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• Serum LCN13 as a valuable dianostic biomarker for MASH patients. • LCN13 expression was decreased in a NASH mouse model and a NASH cell model. • Elevated expression of LCN13 through FXR activation ameliorates hepatocellular lipid accumulation and inflammation both in vivo and in vitro. • LCN13 was transcriptionally activated by Farnesoid X receptor (FXR), and represent a novel direct target gene of FXR. • LCN13-downregulated mice aggravated NASH phenotypes such as increased hepatic lipid accumulation and inflammation. Lipocalin 13 (LCN13) is a member of the lipocalin family that consists of numerous secretory proteins. LCN13 high-expression has been reported to possess anti-obesity and anti-diabetic effects. Although metabolic dysfunction-associated steatotic liver diseases (MASLD) including metabolic dysfunction-associated steatohepatitis (MASH) are frequently associated with obesity and insulin resistance, the functional role of endogenous LCN13 and the therapeutic effect of LCN13 in MASH and related metabolic deterioration have not been evaluated. We employed a methionine-choline deficient diet model and MASH cell models to investigate the role of LCN13 in MASH development. We sought to explore the effects of LCN13 on lipid metabolism and inflammation in hepatocytes under PA/OA exposure using Western blotting, real-time RT-PCR, enzyme-linked immunosorbent assay, hematoxylin and eosin staining, oil red O staining. Using RNA sequencing, chromatin immunoprecipitation assay, and luciferase reporter assays to elucidate whether farnesoid X receptor (FXR) regulates human LCN13 transcription as a transcription factor. Our study found that LCN13 was down-regulated in MASH patients, MASH mouse and cell models. LCN13 overexpression in hepatocyte cells significantly inhibited lipid accumulation and inflammation in vitro. Conversely, LCN13 downregulation significantly exacerbated lipid accumulation and inflammatory responses in vivo and in vitro. Mechanistically, we provided the first evidence that LCN13 was transcriptionally activated by FXR, representing a novel direct target gene of FXR. And the key promoter region of LCN13 binds to FXR was also elucidated. We further revealed that LCN13 overexpression via FXR activation ameliorates hepatocellular lipid accumulation and inflammation in vivo and in vitro. Furthermore, LCN13-down-regulated mice exhibited aggravated MASH phenotypes, including increased hepatic lipid accumulation and inflammation. Our findings provide new insight regarding the protective role of LCN13 in MASH development and suggest an innovative therapeutic strategy for treating MASH or related metabolic disorders. [ABSTRACT FROM AUTHOR]

Background: In 2006, the Canadian Cardiovascular Society (CCS) Access to Care Working Group recommended a 30-day wait time benchmark for cardiac rehabilitation (CR). The objectives of the current study were to: (1) describe cardiac patient perceptions of actual and ideal CR wait times, (2) describe and compare cardiac specialist and CR program perceptions of wait times, as well as whether the recommendations are appropriate and feasible, and (3) investigate actual wait times and factors that CR programs perceive to affect these wait times. Methods: Postal and online surveys to assess perceptions of CR wait times were administered to CR enrollees at intake into 1 of 8 programs, all CCS member cardiac specialists treating patients indicated for CR, and all CR programs listed in Canadian directories. Actual wait times were ascertained from the Canadian Cardiac Rehabilitation Registry. The design was cross-sectional. Responses were described and compared. Results: Responses were received from 163 CR enrollees, 71 cardiac specialists (9.3% response rate), and 92 CR programs (61.7% response rate). Patients reported that their wait time from hospital discharge to CR initiation was 65.6 ± 88.4 days (median, 42 days), while their ideal median wait time was 28 days. Most patients (91.5%) considered their wait to be acceptable, but ideal wait times varied significantly by the type of cardiac indication for CR. There were significant differences between specialist and program perceptions of the appropriate number of days to wait by most indications, with CR programs perceiving shorter waits as appropriate (p < 0.05). CR programs reported that feasible wait times were significantly longer than what was appropriate for all indications (p < 0.05). They perceived that patient travel and staff capacity were the main factors negatively affecting waits. The median wait time from referral to program initiation was 64 days (mean, 80.0 ± 62.8 days), with no difference in wait by indication. Conclusions: Wait times following access to cardiac rehabilitation are prolonged compared with consensus recommendations, and yet are generally acceptable to most patients. Wait times following percutaneous coronary intervention in particular may need to be shortened. Future research is required to provide an evidence base for wait time benchmarks. [ABSTRACT FROM AUTHOR]

• Human metapneumovirus (HMPV) is an important respiratory pathogen that causes acute respiratory tract infection in children ≤5 years old. • The prevalence peak of HMPV in southern China appeared between March and May. • Respiratory syncytial virus is the most common respiratory virus coinfected with HMPV in children. • The predominant subtype of HMPV in this area is B1, followed by A2c subtype. • Long sunshine duration might decrease the HMPV prevalence. This study aimed to determine the epidemiological and genetic features of human metapneumovirus (HMPV) infection in children in southern China, and the effect of meteorological factors on infection. 14,817 children (≤14 years) with acute respiratory tract infections from 2010 to 2019 were examined for HMPV and other respiratory viruses by real-time quantitative polymerase chain reaction. Full-length F gene of 54 positive samples were sequenced and subjected to phylogenetic analysis. The correlation between the HMPV-positive rate and meteorological factors was analyzed by linear regression analysis. HMPV was detected in 524 (3.5%) children, who were mostly younger than 1 year. The seasonal peak of HMPV prevalence mainly occurred in spring. Respiratory syncytial virus was the most common virus coinfected with HMPV (5.3%). Phylogenetic analysis revealed that the sequenced HMPV strains belonged to four sublineages, including A2b (1.9%), A2c (31.5%), B1 (50.0%), and B2 (16.7%). After adjusting for all meteorological factors, sunshine duration was inversely correlated with the HMPV-positive rate. HMPV is an important respiratory pathogen that causes acute respiratory tract infections in children in southern China, particularly in children ≤5 years old. The prevalence peak of HMPV in this area appeared in spring, and the predominant subtype was B1. Meteorological factors, especially long sunshine duration, might decrease the HMPV prevalence. [ABSTRACT FROM AUTHOR]

• It is the first clinical report of Nectria haematococca infection in humans. • N. haematococca keratitis is severe and likely to recur after keratoplasty. • The recurrence occurred primarily in the second week after keratoplasty. • The effect of local use of fluconazole and voriconazole is not ideal. • The next-generation sequencing is useful in the diagnosis of rare fungal infections. Fungal keratitis (FK) is a kind of serious corneal infection and penetrating keratoplasty (PKP) is needed when medical therapy fails. Although Nectria haematococca is found as endophytes in the roots of some plant species, there has been no report of N. haematococca infection in human. We reviewed 46 patients who underwent PKP due to FK in our hospital from July 2021 to December 2021, and there were three patients who had relapsed. The next-generation sequencing revealed that all three corneas were infected with N. haematococca. Based on the ocular manifestation and treatment course of three cases, we summarize the characteristics of N. haematococca FK: the scope of corneal infection was widespread with severe hypopyon. The effect of local use of fluconazole and voriconazole was not ideal, and PKP was the main treatment. Even after a large-scale corneal lesion resection, the lesion may recur. The recurrence occurred primarily in the second week after PKP. This is the first clinical report of N. haematococca infection in humans. Compared with the other currently known FK caused by the Fusarium solani species complex, N. haematococca keratitis is more severe and more likely to recur. [ABSTRACT FROM AUTHOR]

Purpose: (1) To measure the corneal endothelium-Descemet membrane (EDM) layer thickness in Descemet membrane detachment (DMD) patients in vivo using high-definition optical coherence tomography (HD-OCT), and to investigate its correlation with age. (2) To explore whether the detachment time will affect the EDM thickness. (3) To explore whether the EDM thickness of cornea with DMD was different from that without DMD. Participants: Patients with DMD were divided into three groups. Group 1 included twenty-three patients whose Descemet membrane (DM) was partial or complete detached from the corneal stroma after various ocular surgeries. Group 2 included eight patients from group 1 who underwent twice HD-OCT examination on different days before the DM reattached to the stroma. Group 3 included nine patients from group 1 who had clear grayscale boundary between the DM and stroma in HD-OCT images after DM reattachment. Methods: All patients underwent HD-OCT and EDM thickness was measured using Image -Pro Plus 6.0. In Group 1, regression analyses were used to evaluate the correlation between EDM thickness and age, and the thickness difference between the ≤50-year-old group and the >50-year-old group was analyzed by independent sample t-test. In Group 2, paired samples t-test was used to check whether detachment time would affect EDM thickness. In Group 3, paired samples t-test was used to check whether the EDM thickness of cornea with DMD was different from that without DMD. p < 0.05 was considered significant. Results: In Group 1, the EDM thickness measured on the first post-operative day was 27.8 ± 3.6 μm, and a positive correlation was found between EDM thickness and age (r = 0.619, p < 0.05). The EDM thickness of ≤50-year-old group and >50-year-old group were 23.9 ± 3.2 and 29.2 ± 2.6 μm, and there was a significant difference between the two groups (p = 0.001). In Group 2, the first measurement of EDM thickness was 27.5 ± 4.0 μm, the second measurement was 27.6 ± 4.2 μm, the interval between the two measurements was 2.1 ± 1.6 days, and there was no significant difference between the two measurements (p = 0.328). In Group 3, the EDM thickness with DM detachment was 28.3 ± 3.5 μm, with DM reattachment was 23.4 ± 2.4 μm, there was a significant difference between the two measurements (p = 0.002). Conclusions: The EDM thickness in the state of DMD is thicker than its actual thickness in normal cornea, and EDM thickness of the >50-year-old group is much thicker than that of the ≤50-year-old group. [ABSTRACT FROM AUTHOR]

Limbal niche cells (LNCs) are one of the most important supporting cells for corneal epithelial stem cells (CES), however, research on LNCs has been mostly limited to humans and rats previously. To expand the research work into the rabbit animal model, one of the most often used animals in stem cell study, this study was carried out for the in vitro isolation and identification of rabbit LNCs. Rabbit LNCs were isolated by collagenase A digestion method and single cells were obtained, the cells were then seeded on 5% Matrigel-coated plastic surface and cultured in modified embryonic stem cell medium (MESCM). Three biological replicates of the isolating and characterization were recorded from New Zealand White rabbits aged from 2.5 months to 5 months. LNC markers (VIM/CD90/CD105/SCF/PDGFRβ) were analyzed using tyramide signal amplification (TSA) staining, immunohistochemical staining (IHC), western blotting (WB), and real-time reverse transcription polymerase chain reaction (qPCR). TSA staining suggested that VIM was highly expressed in rabbit limbus stroma, which was confirmed by WB, and P63α was expressed in the basal limbus epithelium. Pan-CK and CK12 were highly expressed in the central corneal epithelium but lightly expressed in the limbal epithelium. The WB result indicated that PDGFRβ and VIM expressions in rabbit-LNCs P4 were higher than in P1 and P7. In addition, rabbit corneal epithelium highly expressed Paired Box 6 (PAX6) and Epidermal growth factor-like domain 6(EGFL6). For the three repeat experiments, the cell expansion activity of rabbit-LNC was highest at P4. Rabbit-LNCs were passaged from P0 to P7, and the number of cell doublings (NCD) of P4 for the three repeat experiments was 2.816, 2.737, and 2.849. qPCR showed that high mRNA expression levels of VIM, CD90, CD105, SCF, and PDGFRβ in rabbit-LNCs P4. In conclusion, rabbit-LNCs could be successfully isolated by the collagenase A digestion method as used in human tissue. There were similar characteristics between rabbit and human LNCs (VIM+/CD90+/CD105+/SCF+/PAX6+/PDGFRβ+). • Collagenase A isolates Rabbit LNCs effectively, expanding research possibilities with broader applications. [ABSTRACT FROM AUTHOR]