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Abstract Background Reinfection rates after two-stage revision (TSR) for prosthetic joint infection (PJI) range from 7.9 to 14%. Many factors, including sinus tracts, are associated with reinfection after this procedure. This study aimed to delineate whether the presence of sinus tract could increase reinfection rate after TSR and to investigate other potential risk factors for reinfection after TSR. Methods We conducted a case-control study by retrospectively reviewing patients who underwent TSR for prosthetic hip joint infection from 2002 to 2022. The case group included patients who developed reinfection after TSR, while the control group consisted of patients who did not experience reinfection. PJI and reinfection after TSR were defined based on Delphi-based international consensus criteria. Patient demographics, past medical history, clinical manifestations, laboratory results, interval between stages, microbiological culture results were collected. Univariate analyses were utilized to assess the effect of sinus tract on reinfection and to identify other risk factors for reinfection after TSR. Results Six patients with reinfection after TSR were included as the case group and 32 patients without reinfection were in the control group. Significant difference was observed in percentage of patients with sinus tracts between the two groups (67% in the case group versus 19% in the control group, p = 0.031, OR = 8.7). Significant difference was also found in percentage of patients with positive cultures of synovial fluid and synovium harvested during the first-stage revision between the two groups (100% in the case group versus 50% in the control group, p = 0.030). Additionally, patients in the case group had a significantly higher C-reactive protein (CRP) level prior to the second stage revision than that of patients in the control group (8.80 mg/L versus 2.36 mg/L, p = 0.005), despite normal CRP levels in all patients. Conclusions Our study revealed that the presence of sinus tracts could significantly increase risk of postoperative reinfection after TSR. Positive cultures during the first stage revision and elevated CRP level prior to the second stage revision could also increase the risk of reinfection after TSR. Further studies with a larger sample size are required. Trial registration Retrospectively registered.

Abstract The liver is the most important metabolic organ in the body. While mouse models and cell lines have further deepened our understanding of liver biology and related diseases, they are flawed in replicating key aspects of human liver tissue, particularly its complex structure and metabolic functions. The organoid model represents a major breakthrough in cell biology that revolutionized biomedical research. Organoids are in vitro three-dimensional (3D) physiological structures that recapitulate the morphological and functional characteristics of tissues in vivo, and have significant advantages over traditional cell culture methods. In this review, we discuss the generation strategies and current advances in the field focusing on their application in regenerative medicine, drug discovery and modeling diseases.

Abstract Salt‐sensitive hypertension is common among individuals with essential hypertension, and the prevalence of left ventricular hypertrophy (LVH) has increased. However, data from early identification of the risk of developing LVH in young adults with salt‐sensitive hypertension are lacking. Thus, the present study aimed to design a nomogram for predicting the risk of developing LVH in young adults with salt‐sensitive hypertension. A retrospective analysis of 580 patients with salt‐sensitive hypertension was conducted. The training set consisted of 70% (n = 406) of the patients, while the validation set consisted of the remaining 30% (n = 174). Based on multivariate analysis of the training set, predictors for LVH were extracted to develop a nomogram. Discrimination curves, calibration curves, and clinical utility were employed to assess the predictive performance of the nomogram. The final simplified nomogram model included age, sex, office systolic blood pressure, duration of hypertension, abdominal obesity, triglyceride‐glucose index, and estimated glomerular filtration rate (eGFR). In the training set, the model demonstrated moderate discrimination, as indicated by an area under the receiver operating characteristic (ROC) curve of 0.863 (95% confidence interval: 0.831–0.894). The calibration curve exhibited good agreement between the predicted and actual probabilities of LVH in the training set. Additionally, the validation set further confirmed the reliability of the prediction nomogram. In conclusions, the simplified nomogram, which consists of seven routine clinical variables, has shown good performance and clinical utility in identifying young adults with salt‐sensitive hypertension who are at high risk of LVH at an early stage.

Abstract Background This study compared the survival outcomes after thermal ablation versus wedge resection in patients with stage I non-small cell lung cancer (NSCLC) ≤ 2 cm. Methods Data from the United States (US) National Cancer Institute Surveillance Epidemiology and End Results (SEER) database from 2004 to 2019 were retrospectively analyzed. Patients with stage I NSCLC and lesions ≤ 2 cm who received thermal ablation or wedge resection were included. Patients who received chemotherapy or radiotherapy were excluded. Propensity-score matching (PSM) was applied to balance the baseline characteristics between patients who underwent the two procedures. Results Univariate and Cox regression analyses were performed to determine the associations between study variables, overall survival (OS), and cancer-specific survival (CSS). After PSM, 328 patients remained for analysis. Multivariable Cox regression analysis revealed, compared to wedge resection, thermal ablation was significantly associated with a greater risk of poor OS (adjusted HR [aHR]: 1.34, 95% CI: 1.09–1.63, p = 0.004) but not CSS (aHR: 1.28, 95% CI: 0.96–1.71, p = 0.094). In stratified analyses, no significant differences were observed with respect to OS and CSS between the two procedures regardless of histology and grade. In patients with tumor size 1 to 2 cm, compared to wedge resection, thermal ablation was significantly associated with a higher risk of poor OS (aHR: 1.35, 95% CI: 1.10–1.66, p = 0.004). In contrast, no significant difference was found on OS and CSS between thermal ablation and wedge resection among those with tumor size

Abstract Enhancing infrared images is essential for detecting wind turbine blades using infrared technology. This paper introduces an Infrared Image Enhancement Method based on Adaptive Iterative Cutoff Threshold Difference Multi-Scale Top-Hat Transformation (AICT-DMTH) to address the challenge of low image clarity in infrared detection. The method involves performing a black-white difference top-hat transformation by utilizing structural elements of varying scales for dilation and erosion. Additionally, an iterative threshold method is applied to extract more detailed image features, followed by setting a cutoff constant to determine the final scale of the structural element. The effectiveness of the proposed method is evaluated both qualitatively and quantitatively, with infrared images from laboratory and wind farm settings enhanced and compared against existing methods. The experimental results indicate that the proposed method significantly improves the clarity of infrared images, demonstrating robustness in enhancing images from various environments.

In response to the challenges of high rock strength in deep underground metal mines, difficulty in slotting, and low efficiency in excavation, based on the tunneling project at Xingshan Underground Iron Mine of Shougang Corporation, and utilizing precise per-hole blasting with digital electronic detonators, we propose a phased blasting scheme for slotting areas of straight-eye barrel-shaped grooves, combining segmentation within and between holes, as well as delays within each hole. In combination with numerical simulations and field tests, it presents a trench domain gradient detonation configuration with differential detonation in the hole area, between holes and within holes on the basis of the original conventional scheme, builds a three-dimensional(3D) model of the trench domain μsing LS-DYNA numerical simulation software, sets up the original conventional scheme and three gradient schemes for modelling, and provides a comparative analysis of the evolution of the effective peak stress in the dredged-trench zone for the original conventional blasting solution and the staged solution. The results of the numerical simulations show that the μse of short-delay inter-hole blasting can change the fluctuation pattern of the peak effective stress, and compared to the original conventional scheme, the peak effective stress state of the rock in the dredged-trench zone along the direction of the shell hole is increased by 40% to 57%, while the peak effective stress state of the rock in the radiμs of 0-30 cm at the bottom of the shell hole is increased by 84% to 92%. In addition to the numerical simulation results, field experiments were carried out to verify the results. It is clear that the combination of short-delay differential detonation between holes can improve debris crowding in mine excavation, and short-delay differential detonation within holes can improve throwing capacity, improve debris throwing after blasting in the upper part of the shell hole, and avoid affecting the blasting of subsequent shell holes. Incorporating the two in hard rock blasting can significantly improve the blasting effect and increase the hollowing progress by 28%. And better results can be obtained in rock point-excavation by μsing short delay between holes and long delay within hole settings. The results of this paper could provide a reference for similar mine production.

Data, recognized as a fundamental strategic resource and key production factor for a nation, has served as the foundational resource and innovation engine for economic and social development. The financial industry, characterized by its data-intensive and technology-driven nature, necessitates the optimal allocation of data assets to facilitate industrial upgrading. However, financial data commonly exhibits issues such as uneven distribution, information asymmetry, and data silos, which have prevented data from fully realizing its value. To address these challenges, various generative models have been actively adopted by financial institutions to synthesize highly realistic data, thereby breaking down data barriers and monopolies, and shaping the future trend of the financial industry. Among these models, Generative Adversarial Networks (GANs) have emerged as particularly popular, demonstrating impressive performance across various fields and showing great potential in generating financial tabular data, financial time series, and detecting financial fraud. The advantages of the GAN model compared with other generative models in the financial field were analyzed. The GAN models that have been applied to the financial field since Generative Adversarial Networks were proposed in 2014 were presented, and the principles of each model were introduced. The application practice of the GAN model in generating financial tabular data, generating financial time series, and financial fraud detection, as well as other financial data fields, was explored. Finally, the challenges and development direction of GANs for the future were discussed, taking into account the actual situation in China.

Polymerase β (POLB), with dual functionality as a lyase and polymerase, plays a critical role in the base excision repair (BER) pathway to maintain genomic stability. POLB knockout and rescue studies in BRCA1/2-mutant cancer cell lines revealed that inhibition of lyase and polymerase activity is required for the synthetic lethal interaction observed with PARP inhibitors, highlighting POLB as a valuable therapeutic target. Traditional biochemical assays to screen for enzyme inhibitors focus on a single substrate to product relationship and limit the comprehensive analysis of enzymes such as POLB that utilize multiple substrates or catalyze a multi-step reaction. This report describes the first high-throughput mass spectrometry-based screen to measure the two distinct biochemical activities of POLB in a single assay using a duplexed self-assembled monolayer desorption ionization (SAMDI) mass spectrometry methodology. A multiplexed assay for POLB dual enzymatic activities was developed optimizing for kinetically balanced conditions and a collection of 200,000 diverse small molecules was screened in the duplexed format. Small molecule modulators identified in the screen were confirmed in a traditional fluorescence-based polymerase strand-displacement assay and an orthogonal label-free binding assay using SAMDI affinity selection mass spectrometry (ASMS). This work demonstrates the flexibility of high-throughput mass spectrometry approaches in drug discovery and highlights a novel application of SAMDI technology that opens new avenues for multiplexed high-throughput screening.

Background Dyslipidemia plays a very important role in the occurrence and development of cardiovascular disease (CVD). Genetic factors, including single nucleotide polymorphisms (SNPs), are one of the main risks of dyslipidemia. 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) is not only the rate-limiting enzyme step of endogenous cholesterol production, but also the therapeutic target of statins. Methods We investigated 405 Han Chinese and 373 Uyghur people who took statins for a period of time, recorded their blood lipid levels and baseline data before and after oral statin administration, and extracted DNA from each subject for SNP typing of HMGCR rs17671591 and rs3761740. The effects of HMGCR rs17671591 and rs3761740 on lipid levels and the effect of statins on lipid lowering in Han Chinese and Uyghur ethnic groups were studied. Results In this study, for rs17671591, the CC vs. TT+CT model was significantly correlated with the level of LDL-C before oral statin in the Uyghur population, but there were no correlations between rs17671591 and the level of blood lipid before oral statin in the Han population. The CC vs. TT+CT and CT vs. CC+TT models were significantly correlated with the level of LDL-C after oral statin in the Uyghur population. There was no significant correlation between rs3761740 with blood lipids before and after oral statin in the Han population. For rs3761740, before oral statin, the CC vs. AA+CA model was significantly correlated with the level of LDL-C, and the CA vs. CC+AA model was significantly correlated with the level of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and non-high density lipoprotein cholesterol (HDL-C) in the Uyghur population. After oral statin, the CC vs. AA+CA and CA vs. CC+AA models were significantly correlated with the level of TC, LDL-C, and apolipoprotein (APOB), and the C vs. A model was significantly correlated with the level of TC, triglyceride (TG), LDL-C, and APOB in the Uyghur population. Particularly, the CT vs. CC+TT model of rs17671591 was significantly correlated with the changes of LDL-C after oral statin in the Uyghur population. In this study, we also explored the association of rs17671591 and rs3761740 with the rate of dyslipidemia as a reference. Conclusion We found that HMGCR rs3761740 was correlated with the levels of TC, LDL-C, and non-HDL-C before and after oral statin in Uyghurs, but not with blood lipid levels in the Han population. In the Uyghur population, HMGCR rs17671591 was associated with the level of LDL-C before and after oral statin, and also affected the changes of LDL-C after oral statin.

Abstract Chimeric RNAs, distinct from DNA gene fusions, have emerged as promising therapeutic targets with diverse functions in cancer treatment. However, the functional significance and therapeutic potential of most chimeric RNAs remain unclear. Here we identify a novel fusion transcript of solute carrier family 2‐member 11 (SLC2A11) and macrophage migration inhibitory factor (MIF). In this study, we investigated the upregulation of SLC2A11–MIF in The Cancer Genome Atlas cohort and a cohort of patients from Sun Yat‐Sen Memorial Hospital. Subsequently, functional investigations demonstrated that SLC2A11–MIF enhanced the proliferation, antiapoptotic effects, and metastasis of bladder cancer cells in vitro and in vivo. Mechanistically, the fusion protein encoded by SLC2A11–MIF interacted with polypyrimidine tract binding protein 1 (PTBP1) and regulated the mRNA half‐lives of Polo Like Kinase 1, Roundabout guidance receptor 1, and phosphoinositide‐3‐kinase regulatory subunit 3 in BCa cells. Moreover, PTBP1 knockdown abolished the enhanced impact of SLC2A11–MIF on biological function and mRNA stability. Furthermore, the expression of SLC2A11–MIF mRNA is regulated by CCCTC‐binding factor and stabilized through RNA N4‐acetylcytidine modification facilitated by N‐acetyltransferase 10. Overall, our findings revealed a significant fusion protein orchestrated by the SLC2A11–MIF–PTBP1 axis that governs mRNA stability during the multistep progression of bladder cancer.

Interfacial differences between the Hf0.5Zr0.5O2 (HZO) and the top/bottom electrodes caused by the process sequence could lead to the imprint effect of the TiN/HZO/TiN ferroelectric capacitor, which leads to serious reliability problems. In this article, a method of introducing a HfO2 protective layer is proposed to inhibit the imprint effect of the TiN/HZO/TiN ferroelectric capacitor. By introducing the HfO2 protective layer, the leakage current at the positive electric field is reduced by three orders of magnitude, the asymmetry of the coercive field is reduced from 1.5 to 0.1 MV/cm, and the endurance is improved by two orders of magnitude with no degradation in retention. The proposed method provides a feasible strategy to inhibit the imprint effect of TiN/HZO/TiN ferroelectric capacitors and is more compatible with complementary metal–oxide–semiconductor processes.

The fault current of the photovoltaic (PV)/battery energy storage (BES) hybrid power generation system contains harmonic components, which might cause the maloperation of the distance relay. The time-domain distance protection has attracted more attention recently. However, the distributed capacitance of long transmission lines negatively affects the performance of time-domain distance protection, which hinders its application. To solve this problem, this paper proposes an improved time-domain distance protection based on fault active control. By leveraging the fault active control capability of the BES inverter, a specific low-frequency characteristic voltage is modulated through the phase-locked loop (PLL). By injecting the low-frequency characteristic voltage, the influence of line distributed capacitance can be ignored. Thus, the accuracy of time-domain distance protection based on the equivalent R-L model of transmission lines is guaranteed, which is the first advantage of injecting the low-frequency characteristic voltage. The other advantage is the low-frequency components only exist between the BES and the fault point, and will not flow to the grid on the opposite side of the line. The accuracy of time-domain distance protection has been further improved. In Addition, the faulty line’s derivative equations for different fault types are deduced based on fault active control. Finally, the least square algorithm is used to calculate fault distance. The proposed scheme’s feasibility and effectiveness are verified through simulations in PSCAD/EMTDC.

ABSTRACT Numerous host factors, in addition to human angiotensin-converting enzyme 2 (hACE2), have been identified as coreceptors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demonstrating broad viral tropism and diversified druggable potential. We and others have found that antihistamine drugs, particularly histamine receptor H1 (HRH1) antagonists, potently inhibit SARS-CoV-2 infection. In this study, we provided compelling evidence that HRH1 acts as an alternative receptor for SARS-CoV-2 by directly binding to the viral spike protein. HRH1 also synergistically enhanced hACE2-dependent viral entry by interacting with hACE2. Antihistamine drugs effectively prevent viral infection by competitively binding to HRH1, thereby disrupting the interaction between the spike protein and its receptor. Multiple inhibition assays revealed that antihistamine drugs broadly inhibited the infection of various SARS-CoV-2 mutants with an average IC50 of 2.4 µM. The prophylactic function of these drugs was further confirmed by authentic SARS-CoV-2 infection assays and humanized mouse challenge experiments, demonstrating the therapeutic potential of antihistamine drugs for combating coronavirus disease 19.IMPORTANCEIn addition to human angiotensin-converting enzyme 2, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can utilize alternative cofactors to facilitate viral entry. In this study, we discovered that histamine receptor H1 (HRH1) not only functions as an independent receptor for SARS-CoV-2 but also synergistically enhances ACE2-dependent viral entry by directly interacting with ACE2. Further studies have demonstrated that HRH1 facilitates the entry of SARS-CoV-2 by directly binding to the N-terminal domain of the spike protein. Conversely, antihistamine drugs, primarily HRH1 antagonists, can competitively bind to HRH1 and thereby prevent viral entry. These findings revealed that the administration of repurposable antihistamine drugs could be a therapeutic intervention to combat coronavirus disease 19.

Abstract Cancer stem cells (CSCs) are believed to be responsible for cancer metastasis and recurrence due to their self-renewal ability and resistance to treatment. However, the mechanisms that regulate the stemness of CSCs remain poorly understood. Recently, evidence has emerged suggesting that long non-coding RNAs (lncRNAs) play a crucial role in regulating cancer cell function in different types of malignancies, including gastric cancer (GC). However, the specific means by which lncRNAs regulate the function of gastric cancer stem cells (GCSCs) are yet to be fully understood. In this study, we investigated a lncRNA known as HNF1A-AS1, which is highly expressed in GCSC s and serves as a critical regulator of GCSC stemness and tumorigenesis. Our experiments, both in vitro and in vivo, demonstrated that HNF1A-AS1 maintained the stemness of GC cells. Further analysis revealed that HNF1A-AS1, transcriptionally activated by CMYC, functioned as a competing endogenous RNA by binding to miR-150-5p to upregulate β-catenin expression. This in turn facilitated the entry of β-catenin into the nucleus to activate the Wnt/β-catenin pathway and promote CMYC expression, thereby forming a positive feedback loop that sustained the stemness of GCSCs. We also found that blocking the Wnt/β-catenin pathway effectively inhibited the function of HNF1A-AS1, ultimately resulting in the inhibition of GCSC stemness. Taken together, our results demonstrated that HNF1A-AS1 is a regulator of the stemness of GCSCs and could serve as a potential marker for targeted GC therapy.

Abstract Background We aimed to explore the application value of various machine learning (ML) algorithms based on multicenter CT radiomics in identifying peripheral nerve invasion (PNI) of colorectal cancer (CRC). Methods A total of 268 patients with colorectal cancer who underwent CT examination in two hospitals from January 2016 to December 2022 were considered. Imaging and clinicopathological data were collected through the Picture Archiving and Communication System (PACS). The Feature Explorer software (FAE) was used to identify the peripheral nerve invasion of colorectal patients in center 1, and the best feature selection and classification channels were selected. Finally, the best feature selection and classifier pipeline were verified in center 2. Results The six-feature models using RFE feature selection and GP classifier had the highest AUC values, which were 0.610, 0.699, and 0.640, respectively. FAE generated a more concise model based on one feature (wavelet-HLL-glszm-LargeAreaHighGrayLevelEmphasis) and achieved AUC values of 0.614 and 0.663 on the validation and test sets, respectively, using the “one standard error” rule. Using ANOVA feature selection, the GP classifier had the best AUC value in a one-feature model, with AUC values of 0.611, 0.663, and 0.643 on the validation, internal test, and external test sets, respectively. Similarly, when using the “one standard error” rule, the model based on one feature (wave-let-HLL-glszm-LargeAreaHighGrayLevelEmphasis) achieved AUC values of 0.614 and 0.663 on the validation and test sets, respectively. Conclusions Combining artificial intelligence and radiomics features is a promising approach for identifying peripheral nerve invasion in colorectal cancer. This innovative technique holds significant potential for clinical medicine, offering broader application prospects in the field. Critical relevance statement The multi-channel ML method based on CT radiomics has a simple operation process and can be used to assist in the clinical screening of patients with CRC accompanied by PNI. Key points • Multi-channel ML in the identification of peripheral nerve invasion in CRC. • Multi-channel ML method based on CT-radiomics can detect the PNI of CRC. • Early preoperative identification of PNI in CRC is helpful to improve the formulation of treatment strategies and the prognosis of patients. Graphical Abstract

Abstract Background Patients who underwent knee joint arthroplasty were at risk of venous thromboembolic events (VTEs), however, less studies were conducted to demonstrate the epidemiology and risk factors of deep venous thrombosis (DVT) following unicompartmental knee arthroplasty (UKA). Objective of this study was to explore the incidence and prognostic factors of DVT after UKA. Methods Patients who underwent primary UKA from December 2018 to June 2022 were recruited in this study. Demographic characteristics, operation related variables and laboratory index were extracted and analyzed. Receiver operating characteristic analysis was performed to detect the optimum cut-off value for variables of interest. Univariate and multivariate logistic analysis were performed to identify risk factors of DVT. Results 351 UKAs with a mean age of 65.4 ± 7.1 years were reviewed. After 12.9 ± 11.2 months follow-up, 35 DVTs were confirmed which indicating an incidence of 9.9%. The results showed that occupation (agricultural laborer) (P = 0.008), disease duration > 8.5 years (P = 0.035), operation time > 169 min (P = 0.003), intraoperative blood loss > 102 ml (P 26.8 kg/m 2 (P = 0.001), preoperative D-dimer > 0.29 mg/L (P = 0.001), prothrombin time 102 ml (OR, 3.707; P, 0.001), BMI > 26.8 kg/m 2 (OR, 4.664; P, 0.004) and D-dimer > 0.29 mg/L (OR, 2.882; P, 0.009) were independent risk factors of DVT after UKA. Conclusion The incidence of DVT in the present study was 9.9%, extensive intraoperative blood loss, advanced BMI and high level of D-dimer would increase the risk of lower extremity thrombosis by 2–4 times.

Background and aims: Patients with peripheral artery disease (PAD) presented overall muscle weakness and reduced physical performance. Previous study focused on the impact of muscle weakness on outcomes of established PAD, however the relationship between compromised muscle function and incident PAD remained unclear. Methods: A prospective study involving 430,886 participants aged 40–69 y from UK biobank was conducted. The main outcome was incident PAD. Grip strength and walking pace were used as indicators for muscle function. Grip strength was measured using a Jamar J00105 hydraulic hand dynamometer, while walking pace was self-reported by the participants. Cox proportional hazard models were employed to investigate the relationship between grip strength, walking pace, and incident PAD. Results: A total of 430,886 individuals were included in the final analysis. The mean age of the participants were 56.44 years, and 55.3 % were female. Over a median follow-up period of 13.81 years, 5,661 participants developed PAD. Higher grip strength, whether absolute or relative, exhibited a dose-dependent inverse association with incident PAD. Each 1 kg increment in absolute grip strength and each 0.01 kg/kg increase in relative grip strength were associated with reduced PAD risk by 2 % (HR: 0.98; 95 % CI [0.97–0.98]) and 83 % (HR: 0.17; 95 % CI [0.13–0.23]), respectively. Slow walking pace significantly correlated with increased PAD risk, while brisk walking pace was associated with decreased PAD risk. Conclusion: Absolute grip strength, relative grip strength and walking pace were inversely associated with the risk of incident PAD.

Background: This study aimed at developing and validating a risk score to predict in-stent restenosis (ISR) in patients with premature acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) with drug-eluting stent (DES). Methods: This was a two-center retrospective study. A total of 2185 patients firstly diagnosed with premature AMI (age ≥18 years and

Abstract Fabrication of versatile hydrogels in a facile and effective manner represents a pivotal challenge in the field of biomaterials. Herein, a novel strategy is presented for preparing on‐demand degradable hydrogels with multilevel responsiveness. By employing selenol‐dichlorotetrazine nucleophilic aromatic substitution (SNAr) to synthesize hydrogels under mild conditions in a buffer solution, the necessity of additives or posttreatments can be obviated. The nucleophilic and redox reactions between selenol and tetrazine culminate in the formation of three degradable chemical bonds—diselenide, aryl selenide, and dearomatized selenide—in a single, expeditious step. The resultant hydrogel manifests exceptional adaptability to intricate environments in conjunction with self‐healing and on‐demand degradation properties. Furthermore, the resulting material demonstrated light‐triggered antibacterial activity. Animal studies further underscore the potential of integrating metformin into Se‐Tz hydrogels under green light irradiation, as it effectively stimulates angiogenesis and collagen deposition, thereby fostering efficient wound healing. In comparison to previously documented hydrogels, Se‐Tz hydrogels exhibit controlled degradation and drug release, outstanding antibacterial activity, mechanical robustness, and bioactivity, all without the need for costly and intricate preparation procedures. These findings underscore Se‐Tz hydrogels as a safe and effective therapeutic option for diabetic wound dressings.

Raisins, derived from dried grapes, represent a valuable commodity rich in secondary metabolites, particularly volatile organic compounds (VOCs). The primary objective of this review is to identify the VOCs that are influencing the aromatic profile of raisins to improve consumer preferences. However, extensive research has been done to optimize grape drying methods for different raisin attributes. In the context of this review, an in-depth investigation of published literature revealed the extraction of over 120 VOCs from raisins using SPME. Furthermore, we explored factors shaping raisin aroma and the sources of VOC generation. This review aims to pinpoint research gaps and provide an opportunity for future developments in studying raisins' aroma. This involves integrating advanced analytical techniques, examining processing method impacts, and considering consumer perception to enhance the overall understanding of raisin aromas. The outcomes are anticipated to provide valuable insights for the industry and the scientific community.

Background: The slash disposal-burning forest-in high-intensity management Eucalyptus grandis × urophylla plantation has accelerated soil degradation. Statement of the problem: Slash disposals is a contributing factor, but its specific role in the correlation between rainfall-runoff and soil erosion remains elusive. Objectives: his study investigated the characteristics of rainfall-runoff and soil erosion resistance in different methods of slash disposals in plantation. Methods: Three methods of slash disposal, namely burning forest (BF), moving away (MA), and spreading evenly (SE), were established. A field simulation experiment of rainfall was conducted, and path analysis was used. Results: The findings revealed that the water holding, infiltrating properties and the time the rainfall-runoff generated of SE were increased by approximately 10∼20 %, 100 %, and 80 %, respectively, compared with BF and MA. Water loss, soil loss and nutrient loss were significantly reduced by 62.23 % and 61.56 %, 69.06 % and 49.55 %, and 58.8 % and 65.42 % in SE and BF compared to MA. Path analysis suggested that different from BF and MA, the correlation between soil water properties and rainfall-runoff factors in SE was weakened, simultaneously considering the result that SE had the lower proportions of silt for sediment component (75.31 %), it stabilized the soil structure. Conclusions and prospect: Consequently, SE mitigated the erosion force by reducing rainfall-runoff and enhancing the anti-erosion of soil through improved water properties, making it a viable slash disposal. This work provides a detailed description of the soil erosion characteristics of plantation, including water, soil, and nutrient losses caused by rainfall-runoff, as well as the soil anti-erosion due to different slash disposals. These findings offer valuable insights for the management of high-intensity Eucalyptus grandis × urophylla plantations.

Abstract Background Chikungunya virus (CHIKV) has reemerged as a major public health concern, causing chikungunya fever with increasing cases and neurological complications. Methods In the present study, we investigated a low-passage human isolate of the East/ Central/South African (ECSA) lineage of CHIKV strain LK(EH)CH6708, which exhibited a mix of small and large viral plaques. The small and large plaque variants were isolated and designated as CHIKV-SP and CHIKV-BP, respectively. CHIKV-SP and CHIKV-BP were characterized in vitro and in vivo to compare their virus production and virulence. Additionally, whole viral genome analysis and reverse genetics were employed to identify genomic virulence factors. Results CHIKV-SP demonstrated lower virus production in mammalian cells and attenuated virulence in a murine model. On the other hand, CHIKV-BP induced higher pro-inflammatory cytokine levels, compromised the integrity of the blood–brain barrier, and led to astrocyte infection in mouse brains. Furthermore, the CHIKV-SP variant had limited transmission potential in Aedes albopictus mosquitoes, likely due to restricted dissemination. Whole viral genome analysis revealed multiple genetic mutations in the CHIKV-SP variant, including a Glycine (G) to Arginine (R) mutation at position 55 in the viral E2 glycoprotein. Reverse genetics experiments confirmed that the E2-G55R mutation alone was sufficient to reduce virus production in vitro and virulence in mice. Conclusions These findings highlight the attenuating effects of the E2-G55R mutation on CHIKV pathogenicity and neurovirulence and emphasize the importance of monitoring this mutation in natural infections.

In coastal plains, saline water intrusion (SWI) and potentially hazardous pollutants are harmful to local human health. The southern Laizhou Bay has become a typical representative of the northern silty coast due to its extensive silt sedimentation and the significant impact of human activities. This research focuses on a portion of the southern Laizhou Bay, using GIS-based spatial analysis, water quality index methods and health risk assessments to evaluate the impact of saltwater intrusion and potential hazardous pollutants. The results show that the groundwater in the study area is significantly impacted by saline water intrusion, leading to major ion concentrations that far exceed World Health Organization (WHO) standards. The groundwater chemical types of brine and brackish water in the study area are mainly Cl-Na, and the main chemical types of fresh water are HCO3-Ca·Na. The average concentration sequence of the main ions in groundwater is K+ > HCO3− > Cl− > Na+ > SO42− > Ca2+ > Mg2+. The average hazard quotient (HQ) sequence in typical pollutants is Cl− > F− > NO3-N > Se > Mn > NO2-N > Cu > Pb > Zn > Fe, and the carcinogenic risk (CR) sequence caused by carcinogenic heavy metals is Cd > As > Cr. The noncarcinogenic health risk area is mainly distributed in the northwest of the study area, while the potential carcinogenic risk area is in the central region. The Cl is the greatest noncarcinogenic risk to adults and children. The mean HQ values for adults and children were 95.69 and 146.98, indicating a significant noncarcinogenic risk. The mean CR values for adults and children were 0.00037 and 0.00057, suggesting a relatively low carcinogenic risk. SWI is the main influencing factor on human health; therefore, it is necessary to prevent and control SWI. Moreover, potentially hazardous pollutants are carcinogenic and noncarcinogenic risks and are caused by agriculture, industry and other human activities. The findings of this research offer scientific insights for groundwater pollution control and saline water intrusion management in similar coastal areas.

To address the harmonic issues associated with the pulse width modulation (PWM) method, this article introduces variable delayed time (VDT) space vector pulse width modulation (SVPWM) with double central symmetry for dual three-phase permanent magnet synchronous machines (DTP-PMSMs). Firstly, the switching sequence of four traditional vectors undergoes double central symmetry, resulting in the doubling of the frequency of the phase voltage. This alteration eliminates harmonics occurring at odd multiples of carrier frequency. Additionally, the adopting of a single null vector minimizes the additional switching times introduced by the double central symmetry. Subsequently, VDT-SVPWM is employed to further suppress the harmonics at the even multiples of carrier frequency. The implementation of the proposed double central symmetry method involves directly utilizing the calculated duty cycle of the traditional four vectors. Moreover, integrating VDT-SVPWM with the double central symmetry method is straightforward. Simulation and experimental results validate the efficacy of the proposed method in suppressing harmonics and mitigating vibrations in the DTP-PMSM.

In the context of sustainable development, market competition is intensifying, and financial constraints have emerged as a significant hindrance to green project investment. Green Supply Chain Finance (GSCF), characterized by long-term collaboration, has emerged as a crucial financial approach to mitigate corporate financial limitations and channel capital flows into environmentally friendly industries. We propose a two-echelon supply chain with one supplier and two competing retailers over a single period and investigate ordering, sales, and financing decisions simultaneously under competition. Retailers constrained by financial considerations may secure GSCF or traditional bank financing (BF) loans. This study investigates the influence of competition on pricing and sales strategies during the selling season. The results demonstrate that retailers select between clearance and responsive selling strategies based on the level of market competition. During the ordering season, retailers share the product market equally when interest rates are uniform, and the supplier formulates a supply chain contract while considering the financing interest rate. In the presence of differential interest rates, retailers may not always opt for the GSCF, even when they offer an interest rate advantage, due to the comprehensive impacts of operational and financial strategies. Remarkably, competitive retailers do not choose the GSCF when their initial green investment capital surpasses a certain threshold.

Leaves of Camellia sinensis plants are used to produce tea, one of the most consumed beverages worldwide, containing a wide variety of bioactive compounds that help to promote human health. Tea cultivation is economically important, and its sustainable production can have significant consequences in providing agricultural opportunities and lowering extreme poverty. Soil parameters are well known to affect the quality of the resultant leaves and consequently, the understanding of the diversity and functions of soil microorganisms in tea gardens will provide insight to harnessing soil microbial communities to improve tea yield and quality. Current analyses indicate that tea garden soils possess a rich composition of diverse microorganisms (bacteria and fungi) of which the bacterial Proteobacteria, Actinobacteria, Acidobacteria, Firmicutes and Chloroflexi and fungal Ascomycota, Basidiomycota, Glomeromycota are the prominent groups. When optimized, these microbes’ function in keeping garden soil ecosystems balanced by acting on nutrient cycling processes, biofertilizers, biocontrol of pests and pathogens, and bioremediation of persistent organic chemicals. Here, we summarize research on the activities of (tea garden) soil microorganisms as biofertilizers, biological control agents and as bioremediators to improve soil health and consequently, tea yield and quality, focusing mainly on bacterial and fungal members. Recent advances in molecular techniques that characterize the diverse microorganisms in tea gardens are examined. In terms of viruses there is a paucity of information regarding any beneficial functions of soil viruses in tea gardens, although in some instances insect pathogenic viruses have been used to control tea pests. The potential of soil microorganisms is reported here, as well as recent techniques used to study microbial diversity and their genetic manipulation, aimed at improving the yield and quality of tea plants for sustainable production.

ObjectiveTo investigate the changes in gut microbes and their metabolites after administering synbiotics to patients with new-onset lupus nephritis (LN) treated using a conventional method and provide a theoretical basis for finding new targets for the diagnosis and treatment of LN.MethodsIn this study, a total of 12 participants were divided into the lupus and synbiotic groups. Stool samples and clinical data were collected before and after treatment for metagenomic, nontargeted metabolomic, and statistical analyses.ResultsThe relative abundances of the pathogenic bacteria Prevotella, Bacteroides, and Enterobacteriaceae_unclassified decreased after synbiotic treatment, whereas the abundances of Actinobacteria and Firmicutes increased. Further, the Firmicutes to Bacteroidetes ratio increased; however, the difference was not statistically significant (p > 0.05). α diversity analysis showed no significant differences in the intestinal microbial richness and diversity index of patients with LN between the groups before and after treatment (p > 0.05). β analysis showed the differences in the community structure between the samples of the two groups before and after treatment. Linear discriminant analysis effect size and receiver operating characteristic curve analyses revealed that Negativicutes (AUC = 0.9722) and Enterobacteriaceae_unclassified (AUC = 0.9722) were the best predictors of the lupus and synbiotic groups, respectively, before and after treatment. Joint analyses revealed that amino acid biosynthesis, aminoacyl-tRNA biosynthesis, purine metabolism, and other metabolic pathways may be involved in the changes in the metabolic function of patients with LN after the addition of synbiotics. Spearman’s correlation analysis revealed the interaction between clinical features and flora, and flora exhibited a complex biological network regulatory relationship.ConclusionSynbiotics regulate the metabolic functions of intestinal microorganisms in patients with LN and play a role in various biological functions. Synbiotic supplements may be safe and promising candidates for patients with LN.

Synapse is the fundamental structure for neurons to transmit information between cells. The proper synapse formation is crucial for developing neural circuits and cognitive functions of the brain. The aberrant synapse formation has been proved to cause many neurological disorders, including autism spectrum disorders and intellectual disability. Synaptic cell adhesion molecules (CAMs) are thought to play a major role in achieving mechanistic cell-cell recognition and initiating synapse formation via trans-synaptic interactions. Due to the diversity of synapses in different brain areas, circuits and neurons, although many synaptic CAMs, such as Neurexins (NRXNs), Neuroligins (NLGNs), Synaptic cell adhesion molecules (SynCAMs), Leucine-rich-repeat transmembrane neuronal proteins (LRRTMs), and SLIT and NTRK-like protein (SLITRKs) have been identified as synaptogenic molecules, how these molecules determine specific synapse formation and whether other molecules driving synapse formation remain undiscovered are unclear. Here, to provide a tool for synapse labeling and synaptic CAMs screening by artificial synapse formation (ASF) assay, we generated synaptotagmin-1-tdTomato (Syt1-tdTomato) transgenic mice by inserting the tdTomato-fused synaptotagmin-1 coding sequence into the genome of C57BL/6J mice. In the brain of Syt1-tdTomato transgenic mice, the tdTomato-fused synaptotagmin-1 (SYT1-tdTomato) signals were widely observed in different areas and overlapped with synapsin-1, a widely-used synaptic marker. In the olfactory bulb, the SYT1-tdTomato signals are highly enriched in the glomerulus. In the cultured hippocampal neurons, the SYT1-tdTomato signals showed colocalization with several synaptic markers. Compared to the wild-type (WT) mouse neurons, cultured hippocampal neurons from Syt1-tdTomato transgenic mice presented normal synaptic neurotransmission. In ASF assays, neurons from Syt1-tdTomato transgenic mice could form synaptic connections with HEK293T cells expressing NLGN2, LRRTM2, and SLITRK2 without immunostaining. Therefore, our work suggested that the Syt1-tdTomato transgenic mice with the ability to label synapses by tdTomato, and it will be a convenient tool for screening synaptogenic molecules.

ABSTRACT The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a global pandemic, which severely endangers public health. Our and others’ works have shown that the angiotensin-converting enzyme 2 (ACE2)-containing exosomes (ACE2-exos) have superior antiviral efficacies, especially in response to emerging variants. However, the mechanisms of how the virus counteracts the host and regulates ACE2-exos remain unclear. Here, we identified that SARS-CoV-2 nonstructural protein 6 (NSP6) inhibits the production of ACE2-exos by affecting the protein level of ACE2 as well as tetraspanin-CD63 which is a key factor for exosome biogenesis. We further found that the protein stability of CD63 and ACE2 is maintained by the deubiquitination of proteasome 26S subunit, non-ATPase 12 (PSMD12). NSP6 interacts with PSMD12 and counteracts its function, consequently promoting the degradation of CD63 and ACE2. As a result, NSP6 diminishes the antiviral efficacy of ACE2-exos and facilitates the virus to infect healthy bystander cells. Overall, our study provides a valuable target for the discovery of promising drugs for the treatment of coronavirus disease 2019.IMPORTANCEThe outbreak of coronavirus disease 2019 (COVID-19) severely endangers global public health. The efficacy of vaccines and antibodies declined with the rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants. Angiotensin-converting enzyme 2-containing exosomes (ACE2-exos) therapy exhibits a broad neutralizing activity, which could be used against various viral mutations. Our study here revealed that SARS-CoV-2 nonstructural protein 6 inhibited the production of ACE2-exos, thereby promoting viral infection to the adjacent bystander cells. The identification of a new target for blocking SARS-CoV-2 depends on fully understanding the virus-host interaction networks. Our study sheds light on the mechanism by which the virus resists the host exosome defenses, which would facilitate the study and design of ACE2-exos-based therapeutics for COVID-19.

Summary: Drug resistance is the leading problem in non-small-cell lung cancer (NSCLC) therapy. The contribution of histone methylation in mediating malignant phenotypes of NSCLC is well known. However, the role of histone methylation in NSCLC drug-resistance mechanisms remains unclear. Here, our data show that EZH2 and G9a, two histone methyltransferases, are involved in the drug resistance of NSCLC. Gene manipulation results indicate that the combination of EZH2 and G9a promotes tumor growth and mediates drug resistance in a complementary manner. Importantly, clinical study demonstrates that co-expression of both enzymes predicts a poor outcome in patients with NSCLC. Mechanistically, G9a and EZH2 interact and promote the silencing of the tumor-suppressor gene SMAD4, activating the ERK/c-Myc signaling pathway. Finally, SU08, a compound targeting both EZH2 and G9a, is demonstrated to sensitize resistant cells to therapeutic drugs by regulating the SMAD4/ERK/c-Myc signaling axis. These findings uncover the resistance mechanism and a strategy for reversing NSCLC drug resistance.

Abstract HTO has proven to be a cost-effective surgical procedure in the treatment of KOA, but few investigations have studied radiological changes and clinical effectiveness of OWHTO in geriatric patients. 76 patients were recruited in this retrospective study. According to the age, patients were divided into two groups (≤ 60, Group “Young”; > 60, Group “Geriatric”). Demographic data, radiological imaging and postoperative complications were analyzed. Kellgren–Lawrence grade (K–L), weight-bearing line ratio (WBLR); posterior tibial slope angle (PTS); American knee score (AKS); Western Ontario and McMaster Universities Arthritis Index (WOMAC) and visual analog scale (VAS) were introduced to estimate the clinical outcome of OWHTO. There were 18 male and 58 female patients in the present study with a mean age of 58.5 ± 9.2 years (ranges from 40 to 82 years); the average age was 51.4 ± 4.1 years and 67.3 ± 4.9 years for group Y and G respectively, 44.7% and 31.5% patients were older than 60 and 65 years. BMI for the 76 patients was 26.6 ± 3.2 kg/m2, and geriatric patients were more likely accompanied by one or more comorbidities (70.6 vs. 45.2%). There were 34 and 42 patients in group Geriatric and group Young respectively, and no significant difference of MPTA, WBLR, PTS and WOMAC, VAS, AKS and ROM between the two group (P > 0.05) were found. After more than a two-year follow-up period, postoperative WBLR, AKS, WOMAC and VAS were much more desired than preoperative, and no significant difference of these variables between the young and geriatric group (P > 0.05), however, elderly patients were more likely to suffer from a longer bone union time. OWHTO can avoid geriatric patients from undergoing secondary knee surgery in the short term, however the survival rate of OWHTO in geriatric patients should be ultimately clarified by different studies.

Abstract The dynamic regulation of supramolecular chirality in non-equilibrium systems can provide valuable insights into molecular self-assembly in living systems. Herein, we demonstrate the use of chemical fuels for regulating self-assembly pathway, which thereby controls the supramolecular chirality of assembly in non-equilibrium systems. Depending on the nature of different fuel acids, the system shows pathway-dependent non-equilibrium self-assembly, resulting in either dynamic self-assembly with transient supramolecular chirality or kinetically trapped self-assembly with inverse supramolecular chirality. More importantly, successive conducting of chemical-fueled process and thermal annealing process allows for the sequential programmability of the supramolecular chirality between four different chiral hydrogels, affording a new example of a multistate supramolecular chiroptical switch that can be recycled multiple times. The current finding sheds new light on the design of future supramolecular chiral materials, offering access to alternative self-assembly pathways and kinetically controlled non-equilibrium states.

Abstract Long non-coding RNAs (lncRNAs) are key regulators during the development of breast cancer (BC) and thus may be viable treatment targets. In this study, we found that the expression of the long intergenic non-coding RNA 01016 (LINC01016) was significantly higher in BC tissue samples with positive lymph node metastasis. LINC01016, which is activated by the transcription factor ETS-1, contributes to the overt promotion of cell proliferation activity, enhanced cell migratory ability, S phase cell cycle arrest, and decreased apoptosis rate. By RNA pull-down assays and mass spectrometry analyses, we determined that LINC01016 competitively bound and stabilized DHX9 protein by preventing the E3 ubiquitin ligase RFFL from binding to DHX9, thereby inhibiting DHX9 proteasomal degradation. This ultimately led to an increase in intracellular DHX9 expression and activated PI3K/AKT signaling, with p-AKT, Bcl-2, and MMP-9 involvement. This is the first study to reveal that the LINC01016/DHX9/PI3K/AKT axis plays a critical role in the progression of BC, and thus, LINC01016 may serve as a potential therapeutic target for patients with BC.