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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Research on the Relationship between the Psychological State and Sports Habits of College Students / Investigación sobre la Relación entre el Estado Psicológico y los Hábitos Deportivos de Estudiantes Universitarios

Objective: The current study examines the relationship between psychological state and sports habits of college students. Methods: To understand the relationship between psychological state and sports habits of college students, this study uses a questionnaire as the main instrument of data collection along with the mental scale sc-l 90 surveys with a view to assess the statistics of the relationship between sports of different frequencies and the mental health of Chinese college students. The principle of random sampling was used to conduct a survey in the form of a questionnaire’ a total of 9,876 questionnaires were distributed, and 9,185 questionnaires were returned. After screening of the responses received a final total of 8499 valid questionnaires were used for data analysis (5,324 for boys and 3,175 for girls). Results: Sports of different frequencies have different effects in terms of improving the mental health of college students; The activity time is increased to more than 60 minutes each time, the number of activities is increased to 3 times a week, the percentage drops to 5%. The number of mixed projects and activities has been increased to 3 times a week, the percentage dropped to 2.3%. Conclusion: The effect of improving the mental health of college students is positive. Engaging in sports in their daily life has a positive and important role in regulating the mental health of college students.(AU)

Analysis of Prognostic Alternative Splicing Reveals the Landscape of Immune Microenvironment in Thyroid Cancer.

BACKGROUND: The incidence of thyroid cancer (THCA) continues to increase in recent decades. Accumulating evidence showed that the unbalanced alternative splicing (AS) promotes the occurrence of cancers and leads to poor prognosis of patients. However, the research on alternative splicing events in THCA is lacking, and its underlying mechanism is not fully understood. This study identifies a novel prognostic signature based on AS events to reveal the relationship of AS with tumor immune microenvironment. METHODS: Based on the AS data, transcriptional data, and clinical information, the differentially expressed alternative splicings (DEASs) were screened out. Least absolute shrinkage and selection operator (LASSO) regression and multi-Cox regression analyses were employed to identify prognostic results related to AS events and establish a prognostic signature. The predictive ability of the signature was assessed by Kaplan-Meier (K-M) survival curve, risk plots, and receiver operating characteristic (ROC) curves. Furthermore, correlations between tumor-infiltrating immune cells, immune checkpoints, immune score and prognostic signature were analyzed. RESULTS: According to the LASSO regression analysis, a total of five AS events were selected to construct the signature. K-M survival curve showed that the higher the risk score, the worse the OS of the patients. Risk plots further confirmed this result. ROC curves indicated the high predictive efficiency of the prognostic signature. As for tumor immune microenvironment, patients in the high-risk group had a higher proportion of immune cells, including plasma cell, CD8+ T cell, macrophages (M0 and M2), and activated dendritic cell. Immune checkpoint proteins, such as PDCD1LG2, HAVCR2, CD274, etc., were significantly higher in the high-risk group. We also found that the ESTIMATE score, stromal score, and immune score were lower in the high-risk group, while the result of tumor purity was the opposite. CONCLUSIONS: Collectively, a prognostic signature consisting of five AS events in THCA was established. Furthermore, there was an inextricable correlation between immune cell infiltration, immune checkpoint proteins, and AS events. This study will provide a basis for THCA immunotherapy in the future.

Construction of a Promising Tumor-Infiltrating CD8+ T Cells Gene Signature to Improve Prediction of the Prognosis and Immune Response of Uveal Melanoma.

BACKGROUND: CD8+ T cells work as a key effector of adaptive immunity and are closely associated with immune response for killing tumor cells. It is crucial to understand the role of tumor-infiltrating CD8+ T cells in uveal melanoma (UM) to predict the prognosis and response to immunotherapy. MATERIALS AND METHODS: Single-cell transcriptomes of UM with immune-related genes were combined to screen the CD8+ T-cell-associated immune-related genes (CDIRGs) for subsequent analysis. Next, a prognostic gene signature referred to tumor-infiltrating CD8+ T cells was constructed and validated in several UM bulk RNA sequencing datasets. The risk score of UM patients was calculated and classified into high- or low-risk subgroup. The prognostic value of risk score was estimated by using multivariate Cox analysis and Kaplan-Meier survival analysis. Moreover, the potential ability of gene signature for predicting immunotherapy response was further explored. RESULTS: In total, 202 CDIRGs were screened out from the single-cell RNA sequencing of GSE139829. Next, a gene signature containing three CDIRGs (IFNGR1, ANXA6, and TANK) was identified, which was considered as an independent prognostic indicator to robustly predict overall survival (OS) and metastasis-free survival (MFS) of UM. In addition, the UM patients were classified into high- and low-risk subgroups with different clinical characteristics, distinct CD8+ T-cell immune infiltration, and immunotherapy response. Gene set enrichment analysis (GSEA) showed that immune pathways such as allograft rejection, inflammatory response, interferon alpha and gamma response, and antigen processing and presentation were all positively activated in low-risk phenotype. CONCLUSION: Our work gives an inspiration to explain the limited response for the current immune checkpoint inhibitors to UM. Besides, we constructed a novel gene signature to predict prognosis and immunotherapy responses, which may be regarded as a promising therapeutic target.