Valvar bypass surgery to ameliorate persistent lower limb edema caused by post-thrombotic syndrome: a case report and literature review.

Obstruction and/or reflux compromise during venous emptying can facilitate different pathophysiologies in chronic venous insufficiency (CVI). We present a patient with persistent lower limb CVI edema caused by post-thrombotic syndrome (PTS), who responded well to femoral vein valve therapy via axillary vein bypass after unsuccessful valvuloplasty, and led a normal life. During a 12 month observation period, bridging vessels completely restored original anatomical structures. In a literature study, no similar surgeries were reported, but we show that this operation may be feasible in selected patients.

Neurological manifestations and risk factors associated with poor prognosis in hospitalized children with Omicron variant infection.

There are increasing reports of neurological manifestation in children with coronavirus disease 2019 (COVID-19). However, the frequency and clinical outcomes of in hospitalized children infected with the Omicron variant are unknown. The aim of this study was to describe the clinical characteristics, neurological manifestations, and risk factor associated with poor prognosis of hospitalized children suffering from COVID-19 due to the Omicron variant. Participants included children older than 28 days and younger than 18 years. Patients were recruited from December 10, 2022 through January 5, 2023. They were followed up for 30 days. A total of 509 pediatric patients hospitalized with the Omicron variant infection were recruited into the study. Among them, 167 (32.81%) patients had neurological manifestations. The most common manifestations were febrile convulsions (n = 90, 53.89%), viral encephalitis (n = 34, 20.36%), epilepsy (n = 23, 13.77%), hypoxic-ischemic encephalopathy (n = 9, 5.39%), and acute necrotizing encephalopathy (n = 6, 3.59%). At discharge, 92.81% of patients had a good prognosis according to the Glasgow Outcome Scale (scores ≥ 4). However, 7.19% had a poor prognosis. Eight patients died during the follow-up period with a cumulative 30-day mortality rate of 4.8% (95% confidence interval (CI) 1.5-8.1). Multivariate analysis revealed that albumin (odds ratio 0.711, 95% CI 0.556-0.910) and creatine kinase MB (CK-MB) levels (odds ratio 1.033, 95% CI 1.004-1.063) were independent risk factors of poor prognosis due to neurological manifestations. The area under the curve for the prediction of poor prognosis with albumin and CK-MB was 0.915 (95%CI 0.799-1.000), indicating that these factors can accurately predict a poor prognosis.          Conclusion: In this study, 32.8% of hospitalized children suffering from COVID-19 due to the Omicron variant infection experienced neurological manifestations. Baseline albumin and CK-MB levels could accurately predict poor prognosis in this patient population. What is Known: • Neurological injury has been reported in SARS-CoV-2 infection; compared with other strains, the Omicron strain is more likely to cause neurological manifestations in adults. • Neurologic injury in adults such as cerebral hemorrhage and epilepsy has been reported in patients with Omicron variant infection. What is New: • One-third hospitalized children with Omicron infection experience neurological manifestations, including central nervous system manifestations and peripheral nervous system manifestations. • Albumin and CK-MB combined can accurately predict poor prognosis (AUC 0.915), and the 30-day mortality rate of children with Omicron variant infection and neurological manifestations was 4.8%.

Selective biosynthesis of a rhamnosyl nosiheptide by a novel bacterial rhamnosyltransferase.

Nosiheptide (NOS) is a thiopeptide antibiotic produced by the bacterium Streptomyces actuosus. The hydroxyl group of 3-hydroxypyridine in NOS has been identified as a promising site for modification, which we therefore aimed to rhamnosylate. After screening, Streptomyces sp. 147326 was found to regioselectively attach a rhamnosyl unit to the 3-hydroxypyridine site in NOS, resulting in the formation of a derivative named NOS-R at a productivity of 24.6%. In comparison with NOS, NOS-R exhibited a 17.6-fold increase in aqueous solubility and a new protective effect against MRSA infection in mice, while maintaining a similar in vitro activity. Subsequently, SrGT822 was identified as the rhamnosyltransferase in Streptomyces sp. 147326 responsible for the biosynthesis of NOS-R using dTDP-L-rhamnose. SrGT822 demonstrated an optimal reaction pH of 10.0 and temperature of 55°C, which resulted in a NOS-R yield of 74.9%. Based on the catalytic properties and evolutionary analysis, SrGT822 is anticipated to be a potential rhamnosyltransferase for use in the modification of various complex scaffolds.

Persistence of severe global inequalities in the burden of blindness and vision loss from 1990 to 2019: findings from the Global Burden of Disease Study 2019.

AIMS: To assess the global burden and economic inequalities in the distribution of blindness and vision loss between 1990 and 2019. METHODS: A secondary analysis of the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2019. Data for disability-adjusted life-years (DALYs) due to blindness and vision loss were extracted from the GBD 2019. Data for gross domestic product per capita were extracted from the World Bank database. Slope index of inequality (SII) and concentration index were computed to assess absolute and relative cross-national health inequality, respectively. RESULTS: Countries with high, high-middle, middle, low-middle and low Socio-demographic Index (SDI) had decline of age-standardised DALY rate of 4.3%, 5.2%, 16.0%, 21.4% and 11.30% from 1990 to 2019, respectively. The poorest 50% of world citizens bore 59.0% and 66.2% of the burden of blindness and vision loss in 1990 and 2019, respectively. The absolute cross-national inequality (SII) fell from -303.5 (95% CI -370.8 to -236.2) in 1990 to -256.0 (95% CI -288.1 to -223.8) in 2019. The relative inequality (concentration index) for global blindness and vision loss remained essentially constant between 1991 (-0.197, 95% CI -0.234 to -0.160) and 2019 (-0.193, 95% CI -0.216 to -0.169). CONCLUSION: Though countries with middle and low-middle SDI were the most successful in decreasing burden of blindness and vision loss, a high level of cross-national health inequality persisted over the past three decades. More attention must be paid to the elimination of avoidable blindness and vision loss in low-income and middle-income countries.

Isolation and Culture of Human Meibomian Gland Ductal Cells.

Purpose: Hyperkeratinization of meibomian gland (MG) ducts is currently recognized as the primary pathologic mechanism of meibomian gland dysfunction (MGD). This research figured out a method to isolate the MG ducts and established a novel system to culture the human meibomian gland ductal cells (HMGDCs) for investigating the process of MGD. Methods: The MG ducts were obtained from the eyelids of recently deceased donors and subjected to enzymatic digestion. The acini were then removed to isolate independent ducts. These MG ducts were subsequently cultivated on Matrigel-coated wells and covered with a glass plate to obtain HMGDCs. The HMGDCs were further cultivated until passage 2, and when they reached 60% confluence, they were treated with IL-1ß and rosiglitazone for a duration of 48 hours. Immunofluorescence staining and Western blot techniques were employed to identify ductal cells and analyze the effects of IL-1ß on HMGDCs in an in vitro setting. Results: Ophthalmic micro-forceps and insulin needles can be employed for the purpose of isolating ducts. Within this particular culture system, the rapid expansion of HMGDCs occurred in close proximity to the duct tissue. MG ducts specifically expressed keratin 6 (Krt6) and hardly synthesized lipids. Furthermore, the expression of Krt6 was significantly higher (P < 0.0001) in HMGDCs compared to human meibomian gland cells. Upon treatment with IL-1ß, HMGDCs exhibited an overexpression of keratin 1, which was effectively blocked by the administration of rosiglitazone. Conclusions: The present study successfully isolated human MG ducts and cultured HMGDCs, providing a valuable in vitro model for investigating the mechanism of MGD. Additionally, the potential therapeutic efficacy of rosiglitazone in treating hyperkeratinization of ducts in patients with MGD was identified.

Amniotic membrane transplantation combined with conjunctival flap covering surgery for the treatment of corneal perforations in fungal keratitis.

Purpose: To investigate the efficiency of amniotic membrane transplantation (AMT) combined with conjunctival flap covering surgery (CFCS) for patients with corneal perforations in fungal keratitis (FK). Methods: In this non-comparative, retrospective case series, 16 participants of corneal perforation in FK were successfully treated by a combination of multilayer AMT and bipedicle conjunctival flap with partial tenon's capsule. Corneal healing, recurrence of FK, visual acuity, and relevant complications were reported as outcome measures. Results: Sixteen patients (13 male, 3 female) had a mean age of 58.8 ± 10.3 (range 29-72) years. The mean diameter of corneal perforation was 1.9 ± 0.7 (range 0.5-2.8) mm. Corneal perforations healed and all the patients preserved their eyeballs. During the 11.0 ± 4.4 (range 6-18) months of follow-up, there was no recurrence of FK in any of these cases. Visual acuity improved in 15 eyes (93.8 %) and remained unchanged in 1 patient (6.3 %) who had no light perception when first admitted. All 6 patients who accepted secondary keratoplasty showed improved best corrected visual acuity of more than 4 lines. The most frequently found fungi were Aspergillus species (6 of 16, 37.5 %) and Fusarium species (4 of 16, 25.0 %), followed by 1 Scedosporium apiospermum (1 of 16, 6.3 %). Conclusions: Combination AMT with CFCS is a safe and effective surgery for patients with corneal perforations in FK, particularly where eye banks and fresh corneas are not available. This surgery could preserve the integrity of the eyeball and avoid the recurrence of FK. Besides, it provides a greater opportunity for further optical keratoplasty.

Novel phenoxy-((phenylethynyl) selanyl) propan-2-ol derivatives as potential anticancer agents.

Selenocompounds protect against damage to healthy cells and induce the death of tumor cells by apoptosis; for this reason, they are attractive compounds for cancer research. In the present study, two series of novel phenoxy-((phenylethynyl) selanyl) propan-2-ol derivatives were synthesized, and their anti-proliferation activities were evaluated. Of the 23 compounds synthesized, most showed potent anti-proliferative activity against human cancer cell lines. Specifically, compounds 3h, 3g, and 3h-2, which had a 2- or 4-position halogen substituent on 1-((phenylethynyl)selanyl)-3-phenoxypropan-2-ol, exhibited the best anti-proliferative activity against tumor cells. Flow cytometry demonstrated that 3h, 3g, and 3h-2 induced G2/M phase arrest and apoptosis in A549 cells. Cellular studies demonstrated that the induction of apoptosis by 3h correlated with changes in the expression of cell cycle-related proteins and apoptosis-related proteins. Xenograft tumor experiments in nude mice revealed that compound 3h has antitumor effects in vivo and no evident toxic effects in nude mice. In addition, compound 3h alleviated cisplatin-induced liver and kidney damage. These findings uncover the applicability of compound 3h as a novel lead compound for cancer treatment.

A human-centered safe robot reinforcement learning framework with interactive behaviors.

Deployment of Reinforcement Learning (RL) algorithms for robotics applications in the real world requires ensuring the safety of the robot and its environment. Safe Robot RL (SRRL) is a crucial step toward achieving human-robot coexistence. In this paper, we envision a human-centered SRRL framework consisting of three stages: safe exploration, safety value alignment, and safe collaboration. We examine the research gaps in these areas and propose to leverage interactive behaviors for SRRL. Interactive behaviors enable bi-directional information transfer between humans and robots, such as conversational robot ChatGPT. We argue that interactive behaviors need further attention from the SRRL community. We discuss four open challenges related to the robustness, efficiency, transparency, and adaptability of SRRL with interactive behaviors.

Insights into orbital morphological features and fracture patterns in medial and inferior wall fracture: a retrospective cohort study.

This study investigated the orbital morphological features that lead to fractures at different sites by comparing patients with isolated inferior wall fracture (IWF) to patients with isolated medial wall fracture (MWF). This study analyzed the orbital morphologic characteristics of all orbital fracture patients who underwent orbital computed tomography (CT) scans between January 2017 and October 2022. On CT scans, the bony structures of the orbit were measured. We investigated the bilateral symmetry of orbital. In addition, orbital morphological differences were compared between patients with fractures of the medial wall and those with fractures of the inferior wall. A total of 135 patients with orbital fractures were included in the study. Of these, 91 were isolated MWFs and 44 were isolated IWF. We confirmed the symmetry of bilateral orbits and measured the orbit of the uninjured side. No differences were found between the MWF group and the IWF group in terms of ocular prominence, horizontal orbital diameter, orbital rim angle, sagittal orbital depth, sagittal orbital depth, and angle of inferior wall inclination. The distance between the infraorbital nerve (ION) entry point and the orbital rim was significantly smaller in the inferior lateral wall fracture group than in the MWF group (11.87 ± 2.54 vs 14.90 ± 4.64, P < 0.001), and the percentage of type 1 ION was significantly lower in the IWF group than in the MWF group (40.9% vs 65.9%, P = 0.012). We demonstrated the symmetry of bilateral orbits and found that when the point where the ION enters the infraorbital canal is near the orbital rim, patients are more prone to suffering a fracture of the inferior wall after orbital trauma. It is less likely for patients with type 1 ION to suffer an IWF following an orbital fracture.

[A multi-center observation of the therapeutic efficacy of Bencycloquidium bromide in the treatment of seasonal allergic rhinitis with predominant symptoms of rhinorrhea].

Objective:To observe the efficacy and safety of the M receptor antagonist Bencycloquidium bromide nasal spray in treatment of seasonal allergic rhinitis with runny nose as the main symptom. Methods:From August 2021 to September 2021, 134 patients with seasonal allergic rhinitis were enrolled in the otolaryngology Outpatient Department of Peking University Third Hospital, First Affiliated Hospital of Harbin Medical University and China-Japanese Friendship Hospital of Jilin University, including 71 males and 63 females, with a median age of 38 years. TNSS score and visual analogue scale（VAS） of total nasal symptoms were observed during 2 weeks of treatment with Bencycloquidium bromide nasal spray. Results:TNSS score decreased from （8.89±3.31） on day 0 to （3.71±2.51） on day 14（P<0.001）, VAS score of nasal symptoms decreased from （24.86±7.40） on day 0 to （6.84±5.94） on day 14（P<0.001）, VAS score of rhinorrhoea decreased from （6.88±2.06） on day 0 to （1.91±1.81） on day 14（P<0.001）. Rhinoconjunctivitis quality of life questionnaire（RQLQ） score decreased from （94.63±33.35） on day 0 to （44.95±32.28） on day 14（P<0.001）. The incidence of adverse reaction was low and no serious adverse events occurred during the whole experiment. Conclusion:Bencycloquidium bromide nasal spray has significant efficacy and good safety in the treatment of seasonal allergic rhinitis.

Impacts of the hearing aid intervention on healthcare utilization and costs among middle-aged and older adults: results from a randomized controlled trial in rural China.

Background: Hearing impairment has become a major global health issue. To reduce the burden of hearing impairment, we explored impacts of the hearing aid intervention on healthcare utilization and costs. Methods: In this randomized controlled trial, participants aged 45+ were allocated with a ratio of 1:1.5 (intervention: control). Neither the investigators nor the assessors were blinded to the allocation status. Those in the intervention group were fitted with hearing aids, and those in the control group received no care. We applied the difference-in-difference (DID) approach to examine the impacts on healthcare utilization and costs. Given that social network and age can be significant variables affecting effectiveness of the intervention, subgroup analyses by social network and age were used to explore the heterogeneity. Findings: 395 subjects were successfully recruited and randomized. 10 subjects did not meet the inclusion criteria and therefore, 385 eligible subjects (150 in the treatment group and 235 in the control group) were analyzed. The intervention significantly reduced their total healthcare costs (average treatment effect (ATE) = -1.26, 95% CI = -2.39, -0.14, p = 0.028) and total out-of-pocket (OOP) healthcare costs (ATE = -1.29, 95% CI = -2.37, -0.20, p = 0.021) in the 20-month follow-up. To be exact, it reduced self-medication costs (ATE = -0.82, 95% CI = -1.49, -0.15, p = 0.016) and OOP self-medication costs (ATE = -0.84, 95% CI = -1.46, -0.21, p = 0.009). Subgroup analysis showed that the impacts on self-medication costs and OOP self-medication costs varied by social network (ATE for self-medication costs = -0.26, 95% CI = -0.50, -0.01, p = 0.041; ATE for OOP self-medication costs = -0.27, 95% CI = -0.52, -0.01, p = 0.038). The impacts also varied by age groups (ATE for self-medication costs = -0.22, 95% CI = -0.40, -0.04, p = 0.019; ATE for OOP self-medication costs = -0.17, 95% CI = -0.29, -0.04, p = 0.010). There were no adverse events or side effects during the trial. Interpretation: Hearing aid use significantly lowered self-medication costs and total healthcare costs, but had no impacts on inpatient or outpatient services utilization or costs. The impacts were manifested among people with active social network or younger age. It can be speculated that the intervention may be adapted to other similar settings in developing countries to reduce healthcare costs. Funding: P.H. reports grants from National Natural Science Foundation of China (No. 71874005) and Major Project of the National Social Science Fund of China (No. 21&ZD187). Trial registration: Chinese Clinical Trial Registry: ChiCTR1900024739.

Global, regional, and national burden of multiple sclerosis from 1990 to 2019: Findings of global burden of disease study 2019.

Background: The global rising prevalence and incidence of multiple sclerosis (MS) has been reported during the past decades. However, details regarding the evolution of MS burden have not been fully studied. This study aimed to investigate the global, regional, and national burden and temporal trends in MS incidence, deaths, and disability-adjusted life years (DALYs) from 1990 to 2019 using the age-period-cohort analysis. Methods: We performed a secondary comprehensive analysis of incidence, deaths, and DALYs of MS by calculating the estimated annual percentage change from 1990 to 2019 obtained from the Global Burden of Disease (GBD) 2019 study. The independent age, period, and birth cohort effects were evaluated by an age-period-cohort model. Results: In 2019, there were 59,345 incident MS cases and 22,439 MS deaths worldwide. The global number of incidences, deaths, and DALYs of MS followed an upward trend, whereas the age-standardized rates (ASR) slightly declined from 1990 to 2019. High socio-demographic index (SDI) regions had the highest ASR of incidences, deaths, and DALYs in 2019, while the rate of deaths and DALYs in medium SDI regions are the lowest. Six regions which include high-income North America, Western Europe, Australasia, Central Europe, and Eastern Europe had higher ASR of incidences, deaths, and DALYs than other regions in 2019. The age effect showed that the relative risks (RRs) of incidence and DALYs reached the peak at ages 30-39 and 50-59, respectively. The period effect showed that the RRs of deaths and DALYs increased with the period. The cohort effect showed that the later cohort has lower RRs of deaths and DALYs than the early cohort. Conclusion: The global cases of incidence, deaths, and DALYs of MS have all increased, whereas ASR has declined, with different trends in different regions. High SDI regions such as European countries have a substantial burden of MS. There are significant age effects for incidence, deaths, and DALYs of MS globally, and period effects and cohort effects for deaths and DALYs.

The Effects of Acid and Water in the Formation of Anodic Alumina: DFT and Experiment Study.

The DFT method is employed to study the adsorption and reaction behaviors of HC2O4-, H2PO4-, HSO4- and H2O on neutral and anodic aluminum slabs. With the exception of adsorption, the three acid radicals can successively take the two H atoms from the adsorbed H2O on the anodic aluminum slabs, which is the key step of the formation of anodic alumina. The dehydrogenation reaction is dominated by the Coulombic interaction of O and H, respectively belonging to acid radicals and the adsorbed H2O or OH, rather than by the interaction of electronic orbits located on the two kinds of atoms. The experiment of anodic polarization of aluminum verifies the calculation result well.

Deep learning-based approach for the automatic segmentation of adult and pediatric temporal bone computed tomography images.

Background: Automatic segmentation of temporal bone computed tomography (CT) images is fundamental to image-guided otologic surgery and the intelligent analysis of CT images in the field of otology. This study was conducted to test a convolutional neural network (CNN) model that can automatically segment almost all temporal bone anatomy structures in adult and pediatric CT images. Methods: A dataset comprising 80 annotated CT volumes was collected, of which 40 samples were obtained from adults and 40 from children. A further 60 annotated CT volumes (30 from adults and 30 from children) were used to train the model. The remaining 20 annotated CT volumes were employed to determine the model's generalizability for automatic segmentation. Finally, the Dice coefficient (DC) and average symmetric surface distance (ASSD) were utilized as metrics to evaluate the performance of the CNN model. Two independent-sample t-tests were used to compare the test set results of adults and children. Results: In the adult test set, the mean DC values of all the structures ranged from 0.714 to 0.912, and the ASSD values were less than 0.24 mm for 11 structures. In the pediatric test set, the mean DC values of all the structures ranged from 0.658 to 0.915, and the ASSD values were less than 0.18 mm for 11 structures. There was no statistically significant difference between the adult and child test sets in most temporal bone structures. Conclusions: Our CNN model shows excellent automatic segmentation performance and good generalizability for both adult and pediatric temporal bone CT images, which can help to advance otologist education, intelligent imaging diagnosis, surgery simulation, application of augmented reality, and preoperative planning for image-guided otology surgery.

Ductal Hyperkeratinization and Acinar Renewal Abnormality: New Concepts on Pathogenesis of Meibomian Gland Dysfunction.

Meibomian gland dysfunction (MGD) is a functional and morphological disorder of the meibomian glands which results in qualitative or quantitative alteration in meibum secretion and is the major cause of evaporative dry eye (EDE). EDE is often characterized by tear film instability, increased evaporation, hyperosmolarity, inflammation, and ocular surface disorder. The precise pathogenesis of MGD remains elusive. It has been widely considered that MGD develops as a result of ductal epithelial hyperkeratinization, which obstructs the meibomian orifice, halts meibum secretion, and causes secondary acinar atrophy and gland dropout. Abnormal self-renewal and differentiation of the acinar cells also play a significant role in MGD. This review summarizes the latest research findings regarding the possible pathogenesis of MGD and provides further treatment strategies for MGD-EDE patients.

Characteristics of In Vitro Culture and In Vivo Confocal Microscopy in Patients with Fungal Keratitis in a Tertiary Referral Hospital in Central China.

PURPOSE: To investigate the characteristics of in vitro culture and in vivo confocal microscopy (IVCM) in patients with fungal keratitis (FK) presented in a tertiary referral hospital in central China. METHODS: In this noncomparative retrospective study, patients with the diagnosis of FK between October 2021 and November 2022 were reviewed. An IVCM and fungal culture (corneal scraping specimens) were performed, and the characteristics were analyzed. RESULTS: During October 2021 and November 2022, 85 patients were diagnosed with FK. From 63 culture-positive cases, 8 species of fungus were identified. The proportions of isolated fungal species were Fusarium and Aspergillus equally accounting for 33.3% (21 of 63), Alternaria 9.5% (6 of 63), Curvularia 6.3% (4 of 63), Scedosporium apiospermum 6.3% (4 of 63), Paecilomyces lilacinus 3.2% (2 of 63), Exserohilum 3.2% (2 of 63), and Candida 4.8% (3 of 63), respectively. In positive culture cases, IVCM was found to be positive for hyphae or spores in 61 of 63 patients (96.8%). Different fungal species had a variety of cultural characteristics and IVCM manifestations. CONCLUSIONS: In a tertiary referral hospital in central China, Fusarium species, Aspergillus species, and Alternaria species were the 3 most common isolated fungal pathogens, and the proportion of Aspergillus species was significantly higher than that in other regions of China. Careful lesion depth examination by IVCM and OCT should be taken before lamellar keratoplasty to avoid postoperative recurrence. Identifying the IVCM image and culture characteristics will facilitate rapid diagnosis and proper treatment, but IVCM cannot yet replace fungal cultures to distinguish between different fungal species.

Novel Muscle-Homing Peptide FGF1 Conjugate Based on AlphaFold for Type 2 Diabetes Mellitus.

Drugs for metabolic diseases usually require systemic administration and act on multiple tissues, which may produce some unpredictable side effects. There have been many successful studies on targeted drugs, especially antitumor drugs. However, there is still little research on metabolic disease drugs targeting specific tissues. Fibroblast growth factor 1 (FGF1) is a potential therapy for type 2 diabetes (T2D) without the risk of hypoglycemia. However, the major impediment to the clinical application of FGF1 is its mitogenic potential. We previously engineered an FGF1 variant (named FGF1ΔHBS) to tune down its mitogenic activity via reducing the heparin-binding ability. However, other notable side effects still remained, including severe appetite inhibition, pathogenic loss of body weight, and increase in fatality rate. In this study, we used AlphaFold2 and PyMOL visualization tools to construct a novel FGF1ΔHBS conjugate fused with skeletal muscle-targeted (MT) peptide through a flexible peptide linker termed MT-FGF1ΔHBS. We found that MT-FGF1ΔHBS specifically homed to skeletal muscle tissue after systemic administration and induced a potent glucose-lowering effect in T2D mice without hypoglycemia. Mechanistically, MT-FGF1ΔHBS elicits the glucose-lowering effect via AMPK activation to promote the GLUT4 expression and translocation in skeletal muscle cells. Notably, compared with native FGF1ΔHBS, MT-FGF1ΔHBS had minimal effects on food intake and body weight and did not induce any hyperplasia in major tissues of both T2D and normal mice, indicating that this muscle-homing protein may be a promising candidate for T2D treatment. Our targeted peptide strategy based on computer-aided structure prediction in this study could be effectively applied for delivering agents to functional tissues to treat metabolic or other diseases, offering enhanced efficacy and reducing systemic off-target side effects.

Choroidal Vascular Density Quantification in High Myopia with or without Choroidal Neovascularization Using Optical Coherence Tomography Angiography.

Purpose: The aim of this study was to analyze choroidal vascular density alteration in high myopia with or without choroidal neovascularization by using optical coherence tomography angiography (OCTA). Methods: This was a cross-sectional, observational study that included 60 high-myopia eyes. All the participants had comprehensive ophthalmic assessments with visual acuity, intraocular pressure, slit lamp-assisted biomicroscopy, color fundus photography, axial length, optometry, and OCTA. Age, sex, and comorbidities were collected from their medical charts. Univariate and multiple analyses were made to compare the age, spherical equivalent, choroidal vascular density, gender, and choroidal thickness between normal and patients with choroidal neovascularization. Results: 60 eyes with high myopia were included in our study, including 30 eyes with choroidal neovascularization and 30 eyes without choroidal neovascularization or other fundus pathology. The mean age of high myopic patients was older in the choroidal neovascularization group than in the normal group (48.43 ± 19.06 years vs. 28.83 ± 9.92 years, p < 0.01). The mean choroidal thickness of high myopic patients was thinner in the neovascularization group than in the normal group (68.81 ± 48.81 µm vs. 137.80 ± 66.33 µm, p < 0.01). The mean choroidal vascular density in the normal group was greater than in the choroidal neovascularization group (82.43 ± 8.73 vs. 67.54 ± 12.56, p < 0.01). There was no significant difference in spherical equivalent between the choroidal neovascularization group and the normal group (-10.56 ± 2.97D vs. -11.93 ± 3.38D, p = 0.11). Multivariate analysis showed that after adjusting for covariates, less choroidal vascular density and older age were independent factors associated with choroidal neovascularization in the high myopic eye. Conclusion: Decreased choroidal vascular density and older age played an important role in the development of choroidal neovascularization in high myopic eyes. OCTA may help us to identify the highly myopic patients that need to intervene.

FGF4 Promotes Skin Wound Repair through p38 MAPK and GSK3ß-Mediated Stabilization of Slug.

Cutaneous wound healing is an orderly and intricate process that restores the barrier function and integrity of injured skin. Re-epithelialization, which involves the proliferation and migration of keratinocytes to cover the denuded surface, is essential for successful wound closure. There are many members of the FGF family, of which the paracrine-acting FGF1 and FGF7 subfamily members have been identified as positive regulators of wound repair. However, the role and underlying mechanisms of some other paracrine FGFs in wound repair still remain obscure. In this report, we found that paracrine FGF4 localized predominantly to the epidermal keratinocytes and was markedly upregulated at the wound edges in response to re-epithelialization in human and mouse wound models. Blockade of FGF4 resulted in delayed re-epithelialization of human ex vivo skin wounds, whereas recombinant FGF4 treatment promoted re-epithelialization and wound repair. Mechanistically, recombinant FGF4 promotes p38 MAPK‒GSK3ß‒mediated stabilization of Slug by reducing its ubiquitination, which triggers epithelial-to-mesenchymal transition and promotes the migration and proliferation of keratinocytes and thus wound re-epithelialization. Our findings uncover FGF4 as an important regulator of wound healing, highlighting a promising therapeutic avenue for skin injury.