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Abstract Spinal cord injury (SCI) is a critical condition affecting the central nervous system that often has permanent and debilitating consequences, including secondary injuries. Oxidative damage and inflammation are critical factors in secondary pathological processes. Selenium nanoparticles have demonstrated significant antioxidative and anti-inflammatory properties via a non-immunosuppressive pathway; however, their clinical application has been limited by their inadequate stability and functionality to cross the blood-spinal cord barrier (BSCB). This study proposed a synthesis method for ultra-small-diameter lentinan Se nanoparticles (LNT-UsSeNPs) with significantly superior reactive oxygen species (ROS) scavenging capabilities compared to conventional lentinan Se nanoparticles (LNT-SeNPs). These compounds effectively protected PC-12 cells from oxidative stress-induced cytotoxicity, alleviated mitochondrial dysfunction, reduced apoptosis. In vivo studies indicated that LNT-UsSeNPs efficiently penetrated the BSCB and effectively inhibited the apoptosis of spinal neurons. Ultimately, LNT-UsSeNPs directly regulated the PI3K-AKT-mTOR and Ras-Raf-MEK-ERK signaling pathways by regulating selenoproteins to achieve non-immunosuppressive anti-inflammatory therapy. Owing to their ultra-small size, LNT-UsSeNPs exhibited strong spinal barrier penetration and potent antioxidative and anti-inflammatory effects without compromising immune function. These findings suggest that LNT-UsSeNPs are promising candidates for further development in nanomedicine for the effective treatment of SCI. Graphical abstract

Abstract Fully π-conjugated polymers consisting of plane and rigid aromatic units present a fantastic optoelectronic property, a promising candidate for printed and flexible optoelectronic devices. However, obtaining high-performance conjugated polymers with an excellent intrinsically flexible and printable capacity is a great challenge due to their inherent coffee-ring effect and brittle properties. Here, we report an asymmetric substitution strategy to improve the printable and stretchable properties of deep-blue light-emitting conjugated polymers with a strong inter-aggregate capillary interaction for flexible printed polymer light-emitting diodes. The loose rod-shaped stacking of asymmetric conjugated polymers chain in the precursor printed ink makes it easier to improve the intrinsic stretchability of inkjet-printed films. More interestingly, the anisotropic shape rod-like aggregate of conjugated polymers chains also induced a strong capillary interaction and further suppressed the coffee-ring effect, which is more likely to allow for uniform deposition during printed processing and form uniform printed films.

Aviation accidents, referring to unexpected and undesirable events involving aircraft, often cause great damage to property and human life. Learning from historical accidents is pivotal for improving safety in aviation. However, aviation accidents are typically documented and stored as unstructured or semi-structured free-text, rendering the ability to analyze such data a difficult task. This study presents a novel framework that combines text mining and network analytics techniques to provide the ability to analyze aviation accident reports automatically. The framework comprises a four-step modelling approach to: (1) the transformation of unstructured aviation safety report texts into structured numeric matrices using the TF-IDF matrix; (2) the identification of aviation accident topics using a structural topic model (STM); (3) the production of a word co-occurrence network (WCN) to determine the interrelations between aviation safety risk factors; and (4) quantitative analysis by technology of keywords to pinpoint key causal factors in aviation safety events. The proposed framework is validated by analyzing aviation accident reports collected by the National Transportation Safety Board (NTSB). The results indicate that STM provides a more granular partitioning of topics and better distinguishes between similar events compared to traditional latent dirichlet allocation (LDA). Among the identified topics, “Fuel and Power” and “En-route Phase” have the highest occurrence rate according to STM. Additionally, “Aircraft Crash” is the most prevalent topic in aviation accidents that resulted in fatal injuries, whereas the “Landing phase” is the most prevalent topic in non-fatal injuries on accidents. Based on the WCN, three centrality measures highlight “inspection of equipment” and “take off” as the most important risk factors in aviation safety. The proposed framework provides a comprehensive solution for in-depth analysis of aviation safety reports, offering decision support for aviation safety management and accident prevention, thereby reducing risks and strengthening safety measures.

Abstract Background Studying the physiological growth status of Pinus yunnanensis Franch and Pinus elliottii Engelm. seedlings under different karst fissure thicknesses and rainfall distributions is of great significance for the management, vegetation restoration, and tree species selection in karst rocky desertification areas. In this study, we used a two-factor block experiment and set different rainfall durations, namely reduced rainfall duration (I3d), natural rainfall duration (I6d), and extended rainfall duration (I9d); Different karst small habitats, i.e., stone-free soil (S0), less stone and more soil (S1/4), and half stone and half soil (S1/2), are simulated at these three levels. Analyze the changes in physiological growth and photosynthetic characteristics in two coniferous seedlings under different treatments with different karst thicknesses. Results The results showed that with the increase of karst thickness, the growth volumes of height and diameter of P. yunnanensis seedlings, the biomass of various organs, and the accumulation of K+, Ca2+, Na+, and Mg2+ showed a significant change pattern of first increasing and then decreasing (P stems > roots. The K+, Ca2+, and Mg2+ content in various organs of P. yunnanensis seedlings showed that leaves > roots > stems, while Na+ shows the order of roots > leaves > stems. The accumulation of mineral elements in various organs of P. elliottii seedlings is manifested as roots > stems > leaves and the accumulation of mineral elements in both coniferous seedlings is manifested as Ca2+ > Mg2+ > K+ > Na+. Root length, root volume, root surface area, root diameter, SOD, POD, SP, photosynthetic pigment content, fluorescence parameters, and gas exchange parameters of P. yunnanensis seedlings gradually increase with the increase of karst thickness (except for the 9-day rainfall duration), while those of P. elliottii seedlings gradually decrease. The light saturation point of P. yunnanensis seedlings is highest under the I6dS1/2 treatment, while that of P. elliottii is highest under the I3dS0 treatment. Conclusions In summary, prolonging rainfall duration has an inhibitory effect on the growth of two types of coniferous seedlings. Increasing karst thickness inhibits the growth of P. elliottii seedlings, and to some extent, promotes the growth and development of P. yunnanensis seedlings. I6dS1/4 and I3dS0 treatments have the best growth effects on P. yunnanensis and P. elliottii seedlings. Therefore, we give priority to P. yunnanensis as the tree species for vegetation restoration or rocky desertification management in karst areas. Our study reveals the role of limestone-filled different karst fissures in mitigating the effects of drought as “containers” for plant growth. These findings help us understand the response of plants to drought stress and provide valuable insights for vegetation restoration in karst environments affected by global climate change. Therefore, further experiments with various karst fissure sizes are necessary to test the universality of the reactions of various plants under different karst fissures.

Among various metal oxide nanomaterials, manganese oxides, which can exist in different structures and valence states, are considered highly promising anode materials for lithium-ion batteries (LIBs). However, conventional manganese oxides, such as MnO and MnO2, face significant challenges during cycling process. Specifically, poor electronic conductivity and large volume changes result in low specific capacity during high current charging and discharging, as well as poor fast-charging performance. This work presents an approach to synthesizing porous hexagonal Mn5O8 nanosheets via hydrothermal and annealing methods and applies them as anode materials for LIBs. The Mn5O8 nanomaterials exhibit a thin plate morphology, which effectively reduces the distance for ion/electron transmission and mitigates the phenomenon of volume expansion. Additionally, the large pore size of Mn5O8 results in abundant interlayer and intralayer defects, which further increase the rate of ion transmission. These unique characteristics enable Mn5O8 to demonstrate excellent electrochemical performance (938.7 mAh·g−1 after 100 cycles at 100 mA·g−1) and fast charging performance (675.7 mAh·g−1 after 1000 cycles at 3000 mA·g−1), suggesting that Mn5O8 nanosheets have the potential to be an ideal fast-charging anode material for LIBs.

Traditional obstacle avoidance algorithms usually use a single shallow application, such as sensor-based distance measurement or some logic judgment algorithm, which leads to problems such as the need to manually adjust the parameters first, the inability to recognize complex or unknown environments, and the recognition errors caused by significant noise errors. Therefore, to overcome these limitations, this paper combines convolutional neural network and obstacle avoidance algorithms. A model of obstacle avoidance method based on convolutional neural network established in this paper, and puts forward the theory of obstacle avoidance method based on convolutional neural network, which adopts MobileNet_v3 as the learning framework, roughly classifies all the obstacle maps into three categories, and then, through the research and application of six traditional obstacle avoidance algorithms, finally concludes that the model can be applied according to different kinds of obstacles. The model can learn and discriminate against different obstacle maps, thus improving the performance of obstacle avoidance and avoiding the limitations of traditional obstacle avoidance algorithms. Verified the effectiveness of each algorithm in various scenarios. A single shallow application of the problem is usually used to robotize the traditional obstacle avoidance algorithms, which provides an essential reference.

BackgroundOfatumumab is a humanized monoclonal antibody that targets CD20-positive B cells. It was approved by the FDA in 2020 for the treatment of relapsing multiple sclerosis (RMS) in adult patients, and in 2009 for the treatment of Chronic Lymphocytic Leukemia (CLL). With the escalating clinical application of Ofatumumab, comprehending its safety profile within actual healthcare environments is of considerable importance.MethodsThis study compiled a dataset derived from the FAERS database, which included real-world safety data on Ofatumumab from Q4 2009 to Q2 2024. We applied four distinct methodologies, including ROR, PRR, MGPS, and BCPNN, to perform a disproportionality analysis of adverse events (AEs) associated with Ofatumumab. Furthermore, we utilized the Weibull distribution model to estimate the temporal risk pattern of AEs.ResultsThe investigation incorporated a total of 24,468 case reports pertaining to AEs associated with Ofatumumab. The commonly observed AEs encompass Fatigue, Headache, Chills, Pyrexia, Pain, Nausea, Nasopharyngitis, Vomiting, Urinary tract infection, and Pneumonia. Additionally, we identified potential AEs not specified on the drug label, such as Asthenia, Hypoesthesia, Dizziness, Malaise, Injection site pain, Paresthesia, and Diarrhea.ConclusionsThis investigation has identified several AEs associated with Ofatumumab and revealed previously unacknowledged potential adverse reaction signals. Healthcare providers can refer to these adverse reaction signals to more comprehensively consider the possible conditions that patients may present with during actual clinical practice.

The concept of ‘brain age’, derived from neuroimaging data, serves as a crucial biomarker reflecting cognitive vitality and neurodegenerative trajectories. In the past decade, machine learning (ML) and deep learning (DL) integration has transformed the field, providing advanced models for brain age estimation. However, achieving precise brain age prediction across all ages remains a significant analytical challenge. This comprehensive review scrutinizes advancements in ML- and DL-based brain age prediction, analyzing 52 peer-reviewed studies from 2020 to 2024. It assesses various model architectures, highlighting their effectiveness and nuances in lifespan brain age studies. By comparing ML and DL, strengths in forecasting and methodological limitations are revealed. Finally, key findings from the reviewed articles are summarized and a number of major issues related to ML/DL-based lifespan brain age prediction are discussed. Through this study, we aim at the synthesis of the current state of brain age prediction, emphasizing both advancements and persistent challenges, guiding future research, technological advancements, and improving early intervention strategies for neurodegenerative diseases.

Abstract Alternative polyadenylation (APA) plays a crucial role in cancer biology. Here, we used data from the 3′aQTL-atlas, GTEx, and the China Nanjing Lung Cancer GWAS database to explore the association between apaQTL/eQTL-SNPs and the risk of lung adenocarcinoma (LUAD). The variant T allele of rs277646 in NIT2 is associated with an increased risk of LUAD (OR = 1.12, P = 0.015), lower PDUI values, and higher NIT2 expression. The 3′RACE experiment showed multiple poly (A) sites in NIT2, with the rs277646-T allele causing preferential use of the proximal poly (A) site, resulting in a shorter 3′UTR transcript. This leads to the loss of the hsa-miR-650 binding site, thereby affecting LUAD malignant phenotypes by regulating the expression level of NIT2. Our findings may provide new insights into understanding and exploring APA events in LUAD carcinogenesis.

Aflatoxin G1 (AFG1) is a mycotoxin commonly found in agricultural products, including dried fruits, meat, and milk products. Oral AFG1 administration induced tumor necrosis factor (TNF)-α-dependent chronic pulmonary inflammation, promoting AFG1-induced damage in alveolar epithelial cell, which is associated with lung adenocarcinoma. Pulmonary macrophages may be divided into tissue-resident alveolar macrophages (TRAMs) and monocyte-derived macrophages (MoMs), which involve in chronic lung inflammation. However, whether these macrophages contribute to AFG1-induced chronic pulmonary inflammation remains unknown. In this study, we found oral AFG1 administration disrupted the balance between TRAMs and MoMs, increasing MoMs infiltration and decreasing the number of TRAMs. AFG1 upregulated TNF-α expression in MoMs, but downregulated sialic acid binding Ig-like lectin F (Siglec-F) expression in TRAMs. Inhibition of TNF-α-dependent inflammation rescued the imbalance between TRAMs and MoMs in AFG1-treated lung tissues. Additionally, AFG1 stimulated MoMs differentiation to the proinflammatory M1 phenotype in vitro. Using a specific in vitro TRAM model, AFG1 downregulated Siglec-F and the M2 phenotypic markers arginase 1 and YM1, and upregulated the M1 phenotypic markers IL-6, iNOS and TNF-α, altering the TRAMs phenotype to the pro-inflammatory M1 phenotype in vitro. Additionally, mouse maternal dietary exposure to AFG1 caused an imbalance in pulmonary macrophages, decreasing TRAMs and increasing MoMs population in offspring, which was associated with proliferative lesions in the alveolar septa. Thus, dietary AFG1 exposure triggered an imbalance in pulmonary macrophages in both mother and offspring mice, and induced pro-inflammatory phenotypic alterations, which contributed to AFG1-induced chronic lung inflammation. These results provide clues to how AFG1-induced immunotoxicity and genotoxicity in humans might be prevented.

Abstract The ubiquitination-mediated protein degradation exerts a vital role in the progression of multiple tumors. NEDD4L, which belongs to the E3 ubiquitin ligase NEDD4 family, is related to tumor genesis, metastasis and drug resistance. However, the anti-tumor role of NEDD4L in esophageal carcinoma, and the potential specific recognition substrate remain unclear. Based on public esophageal carcinoma database and clinical sample data, it was discovered in this study that the expression of NEDD4L in esophageal carcinoma was apparently lower than that in atypical hyperplastic esophageal tissue and esophageal squamous epithelium. Besides, patients with high expression of NEDD4L in esophageal carcinoma tissue had longer progression-free survival than those with low expression. Experiments in vivo and in vitro also verified that NEDD4L suppressed the growth and metastasis of esophageal carcinoma. Based on co-immunoprecipitation and proteome analysis, the NEDD4L ubiquitination-degraded protein ITGB4 was obtained. In terms of the mechanism, the HECT domain of NEDD4L specifically bound to the Galx-β domain of ITGB4, which modified the K915 site of ITGB4 in an ubiquitination manner, and promoted the ubiquitination degradation of ITGB4, thus suppressing the malignant phenotype of esophageal carcinoma.

Abstract Ferroptosis is a novel form of programmed cell death which can exacerbate lung injury in septic acute respiratory distress syndrome (ARDS). Alveolar macrophages, crucial innate immune cells, play a pivotal role in the pathogenesis of ARDS. Ferritinophagy is a process of ferritin degradation mediated by nuclear receptor coactivator 4 (NCOA4) which releases large amounts of iron ions thus promoting ferroptosis. Recent evidence revealed that inhibiting macrophage ferroptosis can effectively attenuate pulmonary inflammatory injury. Melatonin (MT), an endogenous neurohormone, has antioxidant and anti-inflammatory effects and can reduce septic ARDS. However, it is not clear whether MT’s pulmonary protective effect is related to the inhibition of macrophage ferritinophagy. Our in vitro experiments demonstrated that MT decreased intracellular malondialdehyde (MDA), Fe2+, and lipid peroxidation levels, increased glutathione (GSH) levels and cell proliferation, and upregulated glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1) protein levels in LPS-treated macrophages. Mechanistically, the antiferroptotic effect of MT on LPS-treated macrophages was significantly compromised by the overexpression of NCOA4. Our in vivo experiments revealed that MT alleviated the protein expression of NCOA4 and FTH1 in the alveolar macrophages of septic mice. Furthermore, MT improved lipid peroxidation and mitigated damage in alveolar macrophages and lung tissue, ultimately increasing the survival rates of septic mice. These findings indicate that MT can inhibit ferroptosis in an NCOA4-mediated ferritinophagy manner, thereby ameliorating septic ARDS.

The underlying therapeutic mechanisms of care farming activities have not been addressed using psychophysiological data. We aimed to understand frontal cortex activation in adults during care farming activities and to explore the psychophysiological effects. Using a randomized crossover study method, 20 adults (average age, 31.3 ± 9.8 years) participated in 10 care farming activities, (four gardening activities, three animal-mediated activities, and three off-farming activities) for 3 minutes each at an actual care farm. Electroencephalography (EEG) was performed during the activity, and emotional states were assessed using subjective emotional questionnaires after each activity. The EEG results revealed that alpha activity increased during gardening activities, such as organizing garden plots and planting plants. Spectral edge frequency 50, which predicts the degree of arousal, increased during interaction with dogs. The results of the subjective emotional questionnaire revealed that participants experienced positive emotions, such as vigor, comfort, naturalness, and relaxation, when participating in care farming activities compared with those while resting. Therefore, this study suggests that care farming activities can induce changes in the frontal cortex activation and positive emotional states in participants. This study elucidates the use of such activities to address mental health-related issues.

Abstract Background and Objective To explore the association between protein quantitative trait loci (pQTL‐SNPs) and the risk of LUAD. Methods “Blood +” high depth blood proteomics analysis was performed on plasma from female LUAD patients and female healthy controls, and combined with proteomics data from tumors and adjacent non‐tumor tissues of female LUAD patients to screen proteins uniformly expressed in plasma and tissues. pQTL‐SNPs were then screened through multiple databases and subjected to multilevel screening. The associations between selected pQTL‐SNPs and LUAD risk were evaluated by Female Lung Cancer Consortium in Asia GWAS (FLCCA GWAS). Enzyme linked immunosorbent assay (ELISA) is used to determine the levels of candidate protein. Results A total of 7 pQTL‐SNPs were significantly associated with altered LUAD risk (p 1, p

Although most source apportionments of VOCs use mixing ratios, about 23 % of published studies use mass concentrations. Thus, systematically exploring the changes in VOC source apportioned results caused by metric differences is important to assess the differences in key precursor apportionment results given the observed increases in O3 pollution situation. Different monitoring instruments measured hourly VOC volumetric concentrations in three typical Chinese cities (i.e., Qingdao, Shijiazhuang, and Zhumadian). Converting volumetric to mass concentrations under standard and/or actual temperature–pressure conditions, VOC values with different metrics were obtained. The impacts of different metrics on the source apportionments were then investigated. Compared to the positive matrix factorization of the volumetric data (VC-PMF), the VOC species concentrations with low relative molecular mass (RMM) in the factor profiles substantially decreased in mass data analyses (MC-PMF). However, those species with high RMM substantially increased. There were no substantial differences in the apportioned source contributions based on standard and actual condition mass concentrations. However, the high-low rankings of percent contributions apportioned using the volumetric and mass data produced substantial differences. Compared with the VC-PMF results, the percent contributions of sources dominated by species with low RMM (e.g., natural gas usage and mixed sources containing natural gas usage) apportioned by MC-PMF decreased, while those of sources that emitted high RMM species (e.g., solvent usage and mixed sources containing solvent usage) increased. Source apportionments based on the volumetric concentration data had more practical significance compared to the mass concentration data results for control strategy development since the mass data analyses created issues.

A 36-year-old unmarried male chef was incidentally diagnosed with hypokalemia during an evaluation for an acute perianal abscess. Despite potassium supplementation, he developed progressive weakness in his lower limbs, culminating in an inability to stand. Investigations confirmed severe hypokalemia, metabolic alkalosis, hypomagnesemia, secondary hyperaldosteronism, and low urinary calcium excretion, with normotension. The patient’s long-standing stunted growth and lean physique since childhood were noted. Biochemical assays further identified type 2 diabetes mellitus and metabolic syndrome. Genetic analysis revealed three heterozygous SLC12A3 mutations (M1: c.421G>A: p.G141R, M2: c.509T>A:p.L170Q, and M3: c.704C>A: p.T235K), compound heterozygo us and derived from both parents, with M1 and M3 reported here for the first time. Treatment with spironolactone and oral potassium chloride stabilized his potassium levels. Following the administration of SGLT2 inhibitors in patients receiving hypoglycemic therapy, we observed a mild decrease in serum sodium levels. This case highlights the criticality of vigilant metabolic surveillance in Gitelman syndrome and advises prudence with SGLT2 inhibitors in those with concurrent type 2 diabetes, given the risk of potentially aggravate sodium loss.

Microbial contamination is an important factor threatening the safety of Chinese medicine preparations, and microfluidic detection methods have demonstrated excellent advantages in the application of rapid bacterial detection. In our study, a novel optical biosensor was developed for the rapid and sensitive detection of Salmonella in traditional Chinese medicine on a microfluidic chip. Immune gold@platinum nanocatalysts (Au@PtNCs) were utilized for specific bacterial labeling, while magnetic nano-beads (MNBs) with a novel high-gradient magnetic field were employed for the specific capture of bacteria. The immune MNBs, immune Au@PtNCs, and bacterial samples were introduced into a novel passive microfluidic micromixer for full mixing, resulting in the formation of a double-antibody sandwich structure due to antigen–antibody immune reactions. Subsequently, the mixture flowed into the reaction cell, where the MNBs-Salmonella-Au@PtNCs complex was captured by the magnetic field. After washing, hydrogen peroxide-tetramethylbenzidine substrate (H2O2-TMB) was added, reacting with the Au@PtNCs peroxidase to produce a blue reaction product. This entire process was automated using a portable device, and Salmonella concentration was analyzed via a phone application. This simple biosensor has good specificity with a detection range of 9 × 101–9 × 105 CFU/mL and can detect Salmonella concentrations as low as 90 CFU/mL within 74 min. The average recoveries of the spiked samples ranged from 76.8% to 109.5%

Sodium-ion batteries (SIBs) have garnered significant interest due to their potential as viable alternatives to conventional lithium-ion batteries (LIBs), particularly in environments where low-temperature (LT) performance is crucial. This paper provides a comprehensive review of current research on LT SIBs, focusing on electrode materials, electrolytes, and operational challenges specific to sub-zero conditions. Recent advancements in electrode materials, such as carbon-based materials and titanium-based materials, are discussed for their ability to enhance ion diffusion kinetics and overall battery performance at colder temperatures. The critical role of electrolyte formulation in maintaining battery efficiency and stability under extreme cold is highlighted, alongside strategies to mitigate capacity loss and cycle degradation. Future research directions underscore the need for further improvements in energy density and durability and scalable manufacturing processes to facilitate commercial adoption. Overall, LT SIBs represent a promising frontier in energy storage technology, with ongoing efforts aimed at overcoming technical barriers to enable widespread deployment in cold-climate applications and beyond.

Abstract Background The timings of reproductive life events have been examined to be associated with various psychiatric disorders. However, studies have not considered the causal pathways from reproductive behaviors to different psychiatric disorders. This study aimed to investigate the nature of the relationships between five reproductive behaviors and twelve psychiatric disorders. Methods Firstly, we calculated genetic correlations between reproductive factors and psychiatric disorders. Then two-sample Mendelian randomization (MR) was conducted to estimate the causal associations among five reproductive behaviors, and these reproductive behaviors on twelve psychiatric disorders, using genome-wide association study (GWAS) summary data from genetic consortia. Multivariable MR was then applied to evaluate the direct effect of reproductive behaviors on these psychiatric disorders whilst accounting for other reproductive factors at different life periods. Results Univariable MR analyses provide evidence that age at menarche, age at first sexual intercourse and age at first birth have effects on one (depression), seven (anxiety disorder, ADHD, bipolar disorder, bipolar disorder II, depression, PTSD and schizophrenia) and three psychiatric disorders (ADHD, depression and PTSD) (based on p

China has focused on pre-warning risks in its national policies, under the pressure of increasing risks associated with urbanization. While developing restrictive indicators assists the government in risk management, tracking the risks associated with urbanization and identifying their critical points remains relatively rare. We addressed this gap by presenting a general framework to quantify the potential risks of urbanization. Within this framework, early warning indicators were selected from four risk dimensions associated with urbanization in China, which include population development, economic growth, resource sustainability, and environmental protection. We then analyzed the historical characteristics of these indicators from 1980 to 2020 using the Hodrick-Prescott (HP) filter method and predicted the trend from 2021 to 2030 using the Auto-Regressive Moving Average (ARMA) model. The findings were as follows: (1) A complete cycle was observed for most indicators within 10 years, and cyclical fluctuations were sensitive to changes in national policies and the external environment, with tipping points after 1–2 years. (2) Certain indicators showed risk warning signals in the next cycle, including total fertility rate, urban unemployment rate, and urban water consumption. The prediction results of these indicators provided thresholds for policy intervention. (3) As indicated by the warning signals, negative population growth, rising unemployment, and the gap between supply and demand of water resources were the main risk factors for urbanization in China. Some policy suggestions were provided for risk response, including dealing with women's job security and work-life balance, ensuring employment opportunities for vulnerable groups, accelerating the upgrading of the tertiary industry to expand domestic market demand, and strictly controlling the consumption of limited resources. These results present contribute to the formulation of national urbanization policies and development plans.

Background: Prostate cancer (PCa) is one of the most prevalent malignancies affecting the male life cycle. The incidence and mortality of prostate cancer are also increasing every year. Detection of MicroRNA expression in serum to diagnose prostate cancer and determine prognosis is a very promising non-invasive modality.Materials and method: A total of 224 study participants were included in our study, including 112 prostate cancer patients and 112 healthy adults. The experiment consisted of three main phases, namely, the screening phase, the testing phase, and the validation phase. The expression levels of serum miRNAs in patients and healthy adults were detected using quantitative reverse transcription-polymerase chain reaction. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to evaluate the diagnostic ability, specificity, and sensitivity of the candidate miRNAs.Result: Eventually, three miRNAs most relevant to prostate cancer diagnosis were selected, namely, miR-106b-5p, miR-129-1-3p and miR-381-3p. We used these three miRNAs to construct a diagnostic panel with very high diagnostic potential for prostate cancer, which had an AUC of 0.912 [95% confidence interval (CI): 0.858 to 0.950; p < 0.001; sensitivity = 91.67%; specificity = 79.76%]. In addition, the three target genes (DTNA, GJB1, and TRPC4) we searched for are also expected to be used for prostate cancer diagnosis and treatment in the future.

Abstract Background Amphibian derived pro-healing peptides as molecular probes might provide a promising strategy for development of drug candidates and elucidation of cellular and molecular mechanisms of skin wound healing. A novel skin amphibian peptide, OA-RD17, was tested for modulation of cellular and molecular mechanisms associated with skin wound healing. Methods Cell scratch, cell proliferation, trans-well, and colony formation assays were used to explore the pro-healing ability of peptide OA-RD17 and microRNA-632 (miR-632). Then, the therapeutic effects of OA-RD17 and miR-632 were assessed in mice, diabetic patient ex vivo skin wounds and SD rats. Moreover, hematoxylin and eosin (H&E), enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and immunofluorescence staining were performed to detect skin wound tissue regeneration, inflammatory factors expression, and macrophage polarization. Finally, RNA sequencing, molecular docking, co-localization, dual luciferase reporter, real-time quantitative reverse transcription PCR (RT-qPCR), and Western blotting were used to explore the mechanism of OA-RD17 and miR-632 on facilitating skin wound healing. Results The non-toxic peptide (OA-RD17) promoted macrophage proliferation and migration by activating MAPK and suppressed inflammation by inhibiting NF-κB. In keratinocytes, OA-RD17 inhibited excessive inflammation, and activated MAPK via the Toll-like receptor 4 (TLR4) to promote proliferation and migration, as well as up-regulate the expression of miR-632, which targeted GSK3β to activate Wnt/β-catenin to boost proliferation and migration in a positive feedback manner. Notably, OA-RD17 promoted transition from the inflammatory to proliferative stage, accelerated epidermal and granulation regeneration, and exhibited therapeutic effects on mouse and diabetic patient ex vivo skin wounds. MiR-632 activated Wnt/β-catenin to promote full-thickness skin wound healing in rats. Conclusions OA-RD17 exhibited promising therapeutic effects on mice (full-thickness, deep second-degree burns), and ex vivo skin wounds in diabetic patients by regulating macrophages proliferation, migration, and polarization (MAPK, NF-κB), and keratinocytes proliferation and migration (TLR4/MAPK/miR-632/Wnt/β-catenin molecular axis). Moreover, miR-632 also activated Wnt/β-catenin to promote full-thickness skin wound healing in rats. Notably, our results indicate that OA-RD17 and miR-632 are promising pro-healing drug candidates. Graphical Abstract

This study investigates the relationship between modifiable risk factors and dementia subtypes using data from 460,799 participants in the UK Biobank. Utilizing univariate Cox proportional hazards regression models, we examined the associations between 83 modifiable risk factors and the risks of all-cause dementia (ACD), Alzheimer’s disease (AD), and vascular dementia (VD). Composite scores for different domains were generated by aggregating risk factors associated with ACD, AD, and VD, respectively, and their joint associations were assessed in multivariable Cox models. Additionally, population attributable fractions (PAF) were utilized to estimate the potential impact of eliminating adverse characteristics of the risk domains. Our findings revealed that an unfavorable medical history significantly increased the risk of ACD, AD, and VD (hazard ratios (HR) = 1.88, 95% confidence interval (95% CI): 1.74–2.03, p < 0.001; HR = 1.80, 95% CI: 1.54–2.10, p < 0.001; HR = 2.39, 95% CI: 2.10–2.71, p < 0.001, respectively). Blood markers (PAF = 12.1%; 17.4%) emerged as the most important risk domain for preventing ACD and VD, while psychiatric factors (PAF = 18.3%) were the most important for preventing AD. This study underscores the potential for preventing dementia and its subtypes through targeted interventions for modifiable risk factors. The distinct insights provided by HR and PAF emphasize the importance of considering both the strength of the associations and the population-level impact of dementia prevention strategies. Our research provides valuable guidance for developing effective public health interventions aimed at reducing the burden of dementia, representing a significant advancement in the field.

As a World Natural Heritage Site primarily focused on protecting migratory bird habitats, the Yancheng coastal wetland is also an important land resource reserve area in China. With a long history of reclamation, the impact of reclamation on waterbird habitats has attracted widespread attention. Therefore, this study was based on the distribution data of wintering Anatidae from 1987 to 2020 and coastal land reclamation data. The landscape development intensity (LDI) index and MaxEnt model were used to reveal the spatiotemporal changes in reclamation development intensity and identify the spatiotemporal evolution characteristics of Anatidae habitats. A geographical weight regression (GWR) model was used to analyze the local differences for the impact of changes in reclamation development intensity on the spatiotemporal distribution of Anatidae habitats. The results showed that the area of land types with higher reclamation intensity in the study area increased rapidly from 1987 to 2020, and the overall reclamation intensity showed a pattern of low in the northeast and high in the southwest. The high-intensity range in 1987 was 5.01 ∼ 6.00, and the reclamation intensity in the western area of Dafeng to Tiaozini was generally greater than 8.01 in 2020. From 1987 to 2020, the population of Anatidae first decreased and then increased, with a clear southward shift in spatial distribution. The evaluation results of suitable habitats revealed that the most suitable area significantly declined from 1280.76 hm2 in 1997 to 60.19 hm2 in 2020, which indicated that the patch space of high-quality habitats was further compressed. The area with the greatest positive impact for the intensity of reclamation and development on habitat suitability from 1987 to 1997 was concentrated near the Beihuanchong area, while in 2007, the negative impact was mostly distributed in the northern and western Hexin area. The regression coefficient ranged from −0.665 ∼ -0.513. The negative impact of reclamation and development further deteriorated in 2020, with a negative correlation coefficient ranging from −1.642 ∼ -0.699. There were significant differences in the impact of environmental variables on the distribution of Anatidae habitats in different periods. In this study, a habitat protection and restoration pattern for Anatidae is proposed, which may provide an important reference for the protection of wintering Anatidae populations and the structural restoration of habitats in Yancheng coastal wetlands.

Summary: Micro-supercapacitors (MSCs) stand out in the field of micro energy storage devices due to their high power density, long cycle life, and environmental friendliness. The key to improving the electrochemical performance of MSCs is the selection of appropriate electrode materials. To date, both the composition and structure of electrode materials in MSCs have become a hot research topic, and it is urgent to compose a review to highlight the most important research achievements, major challenges, opportunities, and encouraging perspectives in this field. In this review, research background of MSCs is first reviewed followed by their working principles, structural classifications, and physiochemical and electrochemical characterization techniques. Next, various materials and preparation methods are summarized, and the relationship between the MSC performance and structure and composition of materials are discussed in depth. Finally, this review provides a comprehensive suggestion on accelerating the development of electrode materials to facilitate the commercialization of MSCs.

Abstract Batteries dissolving active materials in liquids possess safety and size advantages compared to solid‐based batteries, yet the intrinsic liquid properties lead to material cross‐over induced self‐discharge both during cycling and idle when the electrolytes are in contact, thus highly efficient and cost‐effective solutions to minimize cross‐over are in high demand. An ultra‐low self‐discharge aqueous|organic membraneless battery using dichloromethane (CH2Cl2) and tetrabutylammonium bromide (TBABr) added to a zinc bromide (ZnBr2) solution as the electrolyte is demonstrated. The polybromide is confined in the organic phase, and bromine (Br2) diffusion‐induced self‐discharge is minimized. At 90% state of charge (SOC), the membraneless ZnBr2|TBABr (Z|T) battery shows an open circuit voltage (OCV) drop of only 42 mV after 120 days, 152 times longer than the ZnBr2 battery, and superior to 102 previous reports from all types of liquid active material batteries. The 120‐day capacity retention of 95.5% is higher than commercial zinc‐nickel (Zn–Ni) batteries and vanadium redox flow batteries (VRFB, electrolytes stored separately) and close to lithium‐ion (Li‐ion) batteries. Z|T achieves >500 cycles (2670 h, 0.5 m electrolyte, 250 folds of membraneless ZnBr2 battery) with ≈100% Coulombic efficiency (CE). The simple and cost‐effective design of Z|T provides a conceptual inspiration to regulate material cross‐over in liquid‐based batteries to realize extended operation.

Pseudomonas aeruginosa is an opportunistic human pathogen causing various severe infections. Understanding genetic mechanisms of its metabolic versatility aids in developing novel antibacterial drugs and therapeutic strategies to address multidrug-resistant P. aeruginosa infections. The metabolism of nucleotides and amino acids contributes to the cycle of two key biological macromolecules in the genetic central dogma. Guanine deaminase (GuaD) catalyzes the deamination of guanine to produce xanthine to maintain the homeostasis of the nucleotide pool, and transporters specific to BCAAs (termed as BraT) import BCAAs to keep its intracellular availability level. However, little is known about the evolution of GuaD and BraT in P. aeruginosa population. Here, two copies turned out to be widespread in P. aeruginosa population for each of GuaD and BraT. The phylogenic analysis demonstrated that GuaD1 and BraB were inherited from the ancestor of Pseudomonas, while GuaD2 and BraZ were additionally acquired via evolutionary events in the ancestors of P. aeruginosa. The functional divergence of two copies was supported by different distribution patterns of dN/dS ratios, divergent expression levels, differentially co-expressed genes, and their functional enrichment modules with few intersections. Besides, some co-expressed genes with known functions are involved in infecting hosts, forming biofilm and resisting antibiotic treatment. Taken together, functional divergence following copy number increase and differentiation of co-expression networks might confer greater metabolic potential to P. aeruginosa, especially in response to host immune responses and antibiotic treatments in clinical settings.

Abstract Osteoporosis is associated with excessive activity of osteoclasts. In bone turn over, most osteoclasts undergo apoptosis after bone resorption and produce a large number of apoptotic bodies (ABs). However, the biological function of osteoclast-derived apoptotic bodies (OC-ABs) in the progression of osteoporosis is still unknow. In our study, we identified a reduction of OC-AB quantity in the bone marrow cavity during the progression of osteoporosis, an apoptotic body-deficient MRL/lpr mice were used to study the pro-osteogenic ability of OC-ABs. Mechanistically, OC-ABs promote osteogenesis of bone mesenchymal stem cells (BMSCs) by activating the downstream mTOR pathway via RANKL-mediated reverse signaling. Moreover, systemic infusion of exogenous OC-ABs effectively delayed the bone loss in ovariectomized (OVX) mice, validated the role of OC-ABs as bone protective factor in the pathogenesis of osteoporosis. Taken together, our study elucidates the biological function of OC-ABs in the pathological progression of osteoporotic bone loss and suggests a potential therapeutic strategy to delay bone loss.

Abstract Background Titanium (Ti) is now widely used as implant material due to its excellent mechanical properties and superior biocompatibilities, while its inert bioactivities might lead to insufficient osseointegration, and limit its performance in dental applications. Methods We introduced a robust and simple approach of modifying titanium surfaces with polysaccharide complexes. Titanium samples were subjected to hydrothermal treatment to create a uniform porous structure on the surface, followed by coating with a bioinspired and self-assembly polydopamine layer. Strontium Eucommia Ulmoides Polysaccharide (EUP-Sr) complexes are then introduced to the polydopamine-coated porous titanium. Multiple morphological and physiochemical characterizations are employed for material evaluation, while cell proliferation and gene expression tests using macrophages, primary alveolar bone osteoblasts, and vascular endothelial cells are used to provide an overall insight into the functions of the product. The significances of statistical differences were analyzed using student’s t-test. Results Microscopic and spectrometric characterizations confirmed that the Ti surface formed a porous structure with an adequate amount of EUP-Sr loading. The attachment was attributed to hydrogen bonding between the ubiquitous glycosidic linkage of the polysaccharide complex and the ring structure of polydopamine, yet the loaded EUP-Sr complex can be gradually released, consequently benefiting the neighboring microenvironment. Cell experiments showed no cytotoxicity of the material, and the product showed promising anti-inflammation, osseointegration, and angiogenesis properties, which were further confirmed by in vivo evaluations. Conclusion We believe the EUP-Sr modified titanium implant is a promising candidate to be used in dental applications with notable osteoimmunomodulation and angiogenesis functions. And the novel technique proposed in this study would benefit the modification of metal/inorganic surfaces with polysaccharides for future research.

Abstract Background Despite considerable efforts, ischemic stroke (IS) remains a challenging clinical problem. Therefore, the discovery of effective therapeutic and targeted drugs based on the underlying molecular mechanism is crucial for effective IS treatment. Methods A cDNA-encoding peptide was cloned from RNA extracted from Rana limnocharis skin, and the mature amino acid sequence was predicted and synthesized. Hemolysis and acute toxicity of the peptide were tested. Furthermore, its neuroprotective properties were evaluated using a middle cerebral artery occlusion/reperfusion (MCAO/R) model in rats and an oxygen–glucose deprivation/reperfusion (OGD/R) model in neuron-like PC12 cells. The underlying molecular mechanisms were explored using microRNA (miRNA) sequencing, quantitative real-time polymerase chain reaction, dual-luciferase reporter gene assay, and western blotting. Results A new peptide (NP1) with an amino acid sequence of ‘FLPAAICLVIKTC’ was identified. NP1 showed no obvious toxicities in vivo and in vitro and was able to cross the blood–brain barrier. Intraperitoneal administration of NP1 (10 nmol/kg) effectively reduced the volume of cerebral infarction and relieved neurological dysfunction in MCAO/R model rats. Moreover, NP1 significantly alleviated the decrease in viability and increase in apoptosis of neuron-like PC12 cells induced by OGD/R. NP1 effectively suppressed inflammation by reducing interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels in vitro and in vivo. Furthermore, NP1 up-regulated the expression of miR-6328, which, in turn, down-regulated kappa B kinase β (IKKβ). IKKβ reduced the phosphorylation of nuclear factor-kappa B p65 (NF-κB p65) and inhibitor of NF-κB (I-κB), thereby inhibiting activation of the NF-κB pathway. Conclusions The newly discovered non-toxic peptide NP1 (‘FLPAAICLVIKTC’) exerted neuroprotective effects on cerebral ischemia–reperfusion injury by reducing inflammation via the miR-6328/IKKβ/NF-κB axis. Our findings not only provide an exogenous peptide drug candidate and endogenous small nucleic acid drug candidate but also a new drug target for the treatment of IS. This study highlights the importance of peptides in the development of new drugs, elucidation of pathological mechanisms, and discovery of new drug targets.

Abstract Background The high prevalence of depression among older people in China places a heavy burden on the health system. Multimorbidity, mobility limitation and subjective memory impairment are found to be risk indicators for depression. However, most studies on this topic focused on depression at a single point in time, ignoring the dynamic changes in depressive symptoms and the relationship between the trajectories and these three conditions. Therefore, we aimed to identify distinct trajectories of depressive symptoms in older people and investigate their associations with multimorbidity, mobility limitation and subjective memory impairment. Methods Data was drawn from China Health and Retirement Longitudinal Study conducted during 2011–2018. A total of 5196 participants who completed 4 visits, conducted every 2–3 years were included in this study. Group-based trajectory modeling was conducted to identify distinct trajectories of depressive symptoms z-scores. Multinomial logistic regression was used to investigate the relationships. Results Four distinct trajectories of depressive symptoms z-scores were identified, labeled as persistently low symptoms (68.69%, n = 3569), increasing symptoms (12.14%, n = 631), decreasing symptoms (14.05%, n = 730) and persistently high symptoms (5.12%, n = 266). Participants with multimorbidity had unfavorable trajectories of depressive symptoms compared with those without multimorbidity, with adjusted odds ratios (95% CIs) of 1.40 (1.15, 1.70), 1.59 (1.33, 1.90) and 2.19 (1.65, 2.90) for the increasing symptoms, decreasing symptoms and persistently high symptoms, respectively. We also observed a similar trend among participants with mobility limitations. Compared with participants who had poor subjective memory, participants with excellent/very good/good subjective memory had a lower risk of developing unfavorable trajectories of depressive symptoms. The adjusted odds ratios (95% CIs) of the increasing symptoms, decreasing symptoms and persistently high symptoms were 0.54 (0.40, 0.72), 0.50 (0.38, 0.65) and 0.48 (0.31, 0.73), respectively. Conclusions Multimorbidity, mobility limitation and subjective memory impairment were found to be potential risk factors for unfavorable depression trajectories.

Summary: The role of alternative polyadenylation (APA) in tumor development is becoming increasingly evident, but the impact of APA events on the prognosis of LUAD patients is unclear. Therefore, in the present study, we aimed to analyze specific APA events in LUAD to identify novel prognostic biomarkers for LUAD. We first identified prognostic candidate genes for LUAD associated with APA events and validated them in both the East Asian and the USA cohorts, finding that five genes (DCUN1D5, PSMC4, TFAM, THRA, and TMEM100) were of prognostic significance in both populations. Based on this, an APA-based prognostic signature was constructed for the East Asian population. The predictive accuracy of the prognostic signature was further evaluated by the time-dependent ROC, with 1-, 2-, and 3-year AUCs of 0.86, 0.81, and 0.71, respectively. This study may provide new markers for individualized diagnosis and prognostic assessment of LUAD and potential targets for precision treatment.