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In developed countries, age-related macular degeneration (AMD) is the leading cause of irreversible blindness in individuals over the age of 65 years. Vascular endothelial growth factor (VEGF) plays a vital role in the formation of neovascular AMD. VEGF regulates angiogenesis, enhances vascular permeability, and drives the formation of choroidal neovascularization. As a result of the introduction of anti-VEGF drugs, the incidence of blindness from neovascular AMD has greatly reduced. Anti-VEGF drugs are used as a first-line treatment for neovascular AMD. The most recent anti-VEGF drug is conbercept, also named KH902, which was approved for the treatment of neovascular AMD by the China Food and Drug Administration in December 2013. In this review, recent clinical information regarding the use of conbercept to treat neovascular AMD is summarized. Conbercept is a soluble receptor decoy that blocks all isoforms of VEGF-A, VEGF-B, VEGF-C, and PlGF, which has a high binding affinity to VEGF and a long half-life in vitreous. Preclinical studies have demonstrated its anti-angiogenesis activity in both ocular neovascular disease models and tumor models. Clinical trials of conbercept have shown its superior efficacy and safety. Patients respond well even with 3-month treatment intervals following loading doses once a month for 3 months. The potential therapeutic effect of conbercept on the treatment of polypoidal choroidal vasculopathy, a special type of neovascular AMD, is also promising. In summary, conbercept is a new treatment option for ophthalmologists and their patients and may help address the limitations of current anti-VEGF drugs.

Climate warming may affect biological invasions by altering competition between native and non-native species, but these effects may depend on biotic interactions. In field surveys at 33 sites in China along a latitudinal and temperature gradient from 21°N to 30.5°N and a 2-yr field experiment at 30.5°N, we tested the role of the biocontrol beetle Agasicles hygrophila in mediating warming effects on competition between the invasive plant Alternanthera philoxeroides and the native plant Alternanthera sessilis. In surveys, native populations were perennial below 25.8°N but only annual populations were found above 26.5°N where the invader dominated the community. Beetles were present throughout the gradient. Experimental warming (+ 1.8°C) increased native plant performance directly by shifting its lifecycle from annual to perennial, and indirectly by releasing the native from competition via disproportionate increases in herbivory on the invader. Consequently, warming shifted the plant community from invader-dominated to native-dominated but only in the presence of the beetle. Our results show that herbivores can play a critical role in determining warming effects on plant communities and species invasions. Understanding how biotic interactions shape responses of communities to climate change is crucial for predicting the risk of plant invasions.

Background Human granulocytic anaplasmosis is a tick-borne zoonotic disease caused by Anaplasma phagocytophilum . Coinfections with A. phagocytophilum and other tick-borne pathogens are reported frequently, whereas the relationship between A. phagocytophilum and flea-borne Yersnia pestis is rarely concerned. Results A. phagocytophilum and Yersnia pestis were discovered within a Marmota himalayana found dead in the environment, as determined by 16S ribosomal rRNA sequencing. Comparative genomic analyses of marmot-derived A. phagocytophilum isolate demonstrated its similarities and a geographic isolation from other global strains. The 16S rRNA gene and GroEL amino acid sequence identity rates between marmot-derived A. phagocytophilum (JAHLEX000000000) and reference strain HZ (CP000235.1) are 99.73% (1490/1494) and 99.82% (549/550), respectively. 16S rRNA and groESL gene screenings show that A. phagocytophilum is widely distributed in marmots; the bacterium was more common in marmots found dead (24.59%, 15/61) than in captured marmots (19.21%, 29/151). We found a higher Y. pestis isolation rate in dead marmots harboring A. phagocytophilum than in those without it ( 2  = 4.047, p  < 0.05). Marmot-derived A. phagocytophilum was able to live in L929 cells and BALB/c mice but did not propagate well. Conclusions In this study, A. phagocytophilum was identified for the first time in Marmota himalayana , a predominant Yersinia pestis host. Our results provide initial evidence for M. himalayana being a reservoir for A. phagocytophilum ; moreover, we found with the presence of A. phagocytophilum , marmots may be more vulnerable to plague. Humans are at risk for co-infection with both pathogens by exposure to such marmots.

The boll weevil, Anthonomus grandis Boheman (Coleoptera: Curculionidae), is an invasive alien species that can damage cotton plants and cause huge economic losses in the cotton industry. Currently, A. grandis is mainly distributed in the American continent. However, few studies have indicated the distribution and modification of its suitable global habitats after undergoing climate change. Based on the 339 distribution records of A. grandis and eight bioclimatic variables, we used the optimal MaxEnt model to predict the potential global distribution of A. grandis under the current (1970–2000) and future climatic scenarios (SSP5-8.5). The annual mean temperature (bio1) and isothermality (bio3) were the two most important bioclimatic variables, which indicates that the survival of A. grandis is extremely sensitive to temperature fluctuations. Under the current scenario, the highly suitable habitats were mainly distributed in America (the USA, Mexico, Brazil, Argentina, Paraguay, and Uruguay), Africa (South Africa, Ethiopia, and Mozambique), Asia (Pakistan, India, Thailand, Burma, and China), and Oceania (Australia). In future scenarios (SSP5-8.5), the potential suitable global habitats reached the highest level in America, Africa, Asia, and Oceania in the 2090s. Our study provides a meaningful reference for researchers, quarantine officers, and governments to devise suitable management control strategies for A. grandis.

Objectives To evaluate the performance of large language models (LLMs) in automatically generating whole-organ MRI score (WORMS)-based structured MRI reports and predicting osteoarthritis (OA) severity for the knee. Methods A total of 160 consecutive patients suspected of OA were included. Knee MRI reports were reviewed by three radiologists to establish the WORMS reference standard for 39 key features. GPT-4o and GPT-4o-mini were prompted using in-context knowledge (ICK) and chain-of-thought (COT) to generate WORMS-based structured reports from original reports and to automatically predict the OA severity. Four Orthopedic surgeons reviewed original and LLM-generated reports to conduct pairwise preference and difficulty tests, and their review times were recorded. Results GPT-4o demonstrated perfect performance in extracting the laterality of the knee (accuracy = 100%). GPT-4o outperformed GPT-4o mini in generating WORMS reports (Accuracy: 93.9% vs 76.2%, respectively). GPT-4o achieved higher recall (87.3% s 46.7%, p  < 0.001), while maintaining higher precision compared to GPT-4o mini (94.2% vs 71.2%, p  < 0.001). For predicting OA severity, GPT-4o outperformed GPT-4o mini across all prompt strategies (best accuracy: 98.1% vs 68.7%). Surgeons found it easier to extract information and gave more preference to LLM-generated reports over the original reports (both p  < 0.001) while spending less time on each report (51.27 ± 9.41 vs 87.42 ± 20.26 s, p  < 0.001). Conclusion GPT-4o generated expert multi-feature, WORMS-based reports from original free-text knee MRI reports. GPT-4o with COT achieved high accuracy in categorizing OA severity. Surgeons reported greater preference and higher efficiency when using LLM-generated reports. Critical relevance statement The perfect performance of generating WORMS-based reports and the high efficiency and ease of use suggest that integrating LLMs into clinical workflows could greatly enhance productivity and alleviate the documentation burden faced by clinicians in knee OA. Key Points GPT-4o successfully generated WORMS-based knee MRI reports. GPT-4o with COT prompting achieved impressive accuracy in categorizing knee OA severity. Greater preference and higher efficiency were reported for LLM-generated reports. Graphical Abstract

This study aims to enhance the thermal resistance of asphalt mixture to cool asphalt pavement. Four kinds of asphalt mixtures were prepared by replacing basalt aggregate and limestone mineral powder with shale ceramsite (SC) and fly ash cenosphere (FAC), respectively. A series of experiments, including environment scanning electron microscope test, thermophysical parameter test, indoor irradiation test, shear strength test, and rutting test, were performed to verify the purpose of this study. The results show that using low-density SC and FAC could produce lightweight asphalt mixtures, which had lower thermal conductivity than control asphalt mixture. The indoor irradiation test shows that the resultant asphalt mixtures had lower temperatures at the depth of lower than 4 cm. The addition of SC had a negative effect on the shear strength and dynamic stability of asphalt mixture. However, the two indicators increased due to the addition of FAC. The results presented in this study indicate that it is feasible to use lightweight aggregate to prepare low-thermal-conductivity asphalt mixture and use this kind of asphalt mixture to cool asphalt pavement.

Subretinal fibrosis results in local destruction of retinal structures and permanent vision loss, representing the end stage of neovascular age-related macular degeneration (AMD). Histological examination of fibrotic specimens from AMD patients has uncovered a wide range of cellular and acellular components. However, their origins and roles in fibrosis remain largely unexplored. Using laser-induced photocoagulation model with Collagen 1α1-GFP reporter mice, we demonstrate by cell-lineage tracing that a subset of pericytes associating with choroidal microvasculature are activated upon injury and infiltrate into subretinal space as significant components of fibrotic lesions. In contrast to their choroidal precursors, infiltrating pericytes acquire stellate-like structures, upregulate expression of fibrogenic molecules and colocalize with extracellular fibrotic scar. Collectively, our results identify choroidal perivascular niche as a novel source of subretinal fibrosis after photocoagulation and suggest that collagen 1-expressing pericytes are potential targets for therapeutic intervention to suppress subretinal fibrosis and preserve vision.

Backgrounds Climate change is well-known to alter the structure and function of grassland ecosystems, and multifunctionality contributes to a comprehensive understanding of the impacts of climate change on ecosystem functions. Warming and humidification are predicted to be the climate change trend on the northeastern Qinghai-Tibetan Plateau. However, understanding of how long-term warming and increased precipitation affect ecosystem multifunctionality in alpine meadows is still limited. Methods Here, we conducted an 8-year field experiment involving warming and increased precipitation in an alpine meadow to explore how warming, increased precipitation, and their interaction affect ecosystem multifunctionality. Results The results indicated that increased precipitation had a positive effect on ecosystem multifunctionality. However, warming and the interaction of warming and precipitation had no significant effects on it. Warming decreased species richness and plant coverage. Increased precipitation enhanced aboveground carbon (C), nitrogen (N), and phosphorus (P) pools of plant community, and soil moisture, but decreased soil pH. Aboveground P and N pools of plant community and microbial biomass nitrogen (MBN) were important predictors of ecosystem multifunctionality. Conclusion This study demonstrated long-term increased precipitation can enhance ecosystem multifunctionality by indirectly affecting the individual functions (aboveground P and N pools of plant community and MBN), soil moisture, and pH in an alpine meadow. These findings highlighted that increased precipitation is more critical than warming for enhancing ecosystem multifunctionality in semi-arid alpine meadows.

A lytic Yersinia pestis phage vB_YpP - YepMm (also named YepMm for briefly) was first isolated from the bone marrow of a Marmota himalayana who died of natural causes on the Qinghai-Tibet plateau in China. Based on its morphologic (isometric hexagonal head and short non-contractile conical tail) and genomic features, we classified it as belonging to the Podoviridae family. At the MOI of 10, YepMm reached maximum titers; and the one-step growth curve showed that the incubation period of the phage was about 10 min, the rise phase was about 80 min, and the lysis amount of the phage during the lysis period of 80 min was about 187 PFU/cell. The genome of the bacteriophage YepMm had nucleotide-sequence similarity of 99.99% to that of the Y. pestis bacteriophage Yep-phi characterized previously. Analyses of the biological characters showed that YepMm has a short latent period, strong lysis, and a broader lysis spectrum. It could infect Y. pestis , highly pathogenic bioserotype 1B/O:8 Y. enterocolitica , as well as serotype O:1b Y. pseudotuberculosis —the ancestor of Y. pestis . It could be further developed as an important biocontrol agent in pathogenic Yersinia spp. infection.

• Climate and plant invasion can shape biotic communities at large spatial scales. Yet, how diverse groups of organisms associated with an invasive plant change simultaneously with latitude and the roles of climate and plant invasion remains unclear. • We conducted a field survey of plants (native vs exotic), soil fungi (pathogenic, saprotrophic, arbuscular mycorrhiza fungi (AMF) and ectomycorrhizal (EcM) fungi) and arthropods (herbivores, predators and detritivores) associated with the invasive plant Alternanthera philoxeroides at 49 sites spanning 14 latitudinal degrees in China. • Results showed that diversity and composition of these functional groups changed differently with latitude, partially due to their specific responses to climate, invasion of A. philoxeroides and other biotic environments. Moreover, A. philoxeroides invasion and/or composition of other plants, rather than climate, predicted the diversity and richness of major functional groups and partly explained variance in composition of putative fungal pathogens. • Our results suggest that climate and plant invasion could affect the diversity and composition of diverse groups of organisms simultaneously and their relative importance might vary among functional groups. Thus, it is necessary to explore latitudinal patterns and underlying drivers of diverse groups of organisms simultaneously to improve our ability to predict and mitigate threats posed by plant invasion and climate change.