Single-cell hdWGCNA reveals metastatic protective macrophages and development of deep learning model in uveal melanoma.

BACKGROUND: Although there has been some progress in the treatment of primary uveal melanoma (UVM), distant metastasis remains the leading cause of death in patients. Monitoring, staging, and treatment of metastatic disease have not yet reached consensus. Although more than half of metastatic tumors (62%) are diagnosed within five years after primary tumor treatment, the remainder are only detected in the following 25 years. The mechanisms of UVM metastasis and its impact on prognosis are not yet fully understood. METHODS: scRNA-seq data of UVM samples were obtained and processed, followed by cell type identification and characterization of macrophage subpopulations. High-dimensional weighted gene co-expression network analysis (HdWGCNA) was performed to identify key gene modules associated with metastatic protective macrophages (MPMφ) in primary samples, and functional analyses were conducted. Non-negative matrix factorization (NMF) clustering and immune cell infiltration analyses were performed using the MPMφ gene signatures. Machine learning models were developed using the identified metastatic protective macrophages related genes (MPMRGs) to distinguish primary from metastatic patients. A deep learning convolutional neural network (CNN) model was constructed based on MPMRGs and cell type associations. Lastly, a prognostic model was established using the MPMRGs and validated in independent cohorts. RESULTS: Single-cell RNA-seq analysis revealed a unique immune microenvironment landscape in primary samples compared to metastatic samples, with an enrichment of macrophage cells. Using HdWGCNA, MPMφ and marker genes were identified. Functional analysis showed an enrichment of genes related to antigen processing progress and immune response. Machine learning and deep learning models based on key genes showed significant effectiveness in distinguishing between primary and metastatic patients. The prognostic model based on key genes demonstrated substantial predictive value for the survival of UVM patients. CONCLUSION: Our study identified key macrophage subpopulations related to metastatic samples, which have a profound impact on shaping the tumor immune microenvironment. A prognostic model based on macrophage cell genes can be used to predict the prognosis of UVM patients.

Efficacy and Safety of Low-Fluence 730-nm Picosecond Laser in the Treatment of Melasma in Chinese Patients.

BACKGROUND: The 730-nm picosecond laser has shown promise in treating various benign pigmentary conditions, and it is yet to be determined whether it is effective and safe for melasma. OBJECTIVE: The aim of this study was to investigate the potential benefits and risks of using the 730-nm picosecond laser to remove melasma. MATERIALS AND METHODS: This is a retrospective review of all patients who presented to the clinic between April 2021 and April 2022 for the treatment of melasma with 730-nm picosecond laser alone. The efficacy of the laser was assessed based on the Melasma Area and Severity Index (MASI) score using high-resolution photographs evaluated by blinded dermatologists. RESULTS: A total of 25 Chinese with Fitzpatrick skin Type II to IV were included. Patients were treated for an average of 3.56 ± 0.77 treatment sessions. The mean MASI scores decreased by 33.7% from 11.38 ± 6.60 to 7.55 ± 6.08 at an average of 8.48 ± 2.16 weeks of follow-up (p < .001). Among the patients, 1 experienced a 79% decrease, 6 had a decrease ranging from 51% to 75%, 10 had a decrease ranging from 26% to 50%, 5 had a decrease of less than 25%, and 3 experienced no changes in MASI scores. No hyper/hypopigmentation was observed. CONCLUSION: Low-fluence 730-nm picosecond laser is an effective and safe modality for the treatment of melasma in Chinese patients.

Long-Term Effects and Prognosis Following Suction Blister Epidermal Grafting in Vitiligo Patients.

BACKGROUND: Suction blister epidermal grafting (SBEG) is currently one of the most prevalent surgical methods for stable vitiligo. OBJECTIVE: To investigate the long-term outcomes of vitiligo patients who underwent SBEG and to explore risk factors associated with postoperative relapse. METHODS: A retrospective cohort study was conducted in patients who underwent SBEG in our department between January 2016 and December 2022. Treatment outcomes, including repigmentation rate, adverse events, and postoperative relapse, were surveyed via telephone interview or out-=patient visit. Multivariate logistic regression models were used to assess the potential risk factors for postoperative relapse. Statistical significance was assumed at P < .05. RESULTS: A total of 253 patients were included with a repigmentation rate of 96% (243/253) after grafting. Common adverse events included cobblestone-like appearance (73.1%, 185/253) in the donor site, perigraft halo (46.2%, 117/253), and cobblestone-like appearance (26.1%, 66/253) in the recipient site. Postoperative relapse occurred in 20.1% of patients over a mean time of 29.7 months after grafting. Nonsegmental type of vitiligo and coexistence of autoimmune diseases were risk factors for postoperative relapse. CONCLUSION: SBEG is an effective surgical treatment for vitiligo with high repigmentation rate and good safety profile. Nonsegmental vitiligo and comorbid autoimmune diseases may increase the risk of postoperative relapse.

Ultrathin Skin Grafting Versus Suction Blister Epidermal Grafting in the Treatment of Resistant Stable Vitiligo: A Self-Controlled Comparative Study.

BACKGROUND: Surgical therapies are effective methods to treat resistant stable vitiligo, with each method having advantages and disadvantages. OBJECTIVE: This study aimed to compare the efficacy and safety of ultrathin skin grafting (UTSG) and suction blister epidermal grafting (SBEG) to treat stable vitiligo. METHODS: A total of 15 patients with 45 vitiligo patches were recruited. Each vitiligo patch was divided in half; 1 half was treated by UTSG, whereas the other half was treated by SBEG. The patients were followed up monthly for 3 months to assess the repigmentation rate, relative melanin index (RMI), and relative erythema index (REI) at different timepoints. RESULTS: Excellent repigmentation was observed in 97.8% of patches that underwent UTSG and 93.3% that underwent SBEG. The RMI and REI at 1, 2, and 3 months after the grafting procedure did not significantly differ between the 2 methods. At the recipient site, incomplete fall-off of the graft occurred in 4.4% of patches that underwent UTSG, whereas a "cobblestone appearance" was observed in 66.7% of patches that underwent SEBG. UTSG caused fewer complications at the donor site than SBEG. CONCLUSION: Compared with SBEG, UTSG is faster and achieves better cosmetic outcomes at the recipient and donor sites.

Clopidogrel Resistance in a Murine Model of Diet-Induced Obesity Is Mediated by the Interleukin-1 Receptor and Overcome With DT-678.

OBJECTIVE: Clopidogrel is a commonly used P2Y12 inhibitor to treat and prevent arterial thrombotic events. Clopidogrel is a prodrug that requires bioactivation by CYP (cytochrome P450) enzymes to exert antiplatelet activity. Diabetes mellitus is associated with an increased risk of ischemic events, and impaired ability to generate the active metabolite (AM) from clopidogrel. The objective of this study is to identify the mechanism of clopidogrel resistance in a murine model of diet-induced obesity (DIO). Approach and Results: C57BL/6J mice and IL-1R-/- mice were given high-fat diet for 10 weeks to generate a murine model of diet-induced obesity. Platelet aggregation and carotid arterial thrombosis were assessed in response to clopidogrel treatment. Wild-type DIO mice exhibited resistance to antiplatelet and antithrombotic effects of clopidogrel that was associated with reduced hepatic expression of CYP genes and reduced generation of the AM. IL (Interleukin)-1 receptor-deficient DIO (IL1R-/- DIO) mice showed no resistance to clopidogrel. Lack of resistance was accompanied by increased exposure of the clopidogrel AM. This resistance was also absent when wild-type DIO mice were treated with the conjugate of the clopidogrel AM, DT-678. CONCLUSIONS: These findings indicate that antiplatelet effects of clopidogrel may be impaired in the setting of diabetes mellitus due to reduced prodrug bioactivation related to IL-1 receptor signaling. Therapeutic targeting of P2Y12 in patients with diabetes mellitus using the conjugate of clopidogrel AM may lead to improved outcomes.

Comparison of deep anterior lamellar keratoplasty and penetrating keratoplasty with respect to postoperative corneal sensitivity and tear film function.

PURPOSE: To investigate tear film function, central and peripheral corneal sensitivity and corneal subbasal nerve morphology in the cornea after deep anterior lamellar keratoplasty (DALK) compared with penetrating keratoplasty (PK). METHODS: This prospective study compared the changes in 16 eyes of 16 patients who underwent DALK (DALK group) with those in 28 eyes of 28 patients who underwent PK (PK group). Thirty healthy volunteers were also included as controls. Tear functions were evaluated using tear break-up time (TBUT), tear meniscus height (TMH) and corneal fluorescein staining. Corneal sensation was measured with a Cochet-Bonnet esthesiometer. Corneal subbasal nerve morphology was evaluated using in vivo confocal microscopy (IVCM). The patients were examined 1, 3, 6, 9 and 12 months after keratoplasty. RESULTS: Postoperatively, TMH recovered significantly faster in the DALK group than in the PK group (p < 0.05), and the postoperative TBUT was much higher in the DALK group compared with the PK group (p < 0.05). Central and peripheral corneal sensitivity remained lower in both the PK and DALK groups at 12 months after surgery compared with the control group (p < 0.05). The peripheral corneal sensitivity of the host cornea was significantly higher than the central corneal sensitivity (p < 0.05). No significant difference was found in corneal sensitivity between the PK and DALK groups. There was no significant correlation between corneal sensitivity and tear film function after PK or DALK. CONCLUSIONS: Tear film function was restored more rapidly after DALK compared with PK, but there was no significant difference in corneal sensitivity between PK and DALK.

The Association Study on Physical Activity Intensity, Sleep Quality, and Depression among College Students in the Central Plains Region.

This investigation sought to understand how physical activity, sleep quality, and depression interrelate among university students in a particular region of China. It involved a diverse group of 2363 students from three institutions, using a cross-sectional approach with well-established measurement tools. These tools demonstrated strong reliability and validity, with Cronbach's alpha values indicating robust internal consistency. The data revealed that higher levels of physical activity were inversely related to depression and directly related to better sleep quality, highlighting the potential of exercise and sleep improvement to reduce depressive symptoms among this demographic.

Fully human single-domain antibody targeting a highly conserved cryptic epitope on the Nipah virus G protein.

Nipah virus infection, one of the top priority diseases recognized by the World Health Organization, underscores the urgent need to develop effective countermeasures against potential epidemics and pandemics. Here, we identify a fully human single-domain antibody that targets a highly conserved cryptic epitope situated at the dimeric interface of the Nipah virus G protein (receptor binding protein, RBP), as elucidated through structures by high-resolution cryo-electron microscopy (cryo-EM). This unique binding mode disrupts the tetramerization of the G protein, consequently obstructing the activation of the F protein and inhibiting viral membrane fusion. Furthermore, our investigations reveal that this compact antibody displays enhanced permeability across the blood-brain barrier (BBB) and demonstrates superior efficacy in eliminating pseudovirus within the brain in a murine model of Nipah virus infection, particularly compared to the well-characterized antibody m102.4 in an IgG1 format. Consequently, this single-domain antibody holds promise as a therapeutic candidate to prevent Nipah virus infections and has potential implications for vaccine development.

Evaluation of industrial ecology in the π-shaped curve area of China's Yellow River based on the grey Lotka-Volterra model.

Industrial ecology (IE) is the process of constructing industrial-ecological systems (IES) with the realization of the mutual benefits for industrial system (IS) and ecological system (ES). Therefore, the IE level depends on the IES development and the relationship between IS and ES. This paper calculated the development index of ES and IS to account for IES development and adopted the grey Lotka-Volterra to analyze the relationship between IS and ES. Choosing the π-shaped curve area in the Yellow River basin of China as the study area, this paper analyzed its IE level and influence factors from 2005 to 2019. Findings include: (1) The development level of IES in the Area presented significant spatial differentiation and could be classified into three levels. (2) IS and ES remained in the stage of isolated development or mutual restriction. (3) IE was found to be positively correlated with scientific innovation, economic development, openness degree, pollution control, and industrial structure while negatively correlated with urbanization, resource consumption, and government influence.

Impact of COVID-19 Vaccine and COVID-19 Infection on Vitiligo Activity and Progression.

Background: Coronavirus disease 2019 (COVID-19) has given rise to several new onset or exacerbated dermatologic disorders including vitiligo. However, the relationship between COVID-19 infection or its associated vaccines and vitiligo progression is unclear. Aim: We investigate the impact of COVID-19 infection and its associated vaccines on vitiligo progression. Methods: A cross-sectional study was performed among patients who visited Department of Dermatology, Peking University People's Hospital between 2022.1 and 2023.6. Detailed information including demographic characteristics, vitiligo clinical features, information on COVID-19 infection and vaccination and disease progression was collected by an electronic questionnaire. Results: Overall, 314 patients with vitiligo completed the questionnaire. 47.5% were males, with an average age of 25.5±15.9 years. 266 (84.7%) patients had received COVID-19 vaccination, and 70.3% of the patients reported progression of vitiligo after vaccination, mostly within 3 months. 55.6% of the patients had disease progression after the second dose of vaccine. 270 patients experienced COVID-19 infection, and 30.7% of these patients had progression of vitiligo after infection, most of the progression occurred within 1-2 months. 184 patients (68.2%) interrupted treatment. Analysis results indicated patients in active stage had a higher risk for vitiligo progression after COVID-19 infection and vaccination.

Excellent Repigmentation of Generalized Vitiligo with Oral Baricitinib Combined with NB-UVB Phototherapy.

Vitiligo is an acquired autoimmune skin disorder, clinically characterized by distinct white macules and patches resulting from progressive melanocyte destruction. JAK-STAT pathway plays an important role in the loss of epidermal melanocytes. Baricitinib can block the JAK-STAT pathway and the downstream chemokines as a new JAK1/2 inhibitor. In this report, we describe the successful treatment of 2 patients with oral baricitinib combined with NB-UVB phototherapy, which provides a good alternative and supplementary to treat refractory vitiligo.

Association between Beta Oscillations from Subthalamic Nucleus and Quantitative Susceptibility Mapping in Deep Gray Matter Structures in Parkinson's Disease.

This study aimed to investigate the association between beta oscillations and brain iron deposition. Beta oscillations were filtered from the microelectrode recordings of local field potentials (LFP) in the subthalamic nucleus (STN), and the ratio of the power spectral density of beta oscillations (PSDXb) to that of the LFP signals was calculated. Iron deposition in the deep gray matter (DGM) structures was indirectly assessed using quantitative susceptibility mapping (QSM). The Unified Parkinson's Disease Rating Scale (UPDRS), part III, was used to assess the severity of symptoms. Spearman correlation coefficients were applied to assess the associations of PSDXb with QSM values in the DGM structures and the severity of symptoms. PSDXb showed a significant positive correlation with the average QSM values in DGM structures, including caudate and substantia nigra (SN) (p = 0.008 and 0.044). Similarly, the PSDXb showed significant negative correlations with the severity of symptoms, including axial symptoms and the gait in the medicine-off state (p = 0.006 for both). The abnormal iron metabolism in the SN and striatum pathways may be one of the underlying mechanisms for the occurrence of abnormal beta oscillations in the STN, and beta oscillations may serve as important pathophysiological biomarkers of PD.

Yolk precursor synthesis and deposition in hierarchical follicles and effect on egg production performance of hens.

Egg production of hens is related to ovarian follicles development. The hierarchical follicle development accompanies the deposition of a large amount of yolk precursor. The aim of this study was to illustrate the effects of strain and age on yolk deposition and egg production. The experiment compared yolk synthesis, transport, and deposition in 3 groups of hens: one of a high-yield commercial hybrid laying breed (Jinghong No.1) in 2 stages (35 wk and 75 wk; JH35, JH75) and one of Chinese native breed (Lueyang Black-Boned chicken) at 35 wk (LY35). The results showed that the number of hierarchical follicles in JH35 and JH75 was significantly more than in LY35. At the same time, the yolk weight of the LY35 and JH75 was significantly higher than that of JH35. The expression of apolipoprotein A1 and apolipoprotein B genes in the liver of JH35 was higher than that of JH75. The expression of the very low-density lipoprotein receptor gene in the JH75 ovary was higher than that of the other 2 groups. The plasma concentrations of very low-density lipoprotein and vitellogenin were no significant difference among groups. The yolk deposition in hierarchical follicles based on the fat-soluble dyes measurement meant that the rate of yolk deposition of LY35 was lower than the other 2 groups. In most cases, the yolk deposition of JH75 was higher than that of the other groups, but the process showed greater fluctuation over time. These results meant that the rate and stability of yolk deposition played an essential role in affecting egg performance. In summary, both strain and age were related to egg production, but the 2 factors might impact yolk deposition and egg-laying performance differently. The egg performance may be affected by both yolk precursor synthesis and deposition for different strains, but it may be affected by yolk precursor deposition for the old laying hens.

Giant functional parathyroid carcinoma: a case report and literature review.

Background: Parathyroid carcinoma is an infrequent neoplasm of the endocrine system, constituting roughly 0.5% to 5% of cases of primary hyperparathyroidism. The diagnosis of this condition presents a unique challenge for healthcare professionals. Case report: We present a case of a 77-year-old female patient who presented with a longstanding right-sided neck tumor. The Positron emission tomography-computed tomography (PET-CT) scan detected a substantial tumor situated at the inferior border of the thyroid gland. A surgical procedure was conducted, resulting in the total excision of the tumor. The diagnosis of parathyroid carcinoma was confirmed through pathological investigation. At the six-month follow-up, the patient exhibited favorable post-operative outcomes with no evidence of recurrence. Conclusion: The primary approaches for managing parathyroid carcinoma involve precise diagnosis and surgical removal. This case report provides confirmation that the implementation of rigorous treatment measures can yield a substantial improvement in the prognosis.

Asymmetric pendrin homodimer reveals its molecular mechanism as anion exchanger.

Pendrin (SLC26A4) is an anion exchanger expressed in the apical membranes of selected epithelia. Pendrin ablation causes Pendred syndrome, a genetic disorder associated with sensorineural hearing loss, hypothyroid goiter, and reduced blood pressure. However its molecular structure has remained unknown, limiting our understanding of the structural basis of transport. Here, we determine the cryo-electron microscopy structures of mouse pendrin with symmetric and asymmetric homodimer conformations. The asymmetric homodimer consists of one inward-facing protomer and the other outward-facing protomer, representing coincident uptake and secretion- a unique state of pendrin as an electroneutral exchanger. The multiple conformations presented here provide an inverted alternate-access mechanism for anion exchange. The structural and functional data presented here disclose the properties of an anion exchange cleft and help understand the importance of disease-associated variants, which will shed light on the pendrin exchange mechanism.

Sustainable evaluation of the eco-economic systems in the π-shaped Curve Area of the Yellow River basin of China: a study based on the 3D ecological footprint model.

Sustainable evaluation of the eco-economic systems is crucial to resolve the contradiction between environmental protection and economic development and promote healthy urban development. This paper constructed an SEC framework for sustainable development index (SDI) evaluation of the eco-economic systems in the π-shaped Curve Area in the Yellow River basin based on the 3D ecological footprint (EF) model. The study was conducted from three aspects: the capital utilization scale and equity during the ecological supply and demand process, the development efficiency and capacity of the eco-economic systems, and the relations between the systems embodied by the coordination and security evaluation. Also, the SDI and its influence mechanism were studied using the fully arrayed polygon diagram and geographic detector. Findings include the following: EF depth is higher in cities with poor natural resources, while EF size is higher in cities with vast territories and rich resources. The arrangement of EF depth and EF size presents nearly a reverse trend, and the consumption of capital flow and capital stock complements each other. Cities can be classified as heavy utilization type, moderate utilization type, mild utilization type, and low stock appropriation type. From 2005 to 2019, the area's SDI and the three aspects presented evident spatial heterogeneity and formed clusters. The role of government, energy consumption, scientific innovation, industrial structure, urbanization rate, population, economic level, and openness level impact SDI differently. This study proposed a new insight for the sustainability evaluation of eco-economic systems.

Eco-efficiency in China's Loess Plateau Region and its influencing factors: a data envelopment analysis from both static and dynamic perspectives.

China's Loess Plateau Region (LPR) plays a significant role in national ecological security and development. Due to the advantage that relates environment with economy, eco-efficiency has become an important indicator of sustainable analysis. Using cross-level panel data for the period 2006-2017, this paper studied LPR's static eco-efficiency and dynamic performance through a combined application of DEA super-efficient slack-based measure and Malmquist Productivity Index at multi-scales. LPR's eco-efficiency was found to experience a slight increase during the study period. The value decreased roughly from east to west, with high eco-efficiency mainly distributed in provincial cities and resource-based cities. The decomposition of the Malmquist Index indicated that technological change contributed most to the improvement of eco-efficiency in the LPR. Besides, this paper explained the variations of eco-efficiency based on the integrated input-output indicators and TOBIT regression model. Economic scale, population density, government regulation, technical innovation, and openness degree were identified as positive influencing factors, while the structure of the industry and land-use intensity were found to have negative impacts on eco-efficiency. Resource-based cities were found to have stronger potentials for eco-efficiency improvement than non-resource-based cities. This paper revealed the characteristics of LPR's eco-efficiency from three perspectives: a spatiotemporal perspective, a macro-meso-micro perspective, and a static-dynamic perspective. The findings of this study hold important implications for policy makers.

Multiple Lesions at Different Stages of Pyoderma Gangrenosum in a Crohn's Disease Patient.

Pyoderma gangrenosum (PG) is an inflammatory dermatosis characterized by the rapid progression of a painful, necrolytic ulcer with an irregular and undermined border. The prevalence of PG in patients with Crohn's disease (CD) has been estimated to be 0.7%. Here, we report a case that presented various painful skin lesions, including erythema, vesicles, plaques, and ulcers, one week before the fourth infliximab infusion for CD. PG was diagnosed and the lesions subsided after a 390-mg ustekinumab infusion for one month. It suggests that different lesions of PG may occur concomitantly in CD patients, and the therapy should be re-evaluated on time.

Spectrally Stable Blue Light-Emitting Diodes Based on All-Inorganic Halide Perovskite Films.

Substantial progress has been made in perovskite light-emitting diodes (PeLEDs), but the fabrication of high-performance blue PeLEDs still remains a challenge due to its low efficiency, spectral instability and short operational lifetime. How to produce an efficient and stable blue PeLED is the key to realizing the application of PeLEDs in full-color displays. We herein report a blue PeLED usint the ligand-assisted reprecipitation method, in which phenylethylammonium bromide (PEABr) was used as ligands, and chloroform was used as anti-solvent to prepare blue perovskite nanocrystal films. By increasing the PEABr content from 40% to 100% (The ratio of x% PEABr refers to the molar ratio between PEABr and PbBr2), the film quality is highly improved, and the emission exhibits a blue shift. Introducing a poly(9-vinylcarbazole) (PVK) hole transport layer into the device, the PVK layer can not only achieve efficient hole injection, but can also isolate the PEDOT: PSS layer to inhibit the non-radiative recombination of metal halide luminescence layer, reduce surface ion defects and successfully inhibit halide atom migration. Finally, the PeLED presents a stable electroluminescence under different driving voltages without any red shift.

Flexible Quantum-Dot Color-Conversion Layer Based on Microfluidics for Full-Color Micro-LEDs.

In this article, red and green perovskite quantum dots are incorporated into the pixels of a flexible color-conversion layer assembly using microfluidics. The flexible color-conversion layer is then integrated with a blue micro-LED to realize a full-color display with a pixel pitch of 200 µm. Perovskite quantum dots feature a high quantum yield, a tunable wavelength, and high stability. The flexible color-conversion layer using perovskite quantum dots shows good luminous and display performance under different bending conditions; is easy to manufacture, economical, and applicable; and has important potential applications in the development of flexible micro-displays.