Prognostic benefits of His-Purkinje capture in physiological pacemakers for bradycardia.

INTRODUCTION: Clinical outcomes of long-term ventricular septal pacing (VSP) without His-Purkinje capture remain unknown. This study evaluated the differences in clinical outcomes between conduction system pacing (CSP), VSP, and right ventricular pacing (RVP). METHODS: Consecutive patients with bradycardia indicated for pacing from 2016 to 2022 were prospectively followed for the clinical endpoints of heart failure (HF)-hospitalizations and all-cause mortality at 2 years. VSP was defined as septal pacing due to unsuccessful CSP implant or successful CSP followed by loss of His-Purkinje capture within 90 days. RESULTS: Among 1016 patients (age 73.9 ± 11.2 years, 47% female, 48% atrioventricular block), 612 received RVP, 335 received CSP and 69 received VSP. Paced QRS duration was similar between VSP and RVP, but both significantly longer than CSP (p < .05). HF-hospitalizations occurred in 130 (13%) patients (CSP 7% vs. RVP 16% vs. VSP 13%, p = .001), and all-cause mortality in 143 (14%) patients (CSP 7% vs. RVP 19% vs. VSP 9%, p < .001). The association of pacing modality with clinical events was limited to those with ventricular pacing (Vp) > 20% (pinteraction < .05). Adjusting for clinical risk factors among patients with Vp > 20%, VSP (adjusted hazard ratio [AHR]: 4.74, 95% confidence interval [CI]: 1.57-14.36) and RVP (AHR: 3.08, 95% CI: 1.44-6.60) were associated with increased hazard of HF-hospitalizations, and RVP (2.52, 95% CI: 1.19-5.35) with increased mortality, compared to CSP. Clinical endpoints did not differ between VSP and RVP with Vp > 20%, or amongst groups with Vp < 20%. CONCLUSION: Conduction system capture is associated with improved clinical outcomes. CSP should be preferred over VSP or RVP during pacing for bradycardia.

Rho-kinase inhibitor alleviates CD4+T cell mediated corneal graft rejection by modulating its STAT3 and STAT5 activation.

Penetrating keratoplasty remains the most common treatment to restore vision for corneal diseases. Immune rejection after corneal transplantation is one of the major causes of graft failure. In recent years, Rho-associated protein kinase (ROCK) inhibitors have been found to be associated with the activation of the STATs pathway and are widely studied in autoimmune diseases. Therefore, it may be possible that the ROCK inhibitors also participate in the local and systemic immune regulation in corneal transplantation through activation of the STATs pathway and affect the CD4+ T cell differentiation. This study aimed to explore the role of ROCK-STATs pathway in the occurrence of immune rejection in corneal transplantation by applying Y27632, a ROCK inhibitor, to the recipient mice and peripheral CD4+ T cells. We found that Y27632 significantly up-regulated the phosphorylation level of STAT5 in both spleen and lymph nodes, down-regulated the phosphorylation level of STAT3 in the CD4+ T cells in the spleen. It also increased the proportion of CD4+CD25+Foxp3+Helios+ Tregs while decreased CD4+IL17A+ -Th17 cells. Moreover, Y27632 also reduced the proportion of dendritic cells in both spleen and lymph nodes, as well as the expression level of CD86 on their surfaces in the spleen, while the proportion of macrophages was not affected. The expression levels of ROCK1, ROCK2, CD11c and IL-17A mRNA were also found to be low in the graft tissue while the expression of Helios was upregulated. Rho-kinase inhibitor can modulate the balance of Tregs/Th17 by regulating the phosphorylation levels of both STAT3 and STAT5, thereby inhibiting the occurrence of immune rejection in allogeneic corneal transplantation.

Hypoxia-induced ZEB1 promotes cervical cancer immune evasion by strengthening the CD47-SIRPα axis.

BACKGROUND: The dynamic interaction between cancer cells and tumour-associated macrophages (TAMs) in the hypoxic tumour microenvironment (TME) is an active barrier to the effector arm of the antitumour immune response. Cancer-secreted exosomes are emerging mediators of this cancer-stromal cross-talk in the TME; however, the mechanisms underlying this interaction remain unclear. METHODS: Exosomes were isolated with ExoQuick exosome precipitation solution. The polarizing effect of TAMs was evaluated by flow cytometry, western blot analysis, immunofluorescence staining and in vitro phagocytosis assays. Clinical cervical cancer specimens and an in vivo xenograft model were also employed. RESULTS: Our previous study showed that hypoxia increased the expression of ZEB1 in cervical squamous cell carcinoma (CSCC) cells, which resulted in increased infiltration of TAMs. Here, we found that hypoxia-induced ZEB1 expression is closely correlated with CD47-SIRPα axis activity in CSCC, which enables cancer cells to evade phagocytosis by macrophages and promotes tumour progression. ZEB1 was found to directly activate the transcription of the CD47 gene in hypoxic CSCC cells. We further showed that endogenous ZEB1 was characteristically enriched in hypoxic CSCC cell-derived exosomes and transferred into macrophages via these exosomes to promote SIRPα+ TAM polarization. Intriguingly, exosomal ZEB1 retained transcriptional activity and reprogrammed SIRPα+ TAMs via activation of the STAT3 signalling pathway in vitro and in vivo. STAT3 inhibition reduced the polarizing effect induced by exosomal ZEB1. Knockdown of ZEB1 increased the phagocytosis of CSCC cells by macrophages via decreasing CD47 and SIRPα expression. CONCLUSIONS: Our results suggest that hypoxia-induced ZEB1 promotes immune evasion in CSCC by strengthening the CD47-SIRPα axis. ZEB1-targeted therapy in combination with CD47-SIRPα checkpoint immunotherapy may improve the outcomes of CSCC patients in part by disinhibiting innate immunity.

Evaluating disease status in idiopathic inflammatory myopathies with quantitative muscle ultrasound.

INTRODUCTION/AIMS: Muscle strength, functional status, and muscle enzymes are conventionally used to evaluate disease status in idiopathic inflammatory myopathies (IIM). This study aims to investigate the role of quantitative muscle ultrasound in evaluating disease status in IIM patients. METHODS: Patients with IIM, excluding inclusion body myositis, were recruited along with age- and sex-matched healthy controls (HC). All participants underwent muscle ultrasound and clinical assessments. Six limb muscles were unilaterally scanned using a standardized protocol, measuring muscle thickness (MT) and echo intensity (EI). Results were compared with HC, and correlations were made with outcome measures. RESULTS: Twenty IIM patients and 24 HC were recruited. The subtypes of IIM were dermatomyositis (6), necrotizing myositis (6), polymyositis (3), antisynthetase syndrome (3), and nonspecific myositis (2). Mean disease duration was 8.7 ± 6.9 years. There were no significant differences in demographics and anthropometrics between patients and controls. MT of rectus femoris in IIM patients was significantly lower than HC. Muscle EI of biceps brachii and vastus medialis in IIM patients were higher than HC. There were moderate correlations between MT of rectus femoris and modified Rankin Scale, Physician Global Activity Assessment, and Health Assessment Questionnaire, as well as between EI of biceps brachii and Manual Muscle Testing-8. DISCUSSION: Muscle ultrasound can detect proximal muscle atrophy and hyperechogenicity in patients with IIM. The findings correlate with clinical outcome measures, making it a potential tool for evaluating disease activity of patients with IIM in the late phase of the disease.

Chiral anomaly and Weyl orbit in three-dimensional Dirac semimetal Cd3As2grown on Si.

Preparing Cd3As2, which is a three-dimensional (3D) Dirac semimetal in certain crystal orientation, on Si is highly desirable as such a sample may well be fully compatible with existing Si CMOS technology. However, there is a dearth of such a study regarding Cd3As2films grown on Si showing the chiral anomaly. Here,for the first time, we report the novel preparation and fabrication technique of a Cd3As2(112) film on a Si (111) substrate with a ZnTe (111) buffer layer which explicitly shows the chiral anomaly with a nontrivial Berry's phase ofπ. Despite the Hall carrier density (n3D≈9.42×1017cm-3) of our Cd3As2film, which is almost beyond the limit for the portents of a 3D Dirac semimetal to emerge, we observe large linear magnetoresistance in a perpendicular magnetic field and negative magnetoresistance in a parallel magnetic field. These results clearly demonstrate the chiral magnetic effect and 3D Dirac semimetallic behavior in our silicon-based Cd3As2film. Our tailoring growth of Cd3As2on a conventional substrate such as Si keeps the sample quality, while also achieving a low carrier concentration.

Association between sleep quality and dry eye disease: a literature review and meta-analysis.

OBJECTIVE: The purpose of this article is to systematically review the association between dry eye and sleep quality. METHODS: PubMed, EMBASE, Cochrane, Web of Science, and grey literature databases were searched for observational studies published before April 2023. Meta-analysis was performed using STAT15 software. RESULTS: A total of 21 studies with 419,218 participants were included. The results showed that the dry eye subjects had a worse sleep quality than the healthy population, with poorer subjective sleep quality, longer sleep latency, and a higher risk of unhealthy sleep duration such as insufficient sleep or excessive sleep. The Pittsburgh Sleep Quality Index (PSQI) scores of the dry eye subjects were significantly higher than those of the control subjects (WMD = 1.78, 95%CI: 1.06, 2.50, P < 0.001). The dry eye subjects scored higher than the control subjects in sleep quality, sleep latency, and sleep disturbance in PSQI; there was no difference between the dry eye individuals and control subjects in sleep duration, sleep efficiency, daytime dysfunction, and sleep medication scores. The risk of sleep disorders in the dry eye subjects was significantly higher than that in the non-dry eye subjects (RR = 2.20, 95%CI: 1.78, 2.72, P < 0.001); the risk of insufficient sleep in the dry eye subjects was higher than that in the control subjects (RR = 3.76, 95%CI: 3.15, 4.48, P < 0.001), and the prevalence of excessive sleepiness in dry eye subjects was higher than that in the control subjects (RR = 5.53, 95%CI: 3.83, 7.18, P < 0.001). The ESS scores of the dry eye subjects were significantly higher than those of the control subjects (WMD = 3.02, 95%CI: 2.43, 3.60, P < 0.01). CONCLUSION: Our meta-analysis suggests that individuals with dry eye have a worse sleep quality than the healthy population, with poorer subjective sleep quality, longer sleep latency, and higher risk of unhealthy sleep duration such as insufficient sleep or excessive sleepiness.

Cytisine eye drops for benzalkonium chloride-induced dry eye: safety and efficacy evaluation.

This experiment aimed to investigate the feasibility of cytisine (CYT) in treating eye diseases with ocular topical application. An in vitro cytotoxicity test, a hen's egg test-chorioallantoic membrane (HET-CAM), and a mouse eye tolerance test were used to fully reveal the ocular safety profiles of CYT. For the efficacy evaluations, CYT's effects on cell wound healing, against H2O2-induced oxidative stress damages on cells, and on benzalkonium chloride (BAC)-induced dry eye disease (DED) in mice were evaluated. Results showed that CYT did not show any cytotoxicities at concentrations no higher than 250 µg/ml, while lipoic acid (α-LA) at 250 µg/ml and BAC at 1.25 µg/ml showed significant cytotoxicities within 48 h incubation. The HET-CAM and mouse eye tolerance test confirmed that 0.5% CYT eye drops demonstrated good safety characteristics. Efficacy evaluations showed that CTY significantly promoted cell migration and wound healing. CYT significantly improved cell survival against H2O2-induced oxidative stress damage by reversing the imbalance between the reactive oxygen species (ROS) and antioxidant defense mechanisms. The animal evaluation of the BAC-induced dry eye model revealed that CYT demonstrated a strong treatment effect, including reversing ocular surface damages, recovering corneal sensitivity, and inhibiting neovascularization; HMGB1/NF-κB signaling was involved in this DED treatment by CTY. In conclusion, CYT had strong experimental treatment efficacy against DED with good ocular safety profiles, and it might be a novel and promising drug for DED.

The protective effect of vitamin A palmitate eye gel on the ocular surface during general anaesthesia surgery: a randomized controlled trial.

PURPOSE: To investigate the change in tear production associated with general anesthesia and the protective effect of vitamin A palmitate eye gel on the ocular surface during general anesthesia. METHODS: This double-blind, randomized clinical trial included patients undergoing non-ophthalmic surgery under general anesthesia who randomly received vitamin A palmitate eye gel and taping for one eye (Group A, n = 60) or taping alone for the other eye (Group B, n = 60). Symptom assessment in dry eye (SANDE) score, tear film break-up time (TBUT), corneal fluorescein staining (CFS) score, and Schirmer tear test I (STT-1) were analyzed under a hand-held slit lamp before anesthesia (T0), 0.5 h postoperatively (T1), and 24 h postoperatively (T2). RESULTS: At 0.5 h postoperatively, an increase in CFS score was observed in both groups (P < 0.05 in Group A and P < 0.01 in Group B), and the participants in Group A had less corneal abrasions than those in Group B. STT-1 significantly increased in Group A (P < 0.05), while it significantly decreased in Group B (P < 0.001). The changes between the two groups were statistically significant (P < 0.001). At 24 h postoperatively, both CFS score and STT-1 almost returned to baseline levels in the two groups. In both groups, the SANDE score and TBUT showed little change at 0.5 h and 24 h postoperatively (all P > 0.05). CONCLUSION: Vitamin A palmitate eye gel effectively protected the ocular surface and aqueous supplementation during general anesthesia. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (ChiCTR2100052140) on 20/10/2021.

Hydride Doping Effects on the Structure and Properties of Eight-Electron Rh/Ag Superatoms: The [RhHx@Ag21-x{S2P(OnPr)2}12] (x = 0-2) Series.

Three hitherto unknown eight-electron rhodium/silver alloy nanoclusters, [RhAg21{S2P(OnPr)2}12] (1), [RhHAg20{S2P(OnPr)2}12] (2), and [RhH2Ag19{S2P(OnPr)2}12] (3), have been isolated and fully characterized. Cluster 1 contains a regular Rh@Ag12 icosahedral core, whereas 2 and 3 exhibit distorted RhH@Ag12 and RhH2@Ag12 icosahedral cores. The single-crystal neutron structure of 2 located the encapsulated hydride at the center of an enlarged RhAg3 tetrahedron. A similar position was found by neutron diffraction for one of the hydrides in 3, whereas the other hydride is trigonally coordinated to Rh and an elongated Ag-Ag edge. The solid-state structures of 1-3 possess C1 symmetry due to the asymmetric arrangement of the surrounding capping Ag atoms. Our investigation shows that the insertion of one hydride dopant provokes the elimination of one capping silver atom on the cluster surface, resulting in the general formula [RhHx@Ag21-x{S2P(OnPr)2}12] (x = 0-2), which maintains the same number of cluster electrons as well as neutral charge. Clusters 1-3 exhibit an intense emission band in the NIR region. Contrarily to their PdAg21 and PdHAg20 relatives, the 4d orbitals of the encapsulated heterometal are somewhat involved in the optical processes.

Efficient production of natural sunscreens shinorine, porphyra-334, and mycosporine-2-glycine in Saccharomyces cerevisiae.

Mycosporine-like amino acids (MAAs) are promising natural sunscreens mainly produced in marine organisms. Until now, metabolic engineering efforts to produce MAAs in heterologous hosts have mainly focused on shinorine production, and the low production levels are still not suitable for industrial applications. In this study, we successfully developed Saccharomyces cerevisiae strains that can efficiently produce various disubstituted MAAs, including shinorine, porphyra-334, and mycosporine-2-glycine (M2G), which are formed by conjugating serine, threonine, and glycine to mycosporine-glycine (MG), respectively. We first generated an MG-producing strain by multiple integration of the biosynthetic genes from cyanobacteria and applying metabolic engineering strategies to increase sedoheptulose-7-phosphate pool, a substrate for MG production. Next, five mysD genes from cyanobacteria, which encode D-Ala-D-Ala ligase homologues that conjugate an amino acid to MG, were introduced into the MG-producing strain to determine the substrate preference of each MysD enzyme. MysDs from Lyngbya sp., Nostoclinckia, and Euhalothece sp. showed high specificity toward serine, threonine, and glycine, resulting in efficient production of shinorine, porphyra-334, and M2G, respectively. This is the first report on the production of porphyra-334 and M2G in S. cerevisiae. Furthermore, we identified that the substrate specificity of MysD was determined by the omega loop region of 43-45 amino acids predicted based on its structural homology to a D-Ala-D-Ala ligase from Thermus thermophilus involved in peptidoglycan biosynthesis. The substrate specificities of two MysD enzymes were interchangeable by swapping the omega loop region. Using the engineered strain expressing mysD from Lyngbya sp. or N. linckia, up to 1.53 g/L shinorine or 1.21 g/L porphyra-334 was produced by fed-batch fermentation in a 5-L bioreactor, the highest titer reported so far. These results suggest that S. cerevisiae is a promising host for industrial production of different types of MAAs, providing a sustainable and eco-friendly alternative for the development of natural sunscreens.

Augmented-Reality Surgery to Guide Head and Neck Cancer Re-resection: A Feasibility and Accuracy Study.

BACKGROUND: Given the complex three-dimensional (3D) anatomy of head and neck cancer specimens, head and neck surgeons often have difficulty relocating the site of an initial positive margin to perform re-resection. This cadaveric study aimed to determine the feasibility and accuracy of augmented reality surgery to guide head and neck cancer re-resections. METHODS: This study investigated three cadaveric specimens. The head and neck resection specimen was 3D scanned and exported to the HoloLens augmented reality environment. The surgeon manually aligned the 3D specimen hologram into the resection bed. Accuracy of manual alignment and time intervals throughout the protocol were recorded. RESULTS: The 20 head and neck cancer resections performed in this study included 13 cutaneous and 7 oral cavity resections. The mean relocation error was 4 mm (range, 1-15 mm) with a standard deviation of 3.9 mm. The mean overall protocol time, from the start of 3D scanning to alignment into the resection bed, was 25.3 ± 8.9 min (range, 13.2-43.2 min). Relocation error did not differ significantly when stratified by greatest dimension of the specimen. The mean relocation error of complex oral cavity composite specimens (maxillectomy and mandibulectomy) differed significantly from that of all the other specimen types (10.7 vs 2.8; p < 0.01). CONCLUSIONS: This cadaveric study demonstrated the feasibility and accuracy of augmented reality to guide re-resection of initial positive margins in head and neck cancer surgery.

Conduction system versus biventricular pacing in heart failure with non-left bundle branch block.

INTRODUCTION: The benefits of cardiac resynchronization therapy (CRT) with biventricular pacing (BiV) is significantly lower when applied to heart failure (HF) patients with non-left bundle branch block (LBBB) conduction delay. We investigated clinical outcomes of conduction system pacing (CSP) for CRT in non-LBBB HF. METHODS: Consecutive HF patients with non-LBBB conduction delay undergoing CSP were propensity matched for age, sex, HF-etiology, and atrial fibrillation (AF) in a 1:1 ratio to BiV from a prospective registry of CRT recipients. Echocardiographic response was defined as an increase in left ventricular ejection fraction (LVEF) by ≥10%. The primary outcome was the composite of HF-hospitalizations or all-cause mortality. RESULTS: A total of 96 patients were recruited (mean age 70 ± 11years, 22% female, 68% ischemic HF and 49% AF). Significant reductions in QRS duration and LV dimensions were seen only after CSP, while LVEF improved significantly in both groups (p < 0.05). Echocardiographic response occurred more frequently in CSP than BiV (51% vs. 21%, p < 0.01), with CSP independently associated with four-fold increased odds (adjusted odds ratio 4.08, 95% confidence interval [CI] 1.34-12.41). The primary outcome occurred more frequently in BiV than CSP (69% vs. 27%, p < 0.001), with CSP independently associated with 58% risk reduction (adjusted hazard ratio [AHR] 0.42, 95% CI 0.21-0.84, p = 0.01), driven by reduced all-cause mortality (AHR 0.22, 95% CI 0.07-0.68, p < 0.01), and a trend toward reduced HF-hospitalization (AHR 0.51, 95% CI 0.21-1.21, p = 0.12). CONCLUSIONS: CSP provided greater electrical synchrony, reverse remodeling, improved cardiac function and survival compared to BiV in non-LBBB, and may be the preferred CRT strategy for non-LBBB HF.

Single-cell histone chaperones patterns guide intercellular communication of tumor microenvironment that contribute to breast cancer metastases.

BACKGROUND: Histone chaperones (HCs) are crucial for governing genome stability and gene expression in multiple cancers. However, the functioning of HCs in the tumor microenvironment (TME) is still not clearly understood. METHODS: Self-tested single-cell RNA-seq data derived from 6 breast cancer (BC) patients with brain and liver metastases were reanalyzed by nonnegative matrix factorization (NMF) algorithm for 36 HCs. TME subclusters were observed with BC and immunotherapy public cohorts to assess their prognosis and immune response. The biological effect of HSPA8, one of the HCs, was verified by transwell assay and wound-healing assays. RESULTS: Cells including fibroblasts, macrophages, B cells, and T cells, were classified into various subclusters based on marker genes. Additionally, it showed that HCs might be strongly associated with biological and clinical features of BC metastases, along with the pseudotime trajectory of each TME cell type. Besides, the results of bulk-seq analysis revealed that TME cell subclusters mediated by HCs distinguished significant prognostic value for BC patients and were relevant to patients' immunotherapy responses, especially for B cells and macrophages. In particular, CellChat analysis exhibited that HCs-related TME cell subclusters revealed extensive and diverse interactions with malignant cells. Finally, transwell and wound-healing assays exhibited that HSPA8 deficiency inhibited BC cell migration and invasion. CONCLUSIONS: Collectively, our study first dissected HCs-guided intercellular communication of TME that contribute to BC metastases.

Novel bisdemethoxycurcumin@phytomicelle ophthalmic solution: In vitro formulation appraisal and in vivo prompting rapid corneal wound healing evaluations.

A simple and novel phytochemical-based nano-ophthalmic solution was developed for the treatment of eye diseases. This nanoformulation was produced from the mixture of the phytochemicals glycyrrhizin and alpha-glycosyl hesperidin, which serve as the phytonanomaterials that solubilize bisdemethoxycurcumin (BDMC), a promising phytochemical with strong pharmacological activities but with poor water solubility. This novel nanoformulation is a clear solution named as BDMC@phytomicelle ophthalmic solution, which was formulated using a simple preparation process. The BDMC@phytomicelles were characterized by a BDMC encapsulation efficiency of 98.37% ± 2.26%, a small phytomicelle size of 4.06 ± 0.22 nm, and a small polydispersity index of 0.25 ± 0.04. With the optimization of the BDMC@phytomicelles, the apparent solubility of BDMC (i.e., the loading of BDMC in the phytomicelles) in the simulated lacrimal fluid was 3.19 ± 0.02 mg/ml. The BDMC@phytomicelle ophthalmic solution demonstrated a good storage stability. Moreover, it did not cause irritations in rabbit eyes, and it facilitated the excellent corneal permeation of BDMC in mice. The BDMC@phytomicelles demonstrated a marked effect on the in vivo induction of corneal wound healing both in healthy and denervated corneas, as seen in the induction of corneal epithelial wound healing, recovery of corneal sensitivity, and increase in corneal subbasal nerve fiber density. These strong pharmacological activities involve the inhibition of hmgb1 signaling and the induction of VIP signaling. Overall, the BDMC@phytomicelle ophthalmic solution is a novel and promising simple ocular nano-formulation of BDMC with significantly improved in vivo profiles.

Chronic social comparison elicits depression- and anxiety-like behaviors and alterations in brain-derived neurotrophic factor expression in male rats.

Social comparison is a fundamental human characteristic; however, long-term social comparison may induce psychological stress and can lead to depression and anxiety. Recent studies have shown that nonhuman primates compare themselves with others; however, no studies have investigated whether social comparisons exist among rodents. In the present study, we established a rat model of social comparison. This model was subsequently used to examine the effects of the differential environment of a partner on depression- and anxiety-like behaviors in male rats, as well as to assess the changes in serum, medial prefrontal cortex (mPFC), and dorsal hippocampus brain-derived neurotrophic factor (BDNF) levels induced by long-term social comparison. Compared to rats whose partners were exposed to the same environment, rats whose partners were exposed to two combined enriched environmental stimuli for 14 days showed significantly decreased social novelty preference and sucrose consumption. No anxiety-like behaviors were observed. Rats whose partners were exposed to one enriched environment for 31 days showed significantly increased immobility time in the forced swimming test, and significantly decreased time spent in the center area in the open-field test. Further, rats whose partners were exposed to one enriched environment for 31 days showed lower BDNF levels in the mPFC and dorsal hippocampus, but not following partner exposure for 14 days. These results suggest that social comparisons exist in rats and can induce psychosocial stress and other negative affect. This model will not only provide the possibility to reveal the neurobiological basis of the emotional impact of social comparison, but could also be used to confirm the conservative evolutionary characteristics of social comparison as a behavioral attribute.

Rhodamine-based fluorescent sensors for the rapid and selective off-on detection of salicylic acid and their use in plant cell imaging.

Salicylic acid (SA) is a key hormone that regulates plant growth and immunity, and understanding the physiologic processes induced by SA enables the development of highly pathogen-resistant crops. Here, we report the synthesis of three new SA-sensors (R1-R3) from hydroxyphenol derivatives of a rhodamine-acylhydrazone scaffold and their characterization by NMR and HRMS. Spectroscopic analyses revealed that structural variations in R1-R3 resulted in sensors with different sensitivities for SA. Sensor R2 (with the 3-hydroxyphenyl modification) outperformed R1 (2-hydroxyphenyl) and R3 (4-hydroxyphenyl). The SA-detection limit of R2 is 0.9 µM with an ultra-fast response time (<60 s). In addition, their plant imaging indicated that designed sensor R2 is useful for the further study of SA biology and the discovery and development of new inducers of plant immunity.

Validation of the phenol red thread test in a Chinese population.

BACKGROUND: To investigate the validation of phenol red thread (PRT) test in a Chinese population by evaluating the intraobserver repeatability and interobserver reproducibility, determining correlations between the PRT test and other dry eye disease (DED) parameters including tear meniscus height (TMH) and Schirmer I test, and testing the accuracy of diagnosing DED when using the PRT test alone. METHODS: A total of 108 eyes were involved in this prospective and diagnostic study, and were divided into two groups (with and without DED). Each subject underwent a series of ocular surface examinations, including Ocular Surface Disease Index (OSDI) questionnaire, non-invasive tear breakup time (NIBUT), tear meniscus height (TMH) assessment, PRT test, fluorescein tear breakup time (FBUT), corneal fluorescein staining and Schirmer I test. RESULTS: In the experimental group and the control group, the intra-class correlation coefficients (ICCs) of the repeatability were 0.747 and 0.723, respectively (all P < 0.05). The ICCs of the reproducibility in both groups were 0.588 and 0.610, respectively (all P < 0.05). The PRT test correlated weakly with the Schirmer I test and the tear meniscus height, with Spearman coefficients of 0.385 and 0.306, respectively (all P < 0.05). The PRT test is available to diagnose DED, with an area under the curve of 0.806 and a Youden index of 0.556 at the cutoff point of 8.83 mm. CONCLUSIONS: The PRT test can provide patients a comfortable, timesaving and less irritating approach to screening and diagnosing DED compared to Schirmer I test.

Cytological and functional effect of complement 3a on Human Scleral Fibroblasts.

PURPOSE: The complement system is considered to play an important role in the progression of myopia, whereas the influence of complement activation on the human scleral fibroblasts (HSFs) remains unknown. Hence, the effect of complement 3a (C3a) on HSFs was investigated in this study. METHODS: HSFs were cultured with exogenous C3a at 0.1 µM for various periods following different measurement protocols, and cells without C3a treatment served as negative control (NC). Cell viability was investigated using the MTS assay after 3 days of C3a treatment. Cell proliferation was evaluated by the 5-Ethynyl-20-Deoxyuridine (EdU) assay following C3a stimulation for 24 hours. Apoptosis was assessed by Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double staining following C3a stimulation for 48 hours and the stained cells were analysed using flow cytometry. The levels of type I collagen and matrix metalloproteinase-2 (MMP-2) were analysed using ELISA following C3a stimulation for 36 and 60 hours. The level of CD59 were analysed using western blot following C3a stimulation for 60 hours. RESULTS: The MTS assay revealed that cell viability was attenuated by 13% and 8% after C3a for 2 and 3 days, respectively (P < 0.05). The EdU assay demonstrated a 9% decrease in proliferation rate for the C3a-treated cells after 24 hours (P < 0.05). The apoptosis analysis revealed an increased percentage of cells in early apoptosis (P = 0.02) and total apoptosis (P = 0.02) in the C3a-treated group. Compared with NC group, the level of MMP-2 was increased by 17.6% (P = 0.002), whereas the levels of type I collagen and CD59 were respectively decreased by 12.5% (P = 0.024) and 21.6% (P = 0.044) with C3a treatment for 60 hours. CONCLUSIONS: These results indicated that C3a-induced complement activation is potentially involved in inducing myopic-associated scleral extracellular matrix remodelling via mediating the proliferation and function of HSFs.

Patterns of Relapse and Complications of Immunoglobulin G4-Related Disease.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is a multisystemic fibroinflammatory condition potentially resulting in organ dysfunction. We aimed to evaluate imaging characteristics of disease relapse and complications in this cohort of patients. METHODS: This was a cohort study of IgG4-RD patients imaged between 2010 and 2020. Radiological manifestations of disease activity (remission/stability vs. relapse and complications) were correlated with clinical symptoms. Univariate analyses were performed with χ2 , Fisher exact, and Mann-Whitney U tests. Times to relapse and organ atrophy were studied with Kaplan-Meier analyses. RESULTS: A total of 69 patients had imaging surveillance over a median duration of 47 months. Radiological relapse occurred in 50.7% (35/69) with median time to relapse at 74 months (95% confidence interval, 45-122 months); 42.8% (15/35) of this cohort had different-site relapse with the following recognized primary-secondary patterns: pancreas-hepatobiliary ( p = 0.005), hepatobiliary-pancreas ( p = 0.013), and periaortitis-mesenteric ( p = 0.006). Clinical symptoms were significantly associated with imaging characteristics ( p < 0.001). Abdominal complications were detected in 52.2% (36/69) of patients, mostly solid organ atrophy (97.2% [35/36]). New-onset diabetes was more likely in pancreatic IgG4-RD (n = 51) when accompanied by gland atrophy (4/21 vs. 0/30 nonatrophy, p = 0.024). CONCLUSION: Radiological relapse of IgG4-RD is common over prolonged imaging surveillance and is significantly associated with symptomatic relapse. A multisystem review to detect new/different sites of disease and abdominal complications may help predict future organ dysfunction.

Mapping the research on Sjögren's syndrome-related dry eye disease: a bibliometric network analysis of the past 20 years.

PURPOSE: Our study aimed to make a bibliometric analysis on Sjögren's syndrome-related dry eye disease (SS-DED), explore its potential research hotspots, and provide critical information for future research interest and undeveloped topics in this field, which can benefit clinicians and researchers. METHODS: We extracted all publications relating to SS-DED from 2003 to 2022 from the Web of Science Core Collection database. Original articles and reviews in English were included. The contributions of different countries, institutions, journals, and authors were compared, and the research hotspots were visualized for network analysis through GraphPad Prism, CiteSpace, and VOSviewer. RESULTS: We enrolled a total of 987 publications. The United States contributed the most publications (281, 28.5%), followed by China (157, 15.9%) and Japan (80, 8.11%). Publications from the United States were cited more frequently (13,060 citations), with the highest H-index of 57. China ranked second in the total number of publications, the papers were not cited frequently (3790 citations), and the H-index ranked second (H-index = 31). PLoS One (32, 3.24%) published the most papers, and the University of California system had the highest number of publications (45, 4.56%). Bootsma H from the Netherlands published the most papers. The trend of research hotspots evolved mainly from the basic manifestation to pathogenesis and treatment of SS-DED and paid more attention to distinguishing SS-DED from that dry eye disease without SS. CONCLUSIONS: Based on the bibliometric, co-citation, and network analyses in this study, we obtained the annual publications and citations, the growth trends of publications, the productivity of countries, organizations, journals, and authors, high-quality publications, and the emerging hotspots of SS-DED, which may open new doors for promising research directions.