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Abstract The large uncertainties in estimating CH4 emissions from wetland ecosystems, the leading natural source to the atmosphere, substantially hinder the quantification of the global CH4 budget. This study used the IBIS‐CH4 (Integrated BIosphere Simulator‐Methane) model, a process‐based model integrating microbial mechanisms associated with CH4 production and oxidation processes, to simulate global wetland CH4 emissions from 2001 to 2020. Initially, we employed the IBIS‐CH4 model to evaluate its performance across 26 diverse wetland sites worldwide. The results showed that the magnitude and seasonality of observed CH4 fluxes over various wetland sites were well reproduced. We then used this model to estimate the annual global wetland CH4 emissions from 2001 to 2020, averaging 152.67 Tg CH4 yr−1, with a range of 135.72–167.57 Tg CH4 yr−1. The estimated global wetland CH4 emissions are generally in agreement with the current bottom‐up estimates (117–256 Tg CH4 yr−1) and closely overlap with independent top‐down estimates (139–183 Tg CH4 yr−1). During 2001–2020, the estimated global wetland CH4 emissions initially showed an increasing trend, followed by a decline. The peak of CH4 emissions reached in 2010, coinciding with the peak of wetland area. The majority of global wetland CH4 emissions were concentrated in tropical regions, which exhibited a clear seasonality and had a peak in July. The impact of meteorological factors on wetland CH4 emissions was greater than that of leaf area index, indicating the importance of soil hydrothermal conditions on wetland CH4 emissions.

C45H33Cl2F3N4, monoclinic, P21/c (no. 14), a = 11.7076(13) Å, b = 11.8186(13) Å, c = 27.473(3) Å, β = 91.188(2)°, V = 3800.6(7) Å3, Z = 4, Rgt (F) = 0.0591, wRref (F 2) = 0.1856, T = 293 K.

Abstract Traditional Chinese medicine (TCM), AYURVEDA and Indian medicine are essential in disease prevention and treatment. Kelisha capsule (KLSC), a TCM formula listed in the Chinese Pharmacopoeia, has been clinically proven to possess potent antibacterial properties. However, the precise antimicrobial mechanism of KLSC remained unknown. This study aimed to elucidate the dual antibacterial mechanism of KLSC using network pharmacology, molecular docking, and experimental validation. By analyzing the growth curve of Escherichia coli (E. coli), it was observed that KLSC significantly inhibited its growth, showcasing a remarkable antibacterial effect. Furthermore, SEM and TEM analysis revealed that KLSC damaged the cell wall and membrane of E. coli, resulting in cytoplasmic leakage, bacterial death, and the exertion of antibacterial effects. The network pharmacology analysis revealed that KLSC exhibited an effect on E. coli ATP synthase, thereby influencing the energy metabolism process. The molecular docking outcomes provided evidence that the active compounds of KLSC could effectively bind to the ATP synthase subunit. Subsequently, experimental findings substantiated that KLSC effectively suppressed the activity of ATP synthase in E. coli and consequently decreased the ATP content. This study highlighted the dual antibacterial mechanism of KLSC, emphasizing its effects on cell structure and energy metabolism, suggesting its potential as a natural antibacterial agent for E. coli-related infections. These findings offered new insights into exploring the antibacterial mechanisms of TCM by focusing on the energy metabolism process.

Abstract Background Cartilaginous endplate (CEP) degeneration, which is an important contributor to intervertebral disc degeneration (IVDD), is characterized by chondrocyte death. Accumulating evidence has revealed that dynamin-related protein 1 (Drp1)-mediated mitochondrial fission and dysfunction lead to apoptosis during CEP degeneration and IVDD. Exosomes are promising agents for the treatment of many diseases, including osteoporosis, osteosarcoma, osteoarthritis and IVDD. Despite their major success in drug delivery, the full potential of exosomes remains untapped. Materials and methods In vitro and in vivo models of CEP degeneration were established by using lipopolysaccharide (LPS). We designed genetically engineered exosomes (CAP-Nrf2-Exos) expressing chondrocyte-affinity peptide (CAP) on the surface and carrying the antioxidant transcription factor nuclear factor E2-related factor 2 (Nrf2). The affinity between CAP-Nrf2-Exos and CEP was evaluated by in vitro internalization assays and in vivo imaging assays. qRT‒PCR, Western blotting and immunofluorescence assays were performed to examine the expression level of Nrf2 and the subcellular localization of Nrf2 and Drp1. Mitochondrial function was measured by the JC-1 probe and MitoSOX Red. Mitochondrial morphology was visualized by MitoTracker staining and transmission electron microscopy (TEM). After subendplate injection of the engineered exosomes, the degree of CEP degeneration and IVDD was validated radiologically and histologically. Results We found that the cargo delivery efficiency of exosomes after cargo packaging was increased by surface modification. CAP-Nrf2-Exos facilitated chondrocyte-targeted delivery of Nrf2 and activated the endogenous antioxidant defence system in CEP cells. The engineered exosomes inhibited Drp1 S616 phosphorylation and mitochondrial translocation, thereby preventing mitochondrial fragmentation and dysfunction. LPS-induced CEP cell apoptosis was alleviated by CAP-Nrf2-Exo treatment. In a rat model of CEP degeneration, the engineered exosomes successfully attenuated CEP degeneration and IVDD and exhibited better repair capacity than natural exosomes. Conclusion Collectively, our findings showed that exosome-mediated chondrocyte-targeted delivery of Nrf2 was an effective strategy for treating CEP degeneration. Graphic abstract CAP-Nrf2-Exos delivered Nrf2 into CEP cells and alleviated LPS-induced apoptosis by inhibiting Drp1-mediated mitochondrial fission

Abstract Hydrogen-bonded organic frameworks (HOFs) are versatile materials with potential applications in proton conduction. Traditional approaches involve incorporating humidity control to address grain boundary challenges for proton conduction. This study finds vitrification as an alternative strategy to eliminate grain boundary effect in HOFs by rapidly melt quenching the kinetically stable HOF-SXU-8 to glassy state HOF-g. Notably, a remarkable enhancement in proton conductivity without humidity was achieved after vitrification, from 1.31 × 10−7 S cm−1 to 5.62× 10−2 S cm−1 at 100 °C. Long term stability test showed negligible performance degradation, and even at 30 °C, the proton conductivity remained at high level of 1.2 × 10−2 S cm−1. Molecule dynamics (MD) simulations and X-ray total scattering experiments reveal the HOF-g system is consisted of three kinds of clusters, i.e., 1,5-Naphthalenedisulfonic acid (1,5-NSA) anion clusters, N,N-dimethylformamide (DMF) molecule clusters, and H+-H2O clusters. In which, the H+ plays an important role to bridge these clusters and the high conductivity is mainly related to the H+ on H3O+. These findings provide valuable insights for optimizing HOFs, enabling efficient proton conduction, and advancing energy conversion and storage devices.

Abstract Transit operation efficiency and service quality can be enhanced through the implementation of signal and speed control. Previous studies prefer to change driving speed in priority to alleviate the adverse effects of signal timing adjustment on social vehicles. The driving safety and fuel consumption of transit are ignored. To this end, a cooperative control method consisting of three models is proposed. The cooperative control strategy model provides optimal schemes for allocating transit priority time. Based on this, the adjustment of phase time and the transit speed trajectory with the lower fuel consumption are calculated by signal control model and speed control model, respectively. Especially, the signal control model is established in the background of green wave coordinated control to further protect the travelling benefits of social vehicles. The simulation is performed in SUMO to demonstrate the effectiveness of the proposed method. The results show that the cooperative control method improves the crossing efficiency and enhances the fuel economy of transit under different arrival speeds and lengths of control area. Compared with the general signal control, the proposed method can minimize traffic interference, which is particularly obvious in a higher degree of saturation.

Abstract Small bowel vascular malformation disease (SBVM) commonly causes obscure gastrointestinal bleeding (OGIB). However, the pathogenetic mechanism and the role of lncRNAs in SBVM remain largely unknown. Here, we found that hypoxia and low-glucose environments co-augment angiogenesis and existed in SBVM. Mechanistically, hypoxia and low-glucose environments supported angiogenesis via activation of hypoxia and glucose deprivation-induced lncRNA (HGDILnc1) transcription by increasing binding of the NeuroD1 transcription factor to the HGDILnc1 promoter. Raised HGDILnc1 acted as a suppressor of α-Enolase 1 (ENO1) small ubiquitin-like modifier modification (SUMOylation)-triggered ubiquitination, and an activator of transcription of Aldolase C (ALDOC) via upregulation of Histone H2B lysine 16 acetylation (H2BK16ac) level in the promoter of ALDOC, and consequently promoting glycolysis and angiogenesis. Moreover, HGDILnc1 was clinically positively correlated with Neurogenic differentiation 1 (NeuroD1), ENO1, and ALDOC in SBVM tissues, and could function as a biomarker for SBVM diagnosis and therapy. These findings suggest that hypoxia and low-glucose environments were present in SBVM tissues, and co-augmented angiogenesis. Hypoxia and low-glucose environments co-induced HGDILnc1, which is higher expressed in SBVM tissue compared with normal tissue, could promoted glycolysis and angiogenesis.

In this study, 0.3 wt% Ti nanoparticles (Ti NPs) were incorporated into Sn1.0Ag0.5Cu (SAC105) solder, and vacuum thermo-compression soldering was employed to fabricate two distinct solder joints: Cu/SAC105/Cu and Cu/SAC105-0.3Ti/Cu. The research delved into how altering bonding pressures and durations affects the development of interfacial intermetallic compounds (IMCs) and, consequently, the mechanical characteristics of solder joints. The thickness of the solder joints exhibited a gradual decrease with increasing bonding pressure, reaching approximately 13 μm at a bonding pressure of 1.0 MPa. The incorporation of Ti NPs demonstrated an effective inhibition of the interfacial IMC layer growth. This led to a notable decrease in the thickness of the IMC layer in the Cu/SAC105-0.3Ti/Cu solder joints. Furthermore, the introduction of Ti NPs did not cause a notable alteration in the fracture path of the solder joints. Exceptionally high shear strengths exceeding 38 MPa were achieved for both solder joints at a bonding pressure of 0.6 MPa. Moreover, the shear strength of the Cu/SAC105-0.3Ti/Cu solder joints slightly surpassed that of the Cu/SAC105/Cu solder joints. However, at a bonding pressure of 1.0 MPa, the aggregation of Ti NPs in the solder joints adversely affected the microstructure, leading to a deterioration in shear strength.

Dendritic cells (DCs) present an ideal target for delivering immunogenic cargo due to their potent antigen-presenting capabilities. This targeting approach holds promise in vaccine development by enhancing the efficiency of antigen recognition and capture by DCs. To identify a high-affinity targeting peptide binding to rabbit DCs, rabbit monocyte-derived DCs (raMoDCs) were isolated and cultured, and a novel peptide, HS (HSLRHDYGYPGH), was identified using a phage-displayed peptide library. Alongside HS, two other DC-targeting peptides, KC1 and MY, previously validated in our laboratory, were employed to construct recombinant Lactgobacillus reuteri fusion-expressed rabbit hemorrhagic disease virus (RHDV) capsid protein VP60. These recombinant Lactobacillus strains were named HS-VP60/L. reuteri, KC1-VP60/L. reuteri, and MY-VP60/L. reuteri. The ability of these recombinant Lactobacillus to bind rabbit DCs was evaluated both in vivo and in vitro. Results demonstrated that the DC-targeting peptide KC1 significantly enhanced the capture efficiency of recombinant Lactobacillus by raMoDCs, promoted DC maturation, and increased cytokine secretion. Furthermore, oral administration of KC1-VP60/L. reuteri effectively induced SIgA and IgG production in rabbits, prolonged rabbit survival post-challenge, and reduced RHDV copies in organs. In summary, the DC-targeting peptide KC1 exhibited robust binding to raMoDCs, and recombinant Lactobacillus expressing KC1-VP60 protein antigens efficiently induced systemic and mucosal immune responses in rabbits, conferring protective efficacy against RHDV. This study offers valuable insights for the development of novel RHDV vaccines.

ObjectiveBoth 5:2 IF diet (intermittent fasting) and daily caloric restriction eating had been suggested for management of MAFLD (Metabolic-Associated Fatty Liver Disease), this study aimed to evaluate the effects of 5:2 IF diet on body weight and metabolic parameters in adults with MAFLD, in comparison to daily caloric restriction eating.MethodsThis single-center, double-blind, prospective, randomized controlled trial included 60 patients with MAFLD, who were administered either a 5:2 IF diet limited calories consumed for 2 days each week with no restrictions on the remaining 5 (Group 5:2 IF diet) or a daily calorie restriction eating (Group daily calorie restriction). Fibrotouch-B instrument assessment, ultrasound assessment of hepatic steatosis, anthropometric indices and body composition analysis, blood sample measurements were conducted during two distinct visits: initially on the day of study commencement (T1), and subsequently at the conclusion of the 12-week intervention period (T2).ResultsIn comparison to daily calorie restriction eating, the 5:2 IF diet significantly decreased the proportion of hepatic steatosis ≥moderate (29.6% vs. 59.3%, p = 0.028) and the degree of hepatic fibrosis F ≥ 2 (3.7% vs. 25.9%, p = 0.05), and fewer percentage of patients were diagnosed with fatty liver via upper abdominal ultrasound in the 5:2 intermittent fasting diet group (33.3% vs. 63.0%, p = 0.029). Additionally, the CAP (controlled attenuation parameter) and LSM (liver stiffness measurements) value were significantly lower in the 5:2 IF diet group (p 0.05).ConclusionIn summary, although both 5:2 IF diet and daily caloric restriction eating achieved similar effect on body weight, liver enzymes, lipid profile and glycemic indices after 12 weeks treatment, 5:2 IF diet demonstrates better improvement in fibrosis and steatosis scores independently from weight regulation. Consequently, it is anticipated to emerge as a viable dietary modality for lifestyle intervention among patients diagnosed with MAFLD.Clinical trial registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier ChiCTR2400080292.

Microplastics (MPs), recognized as an emerging global environmental concern, have been extensively detected worldwide, with specific attention directed towards the Yangtze River Estuary (YRE) and East China Sea (ECS) regions. Despite their critical research significance, there remains a knowledge gap concerning the distribution of MPs in the benthic layer within this area, particularly regarding interactions governing their occurrence. Here we illuminate the distribution of MPs within the benthic layer and unravel the intricate interplay between bottom water and sediment in the YRE and ECS. We find that MPs are notably more abundant in bottom water, ranging from 8 to 175 times higher than in surface water. These MPs predominantly consist of polyester fibers, exhibit a size range between 0.5 and 5.0 mm, and display distinct coloration. Co-occurrence network analysis and Principal Coordinate Analysis confirm a robust correlation between MPs in bottom water and sediment, signifying the pivotal role of bottom water in mediating the distribution and transportation of MPs within the benthic layer. Furthermore, a positive correlation between MPs in sediment and bottom water turbidity underscores the impact of surface sediment resuspension and upwelling on MPs distribution. This study clarifies the intricate interactions within the benthic layer and highlights the crucial role of bottom water as a mediator in the vertical distribution of MPs, advancing our understanding of the “source-to-sink” transport processes governing MPs within water-sediment systems.

Abstract Objective The genomic and molecular ecology involved in the stepwise continuum progression of lung adenocarcinoma (LUAD) from adenocarcinoma in situ (AIS) to minimally invasive adenocarcinoma (MIA) and subsequent invasive adenocarcinoma (IAC) remains unclear and requires further elucidation. We aimed to characterize gene mutations and expression landscapes, and explore the association between differentially expressed genes (DEGs) and significantly mutated genes (SMGs) during the dynamic evolution from AIS to IAC. Methods Thirty‐five patients with ground‐glass nodules (GGNs) lung adenocarcinomas were enrolled. Whole‐exome sequencing (WES) and transcriptome sequencing (RNA‐Seq) were conducted on all patients, encompassing both tumor samples and corresponding noncancerous tissues. Data obtained from WES and RNA‐Seq were subsequently analyzed. Results The findings from WES delineated that the predominant mutations were observed in EGFR (49%) and ANKRD36C (17%). SMGs, including EGFR and RBM10, were associated with the dynamic evolution from AIS to IAC. Meanwhile, DEGs, including GPR143, CCR9, ADAMTS16, and others were associated with the entire process of invasive LUAD. We found that the signaling pathways related to cell migration and invasion were upregulated, and the signaling pathways of angiogenesis were downregulated across the pathological stages. Furthermore, we found that the messenger RNA (mRNA) levels of FAM83A, MAL2, DEPTOR, and others were significantly correlated with CNVs. Gene set enrichment analysis (GSEA) showed that heme metabolism and cholesterol homeostasis pathways were significantly upregulated in patients with EGFR/RBM10 co‐mutations, and these patients may have poorer overall survival than those with EGFR mutations. Based on the six calculation methods for the immune infiltration score, NK/CD8+ T cells decreased, and Treg/B cells increased with the progression of early LUAD. Conclusions Our findings offer valuable insights into the unique genomic and molecular features of LUAD, facilitating the identification and advancement of precision medicine strategies targeting the invasive progression of LUAD from AIS to IAC.

Condyloma latum is a typical lesion of secondary syphilis，which usually appears in the vicinity of the initial chancre. It is found that treponema pallidum load in condyloma latum is significantly higher than that in other secondary syphilis. We report a case of mesosyphilis presented as giant flat condyloma latum in vulvar and perianal areas. A 17-year female patient came to our clinic，complaining of plaques in vulvar and perianal areas more than 2 months. Physical examination showed giant red moist plaques in vulvar and perianal areas. The titer of non-specific antibody for syphilis was 1∶64 and the specific antibody test for syphilis showed a value of 189.000 COI. The patient was diagnosed as secondary syphilis and treate with benzathine penicillin. The rash subsided after 3-week treatment. This case of condyloma latum with giant red plaques was easily misdiagnosed as condyloma acuminatum.

Abstract Background and aims The older people bears a severe burden of disease due to frailty and depressive symptoms, however, the results of association between the two in the older Chinese people have been conflicting. Therefore, this study aimed to investigate the developmental trajectories and interactions of frailty and depressive symptoms in the Chinese middle-aged and older adults. Methods The study used four waves of data from 2011, 2013, 2015 and 2018 in the China Health and Retirement Longitudinal Study (CHARLS) database, focused on middle-aged and older people ≥ 45 years of age, and analyzed using latent growth models and cross-lagged models. Results The parallel latent growth model showed that the initial level of depressive symptoms had a significant positive predictive effect on the initial level of frailty. The rate of change in depressive symptoms significantly positively predicted the rate of change in frailty. The initial level of frailty had a significant positive predictive effect on the initial level of depressive symptoms, but a significant negative predictive effect on the rate of change in depressive symptoms. The rate of change in frailty had a significant positive predictive effect on the rate of change in depressive symptoms. The results of the cross-lagged analysis indicated a bidirectional causal association between frailty and depressive symptoms in the total sample population. Results for the total sample population grouped by age and gender were consistent with the total sample. Conclusions This study recommends advancing the age of concern for frailty and depressive symptoms to middle-aged adults. Both men and women need early screening and intervention for frailty and depressive symptoms to promote healthy aging.

Abstract Objective To compare the diagnostic power among various machine learning algorithms utilizing multi-sequence magnetic resonance imaging (MRI) radiomics in detecting anterior cruciate ligament (ACL) tears. Additionally, this research aimed to create and validate the optimal diagnostic model. Methods In this retrospective analysis, 526 patients were included, comprising 178 individuals with ACL tears and 348 with a normal ACL. Radiomics features were derived from multi-sequence MRI scans, encompassing T1-weighted imaging and proton density (PD)-weighted imaging. The process of selecting the most reliable radiomics features involved using interclass correlation coefficient (ICC) testing, t tests, and the least absolute shrinkage and selection operator (LASSO) technique. After the feature selection process, five machine learning classifiers were created. These classifiers comprised logistic regression (LR), support vector machine (SVM), K-nearest neighbors (KNN), light gradient boosting machine (LightGBM), and multilayer perceptron (MLP). A thorough performance evaluation was carried out, utilizing diverse metrics like the area under the receiver operating characteristic curve (ROC), specificity, accuracy, sensitivity positive predictive value, and negative predictive value. The classifier exhibiting the best performance was chosen. Subsequently, three models were developed: the PD model, the T1 model, and the combined model, all based on the optimal classifier. The diagnostic performance of these models was assessed by employing AUC values, calibration curves, and decision curve analysis. Results Out of 2032 features, 48 features were selected. The SVM-based multi-sequence radiomics outperformed all others, achieving AUC values of 0.973 and 0.927, sensitivities of 0.933 and 0.857, and specificities of 0.930 and 0.829, in the training and validation cohorts, respectively. Conclusion The multi-sequence MRI radiomics model, which is based on machine learning, exhibits exceptional performance in diagnosing ACL tears. It provides valuable insights crucial for the diagnosis and treatment of knee joint injuries, serving as an accurate and objective supplementary diagnostic tool for clinical practitioners.

Background: The relationship between triglyceride glucose (TyG) index and the incidence of acute kidney injury (AKI) in patients with acute myocardial infarction (AMI) is unclear. This study aims to explore the relationship between the two. Methods: Participants were enrolled from Medical Information Mart for Intensive Care IV (MIMICIV) and grouping of subjects based on the quartile interval of the TyG index. With the presence of AKI as the main outcome, a logistic regression model was constructed. The correlation of the TyG index with the results obtained was examined by using a restricted cubic spline (RCS) model. Results: Among the 1,101 AMI participants, 64.7% were male patients and the overall incidence rate of AKI was 37.1%. The results of multivariate Logistic regression analysis (LRA) revealed independent correlation of the TyG index with increased AKI risk (odds ratio (OR) = 2.23; confidence interval (CI) = 1.59 to 3.17; P < 0.001). Q4 (9.5-12.208) in the TyG index quartile was independently correlated with increased AKI risk (OR = 2.99, 95% CI = 1.64 to 5.46, P < 0.001). The RCS model showed that the AKI risk increased linearly as the TyG index increased (P=0.313). Conclusion: In patients with AMI, the incidence of TyG and AKI is closely related. Nevertheless, further studies are needed to verify the finding.

This study incorporated activated Ti nanoparticles (Ti NPs) into Sn1·0Ag0·5Cu (SAC105) solder for vacuum soldering with Cu substrates. The wettability, microstructure, interfacial, and mechanical properties of SAC105-xTi (x = 0.1, 0.2, 0.3, 0.4, 0.5 wt%) composite solder were systematically investigated. The results showed that adding Ti NPs improved the wettability of SAC105 solder, in which the wetting angle of SAC105-0.3Ti solder was 19.51°. Additionally, Ti NPs helped to refine the microstructure and inhibited the growth of interfacial intermetallic compounds (IMC). The shear strength of SAC105/Cu joints increased and then decreased with increasing Ti NPs content, and the optimum shear strength was obtained for SAC105-0.3Ti/Cu joints at 27.98 MPa. The strength of the solder matrix and the IMC layer was altered by adding Ti NPs, resulting in a modification of the fracture path of the joint, bringing it closer to the IMC layer. Excessive addition of Ti NPs could lead to their agglomeration within the joints and result in damage to the mechanical properties of the joints. Furthermore, adding Ti NPs increased the microhardness of SAC105 solder.