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Lin Zhang, Shou-Ying Du, Yang Lu, Chang Liu, Zhi-Hao Tian, Chang Yang, Hui-Chao Wu, Zhen Wang School of Chinese Materia Medica, Beijing University of Chinese Medicine, Chaoyang District, Beijing, People’s Republic of China Abstract: Nasal administration is a high-potential delivery system, particularly because it can provide a pathway from the nose to the brain. The objective of this research is to characterize puerarin transport across a Calu-3 cell monolayer used as a model of the nasal mucosa and to evaluate the influence of puerarin in combination with paeoniflorin and menthol to explore the enhanced mechanism of the permeability at the cell level. The apparent permeability coefficients (Papp) of puerarin bidirectional transport were both 0.05). However, the addition of menthol significantly (P

Abstract Introduction Smoking has been recognized as a contributing factor to frailty in older adults. Nevertheless, it remains uncertain whether the degree of smoking has a discernible impact on frailty among older smokers. This cross-sectional study was conducted to investigate the correlation between serum cotinine levels, a biomarker reflecting tobacco exposure, and the presence of frailty within a nationally representative cohort of older adults. Method A total of 1626 individuals aged ≥ 60 who identified as smokers were included in the analysis. Participants were selected based on self-reported current smoking status. According to the Fried Phenotype, frailty is assessed through five dimensions: unintentional weight loss, slow walking speed, weakness, self-reported exhaustion, and low physical activity. Participants with three or more of these conditions were categorized as frailty, those with at least one but less than three as pre-frailty, and those with none as robust. Multinomial logistic regression models were employed to explore the relationship between serum cotinine level quartiles, with the lowest quartile as the reference group, and the various frailty statuses, with robustness as the reference category. These models were adjusted for covariates, including age, sex, race/ethnicity, alcohol drinking, daily protein intake, systolic blood pressure, serum albumin level, depressive symptoms, and cognitive function. The data used for this analysis were sourced from the National Health and Nutrition Examination Survey for the years 2011 to 2014. Results The median age of the participants was 69.0 years. The majority were male (62.2%) and non-Hispanic White (49.0%). The distribution of frailty statuses among the participants revealed that the highest proportion had pre-frailty (50.7%), followed by robustness (41.1%), and frailty (8.2%). Multinomial logistic regression showed that participants in the 4th quartile of serum cotinine level exhibited a higher probability of pre-frailty versus robustness (Odds ratio [OR] 1.599, 95% confidence interval [CI] 1.017, 2.513, P = 0.042). Participants in the 3rd quartile of serum cotinine level had higher odds of frailty versus robustness (OR 2.403, 95% CI 1.125, 5.134, P = 0.024). Moreover, participants whose serum cotinine levels were higher than the literature cutoffs (≥ 15 ng/ml) were more likely to be pre-frail (Odds ratio [OR] 1.478, 95% confidence interval [CI] 1.017, 2.150, P = 0.035) or frail (Odds ratio [OR] 2.141, 95% confidence interval [CI] 1.054, 4.351, P = 0.041). Conclusions A higher serum cotinine level is linked to an elevated probability of pre-frailty and frailty among older smokers. Initiatives geared towards assisting older smokers in reducing or quitting their smoking habits might possibly play a crucial role in preventing pre-frailty and frailty.

Abstract Wheat is a crucial crop worldwide, and accurate detection and counting of wheat spikes are vital for yield estimation and breeding. However, these tasks are daunting in complex field environments. To tackle this, we introduce RIA-SpikeNet, a model designed to detect and count wheat spikes in such conditions. First, we introduce an Implicit Decoupling Detection Head to incorporate more implicit knowledge, enabling the model to better distinguish visually similar wheat spikes. Second, Asymmetric Loss is employed as the confidence loss function, enhancing the learning weights of positive and hard samples, thus improving performance in complex scenes. Lastly, the backbone network is modified through reparameterization and the use of larger convolutional kernels, expanding the effective receptive field and improving shape information extraction. These enhancements significantly improve the model’s ability to detect and count wheat spikes accurately. RIA-SpikeNet outperforms the state-of-the-art YOLOv8 detection model, achieving a competitive 81.54% mAP and 90.29% R2. The model demonstrates superior performance in challenging scenarios, providing an effective tool for wheat spike yield estimation in field environments and valuable support for wheat production and breeding efforts.

Abstract Excessive production of reactive oxygen species (ROS) around titanium implants under diabetic conditions causes persistent inflammation, leading to poor osseointegration and even implant failure. Surface modification is an effective way to promote ROS clearance, alleviate inflammation, and stimulate bone formation. In this study, a multifunctional coating is fabricated by introducing cerium (Ce)-containing mesoporous bioactive glass nanoparticles (Ce-MBGNs) onto the titanium surface via an electrophoretic deposition method. The incorporation of Ce-MBGNs remarkably improves surface hydrophilicity by increasing the surface areas. The bioactive ions are appropriately released, thereby promoting mesenchymal stem cell proliferation and differentiation under diabetic conditions. The conversion between Ce(III) and Ce(IV) endows Ce-MBGNs coating with antioxidative nanoenzymes properties to scavenge diabetes-induced ROS, resulting in macrophage polarization towards the anti-inflammatory phenotype. The therapeutic effect of Ce-MBGNs-modified titanium implants is also verified in diabetic rats by inhibiting inflammatory responses and accelerating early osseointegration. Taken together, the findings reveal that the ROS-scavenging and immunomodulation activity of the Ce-MBGNs coating contributes to enhanced osseointegration, and provides a novel implant surface for diabetic patients.

Abstract Global measurements of ocean p C O 2 are critical to monitor and understand changes in the global carbon cycle. However, p C O 2 observations remain sparse as they are mostly collected on opportunistic ship tracks. Several approaches, especially based on direct learning, have been used to upscale and extrapolate sparse point data to dense estimates using globally available input features. However, these estimates tend to exhibit spatially heterogeneous performance. As a result, we propose a physics-informed transfer learning workflow to generate dense p C O 2 estimates that are grounded in real-world measurements and remain physically consistent. The models are initially trained on dense input predictors against p C O 2 estimates from Earth system model simulation, and then fine-tuned to sparse SOCAT observational data. Compared to the benchmark direct learning approach, our transfer learning framework shows major improvements of up to 56-92%. Furthermore, we demonstrate that using models that explicitly account for spatiotemporal structures in the data yield better validation performances by 50-68%. Our strategy thus presents a new monthly global p C O 2 estimate that spans for 35 years between 1982-2017.

Objective·To investigate the imaging features of computed tomography (CT) and magnetic resonance imaging (MRI) in the patients with Kimura disease (KD) in the head and neck.Methods·Sixty-four cases of KD in the head and neck comfirmed by histopathology were retrospectively collected from 2009 to 2023 in Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine. All patients completed CT and/or MRI enhancement imaging before surgery. Clinical and imaging characteristics were collected, recorded and analyzed, including age, gender, peripheral blood eosinophilic ratio, serum IgE level, the lesion location, shape, size, CT density and degree of enhancement, MRI signal intensity and degree of enhancement, apparent diffusion coefficient (ADC), time-signal intensity curve (TIC) patterns, wash-in rate, and time to peak (TTP).Results·The average age of the 64 KD patients was (40±19) years, and 92.2% were males. A total of 73.5% of the patients showed an elevated ratio of peripheral blood eosinophil, and all 10 tested patients exhibited increased serum IgE levels. There were 82 extranodal (subcutaneous and glandular) lesions and 144 lymph node lesions detected by CT and MRI. Among the extranodal lesions, 80.5% were subcutaneous or glandular patchy lesions with unclear boundaries, and the rest were nodular lesions with clear boundaries. All lesions exhibited isodensity on CT scans and showed isointensity on T1-weighted imaging (T1WI) and hyperintensity on T2-weighted imaging (T2WI) in MRI. Most extranodal lesions tended to show heterogeneous enhancement, while most lymph node lesions showed homogeneous enhancement. The median ADCs of the extranodal lesions and the lymph node lesions were 1.04×10-3 mm2/s and 0.67×10-3 mm2/s, respectively, which were significantly different (P=0.000). The dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) results showed that the TIC patterns of extranodal lesions were predominantly type Ⅰ and Ⅱ, accounting for 57.5% and 42.5%, respectively; while the TIC patterns of lymph node lesions were predominantly type Ⅱ (96.6%). The difference in the TTP and the wash-in rate between the extranodal lesions and the lymph node lesions were both statistically significant (P=0.000).Conclusion·Extranodal lesions and lymph node lesions of KD both show isodensity on CT, and isointensity on T1WI and hyperintensity on T2WI in MRI. Extranodal lesions often show high ADC, TIC type Ⅰ or Ⅱ, and mostly heterogeneous enhancement; lymph node lesions often show low ADC, TIC type Ⅱ, and mostly homogenous enhancement.

Abstract Objective To evaluate early bone marrow microvascular changes in alloxan-induced diabetic rabbits using IDEAL-IQ fat quantification, texture analysis based on DCE-MRI Ktrans map, and metabolomics. Materials and methods 24 male Japanese rabbits were randomly divided into diabetic (n = 12) and control (n = 12) groups. All rabbits underwent sagittal MRI of the lumbar vertebrae at the 0th,4th, 8th, 12th, and 16th week, respectively. The fat fraction (FF) ratio and quantitative permeability of the lumbar bone marrow was measured. Texture parameters were extracted from DCE-MRI Ktrans map. At 16th week, lumbar vertebrae 5 and 6 were used for histological analysis. Lumbar vertebra 7 was crushed to obtain bone marrow for metabolomics research. Results The FF ratio and Ktrans of the lumbar bone marrow in diabetic group were increased significantly at 16th week (t = 2.226, P = 0.02; Z = -2.721, P

Abstract Background Patients with non‐small cell lung cancer (NSCLC) with liver metastasis have a poor prognosis, and there are no reliable biomarkers for predicting disease progression. Currently, no recognized and reliable prediction model exists to anticipate liver metastasis in NSCLC, nor have the risk factors influencing its onset time been thoroughly explored. Methods This study conducted a retrospective analysis of 434 NSCLC patients from two hospitals to assess the association between the risk and timing of liver metastasis, as well as several variables. Results The patients were divided into two groups: those without liver metastasis and those with liver metastasis. We constructed a nomogram model for predicting liver metastasis in NSCLC, incorporating elements such as T stage, N stage, M stage, lack of past radical lung cancer surgery, and programmed death ligand 1 (PD‐L1) levels. Furthermore, NSCLC patients with wild‐type EGFR, no prior therapy with tyrosine kinase inhibitors (TKIs), and no prior radical lung cancer surgery showed an elevated risk of early liver metastasis. Conclusion In conclusion, the nomogram model developed in this study has the potential to become a simple, intuitive, and customizable clinical tool for assessing the risk of liver metastasis in NSCLC patients following validation. Furthermore, it provides a framework for investigating the timing of metachronous liver metastasis.

In order to solve the problem of respirable dust pollution in the heading face, a multi-layer spiral spray dust removal method was proposed, in which supersonic pneumatic nozzles were arranged in a spiral shape. Taking the heading face of Qipan Coal Mine as the research object, the three-dimensional numerical model of multi-layer spiral spray dust removal technology device was established by using discrete element and finite element method and k-ω turbulence model and fluid flow particle tracking model in COMSOL software. The velocity field of multi-layer spiral spray air flow, velocity section and trajectory of water mist particles were obtained. The simulation results show that the airflow velocity at the cutting head of the TBM is faster, the farther away from the cutting head, the smaller the airflow velocity, and the airflow near the cutting head is very disorganized; after the nozzle is opened, the water mist particles will form a multi-layer spiral fog curtain, and the spiral fog curtain will cover the entire simulated driving surface after 20 s, and the particle size of the water mist particles is smaller than that of the traditional spray method.

Abstract Low-frequency repetitive transcranial magnetic stimulation (rTMS) has emerged as an effective intervention for alleviating symptoms of psychiatric disorders, particularly schizophrenia characterized by persistent auditory verbal hallucinations (AVH). However, the underlying mechanism of its action remain elusive. This study employed a randomized controlled design to investigate the impact of low-frequency rTMS on the neural connectivity at the stimulate site, specifically left temporoparietal junction (TPJ), in schizophrenia patients with suffering from AVH. Using Dynamic Causal Modeling (DCM), this study assessed changes in directed connectivity patterns and their correlations with clinical symptomatology. The results demonstrated significant improvements in AVH. Notably, significant changes in connectivity were observed, including both abnormal functional connectivity and effective connectivity among multiple brain regions. Particularly, the inhibition effects from the left precentral gyrus and left medial superior frontal gyrus to the left TPJ were closely associated with improvements in AVH. These findings underscore the potential of rTMS to effectively modulate neural pathways implicated in hallucinations in schizophrenia, thereby providing a neurobiological foundation for its therapeutic effects.

Abstract Pseudomonas aeruginosa is a widespread nosocomial pathogen with a significant to cause both severe planktonic acute and biofilm-related chronic infections. Small RNAs (sRNAs) are noncoding regulatory molecules that are stabilized by the RNA chaperone Hfq to trigger various virulence-related signaling pathways. Here, we identified an Hfq-binding sRNA in P. aeruginosa PAO1, PqsS, which promotes bacterial pathogenicity and pseudomonas quinolone signal quorum sensing (pqs QS) system. Specifically, PqsS enhanced acute bacterial infections by inducing host cell death and promoting rhamnolipid-regulated swarming motility. Meanwhile, PqsS reduced chronic infection traits including biofilm formation and antibiotic resistance. Moreover, PqsS repressed pqsL transcript, increasing PQS levels for pqs QS. A PQS-rich environment promoted PqsS expression, thus forming a positive feedback loop. Furthermore, we demonstrated that the PqsS interacts and destabilizes the pqsL mRNA by recruiting RNase E to drive degradation. These findings provide insights for future research on P. aeruginosa pathogenesis and targeted treatment.

Abstract Ferroptosis, triggered by iron overload and excessive lipid peroxidation, plays a pivotal role in the progression of DOX-induced cardiomyopathy (DIC), and thus limits the use of doxorubicin (DOX) in clinic. Here, we further showed that cardiac ferroptosis induced by DOX in mice was attributed to up-regulation of Hmox1, as knockdown of Hmox1 effectively inhibited cardiomyocyte ferroptosis. To targeted delivery of siRNA into cardiomyocytes, siRNA-encapsulated exosomes were injected followed by ultrasound microbubble targeted destruction (UTMD) in the heart region. UTMD greatly facilitated exosome delivery into heart. Consistently, UTMD assisted exosomal delivery of siHomox1 nearly blocked the ferroptosis and the subsequent cardiotoxicity induced by doxorubicin. In summary, our findings reveal that the upregulation of HMOX1 induces ferroptosis in cardiomyocytes and UTMD-assisted exosomal delivery of siHmox1 can be used as a potential therapeutic strategy for DIC. Graphical Abstract

In order to explore the high temperature performance of Cr2O3/8YSZ composite coating, four kinds of Cr2O3/8YSZ composite coatings were prepared on the surface of Q235 steel by using the plasma spraying technology (the content of 8YSZ is 50%, 30%, 20% and 0%, respectively). The morphology of the coating was characterized through thermal field emission scanning electron microscopy, and the distribution of elements in the section of the coating was scanned by using EDS line. The phase composition of the composite coating was analyzed by using X-ray diffractometer, and the surface roughness of the composite coating was measured by using surface profilometer. The microhardness of the coating was measured by using automatic micro-Vickers hardness tester, and the scratch resistance of the coating was compared by using scratch tester. The thermal shock resistance of the coating was tested in Gleeble-3800 thermal physical simulator, and the cross section morphology after thermal shock was observed and analyzed. The results show that when the ratio of Cr2O3 to 8YSZ is 7∶3, the sample coating has good thermal shock resistance due to the deflection effect of 8YSZ on the vertical cracks and the thermal stress release effect of the pores and cracks in the coating.

[Objective] The objective of this study was to analyze the spatial distribution characteristics of surface soil moisture content in the rocky desertification slope under different land preparation measures and to provide references for improving water resources utilization efficiency and agricultural management level on rocky desertification slopes. [Methods] The citrus forest under three land preparation measures of reverse slope, flat terrace, and natural slope on rocky desertification slope were chosen as the research objects. Classical statistics, geostatistics and multifractal theory were used to analyze the spatial distribution characteristics of soil moisture content. [Results] (1) The soil moisture content of the reverse slope was significantly higher than that of the flat terrace and the natural slope (p

N-linked glycosylation is a common posttranslational modification of proteins that results in macroheterogeneity of the modification site. However, unlike simpler modifications, N-glycosylation introduces an additional layer of complexity with tens of thousands of possible structures arising from various dimensions, including different monosaccharide compositions, sequence structures, linking structures, isomerism, and three-dimensional conformations. This results in additional microheterogeneity of the modification site of N-glycosylation, i.e., the same N-glycosylation site can be modified with different glycans with a certain stoichiometric ratio. N-glycosylation regulates the structure and function of N-glycoproteins in a site- and structure-specific manner, and differential expression of N-glycosylation under disease conditions needs to be characterized through site- and structure-specific quantitative analysis. Numerous advanced methods ranging from sample preparation to mass spectrum analysis have been developed to distinguish N-glycan structures. Chemical derivatization of monosaccharides, online liquid chromatography separation and ion mobility spectrometry enable the physical differentiation of samples. Tandem mass spectrometry further analyzes the macro/microheterogeneity of intact N-glycopeptides through the analysis of fragment ions. Moreover, the development of search engines and AI-based software has enhanced our understanding of the dissociation patterns of intact N-glycopeptides and the clinical significance of differentially expressed intact N-glycopeptides. With the help of these modern methods, structure-specific N-glycoproteomics has become an important tool with extensive applications in the biomedical field.

Abstract The nucleolus, a recognized biomolecular condensate, serves as the hub for ribosome biogenesis within the cell nucleus. Its quantity and morphology are discernible indicators of cellular functional states. However, precise identification and quantification of nucleoli remain challenging without specific labeling, particularly for suspended cells, tissue-level analysis and high-throughput applications. Here we introduce a single-cell laser emitting cytometry (SLEC) for label-free nucleolus differentiation through light-matter interactions within a Fabry–Perot resonator. The separated gain medium enhances the threshold difference by 36-fold between nucleolus and its surroundings, enabling selective laser emissions at nucleolar area while maintaining lower-order mode. The laser emission image provides insights into structural inhomogeneity, temporal fluid-like dynamics, and pathological application. Lasing spectral fingerprint depicts the quantity and size of nucleoli within a single cell, showcasing the label-free flow cytometry for nucleolus. This approach holds promise for nucleolus-guided cell screening and drug evaluation, advancing the study of diseases such as cancer and neurodegenerative disorders.

Abstract TFE3 and TFEB, as the master regulators of lysosome biogenesis and autophagy, are well characterized to enhance the synaptic protein α-synuclein degradation in protecting against Parkinson’s disease (PD) and their levels are significantly decreased in the brain of PD patients. However, how TFE3 and TFEB are regulated during PD pathogenesis remains largely vague. Herein, we identified that programmed cell death 4 (PDCD4) promoted pathologic α-synuclein accumulation to facilitate PD development via suppressing both TFE3 and TFEB translation. Conversely, PDCD4 deficiency significantly augmented global and nuclear TFE3 and TFEB distributions to alleviate neurodegeneration in a mouse model of PD with overexpressing α-synuclein in the striatum. Mechanistically, like TFEB as we reported before, PDCD4 also suppressed TFE3 translation, rather than influencing its transcription and protein stability, to restrain its nuclear translocation and lysosomal functions, eventually leading to α-synuclein aggregation. We proved that the two MA3 domains of PDCD4 mediated the translational suppression of TFE3 through binding to its 5’-UTR of mRNA in an eIF-4A dependent manner. Based on this, we developed a blood-brain barrier penetrating RVG polypeptide modified small RNA drug against pdcd4 to efficiently prevent α-synuclein neurodegeneration in improving PD symptoms by intraperitoneal injections. Together, we suggest PDCD4 as a PD-risk protein to facilitate α-synuclein neurodegeneration via suppressing TFE3 and TFEB translation and further provide a potential small RNA drug against pdcd4 to treat PD by intraperitoneal injections.

Rheumatoid arthritis (RA) is an inflammatory disease accompanied by abnormal synovial microenvironment (SM). Sesquiterpene lactones (SLs) are the main anti-inflammatory ingredients of many traditional herbs utilized in RA treatment. α-Methylene-γ-butyrolactone (α-M-γ-B) is a core moiety that widely exists in natural SLs. This study was designed to investigate the anti-arthritic potential of α-M-γ-B as an independent small molecule in vitro and in vivo. α-M-γ-B exhibited stronger electrophilicity and anti-inflammatory effects than the other six analogs. α-M-γ-B inhibited the production of pro-inflammatory mediators via repolarizing M1 macrophages into M2 macrophages. The transcriptome sequencing suggested that α-M-γ-B regulated the immune system pathway. Consistently, α-M-γ-B attenuated collagen type II-induced arthritic (CIA) phenotype, restored the balance of Tregs-macrophages and remodeled SM via repolarizing the synovial-associated macrophages in CIA mice. Mechanistically, although α-M-γ-B did not prevent the trans-nucleus of NF-κB it interfered with the DNA binding activity of NF-κB via direct interaction with the sulfhydryl in cysteine residue of NF-κB p65, which blocked the activation of NF-κB. Inhibition of NF-κB reduced the M1 polarization of macrophage and suppressed the synovial hyperplasia and angiogenesis. α-M-γ-B failed to ameliorate CIA in the presence of N-acetylcysteine or when the mice were subjected to the macrophage-specific deficiency of Rela. In conclusion, α-M-γ-B significantly attenuated the CIA phenotype by directly targeting NF-κB p65 and inhibiting its DNA binding ability. These results suggest that α-M-γ-B has the potential to serve as an alternative candidate for treating RA. The greater electrophilicity of α-M-γ-B, the basis for triggering strong anti-inflammatory activity, accounts for the reason why α-M-γ-B is evolutionarily conserved in the SLs by medical plants.

In the process of coal mining, a large amount of respirable dust is generated, which seriously endangers the miners’ health. As the most widely used dust reduction technology, the spray technology has the advantages of high efficiency and cleanliness, but the existing spray technology does not have a strong ability to capture respirable dust, and the atomization efficiency is low. In order to solve those problems, the supersonic coaxial aerodynamic atomization technology was developed. The atomization characteristics of the technology were studied by experimental and numerical simulations, and the dust reduction characteristics of supersonic water drawing siphon aerodynamic atomization and supersonic coaxial atomization were compared based on the self-designed dust reduction experimental platform. At the same time, the dust separation experiment of the two technologies revealed the sedimentation mechanism of dust under the action of supersonic dynamic micro-fog curtain. The results show that under different aerodynamic pressures, the coaxial probe water injection method adopted by the supersonic coaxial atomization dust reduction device greatly reduces the energy loss of the probe structure on the supersonic flow field, significantly improves the atomization efficiency, and produces a large number of high-speed droplets below 11 μm with an uniform spatial distribution, and the particle size is reduced by 12%−50% compared with the siphon atomization device, forming a large-scale high-speed fine fog area in the spray flow field. The coupling effect of the droplet field and the dust field can be characterized by the instantaneous dispersion of the dust and determined by the distribution characteristics of the droplet field. At different times, the variation trend of the graded dust reduction efficiency in each particle size interval is different, and the contribution to the total dust reduction efficiency under different pressures is also different. The large-scale high-speed fine mist generated by the supersonic coaxial atomization technology is easy to capture respirable dust, and the classification efficiency of PM0−PM2.5 is more than 75%, and the maximum is 90%. The increase of pressure enlarges the range of high-speed fine mist, which is conducive to the capture of fine particles. During the confined space migration of dust-containing airflow, the sedimentation process of dust under the action of supersonic dynamic micro-fog curtain can be divided into droplet dust capture area, condensation and sedimentation area, and evaporation escape area. The different behaviors and concentration distributions of fog droplets and dust in different regions are the results of the drag migration of spray airflow and airborne wind flow, the capture of high-speed micro-fog collision, the condensation and settlement of fog droplets, and the weight loss of fog droplet evaporation.

To reduce energy consumption, a new pulping process called A-D-E-RC (acidification/desalination/electrolysis/recycle-cooking) was developed by a research group in Guangxi University of China. The present work focuses on the step of recycle cooking (RC) to further investigate the technical feasibility of A-D-E-RC methods. Golden bamboo grass was considered as fiber source material for pulp, and it was cooked with the acidic treating of wastewater from black liquor. Then, the pulp obtained from each cooking was made into paper to test the changes in its physical properties. As a result, the pulp yield increased from 43.9% to 50.2%, after re-using acidified black liquor, and the paper's tear index and tensile index were improved. Therefore, this study demonstrated the feasibility of recycle cooking (RC) fiber materials for pulp applied the acidic treating wastewater from black liquor, and thereby, it further identifies the technical feasibility of A-D-E-RC pulping methods.

In the past few years, there have been many breakthroughs in the treatment of heart failure, especially in drug therapy. The classification of chronic heart failure and treatment methods for heart failure and its complications are also constantly updated. In order to apply these achievements to a better diagnosis and treatment of heart failure patients in China, Chinese Society of Cardiology, Chinese Medical Association, Chinese College of Cardiovascular Physician, Chinese Heart Failure Association of Chinese Medical Doctor Association, Editorial Board of Chinese Journal of Cardiology have jointly published the Chinese Guidelines for the Diagnosis and Treatment of Heart Failure 2024, which comprehensively updates the new consensus and evidence-based treatment in the field of heart failure. These contents are of great significance for guiding diagnosis and treatment of heart failure patients in clinical practice. This article, therefore, aims to interpret the main updated contents and key points to provide readers with a better understanding of its key information.

The increasing consumption of paper products has led to a shortage of paper fiber raw materials. It is necessary to develop new plant materials to alleviate the shortage of fiber suitable for papermaking. In this study, the fast-growing plant golden bamboo grass (Arundo donax), which is cultivated and planted in Guangxi province of China, was used as a new material for pulping. The average pulp yield by cyclic-cooking method averaged 48.6%, being 4.1% greater than the pulp yield by the ordinary caustic soda method. Much of the increased yield was attributable to the reprecipitation of lignin onto the fibers. The paper properties of the pulp prepared by cycle-cooked method did not decrease significantly, compared with the pulp prepared by the usual single-cooked method. Therefore, the pulp met the requirements of national standards of many kinds of papers. However, the pulp was not suitable for bleaching, due to its high consumption of oxidizing agents to reach the required brightness. Therefore, this research demonstrates that the fast-growing plant, Arundo donax is a good raw material for pulp, and the innovative method of cycle-cooking method can significantly improve the pulp yield.

Abstract The microglia-mediated neuroinflammation have been shown to play a crucial role in the ocular pathological angiogenesis process, but specific immunotherapies for neovascular ocular diseases are still lacking. This study proposed that targeting GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) might be a novel immunotherapy for these angiogenesis diseases. We found a significant upregulation of CGAS and STING genes in the RNA-seq data derived from retinal tissues of the patients with proliferative diabetic retinopathy. In experimental models of ocular angiogenesis including laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR), the cGAS-STING pathway was activated as angiogenesis progressed. Either genetic deletion or pharmacological inhibition of STING resulted in a remarkable suppression of neovascularization in both models. Furthermore, cGAS-STING signaling was specifically activated in myeloid cells, triggering the subsequent RIP1-RIP3-MLKL pathway activation and leading to necroptosis-mediated inflammation. Notably, targeted inhibition of the cGAS-STING pathway with C-176 or SN-011 could significantly suppress pathological angiogenesis in CNV and OIR. Additionally, the combination of C-176 or SN-011 with anti-VEGF therapy led to least angiogenesis, markedly enhancing the anti-angiogenic effectiveness. Together, our findings provide compelling evidence for the importance of the cGAS-STING-necroptosis axis in pathological angiogenesis, highlighting its potential as a promising immunotherapeutic target for treating neovascular ocular diseases.

Studying the variation characteristics and main influencing factors of PM2.5 concentration in the Yangtze River Basin from 2016 to 2021 could provide references for optimizing the policy of collaborative governance of the atmospheric environment in the basin. Using the PM2.5 concentration data from 110 national stations in the Yangtze River Basin from 2016 to 2021, the temporal and spatial variation characteristics of PM2.5 were analyzed with the Theil-Sen trend analysis and Mann-Kendall statistical test methods. Combined with the Environmental Meteorological Assessment Index (EMI), the relative contributions of the two main influencing factors including the meteorological conditions and emission reduction measures, to the changes in PM2.5 concentration changes during the "13th Five-Year Plan" period (2016—2020) and the first year of the "14th Five-Year Plan" (2021) were quantitatively analyzed. The results were as follows. (1) Significant spatial variations in PM2.5 concentration distribution were found in the Yangtze River Basin was uneven in 2016-2021. The high-value areas were in the eastern part of the Hanjiang River Basin extending southward to the eastern part of the Dongting Lake Basin and the southern part of the Mintuo River, While the low-value area was in the upper and middle reaches of the Jinsha River Basin. (2) During the "13th Five-Year Plan" period, PM2.5 concentration in major cities of the Yangtze River Basin decreased year by year, with an annual variation rate of -3.62μg·m-3·a-1. However, PM2.5 concentration about 40% of the Yangtze River Basin region increased in 2021, which was mainly distributed in the upper reaches of the Yangtze River Basin and Dongting Lake Basin. (3) The PM2.5 in the western part of the basin was greatly affected by meteorological conditions, while the eastern part was greatly affected by emission sources and other factors. (4) Meteorological conditions and emission reduction measures during the "13th Five-Year Plan" period were conducive to the decrease of PM2.5 concentration.Their contribution rates to the increase of PM2.5 were -16.54% and -14.00%, respectively. Compared with the previous year, the emission reduction measures in 2021 were generally beneficial to the decrease of PM2.5 concentration (contribution rate of -5.84%), but adverse meteorological conditions (contribution rate of 4.49 %) offset part of the emission reduction effects, making a slight decrease in the PM2.5 concentration.

Abstract As the severity of global climate change escalates, carbon peak and carbon neutrality have emerged as international imperatives. Green taxation, a crucial fiscal strategy promoting the transition to a green low-carbon economy, demands thorough investigation regarding its efficacy and operational mechanisms. Predominantly, existing research has concentrated on the macroeconomic implications of green taxes, while their influence on regional green growth and innovation remains underexplored. This paper delineates green taxation in both a broad and narrow sense, elucidating its essence and potential in stimulating regional green progress and innovation. Utilizing panel data from 30 provinces in China spanning 2004 to 2021, a bidirectional fixed-effects model was developed for empirical analysis. Moreover, an impact mechanism model was constructed to delve into how green taxation specifically affects regional green development and innovation. Findings reveal that green taxation significantly fosters regional green growth and markedly enhances green innovation. Nonetheless, due to the resource crowding-out effect, it adversely impacts the comprehensive innovation capabilities of regional enterprises. This insight offers a fresh perspective on the paradoxical effects of green taxation, underscoring the necessity for a balanced approach in policy design and implementation. Drawing on these conclusions, the paper presents tailored policy recommendations.

Abstract Tuberous sclerosis complex 2 (TSC2) crucially suppresses Rheb activity to prevent mTORC1 activation. However, mutations in TSC genes lead to mTORC1 overactivation, thereby causing various developmental disorders and cancer. Therefore, the discovery of novel Rheb inhibitors is vital to prevent mTOR overactivation. Here, we reveals that the anti-inflammatory cytokine IL-37d can bind to lysosomal Rheb and suppress its activity independent of TSC2, thereby preventing mTORC1 activation. The binding of IL-37d to Rheb switch-II subregion destabilizes the Rheb-mTOR and mTOR-S6K interactions, further halting mTORC1 signaling. Unlike TSC2, IL-37d is reduced under ethanol stimulation, which results in mitigating the suppression of lysosomal Rheb-mTORC1 activity. Consequently, the recombinant human IL-37d protein (rh-IL-37d) with a TAT peptide greatly improves alcohol-induced liver disorders by hindering Rheb-mTORC1 axis overactivation in a TSC2- independent manner. Together, IL-37d emerges as a novel Rheb suppressor independent of TSC2 to terminate mTORC1 activation and improve abnormal lipid metabolism in the liver.

It is known that load forecasting plays an important role for the smart grids and mostly, the users have the combinational load forecast demands with different time-scales. However, due to various internal or external factors, such as poor management, the available load data set is limited. Therefore, the problem becomes as the high-precision combinational load forecast at different time-scales but with limited valid datasets. In this paper, taking the work in a city power company of China as an example, an empirical study for this problem is considered and then a robust forecasting system is built. The forecasting models are designed and screened and then constructed a model library for the system. In order to improve the robustness of the designed system, a mean absolute percentage error (MAPE) based dynamic model selection method is proposed and finally the performance of the system is verified on the State Grid Chongqing Company of China. The results indicate that our designed multi-temporal-spatial-scales load forecast system can dynamically select the best model for different demands, which demonstrates that the build system is an effective and reliable system-level solution. In particular, for the annual based load forecast, 80% of the industries in the considered city have a MAPE less than 5%, while the MAPE of the whole city is less than 2.160%; for the monthly based load forecast, 87% of the industries in the considered city have a MAPE less than 10%, while the MAPE for the whole city is less than 3.755%. In addition, for the annual based forecast, GM(1,1) is mostly used for the industry-based forecasts, but the model with the highest average forecast accuracy is LR-ER. While for region-based forecasts, the mostly selected models are GM(1,n) and AR. For the monthly based forecast, GM(1,1)-SI and FOA-HW have a higher average accuracy than other models for both industries- and region-based forecasts, respectively.

AimsThe study aims to explore the associations of eczema, Composite Dietary Antioxidant Index (CDAI), with depression symptoms in adults based on the National Health and Nutrition Examination Surveys (NHANES) database.MethodsIn total, 3,402 participant data were extracted from the NHANES 2005–2006. The relationship between eczema, CDAI, and depression symptoms was explored by utilizing weighted univariate and multivariate logistic regression models, presenting as odds ratios (ORs) and 95% confidence intervals (CIs). The additive interaction between eczema, CDAI, and depression symptoms was measured by relative excess risk due to interaction (RERI) and the attributable proportion of interaction (AP). Subsequently, the associations of eczema, CDAI, with depression were also explored in different gender, body mass index (BMI), and smoking subgroups.ResultsOf the 3,402 participants included, the mean age was 46.76 (0.83) years old, and 174 (5.11%) participants had depression symptoms. In the adjusted model, both eczema (OR = 3.60, 95%CI: 2.39–5.40) and CDAI (OR = 1.97, 95%CI: 1.19–3.27) were associated with a higher prevalence of depression symptoms. Compared to the participants with high CDAI and no eczema, those participants with low CDAI (eczema: OR = 7.30, 95%CI: 4.73–11.26; non-eczema: OR = 1.84, 95%CI: 1.06–3.19) have higher odds of depression symptoms, no matter have eczema or not. When under low CDAI levels, eczema was associated with increased odds of depression symptoms (OR = 3.76, 95%CI: 2.34–6.03). When under low CDAI level, eczema was also related to elevated odds of depression symptoms in those males, females, BMI

Abstract The parameterization of suspended sediments in vegetated flows presents a significant challenge, yet it is crucial across various environmental and geophysical disciplines. This study focuses on modeling suspended sediment concentrations (SSC) in vegetated flows with a canopy density of avH ∈ [0.3, 1.0] by examining turbulent dispersive flux. While conventional studies disregard dispersive momentum flux for avH > 0.1, our findings reveal significant dispersive sediment flux for large particles with a diameter‐to‐Kolmogorov length ratio when dp/η > 0.1. Traditional Rouse alike approaches therefore must be revised to account for this effect. We introduce a hybrid methodology that combines physical modeling with machine learning to parameterize dispersive flux, guided by constraints from diffusive and settling fluxes, characterized using recent covariance and turbulent settling methods, respectively. The model predictions align well with reported SSC data, demonstrating the versatility of the model in parameterizing sediment‐vegetation interactions in turbulent flows.

This review underscores the role of natural products in inducing immunogenic cell death (ICD) as a key strategy in tumor immunotherapy. It reveals that natural products can activate ICD through multiple pathways—apoptosis, autophagy, pyroptosis, and necroptosis—leading to the release of danger-associated molecular patterns (DAMPs), dendritic cell activation, and improved antigen presentation, which together stimulate a potent anti-tumor immune response. The study also demonstrates the enhanced therapeutic potential of combining natural products with immune checkpoint inhibitors. With a focus on translating preclinical findings into clinical practice, this review consolidates recent discoveries and suggests future research paths, offering both theoretical insights and practical guidance for advancing cancer immunotherapy.

Intermittent fasting (IF) is a dietary pattern that involves consuming less food during specific periods or not consuming food at all during certain regular feeding periods. The feeding regimen of crayfish affects their growth quality and physiological conditions. In this study, a control group (C group) was fed every day, and three periodic IF groups F1, F2, and F4 were set up, with treatment of 1 day of feeding and 1 day of fasting (1:1), 2 days of feeding and 1 day of fasting (2:1), and 4 days of feeding and 1 day of fasting (4:1), respectively. Growth performance, stress resistant ability and metabolic changes were then evaluated to explore the effects of IF on crayfish. There was no death during the experiment. F2 group exhibited the highest molting rate and weight gain, which were significantly different from those of the other groups. Additionally, F2 group had the lowest feed coefficient, with a significant difference compared to C group (P0.05). 2:1 IF had a great impact on the growth and food intake of crayfish. Results of enzyme activities showed that IF had a certain effect on crayfish protein and starch digestion, but the impact on the improvement of immune and antioxidant capacity was not obvious. Metabolomics analysis of hepatopancreas showed that IF mainly regulated pyrimidines, nucleotides, nucleotide sugar metabolism, biotin and cofactor metabolism, starch and sucrose metabolism, and also made some changes in amino acids with neurotransmitter functions and in sex hormones. The findings suggest that IF promotes the molting and growth of crayfish, and may potentially stimulate cell proliferation, improve exercise ability, and affect gonadal development and reproductive status. This study provides insight into effects of IF on crayfish.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition marked by impairments in social interaction, communication, and repetitive behaviors. Emerging evidence suggests that the insulin-like growth factor (IGF) signaling pathway plays a critical role in ASD pathogenesis; however, the precise pathogenic mechanisms remain elusive. This study utilizes multi-omics approaches to investigate the pathogenic mechanisms of ASD susceptibility genes within the IGF pathway. Whole-exome sequencing (WES) revealed a significant enrichment of rare variants in key IGF signaling components, particularly the IGF receptor 1 (IGF1R), in a cohort of Chinese Han individuals diagnosed with ASD, as well as in ASD patients from the SFARI SPARK WES database. Subsequent single-cell RNA sequencing (scRNA-seq) of cortical tissues from children with ASD demonstrated elevated expression of IGF receptors in parvalbumin (PV) interneurons, suggesting a substantial impact on their development. Notably, IGF1R appears to mediate the effects of IGF2R on these neurons. Additionally, transcriptomic analysis of brain organoids derived from ASD patients indicated a significant association between IGF1R and ASD. Protein-protein interaction (PPI) and gene regulatory network (GRN) analyses further identified ASD susceptibility genes that interact with and regulate IGF1R expression. In conclusion, IGF1R emerges as a central node within the IGF signaling pathway, representing a potential common pathogenic mechanism and therapeutic target for ASD. These findings highlight the need for further investigation into the modulation of this pathway as a strategy for ASD intervention.

Abstract Protein structure prediction (PSP) has been a prominent topic in bioinformatics and computational biology, aiming to predict protein function and structure from sequence data. The three‐dimensional conformation of proteins is pivotal for their intricate biological roles. With the advancement of computational capabilities and the adoption of deep learning (DL) technologies (especially Transformer network architectures), the PSP field has ushered in a brand‐new era of “neuralization.” Here, we focus on reviewing the evolution of PSP from traditional to modern deep learning‐based approaches and the characteristics of various structural prediction methods. This emphasizes the advantages of deep learning‐based hybrid prediction methods over traditional approaches. This study also provides a summary analysis of widely used bioinformatics databases and the latest structure prediction models. It discusses deep learning networks and algorithmic optimization for model training, validation, and evaluation. In addition, a summary discussion of the major advances in deep learning‐based protein structure prediction is presented. The update of AlphaFold 3 further extends the boundaries of prediction models, especially in protein‐small molecule structure prediction. This marks a key shift toward a holistic approach in biomolecular structure elucidation, aiming at solving almost all sequence‐to‐structure puzzles in various biological phenomena.

IntroductionDiarrhea is a common clinical condition that can potentially be fatal. Current treatment options often have side effects, such as constipation and vomiting, and there remains a need for more effective therapies. Pickled vegetables, a famous traditional food in China, have been suggested in clinical studies to alleviate diarrhea in children, particularly through the use of pickle water (PW). However, the pharmacological effects and mechanisms of PW on intestinal health remain unclear. This study aimed to explore the protective effects of PW on castor oil-induced diarrhea in ICR mice and to investigate its potential mechanisms.MethodsTo evaluate the antidiarrheal effects of PW, we used a castor oil-induced diarrhea model in ICR mice. Various indices were measured to assess the severity of diarrhea. After euthanizing the mice, oxidative stress markers in the ileum were assessed using biochemical methods, and the expression of tight junction-related proteins in the ileum was analyzed using Western blot. Additionally, 16S rRNA high-throughput sequencing was used to evaluate the diversity and composition of the intestinal flora.ResultsThe results showed that PW supplementation reduced body weight without significantly affecting organ index and liver function in the castor oil-induced diarrhea mice. PW also effectively reduced the dilution rate, diarrhea index, average loose stool grade, propelling distance of carbon powder, and intestinal propulsive rate while improving the pathological abnormality in the ileum. Furthermore, PW enhanced the activities of total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-PX), and catalase (CAT) while reducing malonaldehyde (MDA) levels. PW also increased the expression of tight junction proteins zonula occludens-1 (ZO-1) and occludin in the ileum. Additionally, the analysis of 16S rDNA revealed that PW increased both α and β diversity, improved the composition of the intestinal flora, and restored it to a normal level.DiscussionCollectively, dietary PW administration ameliorates Castor oil-induced diarrhea by restoring tight junctions between intestinal mucosal cells, suppressing oxidative stress, and regulating the composition of intestinal flora. These findings suggest that PW may be a promising strategy for managing diarrhea.

Working memory (WM) is an essential cognitive function that underpins various higher-order cognitive processes. Improving WM capacity through targeted training interventions has emergered as a potential approach for enhancing cognitive abilities. The present study employed an 8-week regimen of computerized WM training (WMT) to investigate its effect on neuroplasticity in healthy individuals, utilizing neuroimaging data gathered both before and after the training. The key metrics assessed included the amplitude of low-frequency fluctuations (ALFF), voxel-based morphometry (VBM), and the spatial distribution correlations of neurotransmitter. The results indicated that post-training, compared to baseline, there was a reduction in ALFF in the medial superior frontal gyrus and an elevation in ALFF in the left middle occipital gyrus within the training group. In comparison to the control group, the training group also exhibited decreased ALFF in the anterior cingulate cortex, angular gyrus, and superior parietal lobule, along with increased ALFF in the postcentral gyrus post-training. VBM analysis revealed a significant increase in gray matter volume (GMV) in the right dorsal superior frontal gyrus after the training period, compared to the initial baseline measurement. Furthermore, the training group showed GMV increases in the dorsal superior frontal gyrus, Rolandic operculum, precentral gyrus, and postcentral gyrus when compared to the control group. In addition, significant associations were identifed between neuroimaging measurements (AFLL and VBM) and the spatial patterns of neurotransmitters such as serotonin (5-HT), dopamine (DA), and N-methyl-D-aspartate (NMDA), providing insights into the underlying neurochemical processes. These findings clarify the neuroplastic changes caused by WMT, offering a deeper understanding of brain plasticity and highlighting the potential advantages of cognitive training interventions.

Summary: Electroporation temporarily enhances cell membrane permeability and promotes the absorption of external molecules. We have developed a device termed the rolling microneedle electrode array (RoMEA) that combines a densely arranged microneedle array of electrodes with rolling structures. Use RoMEA to create uniform skin micropores for efficient, low-damage transfection of nucleic acids over extended areas of the body. We describe in detail the design, fabrication, and assembly of the device and the application of in vivo electroporation of nucleic acids.For complete details on the use and execution of this protocol, please refer to Tongren Yang et al. 1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Utilizing data that encompass municipalities and regions within China at the prefectural level and beyond, spanning the period from 2012 to 2021, this study employed the spatial Durbin model to assess the spatial spillover impact of the digital economy in propelling low-carbon advancement within regional physical industries. This investigation elucidates the spatial spillover mechanism that underlies the low-carbon evolution of regional industries catalyzed by the digital economy and offers nuanced insights. The findings delineate the following observations: (1) The digital economy propels the low-carbon progression of indigenous physical industries and stimulates the low-carbon development of proximate regions’ physical industries through discernible spatial spillover effects. (2) The spatial spillover ramifications of the digital economy manifest a substantive correlation with urban attributes, including geographical positioning, population size, and market integration levels. Notably, municipalities situated in the southeast coastal region, those characterized by larger population sizes, and those exhibiting heightened market integration levels show greater spatial spillover effects attributable to the digital economy. (3) The safeguarding of intangible asset equity property, a pivotal institutional underpinning for fostering digital economic development, amplifies the spatial spillover effect of the digital economy in propelling low-carbon development within regional industries. (4) As geographical and spatial distances expand, the spatial spillover effect of the digital economy attenuates, indicating a diminishing influence with increasing spatial separation.

Abstract To develop and validate an enhanced CT-based radiomics nomogram for evaluating preoperative metastasis risk of epithelial ovarian cancer (EOC). One hundred and nine patients with histologically confirmed EOC were retrospectively enrolled. The volume of interest (VOI) was delineated in preoperative enhanced CT images, and 851 radiomics features were extracted. The radiomics features were selected by the least absolute shrinkage and selection operator (LASSO), and the rad-score was calculated using the formula of the radiomics label. A clinical model, radiomics model, and combined model were constructed using the logistic regression classification algorithm. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were used to evaluate the diagnostic performance of the models. Seventy-five patients (68.8%) were histologically confirmed to have metastasis. Eleven optimal radiomics features were retained by the LASSO algorithm to develop the radiomic model. The combined model for evaluating metastasis of EOC achieved area under the curve (AUC) values of 0.929 (95% CI 0.8593–0.9996) in the training cohort and 0.909 (95% CI 0.7921–1.0000) in the test cohort. To facilitate clinical use, a radiomic nomogram was built by combining the clinical characteristics with rad-score. The DCA indicated that the nomogram had the most significant net benefit when the threshold probability exceeded 15%, surpassing the benefits of both the treat-all and treat-none strategies. Compared with clinical model and radiomics model, the radiomics nomogram has the best diagnostic performance in evaluating EOC metastasis. The nomogram is a useful and convenient tool for clinical doctors to develop personalized treatment plans for EOC patients.

Abstract Distributed energy systems encompass a diverse range of generation and storage solutions on the user side, where decentralized management schemes to maximize the overall social welfare are preferred considering their dispersed ownership. However, either security or privacy problems occur in recently proposed schemes. Here we report a decentralized framework leveraging the strengths of blockchain and parallelizable mathematical algorithms to overcome these potential drawbacks. The system owners bid cost functions and operating constraints through masked but coupled management subproblems, which are redistributed by the blockchain to be verifiably solved by competent peers. Such processes are iteratively executed as decisions and shadow prices are exchanged among participants, until an equilibrium is reached. The interactive framework ensures decentralized, privacy-preserving, and secure management of multiple energy sources, and reduces the total cost by 3.0 ~ 7.5% in the test system. Our results benefit the energy prosumers and promote a more active and competitive power grid.

Background Gut microbiota is closely related to the occurrence and development of diabetes and affects the prognosis of diabetic complications, and the underlying mechanisms are only partially understood. We aimed to explore the possible link between the gut microbiota and vascular inflammation of diabetic mice. Methods The db/db diabetic and wild-type (WT) mice were used in this study. We profiled gut microbiota and examined the and vascular function in both db/db group and WT group. Gut microbiota was analyzed by 16s rRNA sequencing. Vascular function was examined by ultrasonographic hemodynamics and histological staining. Clostridium butyricum (CB) was orally administered to diabetic mice by intragastric gavage every 2 days for 2 consecutive months. Reactive oxygen species (ROS) and expression of nuclear factor erythroid-derived 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were detected by fluorescence microscopy. The mRNA expression of inflammatory cytokines was tested by quantitative polymerase chain reaction. Results Compared with WT mice, CB abundance was significantly decreased in the gut of db/db mice, together with compromised vascular function and activated inflammation in the arterial tissue. Meanwhile, ROS in the vascular tissue of db/db mice was also significantly increased. Oral administration of CB restored the protective microbiota, and protected the vascular function in the db/db mice via activating the Nrf2/HO-1 pathway. Conclusion This study identified the potential link between decreased CB abundance in gut microbiota and vascular inflammation in diabetes. Therapeutic delivery of CB by gut transplantation alleviates the vascular lesions of diabetes mellitus by activating the Nrf2/HO-1 pathway.

The Al–Zn–Mg–Cu 7055 aluminum alloy was meticulously fabricated through spray forming (SF) technology, followed by hot extrusion and T76 treatment. This comprehensive process allowed for a thorough investigation of its microstructural characteristics, mechanical properties, and fatigue behavior. Post-treatment analysis revealed that the SF-7055 aluminum alloy exhibited no notable segregation or porosity defects, ensuring its exceptional quality and reliability. The microstructural analysis revealed a uniform distribution of refined grains and dispersed precipitates, contributing to the material's strength. Mechanical testing demonstrated that the hot extruded SF-7055 aluminum alloy exhibits superior tensile strength and elongation, with significant anisotropy in mechanical properties favoring the extrusion direction (ED) over the transverse direction (TD). Fatigue testing under varying cyclic stresses revealed an extended fatigue life in the ED-oriented specimens, attributed to the texture-induced resistance to crack initiation and propagation. The study underscores the effectiveness of SF and hot extrusion in enhancing the SF-7055 aluminum alloy's performance, making it a viable candidate for critical aerospace applications. The findings provide valuable insights into the relationship between processing, microstructure, and properties, offering a pathway to the design and fabrication of high-performance aluminum alloys.

To address the issues of shrinkage cracking, high energy consumption and high carbon emission of traditional cement-based sealing materials, the authors investigated the use of sodium alginate (SA) crosslinking metal ions to prepare SA modified alkali activated waste incineration base ash (MSWI-BA) -granulation blast furnace slag (GBFS) based gaging plugging material (SWM). The optimal water-solid ratio was determined by evaluating compressive strength and setting time to be 0.4. The influence of SA modification on the high temperature resistance of the gelling material was investigated by analyzing the compressive strength, shrinkage rate, and fracture morphology of the gelling material at different temperatures. The results showed that after SA modification, the high temperature resistance improved, the surface cracks on the modified cementable material were significantly reduced after heating, and the shrinkage rate was reduced by 26.5% compared to that before modification. The residual compressive strength is still as high as 17.25 MPa after heating at 400 ℃. Combined with microscopic morphology, pore structure properties, and thermal analysis experiments, the generation mechanism of SA modified gelling material was examined. The results revealed that the SA modified MSWI-BA-GBFS based gelling material refines pore size and reduces pore volume via coordination crosslinking of SA and Ca2+/Al3+ and the synergistic effect of the silico-aluminate covalent network, thus maintaining the matrix structure's integrity after heating, improving cracking properties. The simulation findings suggest that the leakage plugging performance of SA modified MSWI-BA-GBFS based gelling material with water solid ratio 0.4 is superior to that of mining cement-based material, demonstrating a better leakage plugging performance. The development of SA modified MSWI-BA-GBFS based gelling plugging material not only provides an effective way for the resource utilization of municipal waste incineration bottom ash, but also provides a type of environmental protection fire-fighting material with high compressive strength, anti-shrinkage cracking, and high temperature resistance, which can completely replace the traditional mine cement based plugging material.

Abstract Uterine myomas are the most common pelvic tumors in women, which can lead to abnormal uterine bleeding, abdominal pain, pelvic compression symptoms, infertility, or adverse pregnancy. In this article, we provide a dataset named uterine myoma MRI dataset (UMD), which can be used for clinical research on uterine myoma imaging. The UMD is the largest publicly available uterine MRI dataset to date including 300 cases of uterine myoma T2-weighted imaging (T2WI) sagittal patient images and their corresponding annotation files. The UMD covers 9 types of uterine myomas classified by the International Federation of Obstetrics and Gynecology (FIGO), which were annotated and reviewed by 11 experienced doctors to ensure the authority of the annotated data. The UMD is helpful for uterine myomas classification and uterine 3D reconstruction tasks, which has important implications for clinical research on uterine myomas.

Abstract Background Endoscopic retrograde cholangiopancreatography (ERCP) has found extensive use in pediatric patients; however, challenges persist in the application of therapeutic ERCP in infants. Case presentation This case report details the presentation of a 5.9-kilogram infant with obstructive jaundice and suspected hemolytic anemia who underwent ERCP to alleviate biliary obstruction. The infant was admitted due to clay-colored stools, jaundice, and liver injury. Ultrasound and magnetic resonance cholangiopancreatography (MRCP) revealed dilation of the common bile duct (CBD) accompanied by the presence of stones. ERCP was conducted using a JF-260V duodenoscope under general anesthesia. Successful stone extraction and biliary drainage were achieved. Conclusions In centers with considerable expertise in ERCP and pediatric anesthesia, the use of a conventional adult duodenoscope for therapeutic ERCP in infants can be considered safe and feasible, provided careful and stringent patient selection criteria are applied. In the future, clear guidelines and standardized protocols for the indications and procedures of pediatric ERCP should be established.

Abstract Background Clearance of apoptotic cells by efferocytosis is crucial for prevention of atherosclerosis progress, and impaired efferocytosis contributes to the aggravated atherosclerosis. Results In this study, we found that diabetic ApoE–/– mice showed aggravated atherosclerosis as hyperglycemia damaged the efferocytosis capacity at least partially due to decreased expression of Mer tyrosine kinase (MerTK) on macrophages. To locally restore MerTK in the macrophages in the plaque, hybrid membrane nanovesicles (HMNVs) were thus developed. Briefly, cell membrane from MerTK overexpressing RAW264.7 cell and transferrin receptor (TfR) overexpressing HEK293T cell were mixed with DOPE polymers to produce nanovesicles designated as HMNVs. HMNVs could fuse with the recipient cell membrane and thus increased MerTK in diabetic macrophages, which in turn restored the efferocytosis capacity. Upon intravenous administration into diabetic ApoE–/– mice, superparamagnetic iron oxide nanoparticles (SMN) decorated HMNVs accumulated at the aorta site significantly under magnetic navigation, where the recipient macrophages cleared the apoptotic cells efficiently and thus decreased the inflammation. Conclusions Our study indicates that MerTK decrease in macrophages contributes to the aggravated atherosclerosis in diabetic ApoE–/– mice and regional restoration of MerTK in macrophages of the plaque via HMNVs could be a promising therapeutic approach. Graphic Abstract

Age-related macular degeneration(ARMD)is a neurodegenerative disease associated with oxidative stress. It is characterized by progressive death of photoreceptors and retinal pigment epithelium(RPE), and is one of the leading causes of irreversible loss of central vision in patients over the age of 65 years old. MicroRNA(miRNA)is a class of regulatory short-chain non-coding RNA that can bind and inhibit multiple gene targets in the same biological pathway. This unique property makes microRNA an ideal target for exploring the pathogenesis, diagnosis and treatment of non-exudative ARMD. Previous studies have found that the pathogenesis of non-exudative ARMD involves age, genetics, environment, oxidative stress, lipid metabolism, autophagy and immunity. However, the exact mechanisms have not been fully clarified. As biomarkers of non-exudative ARMD, miRNA play a role in oxidative stress and lipid metabolism. This article summarizes the role of various miRNA in targeting Nrf2 and HIF-1α to inhibit hypoxia-related angiogenesis signaling, thereby affecting oxidative stress. Additionally, miRNA regulate lipid uptake and the expression of ABCA1 in RPE and macrophages, thereby influencing lipid metabolism. This deepens the understanding of the role of miRNA in oxidative stress and lipid metabolism in non-exudative ARMD, and provides directions for further improving the understanding of the pathogenesis and prevention of non-exudative ARMD.

Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) by Kelch-like ECH-associated protein 1 (Keap1) alkylation plays a central role in anti-inflammatory therapy. However, activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified. Deoxynyboquinone (DNQ) is a natural small molecule discovered from marine actinomycetes. The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1. DNQ exhibited significant anti-inflammatory properties both in vitro and in vivo. The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α, β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine. DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway. Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation. The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry. DNQ triggered the ubiquitination and subsequent degradation of Keap1 by alkylation of the cysteine residue 489 (Cys489) on Keap1-Kelch domain, ultimately enabling the activation of Nrf2. Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α, β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain, suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

Highlights A novel aqueous/aprotic electrolyte with low salt concentration (i.e., 0.5 m Zn(CF3SO3)2+1 m LiTFSI) demonstrated an expanded electrochemical window, which can simultaneously stabilize Zn metal anode and increase the operation voltage of Zn-ion hybrid supercapacitors. The coordination shell of the electrolyte induced by acetonitrile and LiTFSI can not only suppress the Zn corrosion and hydrogen evolution reaction but also promote the cathodic stability and ion migration, which is depicted by the density functional theory simulations together with experimental characterizations. The Zn-ion hybrid supercapacitor based on the developed electrolyte can operate within 0–2.2 V in a wide temperature range with an ultra-long lifespan (> 120,000 cycles).

Abstract Climate change can alter wetland extent and function, but such impacts are perplexing. Here, changes in wetland characteristics over North America from 25° to 53° North are projected under two climate scenarios using a state-of-the-science Earth system model. At the continental scale, annual wetland area decreases by ~10% (6%-14%) under the high emission scenario, but spatiotemporal changes vary, reaching up to ±50%. As the dominant driver of these changes shifts from precipitation to temperature in the higher emission scenario, wetlands undergo substantial drying during summer season when biotic processes peak. The projected disruptions to wetland seasonality cycles imply further impacts on biodiversity in major wetland habitats of upper Mississippi, Southeast Canada, and the Everglades. Furthermore, wetlands are projected to significantly shrink in cold regions due to the increased infiltration as warmer temperature reduces soil ice. The large dependence of the projections on climate change scenarios underscores the importance of emission mitigation to sustaining wetland ecosystems in the future.