A randomized, double-blind, placebo-controlled phase II study to evaluate the efficacy and safety of ivarmacitinib (SHR0302) in adult patients with moderate-to-severe alopecia areata.

BACKGROUND: Alopecia areata (AA) is a CD8+ T cell-mediated autoimmune disease characterized by nonscarring hair loss. Ivarmacitinib, which is a selective oral Janus kinase 1 inhibitor, may interrupt certain cytokine signaling implicated in the pathogenesis of AA. OBJECTIVE: To evaluate the efficacy and safety of ivarmacitinib in adult patients with AA who have ≥25% scalp hair loss. METHODS: Eligible patients were randomized 1:1:1:1 to receive ivarmacitinib 2, 4, or 8 mg once daily or placebo for 24 weeks. The primary end point was the percentage change from baseline in the Severity of Alopecia Tool score at week 24. RESULTS: A total of 94 patients were randomized. At week 24, the least squares mean difference in the percentage change from baseline in the Severity of Alopecia Tool score for ivarmacitinib 2, 4, and 8 mg and placebo groups were -30.51% (90% CI, -45.25, -15.76), -56.11% (90% CI, -70.28, -41.95), -51.01% (90% CI, -65.20, -36.82), and -19.87% (90% CI, -33.99, -5.75), respectively. Two serious adverse events-follicular lymphoma and COVID-19 pneumonia-were reported. LIMITATIONS: A small sample size limits the generalizability of the results. CONCLUSION: Treatment with ivarmacitinib 4 and 8 mg doses in patients with moderate and severe AA for 24 weeks was efficacious and generally tolerated.

Fabrication of Ag-CaCO3 Nanocomposites for SERS Detection of Forchlorfenuron.

In this study, Ag-CaCO3 nanocomposites were synthesized using silver nitrate as the precursor solution based on calcium carbonate nanoparticles (CaCO3 NPs). The synthesis involved the reaction of calcium lignosulphonate and sodium bicarbonate. The properties of Ag-CaCO3 nanocomposites were studied by various technologies, including an ultraviolet-visible spectrophotometer, a transmission electron microscope, and a Raman spectrometer. The results showed that Ag-CaCO3 nanocomposites exhibited a maximum UV absorption peak at 430 nm, the surface-enhanced Raman spectroscopy (SERS) activity of Ag-CaCO3 nanocomposites was evaluated using mercaptobenzoic acid (MBA) as the marker molecule, resulting in an enhancement factor of 6.5 × 104. Additionally, Ag-CaCO3 nanocomposites were utilized for the detection of forchlorfenuron. The results demonstrated a linear relationship in the concentration range of 0.01 mg/mL to 2 mg/mL, described by the equation y = 290.02x + 1598.8. The correlation coefficient was calculated to be 0.9772, and the limit of detection (LOD) was determined to be 0.001 mg/mL. These findings highlight the relatively high SERS activity of Ag-CaCO3 nanocomposites, making them suitable for analyzing pesticide residues and detecting toxic and harmful molecules, thereby contributing to environmental protection.

Binocular visual function after unilateral versus bilateral implantation of segmented refractive multifocal intraocular lenses: a pilot study.

PURPOSE: To evaluate binocular visual function after unilateral and bilateral implantation of segmented refractive multifocal intraocular lenses (MIOLs). METHODS: This prospective comparative pilot study included patients who underwent SBL-3 (Lenstec; + 3.00 D) implantation at Peking University Third Hospital. Patients were divided into two groups (monocular or binocular surgery). Thirty-two patients with emmetropic presbyopic contralateral eyes and 49 patients with bilateral SBL-3 implantation within a week between eyes were included in the unilateral SBL-3 and bilateral groups, respectively. At 3-month follow-up, the main outcomes were binocular uncorrected distant, intermediate, and near visual acuity (UDVA, UIVA, and UNVA). Secondary outcomes included binocular best-corrected visual acuity at all distances, defocus curve, contrast sensitivity, photic phenomena, spectacle independence, patient satisfaction, and National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) score. The essential perceptual phenomena constituting binocular vision, simultaneous perception, fusion, and stereopsis were also evaluated. RESULTS: Both groups showed similar binocular UDVA and UIVA, but UNVA was significantly better in the bilateral group (0.07 ± 0.07 versus 0.12 ± 0.07, P = 0.008). Better binocular defocus curve at intermediate to near focal points, higher percentage of spectacle independence at near distance, and NEI-VFQ-25 near activity scores were observed in the bilateral group. No significant differences in contrast sensitivity, photic phenomena, overall satisfaction, other NEI-VFQ-25 subscales, fusional amplitude, and stereoacuity were found between groups. CONCLUSION: Unilateral implantation of segmented refractive MIOL provided desirable distant visual acuity and high patient satisfaction, but inferior intermediate and near visual outcomes compared with bilateral implantation.

Role of P2X4/NLRP3 Pathway-Mediated Neuroinflammation in Perioperative Neurocognitive Disorders.

Several studies have demonstrated that neuroinflammation is the key to perioperative neurocognitive disorders (PND); however, the specific mechanism postsurgery and anesthesia has not yet been fully clarified. The present study is aimed at exploring the effects of P2X4/NLRP3 signaling pathway in neuroinflammation and cognitive impairment after surgery. 12-14-month-old male C57BL/6 mice undergoing open tibial fracture surgery by sevoflurane anesthesia were administered P2X4R inhibitor 5-BDBD or saline was intraperitoneally for 3 consecutive days after surgery. Then, the animals were subjected to Morris water maze test or sacrificed to collect the hippocampus. The level of P2X4R and NLRP3 was estimated by Western blot, the activation of microglia was detected via immunohistochemistry, and the expression of TNF-α, IL-1ß, and IL-6 was quantified by enzyme-linked immunosorbent assay. These results indicated that tibial surgery caused cognitive impairment, increased the expression of P2X4R and NLRP3, and aggravated the neuroinflammation and microglia activation. However, intraperitoneal injection of 5-BDBD attenuated these effects. In conclusion, these findings indicated that the P2X4/NLRP3 pathway might be involved in the pathophysiology of PND.

Evaluation of Ocular Surface Characteristics in Dry Eye Disease With and Without Soft Contact Lens Wear: A Comparative Study.

OBJECTIVES: To investigate ocular surface alterations and in vivo confocal microscopic characteristics of the cornea in dry eye disease (DED) with contact lens wear (CLW). METHODS: Sixty participants were divided into three groups: DED with CLW (n=20), DED without CLW (n=20), and normal control (n=20). Ocular surface parameters were evaluated. Basal tears and in vivo confocal microscopy images of the cornea were collected. Multiplex bead analysis was used to assess interleukin (IL)-6, IL-1ß, tumor necrosis factor (TNF)-α, nerve growth factor (NGF), and substance P (SP) in tears. Nerve morphology and dendritic cell density in corneal subbasal nerve images were calculated. RESULTS: The DED with CLW group showed significantly higher ocular surface staining scores ( P =0.022) and higher levels of IL-1ß, NGF, and SP in tears ( P =0.014, P =0.004 and P =0.025) than the DED without CLW group. Corneal dendritic cell density in the DED with CLW group was significantly higher than that in the normal controls ( P =0.001) and DED without CLW group ( P =0.043). Tear cytokine levels of IL-1ß, NGF, and SP were correlated with ocular surface parameters in the DED with CLW group. Moreover, the years of CLW were positively correlated with corneal dendritic cell density (r=0.527, P =0.017) and negatively correlated with corneal nerve density (r=-0.511, P =0.021). CONCLUSIONS: Patients with DED with CLW showed greater epithelial damage, elevated inflammatory cytokines and neuromediators in tears, and higher corneal dendritic cell density than patients with DED without CLW. The immune and nervous systems may be involved in contact lens-related DED.

Enhanced store-operated calcium entry (SOCE) exacerbates motor neurons apoptosis following spinal cord injury.

Spinal cord injury is pathologically characterized by the loss of motor function caused by neurons apoptosis. Store-operated calcium entry (SOCE) is widely known to dictate the apoptosis of various cell types. To examine SOCE in spinal cord injury and explore the role of SOCE in apoptosis, patients with spinal cord injury (SCI) and SCI mouse models were included. Expression of SOCE components and apoptosis-related proteins were examined by Western blotting. Calcium imaging was used to assess SOCE activity. As a result, we confirmed the enhanced levels of ORAI1 and STIM1 in SCI patients and SCI mouse models. In vitro study, tunicamycin impaired the viability of VSC4.1 cells (motoneuron-neuroblastoma hybrid cell line) and increased SOCE activity, the effects of which could be abolished by 2-APB. Furthermore, tunicamycinreduced BCL-2/BAX ratio was also reversed by 2-APB. Additionally, EdU assay and DCFH-DA staining confirmed the regulatory role of 2-APB in proliferation and ROS production. Of note is the improved hindlimb motor function and alleviated depression by 2-APB administration. Therefore, we conclude that SOCE may contribute to the pathogenesis of SCI by exacerbating the apoptosis of motoneurons.

An artificial intelligence-based deep learning algorithm for the diagnosis of diabetic neuropathy using corneal confocal microscopy: a development and validation study.

AIMS/HYPOTHESIS: Corneal confocal microscopy is a rapid non-invasive ophthalmic imaging technique that identifies peripheral and central neurodegenerative disease. Quantification of corneal sub-basal nerve plexus morphology, however, requires either time-consuming manual annotation or a less-sensitive automated image analysis approach. We aimed to develop and validate an artificial intelligence-based, deep learning algorithm for the quantification of nerve fibre properties relevant to the diagnosis of diabetic neuropathy and to compare it with a validated automated analysis program, ACCMetrics. METHODS: Our deep learning algorithm, which employs a convolutional neural network with data augmentation, was developed for the automated quantification of the corneal sub-basal nerve plexus for the diagnosis of diabetic neuropathy. The algorithm was trained using a high-end graphics processor unit on 1698 corneal confocal microscopy images; for external validation, it was further tested on 2137 images. The algorithm was developed to identify total nerve fibre length, branch points, tail points, number and length of nerve segments, and fractal numbers. Sensitivity analyses were undertaken to determine the AUC for ACCMetrics and our algorithm for the diagnosis of diabetic neuropathy. RESULTS: The intraclass correlation coefficients for our algorithm were superior to those for ACCMetrics for total corneal nerve fibre length (0.933 vs 0.825), mean length per segment (0.656 vs 0.325), number of branch points (0.891 vs 0.570), number of tail points (0.623 vs 0.257), number of nerve segments (0.878 vs 0.504) and fractals (0.927 vs 0.758). In addition, our proposed algorithm achieved an AUC of 0.83, specificity of 0.87 and sensitivity of 0.68 for the classification of participants without (n = 90) and with (n = 132) neuropathy (defined by the Toronto criteria). CONCLUSIONS/INTERPRETATION: These results demonstrated that our deep learning algorithm provides rapid and excellent localisation performance for the quantification of corneal nerve biomarkers. This model has potential for adoption into clinical screening programmes for diabetic neuropathy. DATA AVAILABILITY: The publicly shared cornea nerve dataset (dataset 1) is available at http://bioimlab.dei.unipd.it/Corneal%20Nerve%20Tortuosity%20Data%20Set.htm and http://bioimlab.dei.unipd.it/Corneal%20Nerve%20Data%20Set.htm.

Malignant acanthosis nigricans: a case report.

BACKGROUND: To report a case of malignant acanthosis nigricans with two unusual aspects, including the patient's young age and the development of filiform papillomas on the eyelid margins. CASE PRESENTATION: A 30-year-old woman presented with dry eye symptoms. Examination revealed filiform papillomas on the eyelid margins, gums, lips, hands, and axillae and excessive pigmentation localized to the neck, axillae, and groin. Biopsies of stomach, pancreatic, and thyroid lesions revealed gastric adenocarcinoma, pancreatic adenocarcinoma, and thyroid cancer, respectively. Systemic investigations showed gastric adenocarcinoma with metastatic spread. The patient was ultimately diagnosed with malignant acanthosis nigricans and died 4 months later. CONCLUSIONS: Acanthosis nigricans on the eyelid margins with a velvety overgrowth is highly suggestive of an internal malignancy, and full systemic investigations are warranted in these cases. In this patient, early signs were ignored, leading to the loss of a timely diagnosis and treatment.

Capsicum-Derived Biomass Quantum Dots Coupled with Alizarin Red S as an Inner-Filter-Mediated Illuminant Nanosystem for Imaging of Intracellular Calcium Ions.

Calcium ion (Ca2+) plays crucial roles in the signal transduction pathways associated with various physiological and pathological events. Monitoring intracellular Ca2+ is of great significance for cell biology research. Here, we report the use of biomass quantum dots (BQDs) as a fluorescent reporter for imaging of intracellular Ca2+, based on the inner-filter-mediated luminescence which was assisted by a Ca2+ chelator alizarin red S (ARS). BQDs were prepared by hydrothermal heating of capsicum. The absorption of ARS overlaps with the excitation of the BQDs, the fluorescence of BQDs being quenched through the inner-filter effect. But the absorption of Ca-ARS complex red shifts and shows a poor inner-filter effect. Thus, Ca2+ can be detected by the inner-filter-mediated luminescence using the BQDs-ARS nanohybrid system. Using the proposed nanosystem, the imaging of intracellular Ca2+ and real-time monitoring of the Ca2+ level change under histamine stimulation were also achieved. Thus, this nanosystem holds potential applications in other Ca2+-related signal transduction study.

Design of a New Near-Infrared Ratiometric Fluorescent Nanoprobe for Real-Time Imaging of Superoxide Anions and Hydroxyl Radicals in Live Cells and in Situ Tracing of the Inflammation Process in Vivo.

The superoxide anion (O2•-) and hydroxyl radical (•OH) are important reactive oxygen species (ROS) used as biomarkers in physiological and pathological processes. ROS generation is closely related to the development of a variety of inflammatory diseases. However, the changes of ROS are difficult to ascertain with in situ tracing of the inflammation process by real-time monitoring, owing to the short half-lives of ROS and high tissue autofluorescence in vivo. Here we developed a new near-infrared (NIR) ratiometric fluorescence imaging approach by using a Förster resonance energy transfer (FRET)-based ratiometric fluorescent nanoprobe for real-time monitoring of O2•- and •OH generation and also by using in situ tracing of the inflammation process in vivo. The proposed nanoprobe was composed of PEG functionalized GQDs as the energy donor connecting to hydroIR783, serving as both the O2•-/•OH recognizing ligand and the energy acceptor. The nanoprobe not only exhibited a fast response to O2•- and •OH but also presented good biocomapatibility as well as a high photostability and signal-to-noise ratio. We have demonstrated that the proposed NIR ratiometric fluorescent nanoprobe can monitor the changes of O2•- and •OH in living RAW 264.7 cells via a drug mediating inflammation model and further realized visual monitoring of the change of O2•- and •OH in mice for in situ tracing of the inflammation process. Our design may provide a new paradigm for long-term and real-time imaging applications for in vivo tracing of the pathological process related to the inflammatory diseases.

Association Analysis of the MHC in Lupus Nephritis.

Lupus nephritis (LN) is one of the most prevalent and serious complications of SLE, with significant effects on patient and renal survival. Although a large number of genetic variants associated with SLE have been identified, biomarkers that correlate with LN are extremely limited. In this study, we performed a comprehensive sequencing analysis of the whole MHC region in 1331 patients with LN and 1296 healthy controls and validated the independent associations in another 950 patients with LN and 1000 controls. We discovered five independent risk variants for LN within the MHC region, including HLA-DRß1 amino acid 11 (Pomnibus<0.001), HLA-DQß1 amino acid 45 (P<0.001; odds ratio, 0.58; 95% confidence interval, 0.52 to 0.65), HLA-A amino acid 156 (Pomnibus<0.001), HLA-DPß1 amino acid 76 (Pomnibus<0.001), and a missense variant in PRRC2A (rs114580964; P<0.001; odds ratio, 0.38; 95% confidence interval, 0.30 to 0.49) at genome-wide significance. These data implicate aberrant peptide presentation by MHC classes 1 and 2 molecules and sex hormone modulation in the development of LN.

In situ Observation of Compression Damage in a Three-Dimensional Braided Carbon Fiber Reinforced Carbon and Silicon Carbide (C/C-SiC) Ceramic Composite.

Deformation and mechanical damage in a three-dimensional braided carbon fiber reinforced carbon and silicon carbide ceramic composite, subjected to compressive loading, has been studied in situ by laboratory X-ray computed tomography. Dimensional change was measured and damage visualized by digital volume correlation analysis of tomographs. Cracks nucleated from defects within the fiber bundles and tended to propagate along the fiber bundle/matrix interface. For longitudinal compression, parallel to the fiber bundles, the initial elastic modulus decreased with increasing compressive strain while significant transverse tensile strains developed due to distributed cracking. For transverse compression, perpendicular to the fiber bundles, the compressive elastic modulus was effectively constant; the tensile strains developed along the fiber direction were small, whereas macroscopic fracture between the fiber bundles caused very large bulk tensile strain perpendicular to the loading. The observations suggest that the mechanical strength might be improved through control of pre-existing defects and application of stitch fibers in the transverse direction.

Diagnostic Value of Contrast-Enhanced Sonography for Differentiation of Breast Lesions: A Meta-analysis.

OBJECTIVES: The purpose of this study was to systematically review and evaluate the diagnostic accuracy of contrast-enhanced sonography in the differential diagnosis of benign and malignant breast lesions. METHODS: The scientific literature databases PubMed and Embase were comprehensively searched for relevant studies before January 2015. Data were pooled to yield the summary sensitivity, specificity, and diagnostic odds ratio using meta-analysis software. RESULTS: A total of 29 studies with 2296 lesions were included in the analysis. The pooled sensitivity and specificity were 0.88 (95% confidence interval [CI], 0.86-0.90; inconsistency index [I(2)] = 77.9%) and 0.80 (95% CI, 0.78-0.83; I(2) = 84.0%), respectively. The pooled diagnostic odds ratio was 30.35 (95% CI, 15.75-58.48; I(2)= 82.1%), and the area under the summary receiver operating characteristic curve was 0.9115 (SE, 0.0243). CONCLUSIONS: The comprehensive results suggest that contrast-enhanced sonography could be a potentially effective method for differential diagnosis of benign and malignant breast lesions.

Contrast-enhanced sonography for the identification of benign and malignant thyroid nodules: Systematic review and meta-analysis.

PURPOSE: The use of contrast-enhanced sonography (CEUS) has yielded promising results in the differentiation of thyroid nodules. We conducted this meta-analysis to assess its performance in identifying and distinguishing between benign and malignant thyroid nodules. METHODS: PubMed, Medline, Embase, and the Cochrane Library were searched for studies published through the end of December 2013. Sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and area under the curve were calculated. RESULTS: A total of 13 studies were included in this meta-analysis. For the diagnosis of malignant thyroid nodules worldwide, the overall mean rates of sensitivity and specificity of CEUS were 90% (95% confidence interval [CI], 88-93%) and 86% (95% CI, 83-89%), respectively. The summary diagnostic odds ratio was 52.83 (95% CI, 21.71-128.55), and the area under the curve for the summary receiver operating characteristic curve was 0.94 (95% CI, 0.90-0.98). CONCLUSIONS: This meta-analysis indicates that CEUS may be a valuable supplemental method, with high rates of sensitivity and specificity, to use for identifying and distinguishing between benign and malignant thyroid nodules.

ASSOCIATION BETWEEN PLASMA TRANSFUSION AND IN-HOSPITAL MORTALITY IN CRITICALLY ILL PATIENTS WITH SEPSIS-INDUCED COAGULOPATHY.

ABSTRACT: Background: Plasma is commonly used in patients with coagulopathy; however, its role in patients with sepsis-induced coagulopathy (SIC) is unclear. This study aimed to evaluate the effect of plasma transfusion on the prognosis of patients with SIC. Methods: Data were collected from the Medical Information Mart for Intensive Care IV database. Multivariable logistic regression analysis was used to determine the association between plasma transfusion and the incidence of in-hospital mortality, pulmonary embolism, and lower extremity deep vein thrombosis in critically ill patients with SIC. Propensity score matching (PSM) and propensity score-based inverse probability of treatment weighting (IPTW) models were used to ensure the robustness of our findings. Furthermore, the nonparametric relationship between in-hospital mortality and plasma transfusion volume was analyzed using restricted cubic spline. Subgroups analyses were performed for age, sex, Charlson score, Sequential Organ Failure Assessment score, SIC score, and with hemorrhage. Results: A total of 8,747 patients with SIC were enrolled: of them, 1874 were in the plasma infusion group, and 6,873 were in the no plasma infusion group. Compared with the no plasma infusion group, the plasma infusion group had higher in-hospital mortality (odds ratio [OR], 1.4411; 95% confidence interval [CI], 1.2280-1.6897, P < 0.05), and the results were robust after PSM (OR, 1.3227; 95% CI, 1.1152-1.5697; P < 0.05) and IPTW (OR, 1.1541; 95% CI, 1.0738-1.2404; P < 0.05). Similar results were also observed in different subgroups. However, because of conflicting results after PSM and IPTW, we were unable to definitively link plasma transfusion with pulmonary embolism and deep vein thrombosis. Compared with the no early plasma transfusion group (≥12 h), the in-hospital mortality rate was lower in the early plasma transfusion group (<12 h) (OR, 0.5426; 95% CI, 0.4398-0.6844; P < 0.05). The restricted cubic spline analysis indicated that increased plasma transfusion was associated with increased in-hospital mortality in patients with SIC. Conclusion: Plasma transfusion increases in-hospital mortality in patients with SIC, and the mortality rate increases with the amount of plasma transfusion. Patients with SIC who received early plasma infusion had lower in-hospital mortality than those who received no early plasma transfusion.

Prospective clinical study of retinal microvascular alteration after ICL implantation.

Purpose: To evaluate the retinal microvascular alteration after implantable collamer lens (ICL) implantation in moderate to high myopia patients using quantitative optical coherence tomography angiography (OCTA). Methods: This prospective cohort study included 50 eyes of 25 patients with preoperative spherical equivalent ≥ -3.00 D. Patients underwent bilateral ICL implantation at the Department of Ophthalmology, Peking University Third Hospital, from November 2018 to July 2019. OCTA was used to image the superficial and deep retinal capillary plexuses before ICL implantation surgery and at 3 months follow-up. Results: There was no significant difference in the microvascular density within each annular zone and all quadrantal zones of the superficial and deep layers found in myopia patients before and after ICL surgery. Conclusion: Levels of microvascular density in retinal capillary plexuses were stable, as detected by the OCTA, showing the high security of ICL implantation, which would not leave adverse effects on retinal microvasculature in myopia patients.

Elevated Neuropeptides in Dry Eye Disease and Their Clinical Correlations.

PURPOSE: The goal of this study was to assess neuropeptide levels in patients with dry eye disease (DED) and investigate their correlations with clinical characteristics. METHODS: This study included 38 eyes of 38 patients diagnosed with DED (DED group) and 38 eyes of 38 healthy volunteers without DED (control group). Ocular surface evaluation was performed. The severity of dry eye symptoms and signs in the DED group was graded. Neuropeptides [substance P (SP), alpha-melanocyte-stimulating hormone (α-MSH), ß-endorphin, neurotensin, and oxytocin] and inflammatory cytokines levels were measured in basal tears. The link between neuropeptides and clinical parameters was investigated using Spearman rank correlation. RESULTS: Overall, 76.3% of patients in the DED group showed dry eye symptoms and signs that were inconsistent in severity. Compared with the control group, the DED group showed higher levels of SP, α-MSH, and oxytocin in tears (P = 0.012, P = 0.030, and P = 0.006, respectively), but similar levels of ß-endorphin and neurotensin (P = 0.269 and P = 0.052). The levels of SP, α-MSH, and oxytocin were elevated in DED patients with higher grading of symptoms than clinical signs (all P < 0.05). SP, α-MSH, and oxytocin levels in tears were positively correlated with Ocular Surface Disease Index scores, frequency of sensitivity to light, and frequency of blurred vision (all P < 0.05). CONCLUSIONS: The increased tear levels of SP, α-MSH, and oxytocin may be linked to ocular discomfort in DED. Neuropeptides may play a key role in the development of DED, especially in DED patients with more severe symptoms than clinical signs.

Biofilm microenvironment-responsive polymeric CO releasing micelles for enhanced amikacin efficacy.

Biofilm-associated infections (BAI) have posed serious threats to public health. Novel therapy based on carbon monoxide (CO) is being increasingly appreciated. However, CO therapy like inhaled gas treatment was impeded owing to its low bioavailability. Besides, the direct use of CO releasing molecules (CORM) showed low therapeutic efficacy in BAI. Therefore, it is vital to improve the efficiency of CO therapy. Herein, we proposed polymeric CO releasing micelles (pCORM) from self-assembly of amphiphilic copolymers containing CORM bearing block as hydrophobic part and acryloylmorpholine block as hydrophilic part. The catechol modified CORM were conjugated through pH cleavable boronate ester bonds and releasing CO passively under biofilm microenvironment. When combined with subminimal inhibitory concentration antibiotic amikacin, pCORM could significantly enhance its bactericidal efficiency against biofilm-encapsulated multidrug-resistant bacteria, representing a promising approach to combat BAI.

Pericyte loss impairs the blood-brain barrier and cognitive function in aged mice after anesthesia/surgery.

AIMS: This study was designed to investigate the role of pericytes in the pathogenesis of perioperative neurocognitive disorder (PND). METHODS: In this study, we established a PND model via sevoflurane anesthesia and tibial fracture surgery in 2-month-old and 16-month-old male C57BL/6 mice. On the third postoperative day, the mice were subjected to behavioral testing or sacrificed to collect brain tissue. The progression of hippocampal blood-brain barrier (BBB) disruption and neuroinflammation was detected using transmission electron microscope and immunofluorescence. We also used western blotting to measure the levels of plasma-derived protein immunoglobulin G (IgG) and albumin in the hippocampus to assess the leakage of the BBB. RESULTS: Aged mice did not experience age-related cognitive decline and BBB disruption compared with younger mice but only increased glial cell activity. Anesthesia/Surgery damaged cognitive function, reduced pericyte coverage, decreased the length of capillaries and levels of occludin and claudin-5, destroyed the structure of the BBB, exacerbated IgG and albumin accumulation in the hippocampus, and enhanced the activation of microglia and astrocytes in the hippocampus of aged mice. However, these negative effects did not occur in young mice. CONCLUSION: Our study showed that the loss of pericytes led to increased BBB permeability and neuroinflammation after anesthesia/surgery in aged mice, ultimately resulting in cognitive dysfunction.

Evaluations of wavefront aberrations and corneal surface regularity in dry eye patients measured with OPD Scan III.

AIM: To compare the wavefront aberrations and corneal surface regularity between dry eye (DE) patients and normal subjects and assess its diagnostic performance for DE measured with OPD Scan-III. METHODS: Fifty right eyes of 50 DE patients and 31 right eyes of normal subjects were included. The examinations for ocular surface including logarithm of the minimum angle of resolution best-corrected distance visual acuity (logMAR BCVA) the ocular surface disease index (OSDI), tear film break-up time (TBUT) and corneal fluorescein staining (CFS). OPD Scan-III was used to measure anterior corneal aberrations including total corneal aberrations, high order aberration (HOA), coma, trefoil, spherical aberration (SA), standard deviation of corneal power (SDP), surface regularity index (SRI) and surface asymmetry index (SAI). Statistical analysis were assessed with nonparametric tests and Spearman's correlations. All parameters were also analyzed for sensitivity, specificity, and receiver operating characteristics (ROC) curves. RESULTS: Wavefront aberrations parameters including total corneal aberrations, HOA, coma, trefoil, and SA in DE group were significantly higher than those in normal group (P<0.001). Corneal surface regularity parameters including SRI and SAI in DE group were significantly higher than both in normal group (P<0.05). All the wavefront aberrations parameters had significant correlations with ocular surface parameters (P<0.05). The logMAR BCVA had positive correlations with SAI and SRI (all P<0.001). CFS scores had positive correlations with SAI and SRI (all P<0.001). All the wavefront aberrations parameters showed good diagnosis sensitivity and specificity, however, the corneal regularity parameters showed only good specificity but poor sensitivity. The cut-off value selected for trefoil in diagnosis DE showed the highest area under the curve (AUC, 0.921) values as compared to the other parameters with sensitivity of 0.955 and specificity of 0.867. CONCLUSION: Wavefront aberrations and corneal surface regularity are increased in DE patients and also correlated with ocular surface parameters. Wavefront aberrations parameters have potential to be indicators to diagnosis and monitor DE.