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Abstract Ionic conductive hydrogels (ICHs) prepared from natural bioresources are promising candidates for constructing flexible electronics for both commercialization and environmental sustainability due to their intrinsic characteristics. However, simultaneous realization of high stiffness, toughness, conductivity, and multifunctionality while ensuring processing simplicity is extremely challenging. Here, a poly(ionic liquid) (PIL)‐macromolecule functionalization strategy within a NaOH/urea system is proposed to construct high‐performance and versatile polysaccharide‐based ICHs (e.g., cellulosic ICHs). In this strategy, the elaborately designed “soft” (PIL chains) and “hard” (cellulose backbone) structures as well as the dynamic covalent and noncovalent bonds of the cross‐linked networks endow the hydrogel with high mechanical strength (9.46 ± 0.23 MPa compressive modulus), exceptional stretchability (214.3%), and toughness (3.64 ± 0.12 MJ m−3). Ingeniously, due to the inherent conductivity, design flexibility, and functional compatibility of the PILs, the hydrogels exhibit high conductivity (6.54 ± 0.17 mS cm−1), self‐healing ability (94.5% ± 2.0% efficiency), antibacterial properties, freezing resistance, water retention, and recyclability. Interestingly, this strategy is extended to fabricate diverse hydrogels from various polysaccharides, including agar, alginate, hyaluronic acid, and guar gum. In addition, multimodal sensing (strain, temperature, and humidity) is realized based on the stimulus‐responsive characteristics of the hydrogels. This strategy opens new perspectives for the design of biomass‐based hydrogels and beyond.

Paediatric Mycoplasma pneumoniae pneumonia (MPP) is a heterogeneous disease with a diverse spectrum of clinical phenotypes. No studies have demonstrated the relationship between underlying endotypes and clinical phenotypes as well as prognosis about this disease. Thus, we conducted a multicentre prospective longitudinal study on children hospitalized for MPP between June 2021 and March 2023, with the end of follow-up in August 2023. Blood samples were collected and processed at multiple time points. Multiplex cytokine assay was performed to characterize serum cytokine profiles and their dynamic changes after admission. Cluster analysis based on different clinical phenotypes was conducted. Among the included 196 patients, the levels of serum IL-17A and IL-6 showed remarkable variabilities. Four cytokine clusters based on the two cytokines and four clinical groups were identified. Significant elevation of IL-17A mainly correlated with diffuse bronchiolitis and lobar lesion by airway mucus hypersecretions, while that of IL-6 was largely associated with lobar lesion which later developed into lung necrosis. Besides, glucocorticoid therapy failed to inhibit IL-17A, and markedly elevated IL-17A and IL-6 levels may correlate with lower airway obliterans. Our study provides critical relationship between molecular signatures (endotypes) and clustered clinical phenotypes in paediatric patients with MPP.

IntroductionThe objective of this study was to assess the clinical characteristics and biometric parameters, as measured by the IOLMaster, of patients suffering from acute secondary angle closure due to zonular dialysis (ASAC-ZD) who were misdiagnosed with acute primary angle closure (APAC).MethodsIn this retrospective study, 34 ASAC-ZD and 39 APAC eyes were examined. Sex, age, best-corrected visual acuity, axial length (AL), anterior chamber depth (ACD), anterior chamber depth standard deviation (ACDSD), lens thickness (LT), and lens thickness standard deviation (LTSD) were measured using the IOLMaster and compared between the two groups. In addition, the difference in ACD (ACD difference) between the affected eye and the contralateral eye was analyzed. Logistic regression analysis was performed to determine the predictive factors of lens subluxation. To determine the appropriate cutoff values for biometric parameters, ROC curves were constructed to distinguish between ASAC-ZD, APAC, and cataracts.ResultsCompared to the APAC group, the ASAC-ZD group was younger (69.92 ± 9.345, 63.74 ± 6.947), had longer AL (22.39 ± 0.7852, 23.23 ± 1.168), shallower ACD (2.120 ± 0.2986, 1.889 ± 0.5167), higher ACDSD (7.605 ± 5.425, 9.941 ± 6.120), higher LTSD (28.00 ± 19.52, 39.79 ± 22.74), and larger ACD differences (−0.1249 ± 0.2349, −0.7306 ± 0.5332) in the affected eye. Younger age, longer AL, lower ACD, higher LTSD, and higher ACD differences were associated with lens subluxation in the univariate logistic regression analysis. ACD difference (p = 0.0003), age (p = 0.0024), and ACD (p = 0.0491) were significantly associated with lens subluxation in the multivariable logistic regression analysis. Furthermore, the ROC curve analysis showed that the cutoff values for lens subluxation were a difference in ACD of 0.225 mm and 1.930 mm.ConclusionAsymmetric ACD in both eyes with normal AL and increasing ACDSD and LTSD may support the clinical diagnosis of lens subluxation.

With the intensification of climate warming, drought has become increasingly severe. Drought seriously impacts tree growth and may even result in tree mortality. However, our understanding of how the hydraulic structure of xylem in different tree species regulates growth and drought resistance remains incomplete. Here, we collected tree-ring samples from three semi-arid natural Chinese pine (Pinus tabuliformis)-broadleaf mixed forests in northern China. We selected Chinese pine (non-porous wood), white birch (Betula platyphylla, diffuse-porous wood), and Liaodong oak (Quercus liaotungensis, ring-porous wood) as target tree species. Using dendrochronology and wood anatomy methods, we evaluated interspecies differences in tree growth, climate sensitivity, and drought resistance, and analyzed the relationships between tree growth, drought resistance, and theoretical xylem-specific hydraulic conductivity (Ks). Our findings revealed distinct differences in the hydraulic structure of xylem among these three tree species as well as their resilience to drought. Liaodong oak exhibited less sensitive to drought compared to Chinese pine and white birch. Meanwhile both Chinese pine and Liaodong oak demonstrated greater resistance to drought than white birch. The positive correlation between specific xylem hydraulic conductivity and both tree growth and drought resistance were observed for Chinese pine, but Liaodong oak was the opposite. This suggested that specific hydraulic conductivity of xylem cannot serve as a consistent or robust predictor of tree growth or drought resistance across different species. As climate warming intensifies, it is anticipated that white birch may experience severe and significant irreversible decline in growth, while Liaodong oak may exhibit the highest potential growth performance. Given the projected intensification of future warming trends along with more frequent extreme climate events, safeguarding biodiversity and productivity within semi-arid Chinese pine-broadleaf mixed forests may hinge on the prioritizing protection efforts for Chinese pine.

This study explores the impact of government subsidies on the production dynamics within the medical product supply chain, particularly focusing on the remanufacturing of medical goods. Amidst the backdrop of the COVID-19 pandemic, which has underscored the critical shortages in medical supplies, our research delves into the adoption of remanufacturing practices by medical product manufacturers as a strategic response to these shortages and environmental concerns. We investigate how government subsidies influence the production volumes of original manufacturers and remanufacturers and examine the competitive interplay between newly manufactured and remanufactured medical products. Through the development of three production game models—Scenario B (manufacturers produce both new and refurbished products), Scenario N (separate production of new and refurbished products by manufacturers and remanufacturers, respectively), and Scenario C (similar to Scenario N but includes a certification fee paid by remanufacturers to original manufacturers)—we analyze the strategies that could mitigate supply deficiencies during medical crises. Our findings indicate that the certification strategy (Scenario C) not only yields the highest total production of medical products but also offers a viable solution to enhance the sustainability of the entire medical production system by alleviating supply chain disruptions. Furthermore, we discuss the managerial implications of our results, emphasizing the potential of a joint remanufacturing strategy to stabilize the supply chain and foster environmental conservation. Lastly, we highlight our study's limitations and suggest future research directions, particularly concerning the variability in product quality and the reliance on government subsidies. This research contributes to a nuanced understanding of green remanufacturing within the pharmaceutical supply chain, offering insights for manufacturers, remanufacturers, and policymakers aiming for sustainable industry practices.

Temperature and dissolved oxygen (DO) are important biological environmental factors for aquatic animal. The sea cucumber Apostichopus japonicus was an important aquaculture species in China, which was highly impacted by temperature and DO. In the present study, the transcriptomics expression profiles under high temperature (HT), hypoxia (LO), and these combined stressors (HL) were investigated by RNA-seq technique. Compared with the control group, 275, 409 and 434 differential expressed genes (DEGs) were detected in HT, LO and HL groups respectively. Further analysis of KEGG pathways revealed that “protein processing in endoplasmic reticulum” pathway was significantly enriched in both HT vs C and HL vs C comparisons. Protein folding-related genes in this pathway, such as HSPs, were up-regulated in the two comparisons. In LO vs C comparison, “fatty acid metabolism” pathway was significantly enriched, and genes related to de novo biogenesis of fatty acids was significantly down-regulated. Some genes related to anti-apoptosis, such as BCL-2 and BAG3, were up-regulated in HL vs C comparison, which revealed that the combined stress threatened the survival of cells. The present research provided new insights for the response to different stressful environments in A. japonicus.

The reverse-mode smart windows, which usually fabricated by polymer stabilized liquid crystal (PSLC), are more practical for scenarios where high transparency is a priority for most of the time. However, the polymer stabilized cholesteric liquid crystal (PSCLC) film exhibits poor spacing stability due to the mobility of CLC molecules during the bending deformation. In this work, a reverse-mode PSCLC flexible film with excellent bending resistance was fabricated by the construction of polymer spacer columns. The effect of the concentration of the polymerizable monomer C6M and chiral dopant R811 on the electro-optical properties and polymer microstructure of the film were studied. The sample B2 containing 3 wt% of C6M and 3 wt% R811 presented the best electro-optical performance. The electrical switch between transparent and opaque state of the flexible PSCLC film after bending not only indicated the excellent electro-optical switching performance, but also demonstrated the outstanding bending resistance of the sample with polymer spacer columns, which makes the PSCLC film containing polymer spacer columns have a great potential to be applied in the field of flexible devices.

The utilization of sheet structure composites as a viable conductive filler has been implemented in polymer-based electromagnetic shielding materials. However, the development of an innovative sheet structure to enhance electromagnetic shielding performance remains a significant challenge. Herein, we propose a novel design incorporating silver-modified nanosheet self-assembled hollow spheres to optimize their performance. The unique microporous structure of the hollow composite, combined with the self-assembled surface nanosheets, facilitates multiple reflections of electromagnetic waves, thereby enhancing the dissipation of electromagnetic energy. The contribution of absorbing and reflecting electromagnetic waves in hollow nanostructures could be attributed to both the inner and outer surfaces. When multiple reflection attenuation is implemented, the self-assembled stack structure of nanosheets outside the composite material significantly enhances the occurrence of multiple reflections, thereby effectively improving its shielding performance. The structure also facilitates multiple reflections of incoming electromagnetic waves at the internal and external interfaces of the material, thereby enhancing the shielding efficiency. Simultaneously, the incorporation of silver particles can enhance conductivity and further augment the shielding properties. Finally, the optimized Ag/NiSi-Ni nanocomposites can demonstrate superior initial permeability (2.1 × 10−6 H m−1), saturation magnetization (13.2 emu g−1), and conductivity (1.2 × 10−3 Ω•m). This work could offer insights for structural design of conductive fillers with improved electromagnetic shielding performance.

A series of tungsten bronze (Sr2–xBixAg0.2Na0.8) (Nb4.8–xZrxSb0.2)O15 compounds were fabricated by solid-state method to systematically study the impacts of co-doping Bi3+/Zr4+ ions in A/B-sites on the structures, relaxor characteristics, and energy-storage performances. The relationship between structures and relaxor behaviors are summarized as three main points: (1) with increasing the amount of co-doping Bi3+/Zr4+ ions, the crystal structure evolved from an orthorhombic Bbm2 to a tetragonal paraelectric P4/mbm symmetry at room temperature; (2) enhancing relaxor characteristics at room temperature was achieved by tailoring the temperature region of Tm−TB (Tm is the dielectric maximum temperature, TB is the Burns temperature), which could be attributed to the incommensurate local structure modulations associated with the orthogonal distortion of P4bm symmetry and the appearance of microdomains; (3) The co-introduction of Bi3+ and Zr4+ could also played an important role in inhibiting the grain sizes, increasing resistivity and band-gap to enhance the breakdown strength. Finally, a superior recoverable energy-storage density (3.61 J/cm3) and an ultrahigh energy efficiency (90%) were obtained simultaneously at 389 kV/cm in BZ0.05 ceramics. Moreover, an outstanding power density (158.98 MW/cm3) together with a current density of 1422.29 A/cm2 was realized at 220 kV/cm from the charging−discharging performance measurements. The excellent energy-storage performance (ESPs) make the environmentally friendly BZ0.05 samples show enormous potential in high-power capacitor applications.

Aquatic plants are fundamental for aquatic ecosystems. Understanding variations in geographic patterns of aquatic plant diversity across growth forms is important for conservation and restoration of aquatic ecosystems. Environmental drivers, including climate, climate heterogeneity, water chemistry, habitat availability and geodiversity, could influence aquatic plant diversity and species composition across communities, yet their relative impacts remain controversial. Here, we examined geographic patterns and drivers of species richness of Chinese aquatic plants with different growth forms. We compiled distributions of 656 aquatic plant species in China at 50 × 50 km2 resolutions, and estimated richness patterns for species with different growth forms (i.e., helophyte, emergent, floating-leaved, free-drifting and submerged) and range sizes. Hierarchical partitioning analysis was employed to evaluate the independent effects of different environmental drivers on species richness. The Sørensen dissimilarity index and Multiple Matrix Regression with Randomization were used to compare the relative effects of environment and dispersal limitation on species dissimilarity between grid cells. Overall species richness was highest in northeastern and southern China, although species richness patterns varied across growth forms. Among environmental drivers examined, climate was the key determinant of the species richness of helophyte, emergent, floating-leaved and free-drifting plants, while habitat availability and water chemistry best explained the richness of submerged species. The richness of narrow-ranged species was dominated by climate, while the strongest determinant of wide-ranged species richness varied across growth forms. Our study mapped the species richness patterns of aquatic plants in China and indicated that the relationship between aquatic plant richness and environment significantly differed between growth forms and between wide-ranged and narrow-ranged species. These findings indicate the necessity of distinguishing growth forms in studies related to aquatic plants, and suggest that future climate change might threaten the distribution of narrow-ranged aquatic plants.

Abstracts Imatinib is highly effective in the treatment of chronic myelogenous leukemia (CML), but the primary and acquired imatinib resistance remains the big hurdle. Molecular mechanisms for CML resistance to tyrosine kinase inhibitors, beyond point mutations in BCR-ABL kinase domain, still need to be addressed. Here, we demonstrated that thioredoxin-interacting protein (TXNIP) is a novel BCR-ABL target gene. Suppression of TXNIP was responsible for BCR-ABL triggered glucose metabolic reprogramming and mitochondrial homeostasis. Mechanistically, Miz-1/P300 complex transactivates TXNIP through the recognition of TXNIP core promoter region, responding to the c-Myc suppression by either imatinib or BCR-ABL knockdown. TXNIP restoration sensitizes CML cells to imatinib treatment and compromises imatinib resistant CML cell survival, predominantly through the blockage of both glycolysis and glucose oxidation which results in the mitochondrial dysfunction and ATP production. In particular, TXNIP suppresses expressions of the key glycolytic enzyme, hexokinase 2 (HK2), and lactate dehydrogenase A (LDHA), potentially through Fbw7-dependent c-Myc degradation. In accordance, BCR-ABL suppression of TXNIP provided a novel survival pathway for the transformation of mouse bone marrow cells. Knockout of TXNIP accelerated BCR-ABL transformation, whereas TXNIP overexpression suppressed this transformation. Combination of drug inducing TXNIP expression with imatinib synergistically kills CML cells from patients and further extends the survival of CML mice. Thus, the activation of TXNIP represents an effective strategy for CML treatment to overcome resistance.

ABSTRACT Public health threats posed by emerging respiratory infections are a significant concern, particularly in children and infants. Traditional culture-based detection methods are time-consuming and typically require 1–3 days. Herein, we developed and evaluated a 23-plex common respiratory pathogen mass spectrometry assay that enables the simultaneous detection of 18 common respiratory pathogens in children. This assay combines matrix-assisted laser desorption/ionization time of flight mass spectrometry with multiplex reverse transcription-PCR and targets 11 bacterial and 7 viral pathogens (including 10 subtypes), and two internal controls. The detection limit of the common respiratory pathogen mass spectrometry assay was as low as 1 copy/µL, with no cross-reactivity with other organisms. We assessed the clinical performance of the common respiratory pathogen mass spectrometry assay using respiratory samples from 450 children. The total 450 clinical specimens underwent analysis via matrix-assisted laser desorption/ionization time of flight mass spectrometry, and the outcomes were juxtaposed with those derived from real-time reverse-transcriptase PCR conducted concurrently. The concordance between these methods was 96.0%, and the multiple infection identification rate was 7.1%. This innovative approach enables the simultaneous analysis of numerous outcomes from a solitary examination across 192 specimens within a timeframe of approximately 7 hours, with a dramatically reduced sample use and cost. In summary, the common respiratory pathogen mass spectrometry assay is a sensitive, accurate, and cost-effective method for detecting common respiratory pathogens in children and has the potential to revolutionize the diagnosis of respiratory tract infections. IMPORTANCE This study aimed to present and evaluate a novel co-detection method that enables the simultaneous identification of 11 bacterial and 7 viral pathogens in about 7 hours using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Our approach utilizes a combination of multiplex reverse transcription-PCR and matrix-assisted laser desorption/ionization time of flight mass spectrometry, which overcomes the limitations of conventional assays, which include a long assessment time, technical difficulty, and high costs. As a screening method for common respiratory pathogens in children, common respiratory pathogen mass spectrometry assay has the potential to revolutionize the diagnosis of respiratory tract infections by providing an accurate etiological diagnosis. The common respiratory pathogen mass spectrometry assay is expected to be a critical tool for the diagnosis of respiratory infections in children, offering a more efficient, cost-effective, and accurate approach for the detection of common respiratory pathogens.

Abstract Influenza B virus circulates yearly with lower activity than that of influenza A virus in China. During winter 2017 to 2018, a sharp surge of influenza activity dominated by type B/Yamagata lineage virus caused unprecedented medical burden in Beijing. This research aimed to understand the underlying mechanism for this circulation and prepare for epidemics in the future. Sera samples collected from the patients in 2016–2017 and 2017–2018 flu seasons were tested for profiling hemagglutinin inhibition (HI) antibodies against both prevailing Victoria and Yamagata lineages of type B influenza viruses. It showed that the seroprevalence against both lineages of the virus in 2017–2018 winter was higher than that in 2016–2017, while no difference of the seroprevalence was observed between the two viruses. Meanwhile, significant elevated geometric mean titer (GMT) against both lineages of influenza B viruses was found in the specimens collected during 2017–2018 flu season than that from 2016 to 2017, suggesting the viruses might undergo antigenic changes. These results also suggested that lower GMT against both type B variants in 2016–2017 might serve as an immunological niche for the dominating of B/Yamagata virus in China during 2017–2018 winter season. Our findings have implication that there was a significantly elevation of HI antibodies to influenza viruses B in 2017–2018 than in 2016–2017. On the other hand, the low level of HI antibodies to both B/Y and B/V in 2016–2017 could contribute to the severe B/Y epidemic in 2017–2018 to some extent.

Abstract Background The complicated hyperglycaemic and chronic inflammation of diabetic wounds in orthopaedic surgery leads to dysregulated immune cell function and potential infection risk. Immune interventions in diabetic wounds face a possible contradiction between simultaneous establishment of the pro-inflammatory microenvironment in response to potential bacterial invasion and the anti-inflammatory microenvironment required for tissue repair. To study this contradiction and accelerate diabetic-wound healing, we developed a photocurable methacryloxylated silk fibroin hydrogel (Sil-MA) system, co-encapsulated with metformin-loaded mesoporous silica microspheres (MET@MSNs) and silver nanoparticles (Ag NPs). Results The hydrogel system (M@M–Ag–Sil-MA) enhanced diabetic-wound healing via spatiotemporal immunomodulation. Sil-MA imparts a hydrogel system with rapid in situ Ultra-Violet-photocurable capability and allows preliminary controlled release of Ag NPs, which can inhibit bacterial aggregation and create a stable, sterile microenvironment. The results confirmed the involvement of Met in the immunomodulatory effects following spatiotemporal dual-controlled release via the mesoporous silica and Sil-MA. Hysteresis-released from Met shifts the M1 phenotype of macrophages in regions of diabetic trauma to an anti-inflammatory M2 phenotype. Simultaneously, the M@M–Ag–Sil-MA system inhibited the formation of neutrophil extracellular traps (NETs) and decreased the release of neutrophil elastase, myeloperoxidase, and NETs-induced pro-inflammatory factors. As a result of modulating the immune microenvironmental, the M@M–Ag–Sil-MA system promoted fibroblast migration and endothelial cell angiogenesis in vivo, with verification of enhanced diabetic-wound healing accompanied with the spatiotemporal immunoregulation of macrophages and NETs in a diabetic mouse model. Conclusions Our findings demonstrated that the M@M–Ag–Sil-MA hydrogel system resolved the immune contradiction in diabetic wounds through spatiotemporal immunomodulation of macrophages and NETs, suggesting its potential as a promising engineered nano-dressing for the treatment of diabetic wounds in orthopaedic surgery. Graphical Abstract

Abstract Background Our study aimed to compare the reference distributions of serum creatinine and urea obtained by direct sampling technique and two indirect sampling techniques including the Gaussian Mixture Model (GMM) and the Self-Organizing Map (SOM) clustering based on clinical laboratory records, so that the feasibility as well as the potential limitations of indirect sampling techniques could be clarified. Methods The direct sampling technique was used in the Pediatric Reference Interval in China (PRINCE) study, in which 15,150 healthy volunteers aged 0 to 19 years were recruited from 11 provinces across China from January 2017 to December 2018. The indirect sampling techniques were used in the Laboratory Information System (LIS) database of Beijing Children’s Hospital, in which 164,710 outpatients were included for partitioning of potential healthy individuals by GMM or SOM from January to December 2016. The reference distributions of creatinine and urea that were established by the PRINCE study and the LIS database were compared. Results The density curves of creatinine and urea based on the PRINCE data and the GMM and SOM partitioned LIS data showed a large overlap. However, deviations were found in reference intervals among the three populations. Conclusions Both GMM and SOM can identify potential healthy individuals from the LIS data. The performance of GMM is consistent and stable. However, GMM relies on Gaussian fitting, and thus is not suitable for skewed data. SOM is applicable for high-dimensional data, and is adaptable to data distribution. But it is susceptible to sample size and outlier detection strategy.

Abstract Neuroblastoma (NB) is the most common extracranial solid tumor and the treatment efficacy of high-risk NB is unsatisfactory. γδT-cell-based adoptive cell transfer is a promising approach for high-risk NB treatment. Our previous study has revealed that γδT cells in NB patients exhibit a poor proliferation activity and a decreased anti-tumor capacity in vitro. In the present study, we found that IL-15 could effectively enhance the proliferation of NB γδT cells, to a level that remains lower than healthy controls though. In addition, IL-15-fostered NB γδT cells robustly boosted cell survival against apoptosis induced by cytokines depletion. Our data revealed that Mcl-1 was a key anti-apoptotic protein in IL-15-fostered γδT cells during cytokine withdrawal and its expression was regulated via the activation of STAT5 and ERK. In addition, IL-2 and IL-15-fostered γδT cells harbored higher levels of tumoricidal capacity which is also beneficial for γδ T-cell based immune therapy in NB. Understanding the survival control of γδT cells in a sub-optimal cytokine supportive microenvironment will expedite the clinical application of γδT cells for immunotherapy.

With the rapid development of the information technology industry, refurbished products play significant roles in this challenge of environmental, economic, and social performance revolution. Meanwhile, when the refurbished product is launched in the market compete with new products, how and whom to repair the used products effectively and what kind of effective coordinate incentive mechanisms utilized to alleviate conflict and achieve the challenge become one of the most significant issues. Therefore, this study compares two refurbishing structures (manufacturer refurbishing and retailer refurbishing) under three different contract incentive mechanisms (wholesale price, revenue sharing, and reward points contracts) in two periods closed-loop supply chain (CLSC) model with demand uncertainty. Our results show that the manufacturer should allow his retailer to refurbish used products under the condition of using reward points contract strategies. It will help improve the whole channel performance and create much higher profits. Meanwhile, all channel members benefit from the reward point contract in the manufacturer refurbishing scenarios. However, manufacturers prefer revenue-sharing contracts while retailers prefer wholesale price contracts in the retailer refurbishing scenarios.

BackgroundThe cblC type methylmalonic acidemia is the most common methylmalonic acidemia (MMA) in China. The biochemical characteristics of this disease include elevated methylmalonic acid and homocysteine (HCY), increased propionylcarnitine (C3), decreased free carnitine (C0). In this study, we aimed to clarify the roles of these biomarkers in cblC-MMA induced cognitive impairment and evaluate the capacity of methylmalonic acid in different fluids or exosomes to distinguish cblC-MMA induced cognitive impairment.Methods15 non-inherited hyperhomocysteinemia (HHcy) patients, 42 cblC-MMA patients and 57 age- and sex-matched healthy children were recruited in this study. The levels of HCY were detected by an automatic immune analyzer. The levels of acylcarnitines and methylmalonic acid were detected by tandem mass spectrometer.ResultsThe main findings were all biomarkers as HCY, acylcarnitines and methylmalonic acid had capacities for distinguishing patients with cblC-MMA induced cognitive impairment from healthy children. The methylmalonic acid in different fluids or exosomes had good performances for distinguishing patients with cblC-MMA induced cognitive impairment from HHcy patients. The methylmalonic acid in serum exosomes and neuronal-derived exosomes were able to distinguishing cblC-MMA patients with cognitive impairment from patients without cognitive impairment. The methylmalonic acid in neuronal-derived exosomes might be helpful to evaluate the severity of cblC-MMA induced cognitive impairment.DiscussionMethylmalonic acid levels in serum exosomes, especially in serum neuronal-derived exosomes, serve as potential biomarkers for distinguishing cblC-MMA induced cognitive impairment.

Understanding the responses of shrub growth to climate changes is key to accurately predicting the dynamic changes in the boreal forest ecosystem. A shrub-ring network based on 12 sites was established to explore the response of Pinus pumila growth to climate change in northeastern China. The sampling sites are distributed along the latitudinal gradient of 44.10° to 52.58° and were divided into three regions: south, central, and north. The results show that there have been significant differences in P. pumila growth trends at different latitudes in recent decades. From 1950 to 1980, P. pumila in the southern and central regions grew faster than in the northern region. From 1981 to 2014, however, the growth of P. pumila increased in the north but slowed in the south and central regions. The temperatures of the previous winter and current spring are the main factors limiting the growth of P. pumila in the north and south. In the central and southern regions, the growth of P. pumila is negatively correlated with precipitation of the previous and current summers. In the north, summer temperatures from 1981 to 2014 gradually inhibit the growth of P. pumila, while summer precipitation has a positive impact on growth. Our model indicates that the radial growth trend of P. pumila in the north is likely to decline as the climate warms. Surprisingly, the growth of P. pumila in the south is predicted to benefit from warming under the RCP4.5, RCP6.0, and RCP8.5 scenarios. Therefore, P. pumila may not expand northward in the context of climate warming.

In the context of the intensification of global urbanization, how urbanization (urban heat island effect and air pollution) affects urban tree growth is not fully understood. In this paper, the radial growth and xylem anatomical characteristics of three different tree species (Quercus mongolica, Fraxinus mandshurica, and Pinus sylvestris var. mongolica) in urban and rural areas of Harbin were compared by means of tree-ring anatomy. The results showed that there were significant differences in the growth of both broadleaf trees and conifers between urban and rural areas. The vessel number, cumulative area of vessels, and theoretical hydraulic conductivity of all tree species in rural areas were higher than those in urban areas, indicating that urbanization may have the effect of slowing down growth. However, broadleaf trees in urban areas had higher vessel density and a greater percentage of a conductive area within xylem and theoretical xylem-specific hydraulic conductivity. The thickness of cell walls and cell wall reinforcement index of P. sylvestris var. mongolica were strongly reduced by air pollution, implying that it may be more sensitive to urbanization. Compared to Q. mongolica, F. mandshurica showed less sensitivity to urbanization. Warming and drying climate in Harbin may be an important factor affecting tree growth.

In recent years, the resource shortage and environmental degradation have made enterprises and governments increasingly aware of the importance of sustainable development. Meanwhile, the COVID-19 pandemic has also increased the shortage of medical materials. Based on this, we investigate the tradeoff of the critical medical devices refurbishing strategies when blockchain is used in three different structures: manufacturer refurbishing, retailer refurbishing, and third-party refurbishing in the two-period refurbishing strategies. We find that the manufacturer always benefits from the adoption of blockchain technology strategy in the manufacturer refurbishing scenario. However, for the retailer in the second period, the retailer references the adoption of blockchain only if the willingness to pay is extremely high. Additionally, when the medical supply chain channel member chooses retailer refurbishing or third-party strategy, the manufacturer always likes to use blockchain technology. That’s because it will help the information value spillover from the retailer to the manufacturer, which leads the manufacturer to get more profits and a lower profit for the retailer. However, in the retailer refurbishing or third-part strategy, the whole channel profits are higher than not adopting blockchain technology. Therefore, business managers can be based on our research to achieve profits Pareto-improving.

Abstract Background The cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is widely considered as a pivotal immune checkpoint molecule to suppress antitumor immunity. However, the significance of soluble CTLA-4 (sCTLA-4) remains unclear in the patients with brain glioma. Here we aimed to investigate the significance of serum sCTLA-4 levels as a noninvasive biomarker for diagnosis and evaluation of the prognosis in glioma patients. Methods In this study, the levels of sCTLA-4 in serum from 50 patients diagnosed with different grade gliomas including preoperative and postoperative, and 50 healthy individuals were measured by an enzyme-linked immunosorbent assay (ELISA). And then ROC curve analysis and survival analyses were performed to explore the clinical significance of sCTLA-4. Results Serum sCTLA-4 levels were significantly increased in patients with glioma compared to that of healthy individuals, and which was also positively correlated with the tumor grade. ROC curve analysis showed that the best cutoff value for sCTLA-4 for glioma is 112.1 pg/ml, as well as the sensitivity and specificity with 82.0 and 78.0%, respectively, and a cut-off value of 220.43 pg/ml was best distinguished in patients between low-grade glioma group and high-grade glioma group with sensitivity 73.1% and specificity 79.2%. Survival analysis revealed that the patients with high sCTLA-4 levels (> 189.64 pg/ml) had shorter progression-free survival (PFS) compared to those with low sCTLA-4 levels (≤189.64 pg/ml). In the univariate analysis, elder, high-grade tumor, high sCTLA-4 levels and high Ki-67 index were significantly associated with shorter PFS. In the multivariate analysis, sCTLA-4 levels and tumor grade remained an independent prognostic factor. Conclusion These findings indicated that serum sCTLA-4 levels play a critical role in the pathogenesis and development of glioma, which might become a valuable predictive biomarker for supplementary diagnosis and evaluation of the progress and prognosis in glioma.

Of all forest biomes, boreal forests are experiencing the most significant warming. Drought caused by warming has a dramatic impact on species in boreal forests. However, little is known about whether the growth of trees and shrubs in boreal forests responds consistently to warming and drought. We obtained the tree-ring width data of 308 trees (Larix gmelinii and Pinus sylvestris var. mongolica) and 133 shrubs (Pinus pumila) from 26 sites in northeastern China. According to the climate data from 1950 to 2014, we determined three extreme drought years (1954, 1967, and 2008). The response difference of radial growth of trees and shrubs in boreal forests to drought was compared using resilience index, moving correlation and response analysis. The results showed that high temperature (mean and maximum temperature) in previous and current growing seasons promoted the growth of P. pumila, but inhibited the growth of trees. On the contrary, wetter conditions (higher PDSI) promoted tree growth but were not conducive to P. pumila growth in high latitudes. Moving correlation analysis showed similar results. In addition, water deficit was more likely to inhibit P. pumila growth in low latitudes. The drought resistance of P. pumila was stronger than that of L. gmelinii and P. sylvestris var. mongolica. Therefore, the growth loss and recovery time of P. pumila during drought was less than those of trees. We concluded that L. gmelinii and P. sylvestris var. mongolica are more prone to growth decline than P. pumila after the drought caused by climate warming. In the future climate warming, shrub growth may benefit more than trees. Our findings are of great significance in predicting the future changes in ecosystem composition and species distribution dynamics in extreme climate susceptible areas.

Previous studies reported that sex and age could influence urine metabolomics, which should be considered in biomarker discovery. As a consequence, for the baseline of urine metabolomics characteristics, it becomes critical to avoid confounding effects in clinical cohort studies. In this study, we provided a comprehensive lifespan characterization of urine metabolomics in a cohort of 348 healthy children and 315 adults, aged 1 to 78 years, using liquid chromatography coupled with high resolution mass spectrometry. Our results suggest that sex-dependent urine metabolites are much greater in adults than in children. The pantothenate and CoA biosynthesis and alanine metabolism pathways were enriched in early life. Androgen and estrogen metabolism showed high activity during adolescence and youth stages. Pyrimidine metabolism was enriched in the geriatric stage. Based on the above analysis, metabolomic characteristics of each age stage were provided. This work could help us understand the baseline of urine metabolism characteristics and contribute to further studies of clinical disease biomarker discovery.

Abstract Background Continuous reference intervals (RIs) allow for more precise consideration of the dynamic changes of physiological development, which can provide new strategies for the presentation of laboratory test results. Our study aimed to establish continuous RIs using four different simulation methods so that the applicability of different methods could be further understood. Methods The data of alkaline phosphatase (ALP) and serum creatinine (Cr) were obtained from the Pediatric Reference Interval in China study (PRINCE), in which healthy children aged 0–19 years were recruited. The improved non-parametric method, the radial smoothing method, the General Additive Model for Location Scale and Shape (GAMLSS), and Lambda-Median-Sigma (LMS) were used to develop continuous RIs. The accuracy and goodness of fit of the continuous RIs were evaluated based on the out of range (OOR) and Akaike Information Criterion (AIC) results. Results Samples from 11,517 and 11,544 participants were used to estimate the continuous RIs of ALP and Cr, respectively. Time frames were partitioned to fulfill the following two criteria: sample size = 120 in each subgroup and mean difference = 2 between adjacent time frames. Cubic spline or penalized spline was used for curve smoothing. The RIs estimated by the four methods approximately overlapped. However, more obvious edge effects were shown in the curves fit by the non-parametric methods than the semi-parametric method, which may be attributed to insufficient sample size. The OOR values of all four methods were smaller than 10%. Conclusions All four methods could be used to establish continuous RIs. GAMLSS and LMS are more reliable than the other two methods for dealing with edge effects.

ObjectivesKnowledge of the urinary metabolomic profiles of healthy children and adolescents plays a promising role in the field of pediatrics. Metabolomics has also been used to diagnose disease, discover novel biomarkers, and elucidate pathophysiological pathways. Attention-deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in childhood. However, large-sample urinary metabolomic studies in children with ADHD are relatively rare. In this study, we aimed to identify specific biomarkers for ADHD diagnosis in children and adolescents by urinary metabolomic profiling.MethodsWe explored the urine metabolome in 363 healthy children aged 1–18 years and 76 patients with ADHD using high-resolution mass spectrometry.ResultsMetabolic pathways, such as arachidonic acid metabolism, steroid hormone biosynthesis, and catecholamine biosynthesis, were found to be related to sex and age in healthy children. The urinary metabolites displaying the largest differences between patients with ADHD and healthy controls belonged to the tyrosine, leucine, and fatty acid metabolic pathways. A metabolite panel consisting of FAPy-adenine, 3-methylazelaic acid, and phenylacetylglutamine was discovered to have good predictive ability for ADHD, with a receiver operating characteristic area under the curve (ROC–AUC) of 0.918. A panel of FAPy-adenine, N-acetylaspartylglutamic acid, dopamine 4-sulfate, aminocaproic acid, and asparaginyl-leucine was used to establish a robust model for ADHD comorbid tic disorders and controls with an AUC of 0.918.

The Melanocortin-3 receptor (MC3R) and Melanocortin-4 receptor (MC4R), two members of the key hypothalamic neuropeptide signaling, function as complex mediators to control the central appetitive and energy homeostasis. The melanocortin 2 receptor accessory protein 2 (MRAP2) is well-known for its modulation on the trafficking and signaling of MC3R and MC4R in mammals. In this study, we cloned and elucidated the pharmacological profiles of MRAP2 on the regulation of central melanocortin signaling in a relatively primitive poikilotherm amphibian species, the Mexican axolotl (Ambystoma mexicanum). Our results showed the higher conservation of axolotl mc3r and mc4r across species than mrap2, especially the transmembrane regions in these proteins. Phylogenetic analysis indicated that the axolotl MC3R/MC4R clustered closer to their counterparts in the clawed frog, whereas MRAP2 fell in between the reptile and amphibian clade. We also identified a clear co-expression of mc3r, mc4r, and mrap2 along with pomc and agrp in the axolotl brain tissue. In the presence of MRAP2, the pharmacological stimulation of MC3R by α-MSH or ACTH significantly decreased. MRAP2 significantly decreased the cell surface expression of MC4R in a dose dependent manner. The co-localization and formation of the functional complex of axolotl MC3R/MC4R and MRAP2 on the plasma membrane were further confirmed in vitro. Dramatic changes of the expression levels of mc3r, mrap2, pomc, and agrp in the fasting axolotl hypothalamus indicated their critical roles in the metabolic regulation of feeding behavior and energy homeostasis in the poikilotherm aquatic amphibian.

Objective. Systemic lupus erythematosus (SLE) is a relatively common rheumatic disease in children. The characteristics of blood lipid metabolism in children with LN are little reported. This study aimed to explore the relationship between blood lipid profiles and the risk of lupus nephritis (LN) in children. Methods. A total of 134 children with newly diagnosed SLE were divided into LN and non-LN groups according to pathological renal biopsy results. Clinical manifestations and blood lipid profiles were analyzed and compared between the two groups, and the relationships between blood lipid profiles and risk of LN were evaluated. Results. The positivity rate of an anti-dsDNA antibody and an SLE disease activity index (SLEDAI) were significantly increased, and C3 and C4 levels were significantly reduced in the LN compared with the non-LN group. The overall incidence of dyslipidemia was 79.9%, with a significantly high incidence in the LN group compared with the non-LN group. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and very LDLC (VLDL-C) were all higher in the LN group than those in the non-LN group. However, there was no significant difference in high-density lipoprotein cholesterol (HDL-C) between the two groups. The blood lipid levels were positively correlated with 24-hour urine protein quantification, urea, creatinine, uric acid, urinary IgG, urinary microalbumin, urinary transferrin, urinary α1 microglobulin, and urinary N-acetyl glucosidase, respectively. Receiver-operating characteristic curves showed that combined detection of TC, TG, LDL-C, and VLDL-C had higher discrimination capacity than that in individual measures. Additionally, increased TC was independently associated with the occurrence of LN. Conclusions. Children with LN have significant dyslipidemia. High levels of TC, TG, LDL-C, and VLDL-C are closely related to the occurrence of pLN. Clinical attention should be paid to monitoring and managing blood lipid profiles in children with LN.

Abstract Importance Regional clonal replacements of methicillin‐resistant Staphylococcus aureus (MRSA) are common. It is necessary to understand the clonal and drug resistance changes in specific areas. Objective To evaluate the clonal and drug resistance dynamics of MRSA in Chinese children from 2010 to 2017. Methods MRSA was isolated from patients in Beijing Children's Hospital from 2010 to 2013 and from 2016 to 2017. The molecular characteristics and antibiotic resistance were determined. Results In total, 211 MRSA isolates were collected, and 104 isolates were classified as community‐associated MRSA (CA‐MRSA). ST59‐SCCmec IV was the most prevalent type in both CA‐MRSA (65.4%) and healthcare‐ associated‐MRSA (HA‐MRSA) (46.7%). ST239‐SCCmec III accounted for 21.5% of all HA‐MRSA, which were not detected in 2016, and only three isolates were detected in 2017. The pvl gene carrying rate of CA‐ MRSA was significantly higher than that of HA‐MRSA (42.3% vs. 29.0%, P = 0.0456). Among CA‐MRSA, resistance rate to all tested antibiotics excluding chloramphenicol remained stable over the periods of 2010–2013 and 2016–2017. HA‐MRSA displayed an overall trend of decreased resistance to oxacillin, gentamicin, tetracycline, ciprofloxacin, and rifampin, and increased resistance to chloramphenicol, consistent with the difference of antibiotic resistance patterns between ST59‐SCCmec IV and ST239‐SCCmec III isolates. Vancomycin minimal inhibitory concentration (MIC) creep was found in the study period in all MRSA and ST59‐SCCmec IV isolates. Interpretation ST59‐SCCmec IV has spread to hospitals and replaced the traditional ST239‐SCCmec III clone, accompanied by changes in drug resistance. Furthermore, vancomycin MIC creep indicated that the rational use of antibiotics should be seriously considered.

Abstract Background Staphylococcus aureus (S. aureus) with accessory gene regulator (agr) dysfunction occurs in health care settings. This study evaluated the prevalence and the molecular and drug resistance characteristics of S. aureus with dysfunctional agr in a pediatric population in Beijing, China. Results A total of 269 nonduplicate S. aureus clinical isolates were isolated from Beijing Children’s Hospital, including 211 methicillin-resistant S. aureus (MRSA) from September 2010–2017 and 58 methicillin-sensitive S. aureus (MSSA) from February 2016–2017. Only 8 MRSA and 2 MSSA isolates were identified as agr dysfunction, and the overall prevalence rate was 3.7%. For MRSA isolates, ST59-SCCmec IV and ST239-SCCmec III were the most common clones, and the prevalence rate of agr dysfunction in ST239-SCCmec III isolates (17.39%) was significantly higher than in ST59-SCCmec IV (1.69%) and other genotype strains (P = 0.006). Among the agr dysfunctional isolates, only one MRSA ST59 isolate and one MSSA ST22 isolate harbored pvl. No significant difference was detected between agr dysfunction and agr functional isolates regarding the biofilm formation ability (P = 0.4972); however, 9/10 agr dysfunctional isolates could effectuate strong biofilm formation and multidrug resistance. Among MRSA, the non-susceptibility rates to ciprofloxacin, gentamicin, and trimethoprim-sulfamethoxazole were significantly higher in agr dysfunctional isolates than in isolates with functional agr (P

Background: No previous study explored the association between serum calcium levels and dyslipidemia in children. This study aimed to explore this relationship in children, based on a multicenter cross-sectional study population in China.Methods: Cross-sectional data was derived from the Pediatric Reference Intervals in China (PRINCE) study conducted between 2017 and 2018 involving 5,252 males and 5,427 females with a mean age of 10.0 ± 4.6 years. Multivariable logistic regression models were applied to calculate odds ratios (ORs), with 95% confidence intervals (CIs), for dyslipidemia of each serum calcium level and albumin-corrected calcium levels, which were sorted into quartiles. The restricted cubic spline model was fitted for the dose-response analysis. An L-shaped dose-response relation between calcium levels and the probability of dyslipidemia was found after the adjustment for multiple potential confounding factors, p for non-linear < 0.001.Results: Using the middle category of calcium level as the reference, multivariable-adjusted ORs and 95% CIs of the lowest and the highest quartile categories were 0.96 (0.82–1.12) and 1.29 (1.12–1.48), respectively, for total serum calcium levels and 1.06 (0.91–1.23) and 1.39 (1.21–1.60) for albumin-corrected calcium levels.Conclusions: Individuals with higher levels of serum calcium were associated with increased risk of dyslipidemia in a sample of a healthy Chinese pediatric population. The association between serum calcium levels and dyslipidemia needs to be examined prospectively in future studies.

Summary: The sterol regulatory element-binding protein (SREBP) pathway monitors the cellular cholesterol level through sterol-regulated association between the SREBP cleavage-activating protein (Scap) and the insulin-induced gene (Insig). Despite structural determination of the Scap and Insig-2 complex bound to 25-hydroxycholesterol, the luminal domains of Scap remain unresolved. In this study, combining cryogenic electron microscopy (cryo-EM) analysis and artificial intelligence-facilitated structural prediction, we report the structure of the human Scap/Insig-2 complex purified in digitonin. The luminal domain loop 1 and a co-folded segment in loop 7 of Scap resemble those of the luminal/extracellular domain in NPC1 and related proteins, providing clues to the cholesterol-regulated interaction of loop 1 and loop 7. An additional luminal interface is observed between Scap and Insig. We also show that Scap(D428A), which inhibits SREBP activation even under sterol depletion, exhibits an identical conformation with the wild-type protein when complexed with Insig-2, and its constitutive suppression of the SREBP pathway may also involve a later step in protein trafficking.

Abstract Background This study aimed to investigate the clinical and molecular epidemiology and biofilm formation of Staphylococcus aureus (SA) isolated from pediatricians in China. Methods SA strains were isolated from Beijing Children’s hospital from February 2016 to January 2017. Isolates were typed by multilocus sequence typing (MLST), spa and SCCmec typing (for Methicillin-resistant SA [MRSA] only). Antimicrobial susceptibility testing was performed by agar dilution method except sulphamethoxazole/trimethoprim (E-test method). Biofilm formation and biofilm associated genes were detected. Results Totally 104 children (41 females and 63 males; median age, 5.2 months) were enrolled in this study, in which 60 patients suffered from MRSA infection. Among the 104 cases, 54.8% were categorized as community associated SA (CA-SA) infections. The children under 3 years were more likely to occur CA-SA infections compared with older ones (P = 0.0131). ST59-SCCmec IV-t437 (61.7%) was the most prevalent genotype of MRSA, and ST22-t309 (18.2%), ST5-t002 (9.1%), ST6-t701 (9.1%), ST188-t189 (9.1%) were the top four genotypes of methicillin-sensitive SA (MSSA). All the present isolates were susceptible to linezolid, vancomycin, trimethoprim-sulfamethoxazole, mupirocin, tigecyclin, fusidic acid. No erythromycin-susceptible isolate was determined, and only a few isolates (3.8%) were identified as susceptible to penicillin. Multi-drug resistant isolates were reponsible for 83.8% of the ST59-SCCmec IV-t437 isolates. The isolates with strong biofilm formation were found in 85% of MRSA and 53.2% of MSSA, and in 88.7% of ST59-SCCmec IV-t437 isolates. Biofilm formation ability varied not only between MRSA and MSSA (P = 0.0053), but also greatly among different genotypes (P

Platelet-rich plasma (PRP) has offered great promise for the treatment of cartilage degradation, and has been proved to have positive effects on the restoration of cartilage lesions. But no comparative work has been done between PRP and hyaluronate acid (HA) concerning their restoring effect on cartilage defect, especially by means of animal experiments and histologic assessments. The purpose of the study was to compare the therapeutic effects of P-PRP and HA on osteoarthritis in rabbit knees. Thirty rabbits were used to establish the animal models by creating a cartilage defect of 5 mm in diameter on the condyles of the femurs, and were randomly divided into three groups: the P-PRP group, HA group and the control group. Then each group was treated with P-PRP, HA or saline solution, respectively. Six and twelve weeks later the rabbits were sacrificed and the samples were collected. The platelet number, the concentrations of growth factors of P-PRP and whole blood, and the IL-1β concentration in the joint fluid were investigated, and the histological assessment of the cartilage were performed according to Mankin's scoring system. Micro-CT was also used to evaluate the restoration of subchondral bone. The platelet concentration in P-PRP is 6.8 fold of that in the whole blood. The IL-1β level in the P-PRP group was lower than in the HA group (p

BACKGROUND: Tuberculosis (TB) is still a big threat to human health, especially in children. However, an isolation of Mycobacterium tuberculosis culture from pediatric cases remains a challenge. In order to provide some scientific basis for children TB control, we investigated the genotyping and drug resistance characteristics of M. tuberculosis isolates from pediatric cases in China. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a total of 440 strains including 90 from children (18 years) isolated in 25 provinces across China were subjected to spoligotyping and drug susceptibility testing. As a result, Beijing family strains were shown to remain predominant in China (85.6%, 81.1% and 75.4% in three above groups, respectively), especially among new children cases (91.0% vs. 69.6% in previously treated cases, P=0.03). The prevalence of the Beijing genotype isolates was higher in northern and central China in the total collection (85.1% in northern and 83.9% in central vs. 61.6% in southern China, P

In this study, we propose a reparameterization You-Only-Look-Once v5 (YOLOv5) algorithm model for strip-steel surface defect detection to address low precision and poor timeliness in traditional methods. The proposed model introduces a re-parameterized VGG Light module, an enhanced bidirectional feature pyramid network feature structure, and a bounding box regression loss function fused with a normalized Gaussian-Wasserstein distance metric to improve small-target-defect detection accuracy. The experimental findings reveal a mean average precision (mAP) of 82.1% on the NEU-DET dataset, representing a notable improvement of 4.1% over the baseline YOLOv5s algorithm. Furthermore, the proposed algorithm model demonstrates superior detection accuracy compared with other prevalent object detection models and effectively mitigates challenges such as false detections and missed detections of small targets. Notably, it achieves an impressive detection speed of 68 FPS, affirming its efficacy in real-time applications. [ABSTRACT FROM AUTHOR]