Prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections.

Osteomyelitis is a devastating disease caused by microbial infection in deep bone tissue. Its high recurrence rate and impaired restoration of bone deficiencies are major challenges in treatment. Microbes have evolved numerous mechanisms to effectively evade host intrinsic and adaptive immune attacks to persistently localize in the host, such as drug-resistant bacteria, biofilms, persister cells, intracellular bacteria, and small colony variants (SCVs). Moreover, microbial-mediated dysregulation of the bone immune microenvironment impedes the bone regeneration process, leading to impaired bone defect repair. Despite advances in surgical strategies and drug applications for the treatment of bone infections within the last decade, challenges remain in clinical management. The development and application of tissue engineering materials have provided new strategies for the treatment of bone infections, but a comprehensive review of their research progress is lacking. This review discusses the critical pathogenic mechanisms of microbes in the skeletal system and their immunomodulatory effects on bone regeneration, and highlights the prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections. It will inform the development and translation of antimicrobial and bone repair tissue engineering materials for the management of bone infections.

Sources and fate of omega-3 polyunsaturated fatty acids in a highly eutrophic lake.

Omega-3 polyunsaturated fatty acids (ω3-PUFA) are central to the growth and reproduction of aquatic consumers. Dissolved nutrients in aquatic ecosystems strongly affect algal taxonomic composition and thus the production and transfer of specific ω3-PUFA to consumers at higher trophic levels. However, most studies were conducted in nutrient-poor, oligotrophic lakes, leading to an insufficient understanding of how water nutrients affect algal ω3-PUFA and their trophic transfer in consumers in highly eutrophic lakes. We conducted a field investigation in a highly eutrophic lake and collected basal food sources (phytoplankton, periphyton and macrophytes) and aquatic consumers (invertebrates, zooplankton and fish), and measured their fatty acid (FA) composition. Our results showed that periphyton and phytoplankton were both important sources of ω3-PUFA supporting the highly eutrophic lake food web. High water nutrient levels led to low ω3-PUFA levels in phytoplankton and periphyton, resulting in decreased nutritional quality. Consequently, ω3-PUFA of invertebrates and zooplankton reflected variations in ω3-PUFA of phytoplankton and periphyton, respectively. The ω3-PUFA levels of fish decreased as phytoplankton and periphyton ω3-PUFA decreased. Among fish, the Redfin Culter (Cultrichthys erythropterus) and Bar Cheek Goby (Rhinogobius giurinus) exhibited significantly higher levels of EPA and DHA compared to the Pond Loach (Misgurnus anguillicaudatus), which may have been caused by their different feeding modes. Decreases in the ω3-PUFA levels of basal food sources may be one of the causes leading to the reduction of trophic links in aquatic food webs. Our study elucidated the sources and fate of ω3-PUFA in highly eutrophic lakes, complemented previous studies in oligo- and mesotrophic lakes, and emphasized the role of high-quality food sources. Our results offer new perspectives for the conservation and management of highly eutrophic lake ecosystems.

Diagnostic and Predictive Efficacy of Synovial Fluid Versus Serum C-Reactive Protein Levels for Periprosthetic Joint Infection and Reimplantation Success.

BACKGROUND: A 2-stage exchange revision for periprosthetic joint infection (PJI) is associated with major risks for reinfection. Although serum markers are frequently used for diagnosis, their effectiveness remains debatable. Synovial fluid markers may offer a more accurate diagnosis of PJI; however, the importance of these biomarkers, notably synovial fluid C-reactive protein (syCRP), remains controversial, particularly in the context of reimplantation. The present study aimed to clarify these diagnostic uncertainties by evaluating the diagnostic efficacy of syCRP versus serum CRP (seCRP) levels in the context of PJI and recurring or persisting infections before reimplantation. METHODS: A total of 186 patients were enrolled and divided into 2 groups: aseptic revision (n = 112) and PJI revision (n = 74). Of the PJI group, 65 were categorized as success and 9 as failure, based on the presence of recurrent or persistent infection before reimplantation. The syCRP and seCRP levels and their changes were assessed preoperatively and in the first-stage and second-stage revisions. Additionally, receiver operating characteristic (ROC) curves and area under the ROC curves (AUCs) were analyzed. RESULTS: Both seCRP and syCRP levels were significantly elevated in the PJI group compared with the aseptic group (P < .001). The ROC curve analysis highlighted the enhanced diagnostic accuracy of syCRP for PJI, with an AUC of 0.93 versus 0.80 for seCRP. Furthermore, syCRP proved to be more reliable in predicting reimplantation success, exhibiting an AUC of 0.86 versus 0.63 for seCRP. In evaluating trends in CRP levels to determine reimplantation timing, changes in syCRP levels demonstrated superior diagnostic utility, exhibiting an AUC of 0.79 versus 0.63 for changes in seCRP levels. CONCLUSIONS: In assessing PJI and infections before reimplantation, syCRP may offer enhanced accuracy compared with seCRP. Nevertheless, variations in both syCRP and seCRP levels did not consistently predict the outcome of reimplantation.

Increasing water nutrient reduces the availability of high-quality food resources for aquatic consumers and consequently simplifies river food webs.

While eutrophication has led to serious habitat degradation and biotic shifts in freshwater ecosystems, most current studies have focused on changes in community assemblages, with few considering the effect of eutrophication on food webs. We conducted a field study in subtropical headwater streams with a gradient of water nutrient levels to examine the effect of increasing water nutrients on food webs by using the long-chain polyunsaturated fatty acid eicosapentaenoic acid (EPA) as a measure of the nutritional quality of food. Basal food resources (macrophytes, submerged leaf litter, and periphyton), and aquatic consumers (macroinvertebrates and fish) were collected, and their fatty acid (FA) profiles were analyzed. Our results showed that periphyton was the dominant source of EPA for macroinvertebrates and fish, and a high-quality resource for consumers. As water nutrient concentrations increased, nutritional quality of periphyton significantly decreased and, in turn, the correlation between FA profiles of periphyton and macroinvertebrates declined. However, periphyton FA profiles did not account for the variability of fish FA, which may be induced by the increasing proportions of omnivorous fish in eutrophic streams that derived EPA from other sources. Further, the reduced periphyton EPA was associated with decreased trophic links and simplified stream food webs. Our study highlights the importance of high-quality food resources for aquatic food webs as water nutrients increased in stream ecosystems and provides a nutritional perspective to understand the mechanisms how eutrophication affects aquatic ecosystems.

CPD-002, a novel VEGFR2 inhibitor, relieves rheumatoid arthritis by reducing angiogenesis through the suppression of the VEGFR2/PI3K/AKT signaling pathway.

Synovial angiogenesis is a key player in the development of rheumatoid arthritis (RA), and anti-angiogenic therapy is considered a promising approach for treating RA. CPD-002 has demonstrated efficacy in suppressing tumor angiogenesis as a VEGFR2 inhibitor, but its specific impacts on RA synovial angiogenesis and possible anti-RA effects need further study. We examined the influences of CPD-002 on the migration and invasion of human umbilical vein endothelial cells (HUVECs) and its impacts on HUVECs' tube formation and vessel sprouting ex vivo. The therapeutic potential of CPD-002 in adjuvant-induced arthritis (AIA) rats and its suppression of synovial angiogenesis were examined. The involvement of the VEGFR2/PI3K/AKT pathway was assessed both in HUVECs and AIA rat synovium. Here, CPD-002 inhibited the migration and invasion of VEGF-stimulated HUVECs, decreased their chemotactic response to RA fibroblast-like synoviocyte-released chemoattractants, and exhibited anti-angiogenic effects in vitro and ex vivo. CPD-002's targeting of VEGFR2 was confirmed with molecular docking and cellular thermal shift assays, supported by the abolishment of CPD-002's effects upon using VEGFR2 siRNA. CPD-002 relieved paw swelling, arthritis index, joint damage, and synovial angiogenesis, indicating its anti-arthritic and anti-angiogenic effects in AIA rats. Moreover, the anti-inflammatory effects in vivo and in vitro of CPD-002 contributed to its anti-angiogenic effects. Mechanistically, CPD-002 hindered the activation of VEGFR2/PI3K/AKT pathway in VEGF-induced HUVECs and AIA rat synovium, as evidenced by reduced p-VEGFR2, p-PI3K, and p-AKT protein levels alongside elevated PTEN protein levels. Totally, CPD-002 showed anti-rheumatoid effects via attenuating angiogenesis through the inhibition of the VEGFR2/PI3K/AKT pathway.

How do small dams alter river food webs? A food quality perspective along the aquatic food web continuum.

Damming of rivers poses a significant threat to freshwater ecosystems. Previous studies about the impact of damming on river ecosystems have mostly focused on large dams, with the impact of small dams largely unknown. Further, while the impacts of dams on aquatic communities have been widely studied, the effect on energy flow across river food webs remains unclear. In recent years, long-chain polyunsaturated fatty acid analysis (LC-PUFA) has emerged as a promising technique for assessing food quality and trophic interactions. In this study, LC-PUFA was applied to explore the nutritional effects of small dams on river food webs. A field investigation was conducted at upstream and downstream areas of three small dams in the headwaters of Dongjiang River, China, to evaluate the impact of small dams on the nutritional quality of basal food sources, and their consequent impacts on aquatic consumers and trophic links. Basal food sources (i.e., submerged leaves, macrophytes and periphyton) and aquatic consumers (i.e., macroinvertebrates and fish) were collected, and their fatty acid (FA) composition was measured. Our results showed that periphyton, rather than submerged leaves and macrophytes, was the primary high-quality food source for aquatic consumers, providing them with LC-PUFA, irrespective of whether sites were upstream or downstream. Damming the streams induced changes in aqueous nutrient concentrations (TP, PO4-P, DIN, and TN) from upstream to downstream of the dams, leading to significant variation in periphyton FA content. Compared with periphyton collected at downstream sites, periphyton at upstream sites contained higher LC-PUFA, but lower short-chain PUFA. Differences in periphyton LC-PUFA between the upstream and downstream areas of dams were reflected in the FA profiles of invertebrate grazers and filterers, and further transferred to fish. Furthermore, decreased periphyton nutritional quality at the downstream of the dams was one of the reasons for the simplification of stream food webs. Our results indicated that small dams negatively affected food webs, emphasizing the importance of high-quality food sources for stream ecosystems. We suggest that the trophic integrity of river food webs hinges on the dietary availability of periphyton supplying physiologically highly required nutrients for consumers and must thus not be compromised by damming of streams or other alterations.

The importance of omega-3 polyunsaturated fatty acids as high-quality food in freshwater ecosystems with implications of global change.

Traditionally, trophic ecology research on aquatic ecosystems has focused more on the quantity of dietary energy flow within food webs rather than food quality and its effects on organisms at various trophic levels. Recent studies emphasize that food quality is central to consumer growth and reproduction, and the importance of food quality for aquatic ecosystems has become increasingly well recognized. It is timely to synthesise these findings and identify potential future research directions. We conducted a systematic review of omega-3 polyunsaturated fatty acids (ω3-PUFAs) as a crucial component of high-quality food sources in freshwater ecosystems to evaluate their impact on a variety of consumers, and explore the effects of global change on these high-quality food sources and their transfer to higher trophic consumers within and across ecosystems. In freshwater ecosystems, algae rich in ω3 long-chain PUFAs, such as diatoms, dinoflagellates and cryptophytes, represent important high-quality food sources for consumers, whereas cyanobacteria, green algae, terrestrial vascular plants and macrophytes low in ω3 long-chain PUFAs are low-quality food sources. High-quality ω3-PUFA-containing food sources usually lead to increased growth and reproduction of aquatic consumers, e.g. benthic invertebrates, zooplankton and fish, and also provide ω3 long-chain PUFAs to riparian terrestrial consumers via emergent aquatic insects. Consumers feeding on high-quality ω3-PUFA-containing foods in turn represent high-quality food for their own predators. However, the ω3-PUFA content of food sources is sensitive to global environmental changes. Warming, eutrophication, increased light intensity (e.g. from loss of riparian shading), and pollutants potentially inhibit the synthesis of algal ω3-PUFAs while at the same time promoting the growth of lower-quality foods, such as cyanobacteria and green algae. These factors combined could lead to a significant reduction in the availability of ω3-PUFAs for consumers and constrain their overall fitness. Although the effect of individual environmental factors on high-quality ω3-PUFA-containing food sources has been investigated, multiple environmental factors (e.g. climate change, human activities, pollution) will act in combination and any synergistic effects on aquatic food webs remain unclear. Identifying the sources and fate of ω3-PUFAs within and across ecosystems could represent an important approach to understand the impact of multiple environmental factors on trophic relationships and the implications for populations of freshwater and riparian consumers. Maintaining the availability of high-quality ω3-PUFA-containing food sources may also be key to mitigating freshwater biodiversity loss due to global change.

Metal-injection and interface density engineering induced nickel diselenide with rapid kinetics for high-energy sodium storage.

The key to the innovation of sodium-ion batteries (SIBs) is to find efficient sodium-storage electrode. Here, metal Mo doping of NiSe2 is proposed by modified electrospinning strategy followed by in situ conversion process. The Mo-NiSe2 anchoring on hollow carbon nanofibers (HCNFs) would make full use of the multi-channel HCNFs in the inner layer and the active sites of Mo-NiSe2 in the outer layer, which plays an important role in buffering the volume stress of Na+ (de)insertion and reducing the adsorption energy barrier of Na+. Innovatively, it is proposed to jointly regulate the SIBs performance of NiSe2 by both metal atom doping and interface effects, thereby adjusting the sodium ion adsorption barrier of NiSe2. The Mo-NiSe2@HCNFs exhibits remarkable performance in SIBs, demonstrating a high specific capacity of 396 mAh/g after 100 cycles at 1 A/g. Moreover, it maintains outstanding cycling stability, retaining 77.6 % of its capacity (211 mAh/g) even after 1000 cycles at 10 A/g. This comprehensive electrochemical performances are due to the structural stability and outstanding electronic conductance of the Mo-NiSe2@HCNFs, as evidenced by the diffusion analysis and ex situ charge-discharge process characterization. Furthermore, coupled with the Na3V2(PO4)2O2F cathodes, the full cell also achieves a high energy density of 123 Wh kg-1. The theoretical calculation of the hypervalent Mo doing further proves the benefit of its Na+ adsorption and denser conduction band distribution. This study provides a reference for the construction of transition metal selenide via doping and interface engineering in sodium storage.

Environmental DNA and remote sensing datasets reveal the spatial distribution of aquatic insects in a disturbed subtropical river system.

Biodiversity datasets with high spatial resolution are critical prerequisites for river protection and management decision-making. However, traditional morphological biomonitoring is inefficient and only provides several site estimates, and there is an urgent need for new approaches to predict biodiversity on fine spatial scales throughout the entire river systems. Here, we combined the environmental DNA (eDNA) and remote sensing (RS) technologies to develop a novel approach for predicting the spatial distribution of aquatic insects with high spatial resolution in a disturbed subtropical Dongjiang River system of southeast China. First, we screened thirteen RS-based vegetation indices that significantly correlated with the eDNA-inferred richness of aquatic insects. In particular, the green normalized difference vegetation index (GNDVI) and normalized difference red-edge2 (NDRE2) were closely related to eDNA-inferred richness. Second, using the gradient boosting decision tree, our data showed that the spatial pattern of eDNA-inferred richness could achieve a high spatial resolution to 500 m reach and accurate prediction of more than 80%, and the prediction efficiency of the headwater streams (Strahler stream order = 1) was slightly higher than the downstream (Strahler stream order >1). Third, using the random forest algorithm, the spatial distribution of aquatic insects could reach a prediction rate of over 70% for the presence or absence of specific genera. Overall, this study provides a new approach to achieving high spatial resolution prediction of the distribution of aquatic insects, which supports decision-making on river diversity protection under climate changes and human impacts.

A Vehicle Simulation Study Examining the Effects of System Interface Design Elements on Performance in Different Vibration Environments Below 3 Hz.

OBJECTIVE: This study aimed to explore the relationship between system interface elements' design features and interaction performance in simulated vehicle vibration environments. BACKGROUND: Touch screens have been widely used in vehicle information systems, but few studies have focused on the decline of touchscreen interaction performance and task load increase when driving on unpaved roads. METHOD: The interaction performance (reaction time and task accuracy rate) with vibration frequencies below 3 Hz (1.5, 2.0, and 2.5 Hz) and different interface design elements was investigated employing a touch screen computer and E-prime software. RESULTS: The results indicate that vehicle vibration (below 3 Hz) can significantly reduce interaction performance with a vehicle information system interface. CONCLUSION: An appropriate increase in the physical size of the interface design features (visual stimulus materials and touch buttons) can help to mitigate this negative effect of vibration. APPLICATION: The results and findings of this study can be utilized for the design of information system interfaces as it relates to the vibration scenario of unpaved roads.

Fishing eDNA in One of the World's Largest Rivers: A Case Study of Cross-Sectional and Depth Profile Sampling in the Yangtze.

The world's largest rivers are home to diverse, endemic, and threatened fish species. However, their sheer sizes make large-scale biomonitoring challenging. While environmental DNA (eDNA) metabarcoding has become an established monitoring approach in smaller freshwater ecosystems, its suitability for large rivers may be challenged by the sheer extent of their cross sections (>1 km wide and tens of meters deep). Here, we sampled fish eDNA from multiple vertical layers and horizontal locations from two cross sections of the lower reach of the Yangtze River in China. Over half of the ASVs (amplicon sequence variants) were detected in only a single combination of the vertical layers and horizontal locations, with ∼7% across all combinations. We estimated the need to sample >100 L of water across the cross-sectional profiles to achieve ASV richness saturation, which translates to ∼60 L of water at the species level. No consistent pattern emerged for prioritizing certain depth and horizontal samples, yet we underline the importance of sampling and integrating different layers and locations simultaneously. Our study highlights the significance of spatially stratified sampling and sampling volumes when using eDNA approaches. Specifically, we developed and tested a scalable and broadly applicable strategy that advances the monitoring and conservation of large rivers.

Assessment of the impact of dams on aquatic food webs using stable isotopes: Current progress and future challenges.

Dams have disrupted natural river systems worldwide and although population and community level effects on aquatic biota have been well documented, food web responses remain poorly understood and difficult to characterize. The application of stable isotope analysis (SIA) provides a means to assess the effect of dams on food webs. Here we review the effect of dams on aquatic food webs using SIA, aiming to detect knowledge gaps in the field of dam impacts on aquatic food webs and propose a conceptual framework to help formulate hypotheses about dam impacts on food webs guided by food web theory. Dams can affect aquatic food webs via two pathways: a bottom-up pathway with altered basal food sources and their transfer to consumers through changes in flow, nutrients, temperature and sediment, and a top-down pathway with consumer species composition altered mainly through habitat fragmentation and related physiochemical changes. Taking these mechanisms into consideration, the impact of dams on food web attributes derived from SIA was evaluated. These studies generally apply mixing models to determine how dams alter the dominant carbon sources supporting food webs, use δ15N to examine how dams alter food-chain length, or use Layman metrics of isotope variability to assess niche changes for invertebrate and fish assemblages. Most studies compare the patterns of SIA metrics spatially (e.g. upstream vs reservoir vs downstream of dams; regulated vs unregulated rivers) and temporally (before vs after dam construction), without explicit hypotheses and/or links to theoretical concepts of food webs. We propose several steps to make SIA studies of dam impacts more rigorous and enhance their potential for producing novel insights. Future studies should quantify the shape and strength of the effect of dams on SIA-measured food web response, be conducted at larger temporal and spatial scales (particularly along the river longitudinal continuum and the lateral connected ecosystems (e.g., floodplains)), and consider effects of dams on food web resilience and tipping points.

A novel telomere-related gene prognostic signature for survival and drug treatment efficiency prediction in lung adenocarcinoma.

OBJECTIVE: Telomere-related genes (TRGs) play a critical role in various types of tumors. However, there is a lack of comprehensive exploration of their relevance in lung cancer. This research aimed to verify the relationship between TRGs gene expression and the prognosis of patients with lung adenocarcinoma (LUAD), as well as the prediction of drug treatment efficiency. METHODS: A total of 2093 TRGs were acquired from TelNet. The clinical information including age, tumor stage, follow up and outcome (death/survival) and TRGs expression profile of LUAD were obtained from the patients in The Cancer Genome Atlas (TCGA) database and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. The two databases were used to construct and verify a prognostic model based on the expression of hubTRGs. The tumor mutation burden, immune infiltration and subtypes, as well as IC50 prediction of multiple targeted drugs were also evaluated in TRGs-divided risk groups. RESULTS: A total of 335 TRGs were significantly differentially expressed in LUAD as compared with normal control. Among them, 9 TRGs (ABCC2, ABCC8, ALDH2, FOXP3, GNMT, JSRP1, MACF1, PLCD3, SULT4A1) were finally identified as hubGenes and used to construct a TRG risk score. The TRG risk score showed favorable performance in constructing a prognostic nomogram in predicting survival of LUAD, and the ROC curves at 1, 3 and 5 years were plotted and the AUROC values were 0.743, 0.754 and 0.735, respectively. Higher TRGs risk score correlated with worse immune subtypes and higher tumor mutation burden in LUAD tissues. In addition, the patients in TRG high risk group harbored a lower TIDE score which indicated potentially better response to immunotherapy. CONCLUSION: This study proposed a broad molecular signature of telomere-related genes that can be used in further functional and therapeutic investigations, and also represents an integrated modality for characterizing critical molecules when exploring novel targets for lung cancer immunotherapy.

eDNA-based diversity and multitrophic network reveal the effects of land use and pollutants on the subtropical Dongjiang River systems.

Biodiversity and its constituted multitrophic network in rivers are accelerating change under human land use and pollutants. However, due to the lack of complete datasets across taxa limited by traditional morphological biomonitoring, the change patterns of biodiversity and multitrophic networks are still unclear. Here, we used the eDNA approach to capture multitrophic communities (including fish, aquatic insects, protozoa, diatom and bacteria) in the Dongjiang River, a typical subtropical river in southeast China, and analyzed the changing patterns of biodiversity and multitrophic networks in relation to land use and water pollution. First, our data showed that the eDNA approach provided a snapshot of the multitrophic communities in the Dongjiang River, and the monitored 5833 OTUs were annotated to 55 phyla, 144 classes, 329 orders, 521 families, 945 genera and 406 species. Second, the multitrophic diversity index had similar patterns on the longitudinal scale of rivers, with significant decreases from the upstream to the downstream, while individual taxonomic groups exhibited variable spatial patterns. While there were similar spatial patterns between network metrics and diversity index, the former had stronger relationships with the spatial distance. Third, the multitrophic diversity and networks were significantly negatively correlated with land use and water pollution (e.g., CODMn), and network structures often had stronger and non-linear responses. Overall, this study highlights that eDNA biomonitoring of multitrophic communities and networks can provide deeper insights into ecosystem changes and help develop more targeted management strategies.

A multi-GPU and CUDA-aware MPI-based spectral element formulation for ultrasonic wave propagation in solid media.

In this paper, we introduce a new multi-GPU-based spectral element (SE) formulation for simulating ultrasonic wave propagation in solids. To maximize communication efficiency, we purposely developed, based on CUDA-aware MPI, two novel message exchange strategies which allow the common nodal forces of different subdomains to be shared between different GPUs in a direct manner, as opposed to via CPU hosts, during central difference-based time integration steps. The new multi-GPU and CUDA-aware MPI-based formulation is benchmarked against a multi-CPU core and classical MPI-based counterpart, demonstrating a remarkable acceleration in each and every stage of the computation of ultrasonic wave propagation, namely matrix assembly, time integration and message exchange. More importantly, both the computational efficiency and the degree-of-freedom limit of the new formulation are actually scalable with the number of GPUs used, potentially allowing larger structures to be computed and higher computational speeds to be realized. Finally, the new formulation was used to simulate the interaction between Lamb waves and randomly shaped thickness loss defects on plates, showing its potential to become an efficient, accurate and robust technique for addressing the propagation of ultrasonic waves in realistic engineering structures.

Destabilizing Effects of Environmental Stressors on Aquatic Communities and Interaction Networks across a Major River Basin.

Human-driven environmental stressors are increasingly threatening species survival and diversity of river systems worldwide. However, it remains unclear how the stressors affect the stability changes across aquatic multiple communities. Here, we used environmental DNA (eDNA) data sets from a human-dominated river in China over 3 years and analyzed the stability changes in multiple communities under persistent anthropogenic stressors, including land use and pollutants. First, we found that persistent stressors significantly reduced multifaceted species diversity (e.g., species richness, Shannon's diversity, and Simpson's diversity) and species stability but increased species synchrony across multiple communities. Second, the structures of interaction networks inferred from an empirical meta-food web were significantly changed under persistent stressors, for example, resulting in decreased network modularity and negative/positive cohesion. Third, piecewise structural equation modeling proved that the persistent stress-induced decline in the stability of multiple communities mainly depended upon diversity-mediated pathways rather than the direct effects of stress per se; specifically, the increase of species synchrony and the decline of interaction network modularity were the main biotic drivers of stability variation. Overall, our study highlights the destabilizing effects of persistent stressors on multiple communities as well as the mechanistic dependencies, mainly through reducing species diversity, increasing species synchrony, and changing interaction networks.

Discovery of highly potent and selective VEGFR2 kinase inhibitors for the treatment of rheumatoid arthritis.

Synovial angiogenesis is essential for the development of rheumatoid arthritis (RA). Human vascular endothelial growth factor receptor 2 tyrosine kinase (VEGFR2) is a direct target gene that is notably elevated in RA synovium. Herein, we report the identification of indazole derivatives as a novel class of potent VEGFR2 inhibitors. The most potent compound, compound 25, displayed single-digit nanomolar potency against VEGFR2 in biochemical assays and achieved good selectivity for other protein kinases in the kinome. In addition, compound 25 dose-dependently inhibited the phosphorylation of VEGFR2 in Human Umbilical Vein Endothelial Cells (HUVECs) and showed an anti-angiogenic effect, as evidenced by the inhibition of capillary-like tube formation in vitro. Moreover, compound 25 reduced the severity and development of adjuvant-induced arthritis in rats by inhibiting synovial VEGFR2 phosphorylation and angiogenesis. Overall, these findings provide evidence that compound 25 is a leading potential drug candidate for anti-arthritic and anti-angiogenic therapy.

[Spatial and Temporal Heterogeneity and Ecological Health Evaluation of Diatom Community Based on eDNA].

In recent years, environmental DNA (eDNA) has been widely used in aquatic biodiversity monitoring, and how to establish a river ecological health assessment method based on eDNA has become a hot topic. This study was intended to develop a molecular diatom index based on eDNA to indicate the ecological health status of rivers under the influence of human activities. Firstly, the diatom community composition and structural changes in the Shaying River basin in spring and autumn were monitored through eDNA, and the driving environmental factors of the diatom community were diagnosed. Further, four strategies (OTU-taxonomy, OTU-free, ASV-taxonomy, and ASV-free) based on eDNA metabarcoding data were compared, and a molecular diatom index suitable for ecological health assessment in the Shaying River basin was constructed. The results showed that: ① there were seasonal differences in diatom community structure, and Discostella pseudostelligera, Nitzschia amphibia, Diatoma vulgaris, and other groups were the main factors to distinguish the seasonal differences. ② Mn, Fe, and TN were the main environmental factors affecting diatom community structure in spring, whereas COD and Cu were the main environmental factors affecting diatom community structure in autumn. ③ Among the four strategies, the diatom index calculated based on OTU-free data better reflected the environmental gradient change; the diatom index showed that the ecological health status of the Shaying River Basin was better in autumn than that in spring in time and better in the upstream than that in the downstream in space. In conclusion, this study monitored diatom community in Shaying River in spring and autumn through eDNA and constructed the molecular diatom index in the Shaying River basin, which promoted the application of eDNA to evaluate river ecological health.

Environmental DNA metabarcoding reveals the impact of different land use on multitrophic biodiversity in riverine systems.

Human-induced changes in land use drive an alarming decline in river biodiversity and related ecosystem services worldwide. However, how different land use shapes aquatic multitrophic communities is still not well understood. Here, we used the biodiversity dataset from bacteria to fish captured by the environmental DNA (eDNA) approach in the four riverine systems with spatially different land use (i.e., Slightly disturbed group, Upstream disturbed group, Downstream disturbed group, and Strongly disturbed group) to reveal the changes in multitrophic biodiversity in relation to human land use. Firstly, our data showed that spatially different land use determined the pollutant loads of the riverine systems, most pollutants (e.g., TN and NH3-N) had significant differences among the four riverine systems. Secondly, taxonomic α diversity across multitrophic levels did not necessarily change significantly, yet the change in community structure can be considered as a more sensitive indicator to reflect different land use, because different land use shaped the unique structure of multitrophic communities, and the dissimilarity of community structure was closely associated with land use gradient (e.g., positive relationships in the Slightly disturbed group, negative relationships in the Strongly disturbed group). Thirdly, different land use induced the shifts of key taxa, resulting in the variation of community structure and the change of co-occurrence network. Overall, these findings suggest that spatially different land use plays a critical role in shaping aquatic multitrophic communities, and an in-depth understanding of the interdependences between biodiversity and land use is a critical prerequisite for formulating river management strategies.

Environmental DNA Biomonitoring Reveals the Interactive Effects of Dams and Nutrient Enrichment on Aquatic Multitrophic Communities.

Dam construction and nutrient enrichment are two pervasive stressors in rivers worldwide, which trigger a sharp decline in biodiversity and ecosystem services. However, the interactive effects of both stressors on multitrophic taxonomic groups remain largely unclear. Here, we used the multitrophic datasets captured by the environmental DNA (eDNA) approach to reveal the interactions between dams and nutrient enrichment on aquatic communities from the aspects of taxonomic α diversity, ß diversity, and food webs. First, our data showed that dams and nutrient enrichment jointly shaped a unique spatial pattern of aquatic communities across the four river systems, and the dissimilarity of community structure significantly declined (i.e., structural homogenization) under both stressors. Second, dams and nutrients together explained 40-50% of the variations in aquatic communities, and dams had a stronger impact on fish, aquatic insects, and bacteria, yet nutrients had a stronger power to drive protozoa, fungi, and eukaryotic algae. Finally, we found that additive, synergistic, and antagonistic interactions of dams and nutrient enrichment were common and coexisted in river systems and led to significantly simplified aquatic food webs, with decreases in modularity (synergistic) and robustness (additive) and an increase in coherence (synergistic). Overall, our study highlights that eDNA-based datasets can provide multitrophic perspectives for fostering the understanding of the interactive effects of multiple stressors on rivers.