-H with DM (HR (95% CI) = 1.71 (1.58-1.86), 2.11 (1.86-2.38), respectively; p < 0.001). FAR-H with PreDM was significantly associated with the highest risk of cancer mortality (HR (95% CI) = 2.27 (1.70-3.02), p < 0.001). Adding FAR to the original model significantly improved the prediction of long-term mortality. Conclusions: Increased FAR was significantly associated with higher risk of all-cause and cause-specific mortality in CAD patients with NGR, PreDM and DM. Abnormal glucose metabolism augments the relationship between FAR and mortality. Clinical Trial Registration: ClinicalTrials.gov NCT05050877.

The Association between Left Ventricular End-Diastolic Diameter and Long-Term Mortality in Patients with Coronary Artery Disease.

Background: Left ventricular end-diastolic diameter (LVEDD) is a common parameter in echocardiography. Increased LVEDD is associated with left ventricular (LV) dysfunction. However, the association between LVEDD and all-cause mortality in patients with coronary artery disease (CAD) is uncertain. Methods: This study enrolled 33,147 patients with CAD who had undergone transthoracic echocardiography between January 2007 and December 2018 from the Cardiorenal Improvement study (NCT04407936). The patients were stratified into four groups based on the quartile of LVEDD (Quartile 1: LVEDD ≤ 43 mm, Quartile 2: 43 mm < LVEDD ≤ 46 mm, Quartile 3: 46 mm < LVEDD ≤ 51 mm, Quartile 4: LVEDD > 51 mm) and were categorized into two groups (Quartile 1-3 versus Quartile 4). Survival curves were generated with the Kaplan-Meier analysis, and the differences between groups were assessed by log-rank test. Restricted cubic splines and cox proportional hazards models were used to investigate the association with LVEDD and all-cause mortality. Results: A total of 33,147 patients (average age: 63.0 ± 10.6 years; 24.0% female) were included in the final analysis. In the average follow-up period of 5.2 years, a total of 4288 patients died. The mortality of the larger LVEDD group (Quartile 4) was significantly higher than the lower LVEDD groups (Quartile 1-3) (18.05% vs 11.15%, p < 0.001). After adjusting for confounding factors, patients with the larger LVEDD (Quartile 4) had a 1.19-fold risk for all-cause mortality (95% CI: 1.09-1.30) compared with the lower quartile (Quartile 1-3). Conclusions: Enlarged LVEDD is an independent predictor of all-cause mortality in patients with CAD. LVEDD measurements may be helpful for risk stratification and providing therapeutic targets for the management of CAD patients.